Biomedical subjects
M Rosen
Publications and source records attributed to M Rosen.
Effects of benzodiazepines on laryngeal reflexes. Comparison of lormetazepam and Diazemuls.
Of 20 volunteers, five were given intravenous Diazemuls 15 mg over 15 seconds, and three groups of five were given lormetazepam 2 mg intravenously over 10, 20 and 60 seconds, respectively. Laryngeal reactivity and psychomotor function were tested at intervals from prior to injection until 4 hours after injection. For equivalent degrees of depression of psychomotor function, lormetazepam depressed the laryngeal reflex less than Diazemuls (p = 0.004). Lormetazepam give over 60 seconds depressed the laryngeal reflex more than when given over 10 seconds (p = 0.008) or over 20 seconds (p = 0.048), although a significant difference was not demonstrated between the 10-second and 20-second groups. These results concur with experimental evidence that benzodiazepine receptor multiplicity exists, which allows various members of the benzodiazepine group of drugs to exhibit differing therapeutic ratios for their various effects.
Future organisation of anaesthetic health care.
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Gastric emptying and small bowel transit times in volunteers after intravenous morphine and nalbuphine.
Gastric emptying half-times and small intestinal transit times were measured in a double-blind crossover study of 17 volunteers who received an intravenous injection of nalbuphine (5 or 10 mg), morphine (5 mg) or placebo. Both times were monitored using a gamma camera after a radioactive test meal and gastric emptying half-time was calculated. Small intestinal transit time was measured by the appearance of radioactivity in the caecum and also of hydrogen in end tidal air. Gastric emptying was prolonged over placebo by nalbuphine 10 mg, which had more effect than nalbuphine 5 mg or morphine 5 mg; morphine 5 mg had less effect than nalbuphine 5 mg. Small intestinal transit time was prolonged over placebo by nalbuphine 10 mg more than by nalbuphine 5 mg or morphine 5 mg, which had approximately equal effects. In these respects, the potency ratio of nalbuphine appears roughly equivalent to morphine. Small intestinal transit times measured by end tidal hydrogen concentration and gamma camera showed close agreement.
Phase II study of megestrol acetate for metastatic carcinoma of the prostate.
Forty-three males with recurrent and metastatic cancer of the prostate were treated with megestrol acetate (160 mg/day orally) after having failed first-line hormonal treatment (orchiectomy or diethylstilboestrol). Thirty-seven patients were evaluated objectively for response, 28 of whom received the drug for more than 6 weeks. One patient had a partial response (National Prostatic Cancer Project criteria) and seven had stable disease. Toxicity was usually mild, although five patients developed a transient rise in liver enzymes and one patient had a grand mal fit. Three patients showed evidence of tumour "flare". Megestrol acetate has only limited efficacy in patients previously treated for prostatic cancer by hormonal manipulation.
Cerebral blood flow in systemic lupus erythematosus with or without cerebral complications.
We measured mean cerebral blood flow (CBF) in 25 lupus patients using the xenon-133 method. The CBF was normal in lupus patients without cerebral disease and also in CNS lupus patients in remission. The CBF was lower than normal during bouts of cerebral lupus (p less than 0.001). Repeat studies showed a stereotyped pattern consisting of depressed CBF during exacerbation of CNS disease and normalization of CBF during remission (p less than 0.01). These results show that CBF is a sensitive indicator of activity of CNS disease and that the direction of change in CBF reflects the clinical course of CNS lupus.
Metabolic and clinical correlates of acute ischemic infarction.
We studied cerebral metabolism, anatomy, and clinical status in 36 patients with acute cerebral ischemia. Results from FDG-PET were compared with CT to find the relationships between the metabolic, anatomic, and clinical findings. Metabolic abnormalities seen on PET frequently were more extensive than the corresponding CT findings. The pattern of metabolic abnormality was significantly related to both the type of clinical syndrome and the degree of eventual recovery. No such relationships were found for the CT results. We conclude that studies of cerebral metabolism are of value in establishing prognosis after acute cerebral ischemia. Also, knowledge of the patterns of cerebral dysmetabolism provides a powerful means for the localization of clinical function.
The influence of the first-mating age of rats on the number of pups born, their weights and their mortality.
Widely differing ranges for the preferred first-mating age for rats have been reported by different investigators. As well as being of physiological interest this information is important for optimum utilization of animal resources. Previously published results, however, do not provide sufficient information on mortality and the numbers of pups born and weaned. We studied 1623 pups born to 36 female Wistar rats. Dams were first mated at the age of 35 days or 70 days or 105 days. The results show that reproduction and weaning weights increase with an increased first-mating age of dams, although the pup mortality rate also increases. This study can be used when a programme for the production and supply of Wistar rats is planned.
Retinoic acid cooperates with tumor necrosis factor and immune interferon in inducing differentiation and growth inhibition of the human promyelocytic leukemic cell line HL-60.
In this study, we analyzed the effect of tumor necrosis factor (TNF) on retinoic acid (RA)-induced myeloid differentiation of the promyelocytic HL-60 leukemia cell line. We show that low concentrations of the two substances, almost inactive in inducing differentiation when used separately, induce differentiation when added simultaneously to the cell cultures. Cells simultaneously expressing both monocyte/macrophage phenotype (typically induced by TNF) and granulocyte characteristics (typically induced by RA) are induced by a combination of the two factors, indicating that TNF and RA potentiate each other's activity. The results obtained using immune interferon (IFN-gamma) in combination with the two inducers suggest that the mechanism of action of TNF and IFN-gamma are possibly different. The inhibitory effect of RA on the expression of HLA class I antigens and of the high-affinity Fc receptor is potentiated by TNF but completely reversed by rIFN-gamma.
Cerebellar glucose consumption in normal and pathologic states using fluorine-FDG and PET.
We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ([18F]FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.
Exposure of midwives to nitrous oxide.
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Tumor necrosis factor and lymphotoxin induce differentiation of human myeloid cell lines in synergy with immune interferon.
We show that the cytotoxins tumor necrosis factor (TNF) or lymphotoxin (LT), at concentrations of approximately 10(-11) M induce monocytic differentiation of human myeloid cell lines. After 5 d of culture in the presence of rTNF and LT, a significant proportion of the myeloid cell lines express monocyte differentiation antigens and ANAE activity, and become able to reduce nitroblue tetrazolium (NBT) and mediate low levels of ADCC against tumor target cells. These markers of differentiation, however, are maximally induced when rIFN-gamma, at concentrations as low as 4 U/ml, is present simultaneously with the cytotoxins, and the two classes of cytokines act synergistically to induce terminal differentiation. The appearance of monocytic antigens is accompanied by acquisition of morphology and other functional properties of mature monocytic cells, such as chemiluminescence and phagocytosis, and by expression of FcR for monomeric IgG. A decrease in cell proliferation accompanies induced differentiation, and is not due to the cytotoxic properties of TNF or LT, as indicated in simultaneous analysis of surface phenotype and cell cycle. The lack of cytotoxicity of TNF on the HL-60 cell line is also demonstrated by the enhancing effect of TNF on HL-60 cell growth and nucleoside uptake in the first 2 d of culture. These data show that the cytotoxins TNF and LT mediate complex effects on cells of the myelomonocytic lineage and, in synergy with IFN-gamma, can fully induce immature myeloid cells to differentiate into cells with phenotypic, functional, and proliferative characteristics of terminally differentiated myelomonocytic cells.
Danazol treatment of advanced prostate cancer: clinical and hormonal effects.
Danazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15-18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration.
Effect of volume of water taken with diazepam tablets on absorption.
Thirty-three patients received either 10 ml (group A) or 50 ml (group B) of water with diazepam tablets as premedication while in the supine position. Plasma diazepam concentrations were measured, a delay in the attainment of the peak plasma concentration being taken as an indication of delayed absorption and oesophageal hold-up. There was no difference between the two groups, although in an important minority (16.7% (group A) and 20% (group B], absorption was delayed to beyond 60 min. There was a wide scatter of plasma diazepam concentrations in both groups. Dysphagia during swallowing did not appear to delay absorption.
Placental transfer of naloxone.
Maternal and umbilical venous serum naloxone concentrations were measured after the i.v. (30 mothers) or i.m. (seven mothers) injection of naloxone 400 micrograms. Following i.v. naloxone there was rapid transfer to the fetus and therapeutic plasma concentrations could be expected in 1 or 2 min. However, following i.m. administration, neonatal concentrations were variable. In five non-pregnant volunteers naloxone 400 micrograms i.v. resulted in concentrations greater than 2.5 micrograms ml-1 for up to 30 min. After naloxone 2 mg i.m., a peak was reached at 10 min, followed by slow clearance over several hours.
"Patient demand" postoperative analgesia with buprenorphine. Comparison between sublingual and i.m. administration.
A randomized, double-blind, placebo-controlled study of buprenorphine was carried out in 20 patients after cholecystectomy. The drug was given on "patient demand" either i.m. (0.15 mg) or sublingually (0.2 mg) with a minimum dose interval of 30 min. Over the 24-h study period the mean demand by the sublingual route was 0.8 mg (range 0.6-1.2 mg) and by the i.m. route 0.66 mg (range 0.45-0.9 mg). Pain relief, by visual analogue scales and grading, was similar. Plasma buprenorphine concentrations varied more after sublingual administration. Either route was effective for the treatment of pain when administered by "patient demand".
Respiratory function following nalbuphine and morphine in anaesthetized man.
In 40 patients anaesthetized with thiopentone, 66% nitrous oxide and 1% halothane, the effects of a single i.v. dose of nalbuphine 4.5, 8, 15, 25 or 50 mg/70 kg or morphine 3, 5, 10 or 17.5 mg/70 kg on total ventilation and end-tidal carbon dioxide concentration have been measured. Depression of respiration occurred with both drugs and with all doses. The lower doses of nalbuphine produced more depression than equianalgesic doses of morphine. Conventional equianalgesic doses produced similar degrees of depression. With the highest dose of morphine, respiratory impairment progressed to apnoea whereas, with nalbuphine, apnoea did not occur in any patient. With increasing dosage of nalbuphine there appeared to be a limit to the extent of respiratory depression. The highest dose of nalbuphine produced less depression than some lower doses, suggesting a reversal effect.
In vitro buffering capacity of Alka Seltzer Effervescent. A comparison with magnesium trisilicate mixture B.P. and sodium citrate 0.3 M.
The variety of antacids used as a prophylaxis for acid aspiration syndrome reflects dissatisfaction with each agent. Alka Seltzer Effervescent is a proprietary product without aspirin. We have shown that it can easily be dissolved in a small volume, readily mixes with hydrous fluids, and has a satisfactory neutralising capacity. Its non-particulate nature, storage in individual packages and palatability, indicated by commercial acceptance overseas, show that further trials in vivo as a method of raising gastric pH may be useful.