Principles of pain management.
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Analgesics, Opioid↗
Biomedical subjects
M Larson
Publications and source records attributed to M Larson.
Immunization by particle-mediated transfer of the granulocyte-macrophage colony-stimulating factor gene into autologous tumor cells in melanoma or sarcoma patients: report of a phase I/IB study.
The primary objective of this phase I study was to determine the safety of an autologous tumor vaccine given by intradermal injection of lethally irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transfected autologous melanoma and sarcoma cells. Secondary objectives included validation of the gene delivery technology (particle-mediated gene transfer), determining the host immune response to the tumor after vaccination, and monitoring patients for evidence of antitumor response. Sixteen patients were treated with either of two different doses of GM-CSF-treated tumor cells. One patient received treatment with both doses of tumor cells. No treatment-related local or systemic toxicity was noted in any patient. Patients administered 100% treated cells (i.e., with a preparation of tumor cells that had all been exposed to GM-CSF DNA transfection) had a more extensive lymphocytic infiltrate at the vaccine site than did patients given 10% treated cells (a preparation of tumor cells in which 10% had been exposed to GM-CSF transfection) or nontreated tumor. The generation of a systemic immune response to autologous tumor by a delayed-type hypersensitivity response to the intradermal placement of nontransfected tumor cells was noted in one patient. One patient had a transient partial response of metastatic tumor sites. The entire procedure, from tumor removal to vaccine placement, was accomplished in less than 6 hr in all patients. Four of 17 patient tumor preparations produced greater than 3.0 ng of GM-CSF per 10(6) cells per 24 hr in vitro. The one patient with greater than 30 ng of GM-CSF per 10(6) cells per 24 hr in vitro had positive DTH, a significant histologic inflammatory response, and clinically stable disease. This technique of gene transfer was safe and feasible, but resulted in clinically relevant levels of gene expression in only a minority of patients.
Biolistics↗
Appearance of peristaltic reflex in isolated guinea pig ileum in response to boluses of air, water, oil, and cellulose.
Distension of an isolated preparation of guinea pig ileum triggers the peristaltic reflex, a characteristic movement of the intestinal walls which generates luminal pressures and clearance of luminal contents. To determine how the reflex responds to properties of luminal contents, we compared the responses triggered by boluses of air, oil, and cellulose to boluses of Krebs' solution. We found that oil and cellulose increased pressures and contraction length and decreased outflow. Cellulose, but not oil, slowed the velocity with which the contraction propagated and increased the delay with which the end point (upstream edge) of the contraction started to propagate after the lead point (downstream edge). Air tended to produce short contraction segments and high velocity. We conclude that bolus properties such as viscosity determine the response that isolated intestinal segments generate to distension. Response patterns are reflected in contraction length, propagation velocity, and other visual parameters that define wall movements.
Air↗
Phase I/II trial of docetaxel and vinorelbine in patients with non-small cell lung cancer previously treated with platinum-based chemotherapy.
We conducted a phase I/II trial of the combination of docetaxel and weekly vinorelbine in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) who were refractory or resistant to platinum-based regimens. The objectives of the study were (1) to determine the maximum tolerated doses of docetaxel and weekly vinorelbine when given in combination and (2) to evaluate the response to and quantitative and qualitative toxicity of this combination of agents. Patients were required to have an ECOG performance status of 0 or 1, evaluable lesions, and no prior treatment with docetaxel or vinorelbine. A total of 30 patients were treated on this phase I/II study. Eight patients were treated at various doses on the phase I portion of the study. Twenty-two patients (11 males, 11 females, median age 64.5 years) were treated at the phase II dose of vinorelbine 15 mg/m(2) weekly with docetaxel 60 mg/m(2) on day 1 of a 21 day cycle. Twenty of these 22 patients enrolled at the phase II dose required dose modification or delay. Sixteen patients experienced absolute neutrophil count (ANC) <500/mm(3), and eight patients had neutropenic fever. Four patients experienced partial response (18%), nine patients had stable disease (41%), and nine patients had progressive disease (41%). With a median follow-up of 11 months, median survival for these 22 patients was 15.9 months (95% CI 8.1, 23.6 months). Median time to disease progression was 3.2 months with a 95% CI of (1.4, 4.1) months. Thus, the combination of docetaxel 60 mg/m(2) every 3 weeks and vinorelbine 15 mg/m(2) weekly appears to be active as a second line regimen in NSCLC, although it is a highly myelosuppressive regimen requiring dose modification in 91% of patients.
Adult↗
Microarray analysis of diurnal and circadian-regulated genes in Arabidopsis.
Plants respond to day/night cycling in a number of physiological ways. At the mRNA level, the expression of some genes changes during the 24-hr period. To identify novel genes regulated in this way, we used microarrays containing 11,521 Arabidopsis expressed sequence tags, representing an estimated 7800 unique genes, to determine gene expression levels at 6-hr intervals throughout the day. Eleven percent of the genes, encompassing genes expressed at both high and low levels, showed a diurnal expression pattern. Approximately 2% cycled with a circadian rhythm. By clustering microarray data from 47 additional nonrelated experiments, we identified groups of genes regulated only by the circadian clock. These groups contained the already characterized clock-associated genes LHY, CCA1, and GI, suggesting that other key circadian clock genes might be found within these clusters.
Arabidopsis↗
Specific heat of helium confined to a 57- &mgr;m planar geometry near the lambda point
We report measurements of the specific heat of liquid helium confined to 57-&mgr;m planar gaps extending to within a few nanokelvin of the bulk lambda transition. The data are in fair agreement with Monte Carlo estimates for finite-size effects and with renormalization-group-theory predictions above the transition. Far from the transition, we find surface specific heat exponents, alpha(s) = 0.64+/-0.05 below, and 0.65+/-0.2 above, which compare well with the prediction of 0.658. Comparison with other recent data on small length scales shows some areas of agreement.
Journal Article↗
A phase Ib/II trial of granulocyte-macrophage-colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases: a case of fatal central nervous system thrombosis.
BACKGROUND: Interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF. METHODS: Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19. RESULTS: Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had >50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage. CONCLUSIONS: The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.
Adult↗
Laparoscopic suturing evaluation among surgical residents.
BACKGROUND: Laparoscopic suturing is an integral part of advanced laparoscopic surgery training. The objective of this study was to evaluate the performance and preference of surgical residents performing intracorporeal and extracorporeal knot-tying techniques using conventional and Endo Stitch instruments. The residents were also evaluated on their suturing techniques using conventional instruments, the Endo Stitch, and the Suture Assistant. METHODS: Using an inanimate laparoscopic trainer model, 39 residents were evaluated as they performed laparoscopic knot tying exercises. Endpoints of the study were execution time and subjective preference of surgical residents with respect to the type of instrument used for knot tying. Forty-three residents were evaluated as they performed laparoscopic suturing exercises with three different types of suturing instruments using the same endpoints. RESULTS: The intracorporeal technique was the preferred (89%) method of knot tying among surgical residents. The time for completion of laparoscopic suturing was significantly (P < 0.05) shorter with the Endo Stitch (114 +/- 64 s) than with the conventional instrument (206 +/- 107 s) or the Suture Assistant (151 +/- 70 s). Residents preferred the use of the Endo Stitch in all three categories for suturing, knot tying, and handling. CONCLUSION: The Endo Stitch enhanced laparoscopic skills and was the preferred instrument for laparoscopic knot tying and suturing among surgical residents.
Humans↗
Selective serotonin reuptake inhibitor-induced mydriasis.
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Adolescent↗
Health indicators and intimate partner violence among women who are members of a managed care organization.
BACKGROUND: There have been no population-based studies estimating the prevalence of intimate partner violence (IPV) in an insured population. There is also little information on how well routinely collected health status information predicts IPV risk. Many women now obtain health care from providers who are members of a managed care organization (MCO). To justify efforts to routinely screen for IPV, it is essential to know the prevalence of IPV in this growing population and to identify correlates of IPV among female MCO members. METHODS: A telephone survey with questions on health status, behavioral risk factors, preventive services use, and the Conflict Tactics Scale was completed by 2,415 female members of a New Mexico MCO. RESULTS: Overall, 13.5% of respondents reported experiencing major verbal aggression and 6.7% reported experiencing physical aggression. Younger age, degree of sadness, and inability to handle stress, and a perception of a poorer general health status were significantly associated with major verbal aggression. Race/ethnicity, degree of sadness, and average number of drinks consumed at one sitting were significantly associated with physical aggression. CONCLUSIONS: There is a low but important annual prevalence of IPV among female members of a MCO that occurs across all variables studied. This information is needed to develop appropriate screening protocols and interventions in this population.
Adult↗
N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.
N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.
Administration, Oral↗
Pain during insertion of peripheral intravenous catheters with and without intradermal lidocaine.
Phase 1 of this study evaluated the perception of pain in 50 patients undergoing peripheral venous catheter insertion without the use of a local anesthetic. Phase 2 evaluated perceived pain in 50 patients who received intradermal lidocaine before the i.v. catheter was inserted. The researchers found that lidocaine injected intradermally before placement of an i.v. catheter resulted in significantly lower self-reported pain perceptions (p < 0.01). No additional time (determined in intervals of 15 minutes) was required for the study group. Based on these findings, the hospital policy was modified so that intradermal lidocaine would be offered to all patients requiring peripherally inserted i.v. catheters.
Anesthetics, Local↗
Classification, recording, and cleft palate surgery at the Uppsala Cleft Palate Centre.
This paper describes the classification system, method of recording, and surgical techniques used in Uppsala for children with isolated cleft palate. The classification is based on the system described by Kernahan and Stark and the more detailed system described by the American Cleft Palate Association. Separation of the hard palate into thirds, and into right and left sides, assures a detailed description of the cleft, and separates small morphological differences. The longitudinal registration system was introduced into the Uppsala Cleft Palate Centre in 1967. After the initial recording at the time of primary surgery, it is repeated at 5, 8, 11, 14, 17, and 20 years. By emphasising the therapeutic aspects of various stages of growth, it has been possible to limit the recording to once every third year. This has resulted in an important reduction in the dose of radiation without compromising the reliability of the results. Children born before 1975 had clefts of both the soft and hard palate closed at 18-24 months in a one-stage procedure. For children born in 1975 and later a two stage technique has been used, while clefts limited to the soft palate only have been closed entirely in the first operation. At first, the soft palate cleft was closed at 18 months of age and the hard palate at 4 to 5 years. The timing was changed in several steps to the present soft palate closure at 6 months and hard palate closure at 2 years of age.
Adolescent↗
Morphology of isolated cleft palate in children, including Robin sequence, treated with one or two-stage operations.
A classification developed at the Uppsala Cleft Palate Centre was used to describe isolated cleft palate in children with and without Robin sequence. The study included 109 patients born between 1968 and 1983 with isolated cleft palate. In 46 patients the cleft was closed in a single operation and 63 were treated by a two-stage procedure. Of the 109 patients 70 (64%) were girls. In 19 patients (17%), the cleft was limited to the soft palate. Ninety of the patients had clefts of the hard palate and in 39 (43%) of these patients the clefts involved less than a third of the hard palate. Only four children (4%) had total clefts of both the hard and soft palate. The Robin sequence was diagnosed in 14 children (13%), and it was more common in boys with isolated cleft palate (7/39; 18%) than in girls (7/70; 10%). In those with Robin sequence the cleft was U-shaped anteriorly in nine (64%), with great variations in width. Generally, however, the clefts were wider than other clefts involving the hard palate. In all cases, closure of the soft palate was followed by a spontaneous reduction in the width of the remaining cleft in the hard palate. The greatest improvement was noted in subjects with the U-shaped clefts, in whom the position of the tongue probably had the greatest influence on the development of wide primary clefts. In 10 subjects with clefts of the soft palate only and 12 patients in whom the cleft included part of the hard palate (35%), only the first operation of the two-stage procedure was done because there was no residual cleft. In these subjects the original cleft had involved less than a third of the length of the hard palate.
Child, Preschool↗
Dental abnormalities and ectopic eruption in patients with isolated cleft palate.
The aim of this study was to evaluate the influence of cleft size and surgical treatment on the development of permanent teeth in patients with isolated cleft palate. The series comprised 109 children with isolated cleft palate, 70 girls and 39 boys, including 14 patients with Robin sequence. The patients were grouped according to the sagittal extent of the palatal cleft, measured on dental casts obtained before the primary palate surgery. Forty-six children were treated by one-stage palatoplasty, and 63 in two stages. The dentition was studied on orthopantomograms taken at 5, 8, 11, and 14 years of age. Congenitally missing permanent teeth (third molars excluded) were found in 33 subjects (30%). Children with large clefts had significantly more missing teeth than children with small clefts. The tooth most usually missing was the mandibular second premolar, followed by the maxillary lateral incisor, and the upper second premolar. The incidence of dental malformation was 23%, mostly mild forms. Ectopic eruption of the upper first permanent molars was seen in 23 (45%) of the subjects with large clefts, and in 18 (31%) of those with small clefts. The surgical method did not significantly affect the direction of the eruption. There is a correlation between cleft size and hypodontia, dental deformity, and ectopic eruption. Children with Robin sequence had almost the same incidence of hypodontia, malformed teeth, and ectopic eruption as children with large clefts. There was no correlation between surgical method and ectopic eruption of the maxillary first permanent molars.
Adolescent↗
The effect of opioids on thermoregulatory responses in humans and the special antishivering action of meperidine.
In summary, both mu-receptor and combined mu/kappa-receptor opioids impair thermoregulatory control. Alfentanil, a pure mu-receptor agonist slightly increased the thresholds for sweating and markedly decreased the thresholds for vasoconstriction and shivering. However, the vasoconstriction-to-shivering range remained normal during alfentanil administration as it does during general anesthesia. Meperidine, a combined mu- and kappa-receptor agonist, also slightly increased the threshold for sweating and reduced the thresholds for vasoconstriction. However, meperidine reduced the shivering threshold twice as much as the vasoconstriction threshold, thus significantly increasing the vasoconstriction-to-shivering range. Furthermore, shivering during meperidine administration, once triggered, was of low intensity suggesting that the drug also decreased the gain of shivering. The special antishivering action of meperidine appears to result, at least in part, from its kappa-receptor activity.
Alfentanil↗
An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92.
The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the maximally tolerated doses of combination therapy with alpha interferon (IFN-alpha) and all-trans-retinoic acid (tRA). Fifty patients with incurable malignancies received IFN-alpha administered subcutaneously three times weekly, and tRA administered by mouth at bedtime. Doses were escalated between patient groups, starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-alpha. Major, dose-limiting toxicities were attributable to either the tRA (rash, chelitis) or IFN (constitutional symptoms), and were observed only at tRA dose levels of 224 mg/m2 and 291 mg/m2, or 6 million units of IFN-alpha. The maximally tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-alpha was well-tolerated, with no grade 3 or 4 toxicities attributable to therapy. One patient at the third dose level (75 mg/m2 of tRA and 3 million units of IFN-alpha) developed acute hepatic and renal failure and a metabolic encephalopathy of unclear etiology. We conclude that tRA and IFN-alpha may be safely administered together at the maximally tolerated dose of tRA as a single agent without unexpected side effects. The recommended doses of IFN-alpha and tRA for Phase II trials are 3 million units of IFN-alpha and 172.5 mg/m2 of tRA.
Adult↗
Risk factor information found in medical records of lung and prostate cancer cases, New Mexico Tumor Registry (United States).
The conduct of public health surveillance and epidemiologic investigations would be enhanced by a cost-effective method for the collection of population-based cancer risk-factor data. We assessed the feasibility of ascertaining such data from hospital medical records during routine abstraction of information from a cancer registry. We examined the medical records of a representative sample of prostate and lung cancer cases diagnosed during 1992 and 1993 from the New Mexico (United States) Tumor Registry (NMTR) database. Registry personnel abstracted ancillary information from the medical records of 575 prostate and 273 lung cancer cases. Of medical records from 848 cases, 90 percent documented a history of tobacco use, 77 percent contained any family medical history, and 48 percent documented occupational information sufficient to allow coding into standard occupational groups. Availability of occupation and industry varied by patient ethnicity, age at diagnosis, marital status, and type of hospital, indicating the potential for bias in studies using occupational information from medical records. Our findings suggest that risk factor information abstracted from medical records may provide valuable information for public health surveillance, but is generally too incomplete to serve as a single source of exposure information for etiologic studies. Family histories in medical records may be sufficient for population-based ascertainment of affected relative pairs for genetic epidemiology studies for some cancer types.
Aged↗