Pulse pressure and peripheral arterial vasoreactivity.
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Aged↗
Biomedical subjects
M Sidhu
Publications and source records attributed to M Sidhu.
[Analysis of cost effectiveness of photodynamic therapy with Foscan (Foscan-PDT) in comparison with palliative chemotherapy in patients with advanced head-neck tumors in Germany].
BACKGROUND: The purpose of this manuscript is to give a cost-effectiveness analysis of the photodynamic therapy by means of Foscan (Foscan-PDT) in Germany. The basis for this paper is provided by a study performed in Great Britain which analyses the costs of Foscan-PDT compared to the costs of palliative chemotherapy and to the option of no treatment in patients with advanced head and neck cancer. METHOD: In order to calculate the cost-effectiveness, an already published model developed on the base of English data was fed with German cost-data. For consideration of the different characteristics of cost-parameters as well as to minimize the over- or underestimation of the costs, sensitivity analyses were performed. RESULTS: The Foscan-PDT revealed the highest health-related effectiveness compared to all other above-mentioned options -- 129 additional days of life in comparison to no treatment or 48 days in comparison to four cycles of palliative chemotherapy. The costs per therapy of Foscan-PDT ( 8,761 euros) were lower than those of four cycles of palliative chemotherapy (11,600 euros). CONCLUSION: Foscan-PDT is a cost-effective treatment option for patients suffering from advanced head and neck cancer. For patients who up to now had only very limited treatment possibilities at their disposition, Foscan-PDT offers a chance for reduction of the tumor, remission, and a prolonged expectancy of life.
Ambulatory Care↗
The cost-effectiveness of Foscan mediated photodynamic therapy (Foscan-PDT) compared with extensive palliative surgery and palliative chemotherapy for patients with advanced head and neck cancer in the UK.
This study aimed to analyse the cost-effectiveness of Foscan mediated photodynamic therapy (Foscan-PDT) compared with palliative chemotherapy, extensive palliative surgery or 'no treatment' for patients with advanced head and neck cancer in the UK. A computerised cost-effectiveness model was constructed using published effectiveness data and unit costs for each of the treatment arms. Where possible, published resource use data were also used. In the absence of such information, expert opinion informed data input. Robust sensitivity analyses were performed to negate the effect of potential over or underestimation of the costs used for any of the interventions. The primary outcome was incremental cost/life year saved (cost/LYS); the secondary outcomes were incremental cost/overall tumour response and incremental cost/remission. Foscan-PDT was associated with the greatest health gains of all three interventions yielding 129 extra days of life compared with no treatment and extensive palliative surgery and 48 extra days of life compared with four cycles of palliative chemotherapy. The unit cost of Foscan-PDT ( pound 5741) was found to be lower than the unit cost for four cycles of palliative chemotherapy ( pound 9924) and extensive palliative surgery ( pound 16912). Foscan-PDT continued to have a lower unit cost than palliative chemotherapy until the number of chemotherapy cycles was reduced to two or fewer. Reducing the number of cycles would be likely to reduce the health gains associated with chemotherapy. However, even with assumed maintenance of chemotherapy efficacy, Foscan-PDT remained cost-effective versus two or fewer chemotherapy cycles. Compared with three or more cycles of palliative chemotherapy and extensive palliative surgery, Foscan-PDT dominated with a lower unit cost and greater health gains. Compared with giving no treatment, Foscan-PDT was a cost-effective treatment option at pound 14206/LYS. Sensitivity analysis showed that Foscan-PDT remained cost-effective when the costs used for the comparators were decreased and/or the costs used for Foscan-PDT were increased. Foscan-PDT is a clinically and cost-effective treatment option for patients with advanced head and neck cancer compared to palliative chemotherapy, extensive palliative surgery or 'no treatment'. Furthermore, Foscan-PDT offers patients, with traditionally very limited treatment options, a unique chance of tumour response, remission and increased life expectancy.
Computer Simulation↗
Surgery for morbid obesity.
BACKGROUND: Obesity is associated with increased morbidity and mortality. Surgery for morbid obesity may be considered when other conventional measures have failed, and a number of procedures are available. However, the effects of these surgical procedures compared with medical management and with each other are uncertain. OBJECTIVES: To assess the effects of surgery for morbid obesity on weight, comorbidities and quality of life. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (issue 4, 2001), Medline (SilverPlatter) up to 2001, PubMed (Internet) 01/01/01-19/10/01, Embase (SilverPlatter) up to 09/2001, PsychINFO up to 10/2001, CINAHL (SilverPlatter) up to 07/2001, Science and Social Sciences Citation Index up to 10/12001, British Nursing Index up to 07/2001, Web of Science Proceedings up to 06/2001, BIOSIS up to10/2001, AMED up to 07/2001, National Research Register (issue 2, 2001), reference lists of relevant articles, and handsearched relevant journals. We also contacted experts in the field. Date of the most recent searches: October 2001. SELECTION CRITERIA: Randomised controlled trials comparing different surgical procedures, and randomised controlled trials and non-randomised controlled trials comparing surgery with non-surgical management for morbid obesity. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked independently by two reviewers. Two reviewers independently assessed trial quality. MAIN RESULTS: 18 trials involving 1891 people were included. One randomised controlled trial and one non-randomised controlled trial compared surgery with non-surgical management, and 11 randomised controlled trials compared different surgical procedures. The overall quality of the trials was variable, with just one trial having adequate allocation concealment. A meta-analysis was not possible due to differences in the surgical procedures performed, measures of weight change and length of follow-up. Compared with conventional management, surgery resulted in greater weight loss (23-28 kg more weight loss at two years), with improvements in quality of life and comorbidities. Some complications of surgery occurred, such as wound infection. Gastric bypass was associated with greater weight loss and fewer revisions, reoperations and/or conversions than gastroplasty, but had more side-effects. Greater weight loss and fewer side-effects and reoperations occurred with adjustable gastric banding than vertical banded gastroplasty, while vertical banded gastroplasty was associated with greater weight loss but more vomiting than horizontal gastroplasty. Some postoperative deaths occurred in the studies. Weight loss was similar between open and laparoscopic procedures. Fewer serious complications occurred with laparoscopic surgery. Laparoscopic surgery had a longer operative time, but resulted in reduced blood loss, reduced proportion of patients requiring intensive care unit stay, reduced length of hospital stay, reduced days to return to activities of daily living and reduced days to return to work. REVIEWER'S CONCLUSIONS: The limited evidence suggests that surgery is more effective than conventional management for weight loss in morbid obesity. The comparative safety and effectiveness of different surgical procedures is unclear.
Gastric Bypass↗
Clinical and cost effectiveness of surgery for morbid obesity: a systematic review and economic evaluation.
OBJECTIVE: To assess the clinical and cost effectiveness of surgery for people with morbid obesity. DESIGN: A systematic review of randomised control trials (RCTs), prospective clinical trials and economic evaluations identified from 14 electronic databases (including Medline, Cochrane library and Embase from their inception to October 2001), bibliographies and consultation with experts and manufacturers was performed to assess the clinical and cost effectiveness of different surgical procedures and nonsurgical management for morbid obesity. An economic evaluation was undertaken to assess cost effectiveness in the UK. SUBJECTS: People diagnosed as morbidly obese, defined as a body mass index (BMI) (weight in kilograms/height in metres(2)) >40 kg/m(2), or with a BMI>35 kg/m(2) with serious comorbid disease, in whom previous nonsurgical interventions had failed. MEASUREMENTS: The outcomes assessed included weight change, quality of life, peri- and postoperative morbidity and mortality, revision rates and obesity comorbidities. Cost effectiveness was modelled from these data and presented as cost per quality-adjusted life year (QALY). RESULTS: Included studies differed in methodological quality. Surgery resulted in a significantly greater loss of weight (23-37 kg more weight) than nonsurgical treatment, which was maintained to 8 years and led to improvements in quality of life and comorbidities. The economic evaluation of surgery compared with nonsurgical management suggested that surgery was cost effective at pound 11000 per QALY. Comparisons of the different types of surgery were equivocal. CONCLUSION: Surgery for morbid obesity appears to be clinically and cost effective. Because of the nature of the evidence, particularly the uncertainty in the clinical and economic evaluations, it is difficult to distinguish between the different surgical procedures.
Cost-Benefit Analysis↗
Protection by SIV VLP DNA prime/protein boost following mucosal SIV challenge is markedly enhanced by IL-12/GM-CSF co-administration.
The ever increasing number of people infected by human immunodeficiency virus (HIV) throughout the world renders the development of effective vaccines an urgent priority. Herein, we report on an attempt to induce and enhance antiviral responses using a deoxyribonucleic acid (DNA) prime/virus-like particles (VLP) protein boost strategy adjuvanted with interleukin (IL)-12/GM-CSF in rhesus macaques challenged with simian immunodeficiency virus (SIV). Thus, groups of monkeys were administered three consecutive doses of pVecB7 a plasmid expressing VLP with or without plasmids expressing IL-12 and GM-CSF at weeks 0, 13 and 26. The VLP boost was administered at week 39 with or without IL-12. All monkeys were challenged intrarectally with SIVsmE660 2 months following the protein boost. All except one immunized monkey became infected. While all immunized monkeys showed a marked reduction of acute viral peaks, reduction of viral load set points was only achieved in groups whose prime-boost immunizations were supplemented with IL-12/GM-CSF (prime) and/or with IL-12 (boost). Control of viremia correlated with lack of disease progression and survival. Detection of virus in rectal washes at 1 year post-challenge was only successful in monkeys whose immunizations did not include cytokine adjuvant, but these loads did not correlate with plasma viral loads. In summary, use of IL-12 and/or GM-CSF was shown to provide significant differences in the outcome of SIV challenge of prime/boost immunized monkeys.
Adjuvants, Immunologic↗
Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review.
BACKGROUND: Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the evidence on the clinical and cost effectiveness of four of the new generation drugs for patients with lung cancer. METHODS: A systematic review of randomised controlled trials (RCTs) identified from 11 electronic databases (including Medline, Cochrane library and Embase), reference lists and contact with experts and industry was performed to assess clinical effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine. Clinical effectiveness was assessed using the outcomes of patient survival, quality of life, and adverse effects. Cost effectiveness was assessed by development of a costing model and presented as incremental cost per life year saved (LYS) compared with best supportive care (BSC). RESULTS: Of the 33 RCTs included, five were judged to be of good quality, 10 of adequate quality, and 18 of poor quality. Gemcitabine, paclitaxel, and vinorelbine as first line treatment and docetaxel as second line treatment appear to be more beneficial for non-small cell lung cancer than BSC and older chemotherapy agents, increasing patient survival by 2-4 months against BSC and some comparator regimes. These gains in survival do not appear to be at the expense of quality of life. Survival gains were delivered at reasonable levels of incremental cost effectiveness for vinorelbine, vinorelbine with cisplatin, gemcitabine, gemcitabine with cisplatin, and paclitaxel with cisplatin regimens compared with BSC. CONCLUSION: Although the clinical benefits of the new drugs appear relatively small, their benefit to patients with lung cancer appears to be worthwhile and cost effective.
Antimetabolites, Antineoplastic↗
Extracapsular cataract extraction compared with small incision surgery by phacoemulsification: a randomised trial.
BACKGROUND: Cataract extraction constitutes the largest surgical workload in ophthalmic units throughout the world. Extracapsular cataract extraction (ECCE), through a large incision, with insertion of an intraocular lens has been the most widely used method from 1982 until recently. Technological advances have led to the increasing use of phacoemulsification (Phako) to emulsify and remove the lens The technique requires a smaller incision, but requires substantial capital investment in theatre equipment. In this randomised trial we assessed the clinical outcomes and carried out an economic evaluation of the two procedures. METHODS: In this two centre randomised trial, 232 patients with age related cataract received ECCE, and 244 received small incision surgery by Phako. The main comparative outcomes were visual acuity, refraction, and complication rates. Resource use was monitored in the two trial centres and in an independent comparator centre. Costs calculated included average cost per procedure, at each stage of follow up. RESULTS: Phako was found to be clinically superior. Surgical complications and capsule opacity within 1 year after surgery were significantly less frequent, and a higher proportion achieved an unaided visual acuity of 6/9 or better (<0.2 logMAR) in the Phako group. Postoperative astigmatism was more stable in Phako. The average cost of a cataract operation and postoperative care within the trial was similar for the two procedures. With the input of additional spectacles for corrected vision at 6 months after surgery, the average cost per procedure was pound359.89 for Phako and pound367.57 for ECCE. CONCLUSION: Phako is clinically superior to ECCE and is cost effective.
Aged↗
A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer.
BACKGROUND: The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion. OBJECTIVES: This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed. METHODS: This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE ANALYSIS: Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on cost-effectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen. CONCLUSIONS: The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE NEWER DRUGS: One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH: Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation.
Antineoplastic Agents↗
Complete hydatidiform mole with coexisting normal fetus-report of two cases.
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Abortion, Induced↗
Epidural analgesia compared with combined spinal-epidural analgesia during labor in nulliparous women.
BACKGROUND: Among nulliparous women, there appears to be an association between the use of epidural analgesia during labor and an increased risk of dystocia. We tested the hypothesis that combined spinal-epidural analgesia, which permits ambulation during labor, is associated with a lower incidence of dystocia than continuous lumbar epidural analgesia. METHODS: Between July 1995 and September 1996, we randomly assigned 761 nulliparous women in spontaneous labor at term who requested epidural analgesia to receive either continuous lumbar epidural analgesia or a combination of spinal and epidural analgesia. Among the women who received combined spinal-epidural analgesia, some were discouraged from walking and others were encouraged to walk. Maternal and neonatal outcomes, the incidence of dystocia necessitating cesarean section, and measures of patients' satisfaction were compared in the two groups. RESULTS: There were no significant differences in the overall rate of cesarean section, the incidence of dystocia, the frequency of maternal or fetal complications, the patients' or nursing staff's assessment of the adequacy of analgesia, or the degree of overall satisfaction between the two groups. Significantly more women receiving combined spinal-epidural analgesia had pruritus (P<0.001) and requested additional epidural bolus doses of local anesthetic (P=0.01). For all the women, dystocia necessitating cesarean section was significantly more likely when analgesia was administered with the fetal vertex at a negative station (odds ratio, 2.5; P<0.001) or at less than 4 cm of cervical dilatation (odds ratio, 2.2; P<0.001). CONCLUSIONS: As compared with continuous lumbar epidural analgesia, the combination of spinal and epidural analgesia is not associated with an overall decrease in the incidence of cesarean delivery.
Adult↗
Activation of 5-HT1P receptors on submucosal afferents subsequently triggers VIP neurons and chloride secretion in the guinea-pig colon.
The role of vasoactive intestinal peptide (VIP) was investigated when mucosal stroking and 5-hydroxytryptamine (5-HT) were used to activate neural reflexes that stimulate chloride secretion in the guinea pig colon. Muscle-stripped segments of colon containing intact submucosal ganglia without myenteric ganglia were set up in modified flux chambers in order to record short-circuit current (Isc). Mucosal stroking with a brush for 1 s or a pulse of 5-HT (injection of 15 microliters of 100 microM 5-HT into 1.5 ml of mucosal solution) caused an increase in Isc that was reduced by the VIP antagonist, neurotensin6-11-VIP7-28, in a concentration-dependent manner. The Isc responses to mucosal stroking and a 5-HT pulse were reduced by 53% and 58%, respectively, by 2 microM neurotensin6-11-VIP7-28. The residual Isc response in the presence of neurotensin6-11-VIP7-28 was abolished by atropine. Blockade of 5-HT1P receptors on submucosal afferent neurons decreased Isc responses to stroking or a 5-HT pulse. The residual Isc response after 5-HT1P receptors were blocked was reduced by only 11-14% by neurotensin6-11-VIP7-28. In the presence of blockade of both 5-HT1P and VIP receptors, atropine abolished the Isc response to both stimuli. The observations suggest that the neural circuitry activated by stroking includes at least two independent pathways. One pathway contains VIP neurons which receive inputs directly or indirectly from 5-HT1P receptor-containing afferents. A second pathway involves muscarinic cholinergic transmission that is independent of 5-HT1P and VIP receptor activation.
Animals↗
Cell death and birth in multiple sclerosis brain.
The hallmark of the brain pathology in multiple sclerosis is the white matter plaque, characterized by myelin destruction and oligodendrocyte loss. To examine the role that cell death plays in the development of MS lesions, we used the in situ TUNEL technique, a method that sensitively detects DNA fragmentation associated with death at the single cell level. We found that patchy areas within acute MS lesions have massive numbers of inflammatory and glial cells undergoing cell death. The punched out areas of some long-standing chronic lesions also had labeled glial cells showing that the attack was not a single event. Immunocytochemical identification of the dying cells with glial specific marker co-labeling showed that 14-40% were the myelin-sustaining oligodendroglial cell. Confocal microscopic evaluation of fluorescein-labeled TUNEL positive cells revealed nuclei with morphologic characteristics of apoptosis, and electrophoresed MS brain DNA produced a ladder characteristic of apoptotic DNA cleavage confirming that substantial numbers of labeled cells, but not necessarily all, were dying by apoptotic mechanisms rather than cell necrosis. Companion studies using a marker for cell proliferation on MS lesions revealed that unexpectedly large populations of perivascular inflammatory cells and parenchymal glial cells had entered the cell proliferation cycle. These findings establish that two opposing glial cell responses - relentless cell death and coincident brisk cellular proliferation - are important features of MS pathology. In the end, however, glial cell loss prevails, and we suspect apoptosis may be the critical death mechanism responsible for the depletion of myelin observed in this condition.
Animals↗
Elevated serum lipoprotein(a) levels in young women with endometriosis.
Elevated serum lipoprotein(a) [Lp(a)] levels increase the risk of cardiovascular disease if levels of low-density lipoproteins (LDLs) are also high. The biological function of Lp(a) is unknown, but plasma levels may be elevated in inflammatory disease. Endometriosis is a common gynecologic disorder in which endometrial tissue is found outside of the lining of the uterine cavity. There is an immune component to this condition whereby the number of peritoneal macrophages is increased and the level of prostanoids and cytokines in peritoneal fluid is elevated. In the present study, we measured serum lipid, lipoprotein, and apolipoprotein levels in 29 women with endometriosis and in 29 matched healthy controls. Fasting serum triglyceride and apolipoprotein (apo) Al levels were higher in women with endometriosis (+28.1%, P < .001, and +12.3%, P < .01, respectively), but there were no significant differences in LDL or high-density lipoprotein (HDL) cholesterol levels. Serum Lp(a) levels were fivefold higher (P < .01) in the patients (median, 15.0 mg/dL; range, 0.05 to 60.0) than in controls (median, 3.1 mg/dL; range, 0.05 to 57.2). The distribution of apo(a) isoforms was similar in the two groups, but in women with endometriosis the individual apo(a) isoforms tended to be associated with higher serum Lp(a) levels. Endometriosis may represent a relatively common condition in which to investigate the role of Lp(a) in human metabolism.
Adult↗
Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: purification and kinetic characterization.
Exposure of animals to cadmium (Cd) (25 mg kg(-1) body wt day(-1)) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IEF) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. alpha, mu and pi, which were serologically identical to human alpha, mu and pi GSTs.
Animals↗
5-HT activates neural reflexes regulating secretion in the guinea-pig colon.
The role of 5-hydroxytryptamine (5-HT) in neural reflexes regulating secretion was examined in muscle-stripped segments of guinea-pig colon set up in modified flux chambers. A 15-microL pulse of 5-HT (100 microM) to the mucosal bath (1.5 mL), which was continuously perfused, evoked an increase in short-circuit current (Isc). The 5-HT-induced increase in Isc was inhibited by tetrodotoxin, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), GR82334 and atropine, but not by tropisetron. 5-HTP-DP reduced the response to a 5-HT pulse over the concentration range of 1 nM to 1 microM. The Isc response to a 5-HT pulse was unaffected by the cyclooxygenase inhibitor, piroxicam. This contrasted with a reduction in the Isc response to mucosal stroking with a brush by piroxicam. The results suggest that a 5-HT pulse, like mucosal stroking, activates a secretory reflex that includes tachykinin and cholinergic neurons but, unlike mucosal stroking, does not release prostaglandins.
Animals↗
Substance P as a mediator of colonic secretory reflexes.
The role of substance P in neural reflex pathways activated by stroking was investigated in muscle-stripped segments of distal colon from guinea pigs. Stroking the mucosal surface with a brush at 1 stroke/s evoked an increase in short-circuit current (Isc) indicative of chloride secretion. The response to mucosal stroking was maximally reduced by 69-75% by the antagonist GR-82334. The agonist [Sar9,Met(O2)11] substance P caused a bumetanide-sensitive increase in Isc when added to the mucosal or serosal bath. Ablation of extrinsic afferents with acute or chronic administration of capsaicin did not alter the mucosal stroking response. Reverse transcription-polymerase chain reaction and in situ hybridization revealed the presence of neurokinin1 (NK1) receptor messenger RNA in isolated colonocytes or crypt glands. Ligand binding of 125I-Bolton-Hunter-labeled substance P was inhibited by GR-82334. The 50% inhibitory concentration was 0.84 nM. The results demonstrate a role for substance P released from capsaicin-insensitive submucosal neurons and in mucosal stroking reflexes. The presence of NK1 receptors on isolated colonocytes suggests that appropriate elements are present for axon reflex activation of intestinal epithelial cells.
Animals↗