Biomedical subjects
Publications and source records attributed to R Birch.
In this study, we discuss 68 cases in which peripheral nerve trunks were inadvertently divided by surgeons. Most of these accidents occurred in the course of planned operations. Delay in diagnosis and in effecting repair was common. We list the nerves particularly at risk and the operations in which special care is needed. We recommend steps to secure prompt diagnosis and early treatment.
Metastases from patients with solid tumors were harvested from 196 patients for the purpose of growing tumor-derived activated cells (TDAC). Cells were prepared from autologous tumor cultures by incubation with Interleukin-2 (IL-2) followed by repeated exposure to tumor antigen and/or anti-CD3 monoclonal antibody. Initial growth success was achieved in 66%; 45/56 (80%) of these early cultures were subsequently expanded for in vivo therapy. It took a mean of 69.4 +/- 24.0 days to grow TDAC for treatment. Thirty-eight patients were treated with cyclophosphamide (1 g/m2) on day one followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/day) on days 2-5 and approximately 10(11) TDAC on day 2. Patients subsequently received monthly IL-2 as a 96-hour constant infusion if their cancers were stable or regressing. Median age was 51 yrs; 58% were male. Performance status was 0-1 in 64%, 29% had lung metastases; 34% had liver metastases. The usual IL-2 toxicities were seen. Responses were seen only in 1/38 patients (3%); a partial response in a patient with lymphoma. Forty-two percent were stable 90 days post-treatment, the rest were progressive or inevaluable. We conclude that a treatment plan for IL-2/TDAC is technically difficult, costly, and not practical under these conditions. Clinical results to date are not clearly different than those obtained with other IL-2 regimens.
We have evaluated the effect of Interleukin-2 [IL-2] after Cyclophosphamide (C) chemotherapy in 41 patients with metastatic cancer. IL-2 was given as a continuous infusion priming cycle 36 hours after C at 1 gm/m2 intravenously. In 39 evaluable patients, there were no complete remissions [CR], 2 partial remissions [PR], and 1 had a minor response [MR]. Stable disease for 30 days was seen in 16 patients whereas 20 progressed. The durations of partial and minor responses were brief, ranging from 1-6 months. Grade 3-4 neutropenia was seen in 41%. This was more severe than seen with IL-2 alone or IL-2 combined with lower doses of C. The marrow suppression was due to the chemotherapy. This combination of IL-2 and C appears to be reasonably well tolerated by patients, but toxicity is greater and the response rate is no better than results achieved by IL-2 alone. Responses of 26 patients with renal cancer appear to be inferior to our historical data using IL-2/LAK cells without C. Immune monitoring demonstrated changes expected with C chemotherapy (i.e., a non-selective decline in immune function). C induced no further differences in IL-2 induced changes in immune function.
PURPOSE: Although weight reduction generally lowers blood pressure, it is unclear whether the response is due to concurrent dietary changes or to reduced body mass itself. In this study, the independent effects of energy restriction and weight reduction were examined prospectively in 24 obese, hypertensive, normoglycemic women whose dietary intake was tightly controlled. SUBJECTS AND METHODS: Sodium, potassium, and calcium intake, the polyunsaturated/saturated fat ratio, and the proportional composition of carbohydrate, fat, and protein were constant throughout the 5-month protocol. Hemodynamic and neuroendocrine status was evaluated in four 10-day hospital phases: two prior to weight loss (energy balance and then 800-kcal intake), and two after an average loss of 13 kg to normal body weight (800 kcal and then return to energy balance). RESULTS: Fasting serum insulin, triiodothyronine:reverse triiodothyronine ratio, resting metabolic rate, and heart rate declined, and sodium and potassium balances were negative during energy restriction. Catecholamines, renin, aldosterone, plasma volume, cardiac output, and blood pressure showed no consistent response to changes in energy intake. By contrast, weight reduction independently lowered blood pressure, plasma volume, cardiac output, and plasma renin activity. Body fat pattern remained unchanged. CONCLUSION: These results demonstrate that weight loss has a blood pressure-lowering effect that is distinct from energy restriction and that is related to changes in blood volume and cardiac output.
The American Medical Association Council on Scientific Affairs recently emphasized the importance of nutritionally sound weight reduction diets and changes in life-style to promote long-term weight control. The purpose of this study was to evaluate long-term effectiveness and to identify predictors of success of an intensive multidisciplinary program utilizing the time-calorie displacement diet, a low-fat, high-complex-carbohydrate diet, to promote and maintain reduced body weight. In 213 obese adults consecutively entering the program, including dropouts, weight loss averaged 6.3 kg (0.4 kg/week) and 16% of excess weight over 7 months of treatment. The 78 (37%) completing the recommended 15 visits lost a mean of 10.8 kg and 28% of their excess weight while under treatment. Weight loss was largely predicted by number of visits, which was more important than treatment duration. An increased number of visits was predicted by being married, being female, and reporting a usual diet low in snack foods. Of 147 patients contacted at posttreatment follow-up, 53% maintained their weight loss or continued to lose weight an average of 25 months later and 24% experienced weight rebound but were still below their pretreatment weight; only 23% regained their lost weight. Mean net weight loss from pretreatment to follow-up was 8.0 +/- 1.0 kg (mean +/- standard error of the mean). No factor significantly predicted posttreatment weight rebound. Results suggest that a nutritionally sound diet, prescribed in a multidisciplinary program and emphasizing life-style changes, can result in long-term weight control in a majority of patients treated.
We evaluated adoptive cellular therapy with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells alternating with sequential dacarbazine chemotherapy in 27 patients with metastatic melanoma. rIL-2 was given to the patients as a 5-day continuous-infusion priming cycle followed by 1 day of rest, 4 days of leukapheresis for in vitro LAK cell expansion, and then 4 1/2 days of continuous rIL-2 infusion in conjunction with reinfusion of LAK cells during the first 3 days of the continuous infusion. Two weeks later, patients received dacarbazine (1,200 mg/m2) chemotherapy. Two patients achieved complete remission, and five achieved a partial remission for a response rate of 26% (95% confidence interval = 12%-47%). Three patients had mixed responses. The partial and mixed responses were brief, ranging from 1 month to 6 months, whereas the two complete responses have been sustained for 13+ and 24+ months. There were no additive toxic effects except for thrombocytopenia, which delayed treatment in two patients. Alternating adoptive immunotherapy and dacarbazine chemotherapy appear to be reasonably tolerated by patients, but the response rate is not clearly better than that achieved with other rIL-2 regimens or with chemotherapy alone.
STUDY OBJECTIVE: To compare the survival of patients with locally advanced non-small cell lung cancer treated with single-agent vindesine, thoracic radiotherapy, or both treatment modalities. DESIGN: Randomized, prospective, phase III trial. SETTING: Multi-institutional, university-based national cooperative oncology group. PATIENTS: The study included 319 patients with locally advanced, unresectable non-small cell lung cancer who had no evidence of extrathoracic metastases. All patients were ambulatory and had measurable disease. Some patients could not have surgery because of coexisting medical conditions. INTERVENTION: Patients were randomly assigned to receive vindesine, 3 mg/m2 body surface area weekly; standard thoracic radiotherapy, 60 Gy over 6 weeks; or both vindesine and thoracic radiotherapy. Vindesine was administered for 6 weeks and then every other week to patients who had no disease progression. Patients who developed progressive disease while receiving vindesine or radiotherapy alone were crossed over to radiotherapy or vindesine, respectively. Response assessment took place at week 6. RESULTS: The overall response rate was superior in the radiotherapy arms (radiotherapy alone, 30%; radiotherapy plus vindesine, 34%; vindesine alone, 10%; P = 0.001). However, with a minimum follow-up of 42 months, no improvement in survival has been seen with radiotherapy. The median survival was 8.6 months for patients receiving radiotherapy alone, 9.4 months for those receiving radiotherapy plus vindesine, and 10.1 months for those receiving vindesine (P = 0.58). Radiotherapy also failed to improve long-term survival. The 5-year survivals were 3%, 3%, and 1%, respectively (P = 0.56). CONCLUSION: Patients with non-small cell lung cancer who have inoperable, nonmetastatic disease gain no clinically meaningful survival advantage with immediate thoracic irradiation, even when modern megavoltage radiation therapy techniques and equipment are used.
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A purpose of this study was to determine the difference in the lumbar curves of subjects while they stood compared with while they sat in two chairs with different seat angles--the Balans Multi-Chair (BMC) and a standard conventional chair (SCC). An additional purpose was to determine the relationship between lumbar curvature and 1) anthropometric factors and hamstring and hip flexor muscle length during standing and during sitting in the two chairs and 2) amount of time spent sitting. Sixty-one men between 20 and 30 years of age served as subjects. Lumbar curve measurements were taken with a flexible ruler with the subjects first standing and then sitting in the two chairs. Hamstring and hip flexor muscle lengths were indicated by range-of-motion measurements taken with a gravity goniometer. Age, number of hours spent sitting per day, upper body length, and right leg length also were recorded. Subjects had significantly more lumbar extension when they sat in the BMC than when they sat in the SCC. Hip flexor length was the only factor that appeared to relate significantly to the difference between the standing lumbar curve and the lumbar curves in the BMC and the SCC.
Patients with advanced nonsmall-cell lung cancer (NSCLC), good performance status, and no prior chemotherapy were randomized to receive one of three regimens: intravenous vindesine (V) 3 mg/m2 every 2 weeks; V 3 mg/m2 weekly for 5 weeks, followed by a dose every 2 weeks plus mitomycin (VM) 20 mg/m2 day 1 and then 15 mg/m2 every 6 weeks; or V at the more intensive dose rate plus cisplatin (VC) 120 mg/m2 with forced diuresis on days 1 and 29 and then every 6 weeks. A total of 435 patients were enrolled in the trial, with 410 (94%) assessable for prognostic characteristics and survival. Among the 375 patients assessable for response, only 58 (15%) achieved objective response. Single-agent V every 2 weeks was inactive (response rate less than 1%), effectively acting as a no-treatment arm. Among assessable patients receiving VM, 33 (27%) responded; among patients receiving VC, 24 (19%) responded. There was no statistically significant survival difference among the treatment arms, with median survival among those treated with V 14.8 weeks, VM 20.4 weeks, and VC 24.7 weeks; VC achieved borderline significance (P = .06) compared with V. In a prognostic factor analysis, treatment was not a significant factor (P = .447) for survival. Thus, in this large multicenter trial, neither a high-dose cisplatin combination nor a noncisplatin regimen (VM) with a comparable response rate had a significant survival advantage over minimal chemotherapy. New approaches are needed in advanced NSCLC.
We report a hitherto undescribed type of peripheral nerve lesion in which pressure results in mechanical demyelinisation of a length of nerve with interruption of conduction. On release of the pressure, early recovery may follow the return of the myelin insulation.
We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care.
We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Descriptive data were collected regarding static standing balance of 71 noninstitutionalized elderly women as they performed two timed balance tests. All subjects performed the sharpened Romberg test and the one-legged stance test on each foot in four test conditions: 1) eyes open, 2) eyes closed, 3) shoes on, and 4) shoes off. Subjects were grouped and analyzed according to the following age ranges: 1) 60 to 64 years, 2) 65 to 69 years, 3) 70 to 74 years, 4) 75 to 79 years, and 5) 80 to 86 years. The best time of three trials was used for data analysis. The maximum balance time for the sharpened Romberg test was 60 seconds. For the one-legged stance test, a maximum balance time was 30 seconds. No significant difference was found between right and left or dominant and nondominant limbs while performing the one-legged stance test. No significant difference was found in mean balance time between subjects who had fallen versus those who had not fallen, nor between shoes-on and shoes-off test performance. Subjects' performance on the eyes-open test was consistently superior to their eyes-closed test performance (p less than .0001). The one-legged stance test mean balance time decreased significantly as age increased. More subjects reached the maximum balance time on the sharpened Romberg test than on the one-legged stance test. The results of this study indicate that additional research is needed in the area of balance maintenance among the elderly population.