Biomedical subjects
Publications and source records attributed to M Simmonds.
The complications of carotid endarterectomy (CEA) under cervical plexus blockade have yet to be fully evaluated. Two different cases are presented; both patients suffered sudden collapse following superficial and deep cervical plexus block in preparation for CEA. The causes, presenting signs and differential diagnoses are discussed. The safest cervical plexus anaesthetic block technique has not yet been established.
The pre-operative anaesthetic records of 195 patients were analysed for the presence of 12 agreed core items of pre-operative assessment. This study showed that anaesthetists recorded 26.8 per cent of this information. In up to one-third of patients the following were recorded: smoking history, family history, gastro-oesophageal reflux, airway assessment, dental assessment, chest examination, heart-sounds and blood pressure. Previous anaesthesia, drug history and allergies were recorded in one to two-thirds of patients. Past medical history was recorded in over two-thirds of patients. With a view to improving the level of record-keeping, a formatted, pre-printed pre-operative assessment record was introduced into practice and two months later the audit was repeated. A small but non-significant improvement in record keeping was observed. An argument is made for the introduction of an interdisciplinary, unified anaesthetic pre-operative record.
A 30-year-old woman at 25 weeks gestation presented to the labour ward complaining of abdominal pain and a painful bruise in her right groin. Over the course of several hours, she developed rapidly spreading necrotising fasciitis of the right thigh. She required emergency radical debridement of the thigh and caesarean delivery of a dead fetus. She was admitted to the intensive care unit (ICU) with septic shock, where she received ventilatory and inotropic support. Streptococcus pyogenes was isolated from the infected tissue and a diagnosis of group A streptococcal toxic shock-like syndrome (GAS TS-LS) was confirmed. Following acute and rapid haemodynamic deterioration, plasmapheresis was given for 6 days, after which the patient's general condition improved and vasoconstrictor requirement was significantly reduced. Subsequently, immunoglobulin was given intravenously for thrombocytopenia, following which the platelet count steadily improved. Despite the development of acute renal failure, acute respiratory distress syndrome and a left hemiplegia, the patient made a remarkable recovery. She was later transferred to a plastic surgical unit for split skin-grafting. The importance of early diagnosis and aggressive treatment of GAS TS-LS is emphasized and the place of plasmapheresis and intravenous immunoglobulin therapy in this condition is discussed.
A primigravida at 41+ weeks gestation presented with spontaneous rupture of membranes. Labour was induced and later an emergency caesarean section was performed for failure to progress. The patient suffered a per-operative uterine tear and post-partum haemorrhage and required postoperative ventilatory support in the intensive care unit. Following tracheal extubation, she developed a left hemiparesis and grand-mal seizures. The differential diagnosis, diagnostic difficulties, investigations and clinical management of this case are all discussed. An examination of existing literature highlights some of the focal neurological abnormalities that present with eclampsia and the possible need for more sophisticated neuroradiological investigations in these cases. Finally, it is emphasized that anaesthetists and intensivists need to be aware of atypical and delayed presentations of eclampsia.
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The aim of this study was to determine the efficacy and toxicity of topotecan administered as a 21-day continuous intravenous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas. 26 previously untreated patients with advanced or metastatic pancreatic adenocarcinoma received topotecan at a dose of 0.5 mg/m2/day or 0.6 mg/m2/day as a continuous intravenous infusion for 21 days. Courses were repeated every 28 days. 26 patients were assessable for response and toxicity on an intent-to-treat basis. The initial 8 patients at a starting dose of 0.6 mg/m2/day experienced unacceptable myelosuppression and dose delays. The subsequent 18 patients, therefore began therapy at a dose of 0.5 mg/m2/day. The major toxicity of topotecan at this dose and schedule was myelosuppression, which was reversible and non-cumulative. There were no complete responses and two partial responses for a total response rate of 8% (95% confidence interval, 1-25%). Response durations were 17 and 45 weeks. Stable disease was seen in 3 patients. The median time to progression for all patients was 8 weeks and the median survival was 20 weeks. Topotecan given as a 21-day continuous intravenous infusion has a similar response rate and median survival to our previously reported study of the 5-day short infusion regimen in pancreatic carcinoma.
BACKGROUND AND PURPOSE: The clinical concept of spinal stiffness provides one basis for applying spinal manipulation. Because the terms used to describe the perceptual results of manual spinal stiffness testing are poorly defined, the nature and number of attributes contained in the concept remain unclear. This study attempted to clarify the concept of spinal stiffness by examining the relationships among 31 published spinal stiffness descriptors using cluster analysis. SUBJECTS AND METHODS: Each stiffness descriptor was printed on a magnetized rubber strip. Physical therapists in Houston (Tex) and Sydney (New South Wales, Australia) judged the similarity of the stiffness descriptors by arranging them on a board. The squared Euclidean distance between words was calculated, and cluster analysis was performed using Ward's method. RESULTS: Cluster analysis reduced the 31 stiffness descriptors to three superclusters (limited mobility, increased mobility, and viscoelasticity) in both the Houston and Sydney data. CONCLUSION AND DISCUSSION: In a step toward improving the reliability of spinal stiffness judgments, this study has identified the fundamental characteristics of the clinical concept of spinal stiffness. Research is now needed to clearly define these characteristics and then develop protocols that will allow physical therapists to reliably rate these attributes.
STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.
PURPOSE: Supplemental, "as-needed," administration of an opioid is a common approach to the problem of breakthrough pain in cancer patients. Oral transmucosal fentanyl citrate (OTFC) is undergoing investigation as a new treatment for breakthrough pain. The primary purpose of the study was to demonstrate that a single-unit dose of OTFC can safely and effectively treat breakthrough pain. A secondary goal was to determine appropriate dosing guidelines. PATIENTS AND METHODS: This was a multicenter, randomized, double-blind, dose-titration study in 62 adult cancer patients using transdermal fentanyl for persistent pain. Consenting patients provided 2 days of baseline data to evaluate the performance of their usual breakthrough pain medication. Patients then randomly received 200 microg or 400 microg OTFC in double-blind fashion. (Patients were always assigned, rather than randomized, to 200 microg if 400 microg represented > 20% of around-the-clock medication.) Pain intensity (PI), pain relief (PR), and global satisfaction scores were recorded. OTFC was then titrated until the patient received adequate PR for each episode using one OTFC unit. Orders to titrate up were ignored one third of the time to improve the blind. Two days of baseline data were compared with 2 days of OTFC data after titration identified an effective dose of OTFC. RESULTS: Most patients (76%) found a safe and effective dose of OTFC. There was no meaningful relationship between the around-the-clock opioid regimen and the effective dose of OTFC. In open-label comparisons, OTFC produced a faster onset of relief and a greater degree of PR than patients' usual breakthrough medication. Somnolence, nausea, and dizziness were the most common side effects associated with OTFC. CONCLUSION: Most patients find a single OTFC dosage that adequately treats breakthrough pain. The optimal dose is found by titration and is not predicted by around-the-clock dose of opioids.
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Two children who developed acute renal failure in the immediate post-renal transplantation period are presented. Each was immunosuppressed with cyclosporin and was also receiving oral acyclovir for prophylaxis against cytomegalovirus infection. Renal biopsy findings suggested drug toxicity. Discontinuation of acyclovir coincided with reversal of renal impairment. As cyclosporin levels were at the lower end of the therapeutic range, we believe acyclovir to be the likely causative agent.
The objective of the study was to measure maximal and subjectively graded submaximal efforts in a pinch grip, power grip, and stoop life activity, subsequently to study the relationship of these efforts across activities and time, and furthermore to determine the reliability of effort perception of activities in different grades of operation. Ten normal male university students with mean age of 22.2 years, mean height of 175.3 cm, and mean weight of 71.4 kg volunteered for the study. All subjects were required to exert their maximal efforts, 80%, 60%, 40%, and 20% (of the maximal) effort in pinching, gripping and stoop lifting for three trials in a random order on four different days. The subjects were tested at the same time of the day on a Monday, Wednesday, Friday of one week, and Friday of the next week. While the activity and perception had significant main effects (p < 0.001) the trial was significant only for average strength (p < 0.04). There was a significant two-way interaction between activity and perception; all other interactions were not significant. There was a systematic bias in perception at all graded contractions except at 40% level of effort. The perceived 60% and 80% of maximal voluntary contractions (MVC) were lower and 20% was higher than their respective objective values based on MVC (p < 0.01). At 40% effort there was no statistical difference between perceived and objective strength effort in all three activities. The reliability of perception was similar for precision, power, or gross activity.
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Contractions of the transmurally stimulated guinea-pig ileum were not affected by 10 microM bicuculline, a competitive GABAA receptor antagonist. The GABAA potentiator alphaxalone depressed the responses to 2 and 20 Hz stimulation by 20% and 40%, respectively, but had no effect on 0.2 Hz responses. The depressions were prevented by 10 microM bicuculline. This suggests that endogenous activation of GABAA receptors during transmural stimulation was normally subthreshold but, when pharmacologically potentiated, inhibitory effects were seen.
The prognosis from human malignant melanoma varies according to sex and to multiple histologic, biologic and cell kinetic parameters. Thus melanomas exhibit a major degree of heterogeneity in their biologic properties and further characterization of their biochemical heterogeneity should yield important information. The present study sought to demonstrate the activity of a biochemical marker of estrogen synthesis, the aromatase enzyme, in melanoma tissue and to determine its range of activity. Initially, we validated a highly sensitive radiometric assay for aromatase by comparing it with a direct product isolation method. We detected production of 417 pmol/g protein/h of estrone and 37.3 pmol/g protein/h of estradiol by direct product isolation in a human melanoma and 398 pmol estrone/g protein/h by the radiometric assay. The activity present was blocked by similar amounts of the aromatase inhibitor, aminoglutethimide, as were necessary to block placental, breast cancer, and rat brain aromatase activity. We then assayed aromatase radiometrically in 19 human melanomas and found measurable activity ranging from 9 to 398 pmol estrone/g protein/h in 15 tissues. No relationship with the patient's age or sex was demonstrated. The activity exceeded by 2-fold that previously detected in 49/61 human breast cancers. This study identified a marker enzyme in melanoma tissue which varied by 40-fold among human tumors. Correlation of aromatase activity with prognosis and response to various types of therapy is now necessary to establish the biologic relevance of this finding.
We conducted a randomized clinical trial in men with stage D2 prostate cancer to test whether androgen priming potentiates the efficacy of cytotoxic chemotherapy. Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion and were administered cyclic intravenous (IV) chemotherapy. The patients were randomized to receive either androgen priming or no additional treatment for three days before and on the day of chemotherapy. Median duration of follow-up was 43 months. Response rate (remission plus disease stabilization) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients (79% v 73%, respectively) or when it was extended to all patients (46% v 61%). Median duration of response was similar for the stimulation and control arm (9 and 10 months, respectively). Median survival was 10 months in the stimulation and 15 months in the control group (P = .0047). The androgen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with androgen administration. Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit, long duration of response to the initial castration, and normalization of an elevated serum acid phosphatase on treatment. We conclude that in this group of patients with advanced disease, androgen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome. Furthermore, our data emphasize the heterogeneity of biologic behavior of prostate cancer.
Seventy-five patients with stage D-2 prostate cancer refractory to orchiectomy have been entered in a controlled trial to test whether androgen priming enhances the efficacy of chemotherapy. All patients are treated with aminoglutethimide and hydrocortisone as a means of achieving medical adrenalectomy and are given cyclic i.v. chemotherapy with cytoxan, adriamycin and 5-fluorouracil. Patients in the stimulation arm (N = 39) receive, in addition, fluoxymesterone (5 mg p.o. b.i.d.) for 3 days before and on the day of chemotherapy. A similar response rate was observed in the stimulation and control arm (83% vs 74% respectively) when the analysis was restricted to evaluable patients. When all patients were included, a significantly higher response rate was observed in the control arm (64% vs 49%, P less than 0.05) as a result of the larger fraction of unevaluable patients in the stimulation arm (41% vs 14%). Median duration of response is 9 months in the stimulation and 10 months in the control arm. Median overall survival in the stimulation and control group is 12 months and 16 months respectively. Significant toxicity consisting of exacerbation of bone pain and, in two patients, development of reversible spinal cord compression was observed following androgen priming. Our results suggest that combined medical adrenalectomy and chemotherapy are highly effective in the treatment of advanced prostate cancer. Thus far, no additional benefit has been observed with androgen priming.
The effect of dietary lipid consumption on plasma levels of sex-hormone binding globulin (SHBG), free testosterone and cholesterol was studied in 6 normal men. After consuming a diet with a high fat content (greater than 100 g fat/day) for two weeks, the mean plasma cholesterol level increased (p less than 0.02) while the mean SHBG level decreased (p less than 0.02). Changing the diet from one with a high fat to low fat content (less than 20 g fat/day) for a further two week period resulted in a significant reduction in mean plasma cholesterol level (p less than 0.001) while the mean SHBG level increased (p less than 0.01). The increase in plasma SHBG was associated with a significant decrease in the free testosterone fraction and free testosterone concentration. No significant changes were detected in plasma samples obtained from the same men during a control period. The results from this study demonstrate that dietary lipid intake is an additional factor involved in the regulation of plasma levels of SHBG.