The Association of Respiratory Infection, Recurrent Hematuria, and Focal Glomerulonephritis with Activation of the Complement System in the Cold

The study of the activation of C3, C5, and C7 associated with the conversion of C3 in the serum of a 9-yr old girl after incubation at 0 degrees C for 6-8 h without utilization of C1, C4, and C2 is described. The patient has upper respiratory infections associated with recurrent gross hematuria, focal glomerulonephritis, and transient renal insufficiency. Histological lesions demonstrated the presence of B1c globulin IgA and properdin in the glomeruli. The activation of complement (C) in the cold requires the patient's IgA. Removal of IgA from the serum by immunoadsorption prevents activation and conversion of C3. Bactericidal and phagocytic activity is also impaired after incubation. C3 proactivator (C3PA) level is reduced before and after incubation. Properdin level drops after incubation. These findings suggest that the activation of C3 which is demonstrable in vitro may be a continuous process in vivo.     

Hospitalization of medicaid children: analysis of small area variations in admission rates.

Population-based hospitalization rates were computed and analyzed for AFDC children among 14 small area subdivisions of the State of Washington. Medical-surgical admission rates ranged from 65.3 to 161.7 per 1,000 person-years among the 14 areas. Surgical admission rates were significantly higher in urban areas; medical admission rates were significantly higher in rural areas. The majority of variance in overall rates was accounted for by admissions for four diagnostic categories: gastroenteritis (18-fold differences), lower respiratory infections (15-fold differences), upper respiratory infections (8-fold differences), and ear, nose, and throat (ENT) surgery (6-fold differences). Secondary analysis indicates that these differences in admission rates were not associated with: medical need or demographic factors, epidemic patterns of disease, physician supply, hospital bed supply or occupancy rates, or severity of disease or delay in seeking medical care as reflected by average length of stay. It is possible that the observed variations may reflect either differences in the propensity of local physicians to hospitalize or differences in the use or adequacy of community, ambulatory, and preventive care.     

CELL KINETIC STUDIES IN MIXED LEUKOCYTE CULTURES: AN in vitro MODEL OF HOMOGRAFT REACTIVITY

The recognition phase of homograft immunity can be studied in vitro in the mixed leukocyte culture reaction. In this reaction, at the end of seven days, up to 30 per cent of the lymphocytes in culture "respond" to a single allogeneic cell stimulus. This paper presents evidence that the lymphocytes responding in culture divide with the generation time of 18-21 hours, with some asynchrony, and that a large percentage of the cells found at the end of the culture period may be the products by division of a small number of cells initially responding. Two estimates are made of the frequency of the initially responding unit (the cell(s) responsible for initiating the response). These are probably minimum estimates and are in the range of 1 in 200 to 1 in 2000 cells which can initially respond. This very high frequency of responding units as compared with the responding units in immediate type hypersensitivity (antibody production) is discussed.     

The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Benefits provided by an integrated education and clinical diabetes centre: a follow-up study.

The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purposed design diabetes centre, on diabetes control, attendance and cancellation rates, and admission for diabetic emergencies have been reviewed. Glycaemic control was examined in: (a) a cohort of 163 insulin-treated and 47 non-insulin treated diabetic subjects (age < 65 years) studied prospectively before and 3 years following the introduction of a new system of care; (b) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over; (c) a cross-sectional study of the clinic population (n = 700) the year before and 3 years after the changeover; (d) a group of patients attending standard unaltered clinics in the same district (n = 157). Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre, with the means for those aged less than 65 falling from 11.9 +/- 2.3% to 9.9 +/- 1.9% and for those aged over 65 from a mean of 11.7 +/- 2.0% to 10.3 +/- 2.3%, 3 years later. The cross-sectional study provided similar results with a mean HbA1 of 12.2 +/- 3.0% prior to changeover and 10.4 +/- 4.4%, 3 years later. Smaller but significant changes were observed in patients continuing to attend the routine clinic (from 12.2 +/- 2.3% to 11.3 +/- 2.6%) over a similar period. Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23, to 33 and 5 per annum, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of metformin on glucose metabolism in the splanchnic bed.

1. Use of the antihyperglycaemic agent, metformin, is often associated with a small rise in circulating lactate. This study investigates the source of the lactate and examines the effect of metformin on glucose metabolism by the intestine and liver of rats. 2. Changes in plasma glucose and lactate were measured in the inferior vena cava (IVC), hepatic portal vein (HPV), hepatic vein (HV) and aorta (A) after intrajejunal administration of metformin (50 and 250 mg kg-1) without and with glucose (2 g kg-1). 3. Metformin 250 mg kg-1 reduced the hyperglycaemic response to a glucose challenge, associated with a greater reduction of glucose concentrations in the HPV (average decrease of 33% at 60 and 120 min) than at other sites. 4. Both doses of metformin increased lactate concentrations in the glucose-loaded state: the highest concentration (2.5 fold increase) was recorded in the HPV 60 min after administration of 250 mg kg-1 metformin, with a high lactate concentration persisting in the HV at 120 min. Metformin 250 mg kg-1 also increased lactate concentrations in the basal state, with highest concentrations (2 fold increase) in the HPV. 5. Two hours after intrajejunal administration of metformin, 50 mg kg-1, rings of tissue from the small intestine showed an average 22% decrease in glucose oxidation ([14C]-glucose conversion to 14CO2) and a 10% increase in lactate production. Since glucose metabolism in the gut is predominantly anaerobic, metformin caused an overall 9.5% increase of intestinal glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal monitoring in perinatal sepsis.

To evaluate the utility of conventional electronic fetal monitoring in detection of established perinatal sepsis, we conducted a case-controlled study of fetal monitor results in 18 patients delivering newborns with sepsis. Eleven of the 18 newborns (61%) demonstrated clinically reassuring fetal heart rate patterns, not significantly different from controls (p = 0.80). No pattern predictive of presumed perinatal sepsis could be identified. Obstetric factors traditionally associated with increased risk of perinatal infection, such as long duration of labor, use of internal fetal monitoring, and increased number of vaginal examinations were not significantly different from controls. Preterm rupture of membranes greater than 24 hours occurred in less than 50% of the cases. Clinical diagnosis of chorioamnionitis was established in only one third of the patients who delivered newborns with sepsis. In this study, use of conventional electronic fetal monitoring did not accurately identify newborns with presumed intrauterine infection.     

Virtual head rotation reveals a process of route reconstruction from human vestibular signals

The vestibular organs can feed perceptual processes that build a picture of our route as we move about in the world. However, raw vestibular signals do not define the path taken because, during travel, the head can undergo accelerations unrelated to the route and also be orientated in any direction to vary the signal. This study investigated the computational process by which the brain transforms raw vestibular signals for the purpose of route reconstruction. We electrically stimulated the vestibular nerves of human subjects to evoke a virtual head rotation fixed in skull co-ordinates and measure its perceptual effect. The virtual head rotation caused subjects to perceive an illusory whole-body rotation that was a cyclic function of head-pitch angle. They perceived whole-body yaw rotation in one direction with the head pitched forwards, the opposite direction with the head pitched backwards, and no rotation with the head in an intermediate position. A model based on vector operations and the anatomy and firing properties of semicircular canals precisely predicted these perceptions. In effect, a neural process computes the vector dot product between the craniocentric vestibular vector of head rotation and the gravitational unit vector. This computation yields the signal of body rotation in the horizontal plane that feeds our perception of the route travelled.     

Drug and therapeutics committees — are they fulfilling their potential to improve the quality use of medicines?

Objective Drug and therapeutics committees (DTCs) promote the quality use of medicines (QUM). DTC functions have expanded beyond overseeing the hospital formulary. They are in a position to influence prescribing practice, within and beyond the hospital setting into community practice, and it is important to evaluate and augment the quality of their performance. A survey was conducted to document and investigate perceived and ideal DTC principal functions and the level to which DTCs were achieving these. Method A questionnaire was sent to 300 directors of pharmacy/chief pharmacists in Australian hospitals. Non‐responses within two weeks of mail‐out were followed‐up. Returned questionnaires were anonymised, collated and analysed. The questionnaire asked about the DTC's functions, the extent to which DTC performance indicators were used, and barriers to the use of these indicators. Respondents were asked for their perceptions of the DTC's influence on prescribers' practices. Key findings The response rate was 73.3% (220) and 127 respondents had an in‐house DTC. The final dataset comprised 125 responses (two incomplete questionnaires excluded). The most common principal function of DTCs was “ensuring patient safety” (83.3%). Only 16% of respondents used indicators developed specifically for DTC performance evaluation. Data collected by DTCs were primarily for accreditation. Lack of resources contributed to barriers to indicator data collection. Most respondents (92%) believed that DTCs have some influence on prescribers' practices. Conclusion DTCs are seen to be in a position to have an influence on the quality of medicines use. A means to enhance DTC performance can be explored if potential problems in quality are detected. Although there is a desire to use the available indicators, assistance in data collection is needed. Adequate resources and strong leadership may result in more effective DTCs with greater influence on medical practice, leading to better patient outcomes.