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PubMed2001

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients.

To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg(-1) i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day(-1)) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.

Adult↗

PubMed2000

Neonatal cerebral oxygen regulation after hypothermic cardiopulmonary bypass and circulatory arrest.

OBJECTIVE: Despite technical advances, neurologic sequelae continue to occur in neonates after heart surgery using deep hypothermic cardiopulmonary bypass (dhCPB) and circulatory arrest (DHCA). This study sought to determine the cerebral microcirculatory responses to hypoxia, hypotension, hypocapnia, and hypercapnia after dhCPB and DHCA. DESIGN: Prospective laboratory animal trial. SETTING: Research laboratory. SUBJECTS: Twenty-eight newborn pigs. INTERVENTIONS: Piglets were divided into control, dhCPB, and DHCA groups. The control group received surgery. The dhCPB group received surgery and deep hypothermic CPB for 40 mins. The DHCA group received surgery, deep hypothermic CPB for 40 mins, and circulatory arrest for 60 mins. Two hours after the intervention, cerebral microcirculatory responses were examined. MEASUREMENTS AND MAIN RESULTS: Cerebral microcirculatory responses consisted of changes in cerebral oxygen saturation (Sco2) and pial arteriolar diameter measured by near- infrared spectroscopy and intravital microscopy, respectively. All groups experienced similar decreases in Sco2 and increases in pial arteriolar diameter in response to moderate and severe hypoxia (Pao2, 35 and 25 torr, respectively) and moderate and severe hypotension (mean pressure, 30 and 20 mm Hg, respectively). Sco2 and pial arteriolar diameter decreased to hypocapnia (Paco2, 25 torr) similarly in all groups. To hypercapnia (Paco2, 70 torr), Sco2 increased in the control group, did not change in the dhCPB group, and decreased in the DHCA group. Pial arteriolar diameter to hypercapnia increased in the control and the dhCPB groups but did not change in the DHCA group. CONCLUSIONS: Cerebral vascular and oxygenation responses to hypoxia, hypocapnia, and hypotension were preserved after dhCPB and 1 hr of DHCA. By comparison, cerebral vascular and oxygenation responses to hypercapnia were not; both vascular and oxygenation responses were altered after DHCA, but only the oxygenation response was altered after dhCPB. These data suggest a selective disturbance in the microcirculation and/or parenchymal oxygen metabolism after DHCA and dhCPB.

Animals↗

PubMed2005

Carotid endarterectomy--an evidence-based review [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the efficacy of carotid endarterectomy for stroke prevention in asymptomatic and symptomatic patients with internal carotid artery stenosis. Additional clinical scenarios, such as use of endarterectomy combined with cardiac surgery, are also reviewed. METHODS: The authors selected nine important clinical questions. A systematic search was performed for articles from 1990 (the year of the last statement) until 2001. Additional articles from 2002 through 2004 were included using prespecified criteria. Two reviewers also screened for other relevant articles from 2002 to 2004. Case reports, review articles, technical studies, and single surgeon case series were excluded. RESULTS: For several questions, high quality randomized clinical trials had been completed. Carotid endarterectomy reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis (16% absolute risk reduction at 5 years). There is a smaller benefit for patients with 50 to 69% symptomatic stenosis (absolute risk reduction 4.6% at 5 years). There is a small benefit for asymptomatic patients with 60 to 99% stenosis if the perioperative complication rate is low. Aspirin in a dose of 81 to 325 mg per day is preferred vs higher doses (650 to 1,300 mg per day) in patients undergoing endarterectomy. CONCLUSIONS: Evidence supports carotid endarterectomy for severe (70 to 99%) symptomatic stenosis (Level A). Endarterectomy is moderately useful for symptomatic patients with 50 to 69% stenosis (Level B) and not indicated for symptomatic patients with <50% stenosis (Level A). For asymptomatic patients with 60 to 99% stenosis, the benefit/risk ratio is smaller compared to symptomatic patients and individual decisions must be made. Endarterectomy can reduce the future stroke rate if the perioperative stroke/death rate is kept low (<3%) (Level A). Low dose aspirin (81 to 325 mg) is preferred for patients before and after carotid endarterectomy to reduce the rate of stroke, myocardial infarction, and death (Level A).

Aspirin↗

PubMed1995

Interferon-alpha 2b, with or without prior hepatic artery embolization: clinical response and survival in mid-gut carcinoid patients. The Norwegian carcinoid study.

BACKGROUND: Mid-gut carcinoid tumours often present with liver metastases, and survival has then been less than 2 years in earlier reports. We have evaluated the effects of interferon therapy on clinical response and survival, with or without hepatic artery embolization in these patients. METHODS: In a prospective study 30 female and 12 male patients, aged 23 to 75 years, with mid-gut carcinoid tumours and liver metastases underwent surgery with removal of as much as possible of their primary tumour. If technically feasible, embolization of hepatic arteries was performed in the absence of contraindications. Seventeen patients were embolized, and all patients received interferon-alpha 2b treatment for 1 year. Response factors were computer tomography (CT) measurement of the largest liver metastasis and the 24-h urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). After 12 months patients with objective response or stable disease either continued or withdrew from interferon therapy. Survival was estimated when all patients had been observed for at least 36 months. RESULTS: Nine patients reduced the dose, and five withdrew from interferon treatment owing to side-effects the 1st year. Three patients died. Fifteen patients (39%) showed objective response 12 months after inclusion. Cumulative 5-year survival estimated from inclusion was 37.5% in all 42 patients but 71.4% in those who continued interferon therapy. The difference in survival between the interferon-treated and those who withdrew from interferon therapy at 12 months was significant when embolization was corrected for in a Cox model (p < 0.0125). The seemingly increased survival in embolized versus non-embolized patients did not reach statistical significance (p = 0.07). CONCLUSION: Interferon induced an objective response in mid-gut carcinoid patients as judged by the 24-h urinary 5-HIAA excretion. Patients receiving continuous interferon therapy showed improved response and survival compared with patients who stopped the treatment. Regardless of medical therapy, more survivors and more responders, as evaluated from CT measurements, were found among the embolized patients than among the non-embolized. Embolization could, however, not be shown to have a significant effect on survival.

Carcinoid Tumor↗

PubMed2002

Endometrial destruction techniques for heavy menstrual bleeding: a Cochrane review.

UNLABELLED: This paper is based on a Cochrane review published in The Cochrane Library, issue 3, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and Update Software. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: The objective of this review was to compare the efficacy, safety and acceptability of methods used to destroy the endometrium to reduce heavy menstrual bleeding (HMB) in premenopausal women. METHODS: We searched the Cochrane Controlled Trials Register, Medline, Embase, Current Contents, Biological Abstracts, Psyclit and CINAHL. We also searched the specialized register of the Cochrane Menstrual Disorders and Subfertility Group and reference lists of articles, and contacted pharmaceutical companies and experts in the field. Randomized controlled trials comparing endometrial ablation techniques in women with a complaint of HMB without uterine pathology were selected. The outcomes included reduction of HMB, improvement in quality of life, operative outcomes, satisfaction with outcome, complications and need for further surgery. The two reviewers independently selected trials for inclusion, assessed trials for quality and extracted data. Attempts were made to contact authors for clarification of data in some trials. Adverse events were only assessed if they were separately measured in the included trials. RESULTS: In comparing hysteroscopic techniques, the vaporizing electrode procedure was less difficult to perform [odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.1, 0.7] and had less fluid deficit [weighted mean difference (WMD) = -258 ml; 95% CI: -342.1, -174.0] than transcervical resection of the endometrium (TCRE). The odds of fluid overload and equipment failure were higher (OR = 5.2; 95% CI: 1.5, 18.4 and OR = 6.0; 95% CI: 1.7, 20.9 respectively) for those women having laser treatment as compared with TCRE. In comparing traditional hysteroscopic endometrial ablation with the newer second generation techniques overall, the newer techniques took less time to perform (WMD = -11 min; 95% CI: -18.6, -2.6) and were more likely to be performed under local anaesthesia (OR = 7.6; 95% CI: 1.1, 52.7) but had a greater chance of equipment failure (OR = 4.1; 95% CI: 1.1, 15.0). The reduction in HMB did not differ significantly between any of the groups. CONCLUSIONS: The rapid development of a number of new methods of endometrial destruction has made systematic comparisons between methods and with the 'gold standard' of TCRE difficult. Most of the newer techniques are performed blind and are technically easier than hysteroscopy-based methods. Overall, the existing evidence suggests that success rates and complication profile of newer techniques of ablation compare favourably with TCRE, although technical difficulties with new equipment need to be ironed out.

Endometrium↗

PubMed1996

Evaluating the benefits of nuclear cardiology.

This paper reviews the role of nuclear cardiology in the context of health care evaluation and resource utilisation. Nuclear cardiology procedures are used to detect disease, to define the extent of disease, to predict the outcome of therapy and to monitor the response to treatment. The evaluation of the effectiveness will depend on the role for which the tests are being used. The evaluation of diagnostic tests most commonly follows the five level Fineberg classification. I) Technical capacity; II) diagnostic accuracy; III) diagnostic impact; IV) therapeutic impact; V) patient outcome. Tests may succeed or fail at each of these hierarchical levels. In addition to the clinical impact which is evaluated, the appropriate use of health care resources has to be considered, i.e. the cost effectiveness of the investigation. For this the costs of diagnosis and treatment in the resources used, together with the direct cost on the patient and patient carers needs to be considered. In addition to these direct costs to the community and to the patient and the carers the secondary downstream costs and opportunity costs have to be taken into account. The common methods for assessing the costs and benefits include cost minimalisation, cost effectiveness, cost utility, and cost benefit studies. The advantages and disadvantages and appropriate use of these methods are reviewed. There are seven clinical methods for evaluating diagnostic tests in nuclear cardiology which are: I) case reports; II) consensus studies; III) databases; IV) case control studies; V) modeling techniques; VI) management impact studies; VII) randomised control trial. Each of these has a role with advantages and disadvantages which are reviewed. It is no long sufficient to investigate the usefulness of a diagnostic test used in nuclear cardiology in isolation but it has to be within the context of the health care system and the resources used.

Coronary Disease↗

PubMed1986

Autologous bone marrow transplantation in paediatric solid tumours.

Massive therapy with ABMT is now an established treatment modality in paediatric oncology. The technical aspects and most treatment-related complications have been clarified and many phase II studies have shown encouraging results. In advanced neuroblastoma the poor outlook with conventional chemotherapy has stimulated extensive investigation of forms of massive therapy. Current results from several centres indicate that although the median survival is increased, long-term survival in an unselected group of stage IV patients is unlikely to exceed 30% with current regimens. In the future, management of this disease may involve the use of more intensive induction regimens to improve the quality of remission at the time of ABMT, which remains the single most important prognostic factor. Improved purging procedures involve the possible use of double massive therapy regimens and a combination of immunological and chemical treatments. In other paediatric tumours, the relative rarity and limited indications for ABMT make the evaluation of its role more difficult. Preliminary results in advanced rhabdomyosarcoma and Ewing's sarcoma are none the less encouraging and justify further investigation. The value of purging procedures remains controversial and their assessment has been hampered by the lack of sensitive clonogenic assays to detect residual tumour cells. However, neuroblastoma has provided a useful model for the investigation of physical, immunological and chemical procedures. Massive therapy is expensive, time consuming, and carries a high cost in patient morbidity and stress to the families involved. As with any new treatment, it must be adequately assessed in phase III, randomized studies. The ENSG and SIOP trials are a beginning and the future of massive therapy in the paediatric patient will, we hope, be based on a rigorous and scientific comparison with other treatment modalities.

Alkylating Agents↗

PubMed1996

Bicarbonate: the alternative buffer for peritoneal dialysis.

For a long time bicarbonate, the physiological buffer of the body, was suggested to be the best buffer for peritoneal dialysis. However, since the production of bicarbonate-containing solutions is associated with technical problems, lactate was favored. To avoid the well-known disadvantages of lactate solution concerning biocompatibility and possible metabolic side effects, different attempts have been made to use bicarbonate as a buffer in peritoneal dialysis. One of the major approaches was the total replacement of lactate by bicarbonate combined with storage of the fluid in a specially designed double-chamber bag. Further solutions of the above-mentioned problem were the on-line preparation of bicarbonate fluids for intermittent peritoneal dialysis, the addition of bicarbonate just before use, the combination of bicarbonate with organic acids, or its combination with the dipeptide glycylglycine as a stabilizing agent. By now, the beneficial effect of the neutral bicarbonate fluid, for example, on cell viability and cell functions, has been demonstrated in many different in vitro and animal studies. However, only few reports on clinical experience have been published. These investigations demonstrated independently that bicarbonate fluids diminish inflow pain, are well tolerated by the patients, and may correct metabolic acidosis of uremic patients. A controlled randomized multicenter trial using 34 mmol/L bicarbonate for at least three months confirmed that bicarbonate is as efficacious as lactate in equimolar concentrations. Concomitant investigations on energy metabolism and redox state of red blood cells and phospholipid secretion of mesothelial cells additionally demonstrated the improvement of cell function with bicarbonate solutions. For some patients with severe metabolic acidosis the bicarbonate concentration used in the multicenter trial seemed to be too low. Thus, a fluid containing a higher bicarbonate concentration was tested in a pilot study resulting in the expected significant increase of arterial bicarbonate levels. In summary, bicarbonate-containing peritoneal dialysis solutions are a promising alternative to lactate, especially if bicarbonate concentrations are adjusted individually to the patient's need.

Acid-Base Equilibrium↗

PubMed2004

Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent.

AIM: The aim of this study was to assess technical feasibility, biocompatibility, and impact on coronary stenosis of a new biodegradable paclitaxel-loaded polylactide stent. Due to high rates of in-stent restenosis and permanent nature of metal stent implants, synthetic polymers have been proposed as surrogate materials for stents and local delivery systems for drugs. Paclitaxel was shown to inhibit vascular smooth muscle cell proliferation and migration. METHODS AND RESULTS: A novel biodegradable double-helical stent was manufactured using controlled expansion of saturated polymers (CESP) for the moulding of a bioresorbable poly(D,L)-lactic acid (PDLLA). A modified balloon catheter for stent deployment was developed according to the mechanical stent properties. Twelve paclitaxel-loaded (170 microg) polylactide stents, 12 unloaded polylactide stents, and 12 316L bare metal stents were deployed in porcine coronary arteries of 36 animals. Six pigs of each group were sacrificed after 3 weeks and 3 months, respectively, for every setting. Drug release kinetics as well as histomorphometrical and histopathological analyses were performed. A slow paclitaxel release kinetic for more than 2 months and therapeutic tissue concentrations were demonstrated. Coronary stenosis after implantation of paclitaxel-loaded stents (30+/-5% or 49+/-4%) was significantly inhibited compared to unloaded PDLLA stents (65+/-10%, P=0.021 or 71+/-4%, P=0.004) and metal stents (53+/-6% or 68+/-8%, P=0.029 and P=0.020) after 3 weeks or 3 months. Early complete endothelialisation was shown. Nevertheless, a local inflammatory response to the polylactide as a result of the polymer resorption process was observed. CONCLUSIONS: This novel polylactide stent showed sufficient mechanic stability, and by incorporation of paclitaxel, a significant potential to reduce restenosis development after vascular intervention was seen.

Animals↗

PubMed2006

Uterine artery embolization as a treatment option for uterine myomas.

Information is still being collected on the long-term clinical responses and appropriate patient selection for UAE. Prospective RCTs have not been performed to compare the clinical results from UAE with more conventional therapies for symptomatic uterine leiomyomata. At least three attempts at conducting such RCTs have been unsuccessful because of poor patient accrual that related to differing patient expectation and desires, clinical bias, insurance coverage, and the tendency that patients who have exhausted other treatment options may be disposed more favorably to less invasive treatments. Other comparative studies have serious limitations. For example, the retrospective study that compared outcomes after abdominal myomectomy with UAE suggested that patients who received UAE were more likely to require further invasive treatment by 3 years than were recipients of myomectomy. Lack of randomization introduced a selection bias because women in the group that underwent UAEwere older and were more likely to have had previous surgeries. A prospective study of "contemporaneous cohorts," which excluded patients who had sub-mucosal and pedunculated subserosal myomas, sought to compare quality of life measures and adverse events in patients who underwent UAE or hysterectomy. The investigators concluded that both treatments resulted in marked improvement in symptoms and quality of life scores, but complications were higher in the group that underwent hysterectomy over 1 year. In this study,however, a greater proportion of patients who underwent hysterectomy had improved pelvic pain scores. Furthermore, hysterectomy eliminates uterine bleeding and the risk for recurrence of myomas. Despite the lack of controlled studies that compared UAE with conventional surgery, and despite limited extended outcome data, UAE has gained rapid acceptance, primarily because the procedure preserves the uterus, is less invasive, and has less short-term morbidity than do most surgical options. The cost of UAE varies by region, but is comparable to the charges for hysterectomy and is less expensive than abdominal myomectomy. The evaluation before UAE may entail additional fees for diagnostic testing, such as MRI, to assess the uterine size and screen for adenomyosis. Other centers have recommended pretreatment ultrasonography, laparoscopy, hysteroscopy, endometrial biopsy, and biopsy of large fibroids to evaluate sarcoma. Generally,after UAE the recovery time and time lost from work are less; however, the potential need for subsequent surgery may be greater when compared with abdominal myomectomy. Any center that offers UAE should adhere to published clinical guidelines,maintain ongoing assessment of quality improvements measures, and observe strict criteria for obtaining procedural privileges. After McLucas advocated that gynecologists learn the skill to perform UAE for managing symptomatic myomas, the Society of Interventional Radiology responded with a precautionary commentary on the level of technical proficiency that is necessary to maintain optimum results from UAE. The complexity of pelvic arterial anatomy, the skill that is required to master modern coaxial microcatheters, and the hazards of significant patient radiation exposure were cited as reasons why sound training and demonstration of expertise be obtained before clinicians are credentialed to perform UAE.A collaboration between the gynecologist and the interventional radiologist is necessary to optimize the safety and efficacy of UAE. The primary candidates for this procedure include women who have symptomatic uterine fibroids who no longer desire fertility, but wish to avoid surgery or are poor surgical risks. The gynecologist is likely to be the primary initial consultant to patients who present with complaints of symptomatic myomas. Therefore, they must be familiar with the indications, exclusions, outcome expectations, and complications of UAE in their particular center. When hysterectomy is the only option, UAE should be considered. Appropriate diagnostic testing should aid in the exclusion of most, but not all, gynecologic cancers and pregnancy. Other contraindications include severe contrast medium allergy, renal insufficiency, and coagulopathy. MRI may be used to screen women before treatment in an attempt to detect those who have adenomyosis; patients should be aware that UAE is less effective in the presence of solitary or coexistent adenomyosis. Because some women may experience ovarian failure after UAE, additional studies to determine basal follicle-stimulating hormone and estradiol before and after the procedure may provide insight into UAE-induced follicle depletion.UAE is a unique new treatment for uterine myomas, and is no longer considered investigational for symptomatic uterine fibroids. There is international recognition that data are needed from RCTs that compare UAE with surgical alternatives. Current efforts to provide prospective objective assessment of treatment outcomes and complications after UAE will help to optimize patient selection and clinical guidelines. FIBROID should provide critical data for the assessment of safety and outcomes measures for women who receive UAE for symptomatic uterine myomas.

Angiography↗

PubMed2006

Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial.

BACKGROUND: A key component of the DOTS strategy for tuberculosis control (short-course chemotherapy following WHO guidelines) is direct observation of treatment. WHO technical guidelines recommend that health workers should undertake this part of the strategy, but will also accept direct observation of treatment in the community; WHO does not think that a family member should undertake this role. Supporting evidence for these recommendations is not available. The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal, where direct observation of treatment by health workers is not feasible. We aimed to assess the success rates of two DOTS strategies developed for such areas. METHODS: Between mid-July, 2002, and mid-July, 2003, we undertook a cluster-randomised controlled trial to compare two strategies-community DOTS and family-member DOTS--in ten hill and mountain districts of Nepal. Districts were used as the unit of randomisation. Primary outcome was success rate (proportion of registered patients who achieved cure or completed treatment), and analysis was by intention to treat. FINDINGS: Five districts (549 patients) were allocated to community DOTS and five (358 patients) were allocated family-member DOTS. Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p=0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS. INTERPRETATION: The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions, and thus are appropriate for the hill and mountain districts of Nepal. Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible. Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy.

Adolescent↗

PubMed2004

Radioiodine dose for remnant ablation in differentiated thyroid carcinoma: a randomized clinical trial in 509 patients.

Remnant ablation can be achieved by either administering an empiric fixed dose or using dosimetry-guided techniques. Because of the technical and logistic difficulties, most centers have adapted the fixed-dose or standard-dose technique for remnant ablation using (131)I. In the late 1970s, low-dose (131)I remnant ablation was introduced, and subsequently many centers confirmed the effectiveness of such therapy. However, the optimal dose (administered activity) of (131)I for remnant ablation is not yet settled. In a randomized clinical trial to find out the smallest possible effective dose for remnant ablation in cases of differentiated thyroid carcinoma, between July 1995 and January 2002, 565 patients were randomized into eight groups according to (131)I administered activity, starting at 15 mCi and increasing activity in increments of 5 mCi until 50 mCi. In the postrandomization phase, 56 patients were excluded from the study for various reasons, and final analysis was done with 509 patients. The mean age of the patients was 37.5 +/- 12.7 yr with a female to male ratio of 2.6. The surgical procedure was total/near-total thyroidectomy in 72% and subtotal or hemithyroidectomy in the rest. Histology was papillary thyroid carcinoma in 80.6% of patients and follicular thyroid carcinoma in the rest. With one dose of (131)I, remnant ablation was achieved in 59.6, 63.6, 81.4, 83.6, 79.4, 78.3, 84.4, and 81.8% of patients in the 15- to 50-mCi groups, respectively (overall ablation rate, 77.6%). The successful ablation rate was statistically different in patients receiving less than 25 mCi of (131)I compared with those receiving at least 25 mCi [63 of 102 (61.8%) vs. 332 of 407 (81.6%); P = 0.006]. However, there was no significant intergroup difference in outcome among patients receiving 25-50 mCi of (131)I. Patients with small tumor size (</=5 cm), adequate surgery (total/near-total thyroidectomy), and radioiodine neck uptake of less than or equal to 10% had odds ratios of 2.4 [confidence interval (CI), 1.3-3.98], 2.6 (CI, 1.6-4.2), and 2.2 (CI, 1.4-3.5), respectively, for successful remnant ablation. Patients receiving at least 25 mCi of (131)I had a three times better chance of getting remnant ablation than patients receiving lesser activity of (131)I. Any activity of (131)I between 25 and 50 mCi appears to be adequate for remnant ablation.

Adenocarcinoma, Follicular↗

PubMed1993

Relationship between dialyser type and signs and symptoms.

A crossover study to compare the effects of seven different dialysers on intradialytic symptoms in 37 patients during dialysis with acetate-containing dialysate was performed at five centres in four countries. The same manufacturing lot of each dialyser and of blood line sets were used by all centres. The same clinical data (duration of dialysis, blood pressure, weights, temperature, drugs, symptoms, and treatments) and technical data (blood flow, dialyser clearance, and ultrafiltration rate) were collected. Kt/V for urea was used to determine dialysis prescribed. Intradialytic symptoms and signs were measured hourly or when observed by staff using the haemodialysis treatment form (see Introduction). After each week of treatment with a particular dialyser, patients completed a questionnaire relating to the presence and severity of symptoms. (Only presence or absence of symptoms are presented.) Wide differences in dialysis duration and blood flow between centres were noted. These may have contributed to the differences between centres in relationship to staff reported responses to different dialyser: Dialysers with the lowest incidence of both signs and symptoms and of chest pain, back pain, and itching (arbitrarily designated bioincompatibility symptoms) were the Duo-Flux and Filtral, with the G120 M, the CD 4000, and the T 150 having the highest incidence. By patient questionnaire the most biocompatible dialysers were the T 150, F 60, and the Filtral, with the most symptom producing being the G120 M and the G10-3N. Perceptions of symptoms between patients and staff differed substantially overall and between centres. Hypersensitivity reactions were noted in two patients, both occurring with cuprammonium cellulose hollow-fibre dialysis, despite adherence to manufacturers' instructions concerning saline priming and removal. Both patients showed antibody titres greater than 1:160 against ethylene oxide-HSA. Ethylene oxide was not detected (limit of detection 1 part per million) in dialysers, blood line sets, or fistula needles. The study suggests that dialysis symptom reporting is complicated by individual perceptions, staff reactions, and the efficiency of recording. In this study ethnic and cultural differences must be added to the haemodynamic differences and other prescription-related elements in influencing symptoms. Despite these problems a hierarchy of dialyser-related symptoms and signs could be discerned which largely paralleled laboratory findings of biocompatibility. Future comparative studies relating symptomatology to membrane and dialyser structure should consider the variables identified as influencing symptoms and their reporting.

Biocompatible Materials↗

PubMedDate not supplied

[Does parenteral gold inhibit roentgen progression of chronic polyarthritis?].

The retardation of radiological progression is one of the most important characteristics of a disease-modifying effect of an antirheumatic drug. For the following overview 10 trials were identified dealing with x-ray progression under treatment with parenteral gold. Nine of these trials were randomised parallel studies, one was a retrospective long-term observational study, all had a control group, in five this control group was treated with placebo, in two trials parenteral gold was compared with another DMARD (auranofin and methotrexate, respectively), in two trials different doses of gold were compared and in two trials the radiological progression during the first 6 months was compared with the following treatment period (in one of these trials gold was compared with methotrexate as well). The duration of treatment and follow-up was up to 1 year in two trials, up to 2 years in six, and over 2 years in only two studies. There is a great number of limitations in these studies: for instance, there was a large number of withdrawals who were not followed, x-rays were available for evaluation only in a relatively small proportion of treated patients in five studies, in six studies the disease duration was over 2 years at baseline, which limits the evaluability of x-ray progression for technical reasons. In one study juxta articular osteoporosis and joint swelling were evaluated; but these parameters are very difficult to evaluate in a multicenter study because of the different quality of the films. In spite of all limitations and reservations with the studies reviewed the published results indicate a reduction of radiological progression with parenteral gold treatment of rheumatoid arthritis patients: in the placebo-controlled studies outcome in the gold group was significantly better than in the placebo group. The study of the Empire Rheumatism Council failed to show a significant difference compared to the control group after 30 months, but the patients had been treated sufficiently only for 5 months. The study of Cats indicated a better outcome in the group of patients with a high gold dose, which is confirmed by the retrospective analysis of Luukkainen. In a comparison between 113 patients treated with parenteral gold and 119 patients treated with auranofin for 1 year Larsen found a significantly smaller progression in the patients treated with parenteral gold. In a patient population of 73 and 53 the difference between methotrexate and parenteral gold was too small to be detectable, but the progression curve was significantly flattened after the first 6 months, indicating a treatment effect. In a macroradiographic study the erosion surface area increased during the first 6 months of gold treatment, it did not change during the second 6 months, and decreased during the third 6 months together with healing of erosions. In conclusion, the studies reviewed in this paper indicate a disease-modifying potency of parenteral gold treatment, especially when the treatment is started early and sufficiently dosed.

Animals↗

PubMed1992

Reproductive and developmental toxicity of N,N-diethyl-m-toluamide in rats.

N,N-Diethyl-m-toluamide (mDET, DEET) is widely used as a topical insect repellent. It is the active ingredient in many consumer formulations, which usually contain 10-25% mDET in an alcohol base. More concentrated consumer products are also available, including some that are pure technical grade mDET. Persons living or employed in mosquito-infested areas may have very high seasonal exposures to mDET. Because contradictory reports had been published on the reproductive and developmental toxicity of mDET, a series of studies was conducted in male and female Sprague-Dawley rats. All treatments were administered by daily subcutaneous injections of undiluted mDET. A dose finding study was done using 12 time-mated females per group treated on Gestational Days (GD) 6-15 with 0.50, 0.62, 0.78, 0.92, or 1.2 ml mDET/kg/day. No females survived 10 days of mDET dosing with 1.2 ml/kg/day. Deaths occurred in all other groups except the low dose (0.50 ml/kg/day). Pregnant females treated on GD 6-15 with 0 or 0.30 ml/kg/day were used for the teratology study. Half of each group was euthanized on GD 20: the second half was singly housed in nesting boxes and allowed to deliver litters. Live pups were counted and weighed soon after birth on Postnatal Day (PD) 0 and again on PD 3, 9, and 14. Proven fertile males were treated 5 days/week for 9 weeks with 0, 0.30, 0.73, 1.15, or 1.80 ml mDET/kg/day for a male dose-finding study. Each group consisted of 20 males. No males survived the 1.80 ml/kg/day. Deaths occurred in all remaining dose groups except the 0.30 ml/kg/day and control group. Immediately following the final treatment of the male dose study, 11 males were randomly selected from the 0.30 and 0.73 ml/kg/day groups. They were cohabited for 7 days with 4 females per male during post-treatment Weeks 1 and 2. Half of the females were euthanized 12-14 days after the last day of cohabitation for a dominant lethal study; the remaining females were singly housed in nesting boxes and allowed to deliver litters. Live pups were counted and weighted on PD 0 and 3. There was no evidence of reproductive or developmental toxicity in any of these assays, but there were signs of neurotoxicity in treated adult male and female rats, which may relate to reports of neurotoxicity in humans heavily exposed to mDET-containing insect repellents.

Abnormalities, Drug-Induced↗

PubMed2002

Interactive dysmorphogenic effects of toxaphene or toxaphene congeners and hyperglycemia on cultured whole rat embryos during organogenesis.

Both diabetes mellitus and exposure to environmental contaminants are becoming health hazards to many indigenous populations in the world. In earlier work, we established the embryopathy of the chlorinated pesticide, toxaphene technical mixture (TOX) and its two physiologically most important congeners, T(2) (2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane) and T(12) (2-exo,3-endo,5-exo,6-endo,8,8,9,10,10-nonachlorobornane). In this study, the combined effects of toxaphene or its two congeners and high glucose concentrations were studied using rat embryo culture in order to investigate the potential interactions between hyperglycemia and toxaphene exposure. Whole rat embryos (0-2 somite) were explanted and cultured into a normal (8 mM) or hyperglycemic 12.5 mM (12.5 G) or 18.75 mM (18.75 G) culture medium containing TOX, T(2), or T(12) at various concentrations (0, 100, 1000, 5000 ng/ml) for 48 h at 37 degrees C. All treatments, except mild hyperglycemic exposure (12.5 G), had significant adverse effects on the total morphological score, head and crown-rump length, yolk sac diameter and yolk sac circulation. Embryos exposed to 18.75 G did not show malformations but when hyperglycemia at 18.75 G was combined with higher doses of TOX or T(2) synergistic effects on the incidence of neural tube defects were observed. The embryos cultured with T(12) under severe hyperglycemic conditions of 18.75 G showed an inhibition of T(12)-induced neural tube defects, but there was a concurrent underdevelopment of forelimbs or hindlimbs at the highest T(12) dose. The results suggest that there is a site-specific and dose-related interactive dysmorphogenesis elicited by TOX or its congeners with high levels of glucose on rat embryonic development. Because of the relatively high TOX doses used in this study, the drastic growth retardation and malformation observed are unlikely to be observed in human populations. More subtle effects, however, may not be ruled out.

Animals↗

PubMed2000

Nutritional support for head-injured patients.

BACKGROUND: Head injury increases the body's metabolic responses, and therefore nutritional demands. Provision of an adequate supply of nutrients is associated with improved outcome. The best route for administering nutrition (parenterally (TPN) or enterally (EN)), and the best timing of administration (e.g early versus late) of nutrients needs to be established. OBJECTIVES: To quantify the effect on mortality and morbidity of alternative strategies of providing nutritional support following head injury. SEARCH STRATEGY: Trials were identified by computerised searches of the Injuries Group specialised register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings, and by checking the reference lists of trials and review articles. SELECTION CRITERIA: Randomised controlled trials of nutritional support following acute traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. Information was collected on death, disability, and incidence of infection. If trial quality was unclear, or if there were missing outcome data, trialists were contacted in an attempt to get further information. MAIN RESULTS: The timing of support: early versus delayed Of the six trials addressing the timing of support, data on mortality were obtained for all six trials, with a total of 257 patients. The relative risk (RR) for death with early nutritional support was 0.71 (95% CI 0.43 to 1.16). Data on disability were available for three trials. The RR for death or disability at the end of follow-up was 0.75 (0.50 to 1.11). The route of feeding: parenteral versus enteral Six trials compared parenteral versus enteral nutrition. Because early support often involves parenteral nutrition, three of the six trials are also included in the previous analyses. Five trials (207 participants) reported mortality. The RR for mortality at the end of follow-up period was 0.66 (0.41 to 1.07). Two trials provided data on death and disability. The RR was 0.69 (95%Cl 0.40 to 1.19). 3. Enteral nutrition: jejunal versus gastric. There was one trial with no deaths and the RR is not estimable. REVIEWER'S CONCLUSIONS: This review suggests that early feeding may be associated with a trend towards better outcomes in terms of survival and disability. Further trials are required. These trials should report not only nutritional outcomes but also the effect on death and disability.

Craniocerebral Trauma↗

PubMed1994

Improved utilization of spacing methods--intrauterine devices (IUDs) and low-dose combined oral contraceptives (OCs)--through re-orientation training for improving quality of services. Indian Council of Medical Research Task Force on IUD and Hormonal Contraceptives.

A multicentre study was conducted by the Indian Council of Medical Research (ICMR) for improving the utilization of intrauterine devices (IUDs) and oral contraceptives (OCs) at the Post Partum Centres (PPCs) run by District/State Health Authorities. The ICMR's network of Human Reproduction Research Centres (HRRCs) had the technical responsibility for providing re-orientation training to health functionaries (medical and paramedical) of the PPCs for better quality of services and follow-up care for IUD and OC users. The uniform training module was utilized by all HRRCs which specifically assured for improving the counselling/motivational skills as well as screening procedures and management of side-effects and follow-up care by the health functionaries. A total of 4,808 IUD acceptors (2,446 of CuT 200 and 2,362 of CuT 380A) were observed for 84,070 women-months of use (42,433 and 41,637 months for CuT 200 and CuT 380A, respectively). The cumulative method failure rate at the end of two years was 0.7 per 100 users with CuT 200 and 0.3 per 100 users with CuT 380A. No perforations were reported with either types of the CuT devices. The reasons for discontinuations, like pain/bleeding and pelvic infections, were similar with both types of devices. The continuation rates with either CuT 200 or CuT 380A were around 89 and 76 per 100 users at the end of first year and second year of use, respectively, and were comparable. These observations at the post partum centres were similar to those observed earlier by the ICMR in phase III controlled clinical study. A total of 1,961 women were enrolled in the low-dose combined oral contraceptive (OC) group and were followed for 26,462 women-months of use. Two subjects reported pregnancy during regular use of pill, giving the method failure rate of 0.2 per 100 users at 2 years. The continuation rates of OC users were 58 and 37 per 100 users at the end of first year and second year, respectively. The major reasons for discontinuations were lost to follow-up, desire for pregnancy and other personal reasons. In spite of all efforts made by PPC staff as well as HRRCs to do follow-up, the lost to follow-up at two years was around 20 percent for IUD and 31 percent for oral pill users. These data suggest that while the re-orientation training package improved the quality of care resulting in higher continuation rates of IUDs and OCs at PPCs, the issue of follow-up care still requires further improvement in the National Programme.

Adult↗