Flumazenil, a GABA antagonist, may improve features of Parkinson's disease.

Manipulation of gamma-aminobutyrate (GABA) system has been little studied in Parkinson's disease, despite the fact that GABA subserves a large part of the basal ganglia, including the outflow tracts. To test whether antagonism of GABA could improve features of PD, we administered open label intravenous flumazenil to eight practically defined off patients and assessed UPDRS scores, bilateral 1-minute hand-tapping speed, and timed gait tests. Patients demonstrated significantly greater tapping speed, which peaked 40 minutes after injection (P < 0.05). Total motor Unified Parkinson's Disease Rating Scale scores modestly improved (P < 0.05). There were no adverse events. Mechanisms by which flumazenil could improve PD are discussed.     

The role of morphogens in endochondral ossification

Summary The formation of bone occurs normally by one of two developmental processes: intramembranous or endochondral ossification. Endochondral ossification occurs in the morphogenesis of the limb buds and growth plates, and in the regeneration of bone following injury (fracture callus). Two classes of diffusible morphogen-like molecules (MLMs) involved in limb development are the bone morphogenetic proteins (BMPs) and retinoic acid (RA). These MLMs are associated, respectively, with the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) of the primitive limb bud. They function as potent regulators of pattern formation and are involved in tissue proliferation and differentiation. The presence of endochondral ossification in fracture callus suggests a role for MLMs in that process as well. To date, virtually nothing is known about the role of morphogens in the regeneration of bone (fracture healing). In this article, we review the current knowledge of MLMs in bone formation and propose a theory on their role in fracture healing. We hypothesize that MLMs involved in fracture healing may also express spatial and temporal information. A more complete understanding of the role of morphogens in both limb development and fracture healing is of major importance to practicing orthopedists and their patients.     

The impact of hospital structure and restructuring on the nursing workforce.

OBJECTIVE: Health systems throughout much of the world have been subject to 'reform' in recent years as countries have attempted to contain the rapidly rising costs of health care. Changes to hospital structures (restructuring) have been an important part of these reforms. A significant impact of current approaches to restructuring is the loss of, or changes to, nursing management roles and functions. SETTING: Australian hospitals PRIMARY ARGUMENT: Little evaluation has been undertaken to determine the impact of hospital structure and organisational restructuring on the nursing workforce. CONCLUSIONS: There is some indication that nurses have experienced a loss of key management positions, which may impact on their capacity to ensure that adequate and safe care is provided at the ward level.     

Management of major colonic haemorrhage

Major colonic haemorrhage remains a difficult diagnostic and therapeutic problem. We propose that those patients who continue to bleed after resuscitation are best served by immediate laparotomy. High flow antegrade irrigation and intra-operative colonoscopy can then be used to localize the site of bleeding and allow appropriate excisional surgery rather than blind colonic resection.     

Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus.

AIMS: To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes ('at risk' group, AR) and control females (control group, C). METHODS: At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R') and insulin secretion (HOMA beta') were obtained from fasting insulin and glucose concentrations. RESULTS: At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R' and HOMA beta'. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 +/- 0.2 vs. 4.3 +/- 0.2 mmol/l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA beta' (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA beta'. CONCLUSIONS: Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major predictors of the subsequent decline of insulin secretion index and the consequent rise in FPG.     

Provision of, and patient satisfaction with, primary care services in a relatively affluent area and a relatively deprived area of Glasgow.

This paper presents the results of a survey of the structure of general practice in two contrasting areas within Greater Glasgow health board: the south west area had a more deprived social profile at the 1981 census and higher than average all cause and selected major cause standardized mortality ratios than the health board as a whole while the north west area had a more affluent social profile at the 1981 census and lower than average all cause and selected major cause standardized mortality ratios. The general practice survey data gathered in 1989 were supplemented with data from a survey of residents of the localities in three age cohorts carried out in 1987-88, which provided information on use of services, as well as perceived accessibility of and satisfaction with them. Despite the more deprived social and mortality profile of the south west area, and greater use of services, few systematic differences in the structure of general practices were found in the two areas. These findings support other studies which suggest that the stereotype of poorly resourced, low quality primary care in inner city areas may apply in London, but not elsewhere. Respondents in both areas were equally satisfied with services and found them accessible.     

Structure of autonomic neuromuscular junctions in the sinus venosus of the toad.

The structure of cholinergic and adrenergic neuromuscular junctions in the sinus venosus of the toad, Bufo marinus, was determined by electron microscopy. From random sections of sinus venosus tissue it appeared that there were variable separations between cholinergic or adrenergic varicosities and the nearest sinus venosus muscle cell. However, when the structure of complete cholinergic and adrenergic varicosities was determined by examining serial electron micrographs, virtually all varicosities that lost their covering of Schwann cell were found to form an area of close apposition with an adjacent muscle cell. At the region of close apposition, the neuromuscular cleft was filled with a single layer of basal lamina to give a neuromuscular separation of about 70 nm. Synaptic vesicles within a varicosity were usually found to be concentrated towards the region of close apposition. These observations are discussed in relationship to the idea that when transmission occurs at these neuromuscular junctions the transmitters act on discrete pools of specialized subsynaptic receptors.