Preclinical curriculum characteristics and institutional performance on NBME. Part I

A study was conducted that analyzed the relationship between various characteristics of the preclinical curriculum and institutional performance on the Part I examination of the National Board of Medical Examiners (NBME) at a sample of 85 U.S. medical schools. Total scheduled hours per week was the single curriculum characteristic having a positive and significant relationship with institutional NBME examination performance. However, when the data were controlled by medical school selectivity in admissions and institutional policy on the taking of the examination, total scheduled hours per week failed to make a significant contribution to the prediction of performance. The results were viewed as failing to provide support and justification for intense preclinical curriculum loads on the basis that this would enhance NBME examination performance. The authors conclude that simple comparisons of schools on the basis of mean NBME examination performance are meaningless unless the entering abilities of students and school policies on the examination are taken into account. The authors also suggest that those schools that prescribe heavy and intense preclinical curriculum loads should reexamine those policies in light of recommendations of the Project Panel on the General Professional Education of the Physician and College Preparation for Medicine.     

Pharmacological characterization of the receptor mediating the adrenergic inhibition of responses to substance P in the cingulate cortex

The excitatory responses of neurones in the anterior cingulate cortex of the rat to iontophoretically applied substance P (SP) are reduced by noradrenaline (NA) applied iontophoretically or released from noradrenergic pathways. In order to determine the receptor involved in this inhibitory effect we have studied the effects of a number of receptor-specific adrenergic agonists and antagonists on responses of cingulate neurones to SP in rats anaesthetized with chloral hydrate. Low iontophoretic currents (0-15 nA) of NA, adrenaline and the beta-agonist, clenbuterol, all strongly reduced responses to SP. Isoprenaline was also effective but less consistently so, although problems were experienced with its iontophoretic release from micropipettes. The alpha 1-agonists, phenylephrine and methoxamine were also able to reduce responses to SP. However, this reduction required higher iontophoretic currents (15-60 nA) and was associated with depressant effects on baseline firing rate. The alpha 2-agonist clonidine was only weakly active at high currents and this too was associated with depression of baseline firing. Similar weak effects were noted with dopamine. The inhibitory effects of NA on SP responses were convincingly blocked or reversed by the beta-antagonist, practolol, but not by the alpha 1-antagonist, prazosin. The reduction of SP responses by phenylephrine was also blocked by practolol but unaffected by prazosin. Finally, reduction of SP excitations by activation of the coeruleocortical pathway was also blocked by practolol applied iontophoretically to the cortical cells. These results are consistent with the hypothesis that the effect of NA on SP responsiveness in the cingulate cortex is mediated by beta-adrenoreceptors.     

A morphometric analysis of the development of the fourth ventricle choroid plexus in the rat

The choroid plexus from the rat fourth ventricle was investigated at ages from 16 days of gestation to 30 days after birth. Choroid plexus weights were measured and light and electron micrographs were analysed by quantitative stereological techniques at 4 levels of magnification. There was a 10-fold increase in plexus weight between 19 days of gestation and 30 days after birth which was largely due to an increase in epithelial weight, with little change occurring in the connective tissue core. Before birth, epithelial cell height decreased whereas between 10 and 30 days after birth cross-sectional area increased, both events being accompanied by corresponding changes in cell volume. Large intracellular stores of glycogen were present around birth, when they occupied up to 20% of the cell volume. After birth there were significant increases in apical microvillus height, the number of microvilli per cell and in the size of the mitochondria, suggesting that a large increase in choroid plexus secretory function, or the commencement of a new function, occurs after birth in the rat.     

A cell line from Wilms' tumour with deletion in short arm of chromosome II

A cell line (T3/73) from a Wilms' tumour has been established from a 9 month-old boy with aniridia. The tumour was removed in 1973. On histological examination a diagnosis of Wilms' tumour was made which showed undifferentiated areas, marked tubule formation and abundant striped muscle fibres. The tumour cells, which are fusiform, grew rapidly in culture without the addition of growth factors, and have undergone over 100 passages. Approximately 95% and 5% were positive for desmin and cytokeratin, respectively. The cell doubling time was 28 hr. Cytogenetic studies revealed a karyotype of 46,XY,del(11) (p12::p14). Although the cells stained very intensely with a monoclonal antibody that detects oncogene ras p 21 antigen, Southern blot analysis using c-Ha-ras as a probe failed to reveal an obvious deletion or amplification of either Ha-ras allele.     

Giant hepatic hemangiomas: diagnostic and therapeutic dilemmas

This report describes four cases of surgically treated giant hepatic hemangiomas which illustrate some diagnostic and therapeutic difficulties encountered in the management of this condition. An important diagnostic triad has emerged, which should alert the physician to the possibility of a complicated hepatic hemangioma: the clinical signs of an acute inflammatory liver process contrasted with a normal white blood cell count and liver function tests. Hemangiomas of the left lobe were either missed or poorly demonstrated on selective hepatic angiographic examination, and in two patients the diagnosis was made only at the time of laparotomy. Hepatic resection was successfully performed in all patients; there was minimal morbidity and none of the patients died. In two patients with multiple hemangiomas, only symptomatic or easily resectable lesions were removed. All patients are alive and well; three have been followed up for more than 5 years. We conclude that resection in asymptomatic cases should be carried out only in those cases that require a diagnostic laparotomy and in those where the lesion is easily resectable. The majority of patients with symptomatic and complicated tumors should undergo resection, but even in these patients continued conservative treatment is appropriate when the risk of major resection outweighs the small risk of live-threatening bleeding.     

Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.     

Dithiocarbamate-induced biliary platinum excretion and the control of cis-platinum nephrotoxicity

Treatment with any one of six different dithiocarbamates subsequent to the administration of cis-platinum (CDDP) is shown to promote the biliary excretion of platinum. The administration of the most effective of these compounds, sodium diethyldithiocarbamate (DDTC) at 1.57 mmol/kg, led to a 30-fold increase in the biliary excretion of platinum. For the other dithiocarbamates investigated, a similar dosage led to increases ranging from approximately 5-fold for sodium iminodiacetic acid dithiocarbamate, to 26-fold for sodium sarcosine dithiocarbamate. The presence of alkyl groups on the nitrogen of the dithiocarbamate increased the effectiveness of the compounds. There is no increase in the platinum levels of the brain when DDTC is used in this manner. A histopathological evaluation of the kidneys of rats given 15 mg CDDP/kg in 6.3% saline with and without the use of dithiocarbamates for renal protection shows significant additional protection due to the use of the dithiocarbamates. Dithiocarbamates given at an appropriate dosing schedule can lead to a significant reduction in the renal damage which is revealed by microphotographs. It is suggested that part of the renal protection obtained by the use of dithiocarbamates may be due to this shift of platinum excretion to the bile which obviates additional renal exposure to platinum. It was also found that the simultaneous injection of a dithiocarbamate with the cis-platinum has no obvious effect on the anti-cancer action of cis-platinum against the Walker 256 carcinosarcoma in rats.     

Parapubic hernia: case report and review of the literature

Parapubic hernia is considered rare, with 18 hernias described in five articles published since 1971. The hernia results from iatrogenically or traumatically detached rectus abdominis muscles at the pubic bone and presents a therapeutic challenge because there is no strong aponeurotic anchoring structure in the defect's caudal aspect. We describe a patient with a large parapubic hernia repaired by a combined preperitoneal and onlay prosthetic method. This report adds another dimension to the prosthetic repair options in parapubic hernias and illustrates the effectiveness of the tension-free repair principle in their definitive management. Electronic Publication     

Immunomodulation of Delayed Hypersensitivity to Methylated Bovine Serum Albumin (MBSA) in Mice Using Subliminal and Normal Sensitization Procedures

Delayed hypersensitivity (DH) was induced in the footpads of mice sensitized to methylated bovine serum albumin (MBSA). The magnitude of this DH response increased with increasing sensitizing concentration of MBSA. Levamisole administered 1 hr prior to MBSA challenge stimulated the DH response and this was optimal using subliminal sensitizing concentrations of antigen. A number of antirheumatic agents, immunomodulators mediator antagonists and antiallergies were subsequently examined using the subliminal sensitizing concentration of MBSA. The same drugs were also evaluated using a normal sensitizing procedure. These studies indicate that the sensitizing concentration of antigen is critical in establishing whether a drug will stimulate or suppress a DH response.