The haemodynamic effects of dopexamine infusion in the critically ill

Superficial dorsal penile vein thrombosis was diagnosed 8 times in 7 patients between 19 and 40 years old (mean age 27 years). All patients related the onset of the thrombosis to vigorous sexual intercourse. No other etiological medications, drugs or constricting devices were implicated. Three patients were treated acutely with anti-inflammatory medications, while 4 were managed expectantly. The mean interval to resolution of symptoms was 7 weeks. Followup ranged from 3 to 30 months (mean 11) at which time all patients noticed normal erectile function. Only 1 patient had recurrent thrombosis 3 months after the initial episode, again related to intercourse. We conclude that this is a benign self-limited condition. Anti-inflammatory agents are useful for acute discomfort but they do not affect the rate of resolution.     

Clinical effectiveness of influenza vaccination in Manitoba

OBJECTIVE: To assess the clinical effectiveness of influenza vaccination in preventing influenza-associated hospitalization and death. DESIGN: Case-control study. SETTING AND PATIENTS: Noninstitutionalized persons aged 45 years or older living in Manitoba, on December 1, 1982, and December 1, 1985. METHODS: Linked records of the Manitoba population registry, hospital-discharge abstracts, physician claims for ambulatory-patient visits and influenza vaccination, and vital statistics were used. A matched-set analysis estimated the clinical effectiveness of influenza vaccination in preventing hospital admissions and deaths from influenza-associated conditions during influenza A (H3N2) outbreak periods in 1982 to 1983 (12 weeks) and 1985 to 1986 (10 weeks). The analysis adjusted for hospital discharge and ambulatory care for high-risk conditions within the previous 15 months and 3 months, respectively. RESULTS: Influenza vaccination prevented 32% to 39% of hospital admissions with pneumonia and influenza and 15% to 34% of admissions with all respiratory conditions. Vaccination was 43% to 65% effective in preventing hospital deaths with these conditions (all listed diagnoses) and 27% to 30% effective in preventing deaths from all causes. CONCLUSION: Influenza vaccination has substantial clinical effectiveness in preventing hospital admission and death from influenza-associated conditions in noninstitutionalized individuals.     

Mastoparan stimulates exocytosis at a Ca(2+)-independent late site in stimulus-secretion coupling. Studies with the RINm5F beta-cell line

Mastoparan, a tetradecapeptide from wasp venom, stimulated exocytosis in a concentration-dependent manner, which was enhanced by pertussis toxin pre-treatment, in the insulin secreting beta-cell line RINm5F. Mastoparan (3-20 microM) also elevated cytosolic free calcium concentration ([Ca2+]i), a rise that was not attenuated by nitrendipine. Divalent cation-free Krebs-Ringer bicarbonate (KRB) medium with 0.1 mM EGTA nullified the mastoparan-induced increase in [Ca2+]i, suggesting that the peptide increased Ca2+ influx but not through the L-type voltage-dependent Ca2+ channel. Depletion of the intracellular Ca2+ pool did not affect the mastoparan-induced elevation of [Ca2+]i. Remarkably, in divalent cation-free KRB medium with 0.1 mM EGTA and 2 microM thapsigargin in which mastoparan reduced [Ca2+]i, the mastoparan-stimulated insulin release was similar to that in normal Ca(2+)-containing KRB medium. Inhibitors of protein kinase C, such as bisindolylmaleimide, staurosporine, and 1-O-hexadecyl-2-O-methyl-rac-glycerol did not suppress the mastoparan-stimulated insulin release. Mastoparan at 10-20 microM did not increase cellular cAMP levels, nor did mastoparan at 5-10 microM affect [3H]arachidonic acid release. In conclusion, although mastoparan increased [Ca2+]i, this increase was not involved in the stimulation of insulin release. Rather, the data suggest that mastoparan directly stimulates exocytosis in a Ca(2+)-independent manner. As GTP-binding proteins (G proteins) are thought to be involved in the process of exocytosis and as mastoparan is known to exert at least some of its effects by activation of G proteins, an action of mastoparan to activate the putative stimulatory Ge (exocytosis) protein is likely.     

Regional homovanillic acid production in humans

Peripheral plasma levels of homovanillic acid (HVA), the deaminated and o-methylated metabolite of dopamine, are often used as an indicator of central nervous system dopaminergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma HVA pool in 60 healthy volunteers. Veno-arterial differences and organ plasma flows were used to quantify the relative amounts of HVA contributed by various sites into the peripheral circulation. Positive arterio-venous HVA gradients were found in the pulmonary, hepatosplanchnic, skeletal muscle and jugular vessels of the normal volunteers. No HVA increment was found in the coronary sinus. The renal circulation was determined to be the principal site of HVA clearance, extracting 27 nmol/min. The regional contributions of HVA were as follows: lungs 21 nmol/min, hepatosplanchnic organs 3 nmol/min, skeletal muscle 3 nmol/min and the brain 4 nmol/min. The pattern of regional HVA production contrasted with that of the deaminated dopamine metabolite, dihydroxyphenylacetic acid, for which the heart was the principal site of production identified. Sixteen patients with chronic congestive heart failure (CHF) and 6 patients with pure autonomic failure (PAF) were also studied to investigate possible effects of sympathetic nervous system overactivity and underactivity on peripheral HVA production and plasma HVA concentration. The resting arterial plasma HVA concentration in CHF was increased approximately 3-fold. Unexpectedly, this was attributable to reduced HVA plasma clearance, not increased HVA production. Total HVA production in PAF was diminished by 40%. PAF patients had normal resting arterial HVA levels, this being accounted for by a 57% fall in the renal plasma clearance of HVA. Acute sympathetic nervous system activation in response to bicycle riding was accompanied by a 34% increase in the arterial concentration of HVA. It can be concluded that HVA is produced at a number of sites throughout the body not renowned for their dopaminergic innervation. Regional HVA production is associated, in part, with the metabolism of precursor dopamine in sympathetic nerves and at a rate which appears to be influenced by sympathetic nervous activity. To obtain an accurate indication of central dopaminergic activity the confounding influences of HVA plasma clearance and peripheral HVA production must be excluded.     

The first cryogenic dark matter experiment

An experimental search for dark matter particle candidates using cryogenic detectors requires a low radioactive background environment. We discuss the status of a cryogenic dark matter experiment to be performed in the Stanford Underground Facility. The detectors will be cooled in a specially designed cryostat connected to a modified side access Oxford 400 dilution refrigerator. Details of the cryostat design and its operating performance are presented. The effectiveness of the multi-level shield surrounding the cryostat, as well as the background levels we expect to achieve in the pilot experiment are discussed. Finally, we examine the limits which can be set on dark matter candidates with such an experiment.Deceased     

A study of the dynamics of a continuously stirred tank reactor with feedback control of the temperature

Feedback control of the temperature in the continuously stirred tank reactor (CSTR) will be studied in this paper. The control is achieved by continuously changing the input flow rate in response to the temperature. In particular the effect the control has on the temperature-dependent oscillations will be investigated. The steady-state solutions and emergence of periodic solutions through the Hopf bifurcation will be analyzed both theoretically and numerically. The region into which all trajectories are ultimately drawn will be defined in the phase plane^ as well as the areas in parameter space to which oscillations will be confined. Finally several nonlinear controlling functions are presented which ensure the system does not exhibit oscillations.     

The lung as an alternative route of delivery for insulin in controlling postprandial glucose levels in patients with diabetes

STUDY OBJECTIVES: To determine the efficacy of the lung as an alternative route of delivery for insulin in controlling glucose below diabetic levels (11.2 mmol/L) 2 h after the ingestion of a meal in patients with type 2 diabetes mellitus. DESIGN: Single-blinded, nonrandomized, placebo-controlled pilot study consisting of two visits. SETTING: A primary care facility. PATIENTS: Seven patients with type 2 diabetes mellitus. INTERVENTIONS: On the first study visit, fasting glucose levels were normalized. Then, patients inhaled 1.5 U/kg insulin by aerosol into the lungs 5 min before ingesting a test meal. On the second visit, patients inhaled placebo aerosol 5 min before ingesting the same meal. On both visits, plasma samples were collected and analyzed for glucose levels for 3 h during the postprandial state. MEASUREMENTS AND RESULTS: No one coughed after inhalation of insulin aerosol or demonstrated hypoglycemia. During the postprandial period, glucose levels were significantly lower at 20 min (5.12+/-1.08 mmol/L), 1 h (7.87+/-0.73 mmol/L), 2 h (8.05+/-1.24 mmol/L) and 3 h (7.50+/-1.43 mmol/L) following inhalation of insulin than when the placebo was used. Data for the placebo were 10.36+/-1.23 mmol/L at 20 min, 14.0+/-1.68 mmol/L at 1 h, 16.18+/-1.45 mmol/L at 2 h, and 14.37+/-2.11 mmol/L at 3h (for all comparisons, p < 0.05). On the insulin visit, glucose levels were < 11.2 mmol/L 2 h after the meal in six of seven patients. None attained this level at the placebo visit. In addition, glucose levels were within the normal postprandial range of < 7.84 mmol/L in four of seven patients 2 h after eating on the insulin visit. CONCLUSIONS: These results suggest that, once plasma glucose levels are normalized, postprandial glucose levels can be maintained below diabetic levels by delivering 1.5 U/kg insulin into the lungs 5 min before the ingestion of a meal.     

Pregnancy following gastric bypass for morbid obesity

BACKGROUND: Women who suffer from morbid obesity are often infertile. If these women are able to become pregnant, they are considered high risk because of the hypertension, diabetes and other associated risk factors. Following the pregnancy is difficult due to limitations of the physical examinations. More costly ultrasound examinations are needed at a higher frequency. Bariatric surgery reduces the woman's weight and the incidence of obesity related co-morbidities. The number of pregnancies and rate of complications during those pregnancies in our post-bariatirc surgical patients were evaluated. METHOD: Our group has been doing bariatric surgery since the early 1980s. We have over 2000 active patients on our current newsletter mailing list. The patients also have a series of networks through support groups. The patients are informed to contact us when they become pregnant so we may assist the obstetrician with their care. Through these various means, we have been able to identify 41 women in our patient population who have become pregnant. Using personal interview, questionnaire, and review of perinatal records, pregnancy-related risks and complications were studied. RESULTS: With over a 95% follow-up rate on the patients identified as having been pregnant following surgery, we found less risk of gestational diabetes, macrosomia, and cesarean section than associated with obesity. There were no patients with clinically significant anemia. CONCLUSION: Since the patients had an operation that restricts their food intake, some basic precautions should be taken when they become pregnant. With this in mind, our patients have done well with their pregnancies. The post-surgical group had fewer pregnancy-related complications than did an internally controlled group that were morbidly obese during their previous pregnancies.