Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain

Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (K_d= 0.045nM) and low (K_d= 21nM) affinity¹²⁵I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.     

Apramycin and gentamicin resistance in Escherichia coli and salmonellas isolated from farm animals

Since the aminoglycoside antibiotic apramycin was licensed for veterinary use in 1980, all isolates of Escherichia coli and salmonellas received at the Central Veterinary Laboratory have been monitored for resistance to apramycin and the related antibiotic gentamicin. During the period 1982-4, the incidence of resistance in E. coli to apramycin increased from 0.6% in 1982 to 2.6% in 1984. In salmonellas the incidence of resistance to apramycin increased from 0.1% in 1982 to 1.4% in 1984. Resistance to both apramycin and gentamicin was detected in six different salmonella serotypes, although an isolate of Salmonella thompson from poultry was resistant to gentamicin but not apramycin. Most of the cultures were isolated from pigs, although the incidence of apramycin resistance in S. typhimurium (DT 204C) from calves has shown a recent dramatic increase. All the isolates with one exception produced the enzyme aminoglycoside 3-N-acetyltransferase IV (ACC(3)IV). The resistance was transferable by conjugation in most of the strains examined, and the plasmids specifying the resistance have been found to belong to a number of different incompatibility groups. Plasmids from three E. coli strains were compatible with all the reference plasmids and belonged to a previously undescribed group which was investigated further. It is suggested that bacteria from humans should be examined for resistance to apramycin and gentamicin to determine the possibility of the antibiotic-resistance bacteria, and their genes, spreading from animals to humans.     

Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation—Efficacy and Safety at Five Years

Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20 mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75-125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy.     

Linear and angular measurements of computer-generated models: are they accurate, valid, and reliable?

INTRODUCTION: Traditional advanced imaging modalities such as CT and MRI are limited in their ability to perform accurate linear distance and angular measurements regardless of anatomical orientation. The construction of 3D models has been used to perform anthropometric analyses as well as in the reconstruction of rapid prototypes. We hypothesized that such measurements would be precise to within 2 mm or 2 degrees of measurements performed with a coordinate measurement machine (CMM). We also hypothesized that there would be a high degree of interobserver reliability with these measurements. MATERIALS AND METHODS: Multiple aluminum screws were implanted in various positions in three foam pelvises which were subsequently scanned by CT and rendered as 3D models using a commercially available software package (Mimics). Linear and angular measurements were performed using a CMM machine, the software package, and a dial caliper or goniometer. The deviation of the measurements from the CMM data was compared using ANOVA. The interobserver reliability of both the manual and computer-generated measurements was calculated. RESULTS: The mean difference between the CMM distances and those measured manually and with the software was 2.12 +/- 1.20 mm and 1.57 +/- 1.05 mm, respectively. The mean difference between the CMM angular measurements and the angular measurements performed manually and with the software was 4.07 +/- 4.70 degrees and 1.62 +/- 1.32 degrees, respectively. In all cases, the manual measurements were significantly less accurate (p < 0.0001) and there was a high degree of interobserver reliability. CONCLUSIONS: Computer-generated measurements taken from three-dimensionally reconstructed models are more accurate than manual measurements and are within 2 mm and 2 degrees of measurements performed with a CMM. These measurements have high interobserver reliability.     

Hypoplasia of the cerebellar vermis in neurogenetic syndromes

There are conflicting reports on the relationship between cerebellar vermal lobule hypoplasia and autism. Using quantitative magnetic resonance image analysis, we measured the cerebellar vermis in 125 normal individuals with a broad age range and 102 patients with a variety of neurogenetic abnormalities. We conclude that hypoplasia of cerebellar vermal lobules VI and VII is a nonspecific finding that even occurs in several conditions without autistic behavior. This suggests that it is not a specific neuroanatomical marker for autism, nor is cerebellar dys- genesis likely to be solely responsible for clinical autistic behaviors.     

Patient-Physician Pairing: Does Racial and Ethnic Congruity Influence Selection of a Regular Physician?

Many public and private sector efforts are devoted toward increasing the training of physicians from under-represented minority groups, yet little has been documented regarding the association between physicians' racial backgrounds and the patient populations they serve. To address this question, we use 1987 National Medical Expenditure Survey to examine the impact of race/ethnicity on the matching between physician and patients. Our results show that minority patients are significantly more likely to report having a minority physician as their regular doctor. We estimate that minority patients are five times as likely as non-minorities to report that their regular physician is a member of a racial/ethnic minority. This effect is especially pronounced among Hispanics who identify a Hispanic physician as their regular provider 19 times more often than non-minorities. After controlling for other socio-economic factors, both these figures remain significant, but drop by approximately one-half. These results support the notion that minority patients tend to see minority physicians at a disproportional rate independent of other socio-economic factors.     

Preventive care for patients following myocardial infarction. The Wessex Research Network (WReN)

OBJECTIVE: We aimed to assess general practice care for patients following a myocardial infarction (MI). METHOD: A structured review was carried out of general practice records of patients identified from hospital administration data. A total of 266 survivors following MI were identified from the discharge data of 13 hospitals in Southern England and registered with 71 GPs belonging to the Wessex Research Network. Median time since hospital discharge was 2.1 years. The main outcome measures were the provision of appropriate preventive care, including cardiac rehabilitation, drug therapy, and lifestyle advice for modifiable risk factors. RESULTS: Basic care was provided to nearly all patients; 253 (95.1%, 95% Cl 91.8-97.4) had blood pressure documented after their MI, 216 of 234 patients eligible for aspirin (92.3%; 88.1-95.4) had been recommended treatment, and the provision of advice on smoking cessation was documented for 27 of 33 continuing smokers (81.8%; 64.5-93.0). However, only 73 of 236 patients eligible to attend a structured rehabilitation programme (30.9%; 25.0-36.8) were documented as having received rehabilitation. Of 89 patients with heart failure following MI, 33 (37.1%; 27.1-48.0) had no record of having been offered treatment with an ACE inhibitor. Total cholesterol measurement was documented for only 144 patients (54.1%; 48.1-60.1). We estimate that there is still the potential to prevent between 4 and 9 deaths in this group of 266 surviving patients in the next 2 years by further improving the quality of follow-up care. CONCLUSIONS: Preventive care in patients with proven ischaemic heart disease in general practice remains haphazard, even among doctors enthusiastic to participate in research and to audit their quality of care. As general practitioners we should ensure that we are providing high quality preventive care to patients with clinical disease before we focus on the even more demanding task of primary prevention.