Ontogenesis of the pyramidal cell of the mammalian neocortex and developmental cytoarchitectonics: a unifying theory.

The prenatal development of the mammalian neocortex has been analyzed, with the rapid Golgi method, in a variety of experimental animals (hamster, mouse, rat, and cat) and in humans. A new developmental conception of the structural organization of the mammalian neocortex is discussed. Neocortical development begins with the establishment of the primordial plexiform layer (PPL) which precedes and is a prerequisite for the subsequent formation of the cortical plate (CP). The formation of the CP occurs, in its entirety, within the PPL. During its development, three fundamental neuronal events occur: migration, early differentiation, and late maturation. All migrating neurons, travelling on radial glial fibers, reach layer I, develop an apical dendrite, and establish contacts with its elements. These newly differentiated neurons assume similar morphology resembling embryonic pyramidal cells. As such, an early differentiation stage common to all neurons of the CP is established. During the late maturation stage, all CP neurons acquire their specific phenotypic structural and functional features. Only pyramidal neurons retain and expand their original connections with layer I while other neuronal types lose these connections. The pyramidal cell is redefined in developmental terms: the neocortex's pyramidal cell is both structurally and functionally locked into position between layer I and the cortical depth of its soma. During mammalian evolution pyramidal cells are forced to structurally and functionally elongate their apical dendrite outwardly to accommodate an increasing amount of information without losing either their original anchorage to layer I or their cortical depth. This unique property of pyramidal neurons is considered to be a mammalian innovation. Based on these observations, a unifying developmental cytoarchitectonic theory applicable to all mammals is proposed. The theory considers the CP to be a mammalian innovation and to represent a single, stratified, and expanding telencephalic nucleus. The theory envisions the mammalian neocortex as an open biological system capable of progressive expansion by the recruitment and transformation of primitive neurons from upper layer II into pyramidal cells. Hence, the number of pyramidal cell strata increases over the course of mammalian phylogeny. The developmental roles of layer I in the migration of neurons, formation of the CP, unique morphology of pyramidal cells, and overall structural organization of the mammalian neocortex are emphasized.     

Late postpartum eclampsia. Apropos of a case

We report the case of a 32-year-old multipara who presented preeclampsia on the fourth day after childbirth without receiving proper treatment that progressed to eclampsia 4 days later. Pregnancy and delivery had been uneventful. The patient presented proteinuria (30 mg/dl), serum total proteins 5.3 g/dl and serum albumin 3.3 g/dl. Blood pressure was controlled with methyldopa, 500 mg at six-hour intervals by intravenous route. The patient presented hypoxemia secondary to bilateral pleural effusion and aspirative pneumonia requiring mechanical ventilation and invasive hemodynamic monitoring. Treatment with cefotaxime, 1 g at six-hour intervals by intravenous route and clindamycin, 600 mg at six-hour intervals by intravenous route was initiated. Sedation was maintained with thiopental sodium, 3 mg/kg/hour in continuous infusion. At dismission, the patient was completely recovered from her clinical picture and needed no antihypertensive therapy. Physiopathologic features and the aforementioned complications are discussed with particular reference to differential diagnosis.     

Decision analysis applied to selection of histamine H2-receptor antagonists for the formulary

The use of decision analysis in selecting a histamine H2-receptor antagonist for the formulary at a hospital in Spain is described. Cimetidine, ranitidine, and famotidine were identified as the possible alternatives. The evaluation criteria established were therapeutic efficacy, adverse effects, drug interactions, years of clinical use, dosage interval, cost, and dosage forms. The relative importance of the criteria was determined by assigning utility values to each. Probability values were assigned to estimate how well each drug met each criterion. By multiplying the utility and probability values for each criterion and summing the scores, a total score was calculated for each drug. The alternative with the highest total score was ranitidine. A sensitivity analysis showed that the results were stable over a plausible range of probability and utility values. Accordingly, ranitidine was selected for inclusion on the formulary. Decision analysis provided an effective method for selecting which histamine H2-receptor antagonist to include on the hospital's formulary.     

Conventional viral cultures and shell vial assay for diagnosis of apparently culture-negativeCoxiella burnetii endocarditis

A patient with culture-negative endocarditis was diagnosed with Q fever endocarditis based on the results of serological tests and positive leukocyte cultures obtained using conventional viral cultures and the shell vial technique. This case report suggests that isolation ofCoxiella burnetii from blood may allow better diagnostic and therapeutical evaluation of patients with Q fever endocarditis. The use of both conventional and shell vial viral cultures is recommended for the isolation ofCoxiella burnetii from the blood of patients with apparently culture-negative endocarditis.     

Implications of postvaccination hepatitis B surface antigenemia in the management of exposures to body fluids.

A neonate vaccinated against HBV was the source of an occupational exposure to blood. She was tested for hepatitis B surface antigen and found to be positive, leading to unnecessary treatment, retesting, and concern. Evaluation of the infectious status of HBV should rely on other means if vaccination has recently occurred.     

Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.     

Skeletal muscle characteristics of sprint cyclists and nonathletes

Muscle fiber distribution and muscle enzyme activity (m. vastus lat.) were investigated in 10 elite sprint cyclists and 12 nonathletes. The ratio of fast to slow muscle fibers was 2:3 in cyclists and 3:2 in nonathletes. The mean diameter of each muscle fiber type was significantly higher in the athletes. The mean enzyme activity values in mu kat X g-1 w.w. for cyclists and nonathletes, respectively, were as follows: triosephosphate dehydrogenase (TPDH), 6.2 and 3.78; lactate dehydrogenase (LDH), 4.4 and 4.59; citrate synthase (CS), 0.154 and 0.13; hydroxyacyl-CoA dehydrogenase (HAD), 0.041 and 0.07. The mean difference between groups in TPDH and in (TPDH + LDH)/(CS + HAD) ratio were statistically significant. Maximum voluntary isometric strength (knee extension) was about 17% greater in cyclists than the mean value for Czechoslovakian men of the same age. A strong positive correlation (r = 0.72) between the percent of fast glycolytic fibers (type II B) and isometric strength was observed in the cyclists. Furthermore, mean weight-compensated maximal oxygen consumption (VO2 max, ml X kg-1 X min-1) for all subjects (n = 22) was significantly related to percent of slow oxidative fibers (type I) (r = 0.75) and to the mean diameter of type II B (r = 0.58), fast oxidative-glycolytic fibers (type II A) (r = 0.68) and type I fibers (r = 0.59).     

Strategies for Reducing Risks in Smoking: Opportunity or Threat?

The smoking control policies recommended by the World Health Organisation have achieved a slight decrease in smoking prevalence in developed countries, although associated mortality is still very high. The use of tobacco products other than cigarettes and even medicinal nicotine (known as nicotine replacement therapy [NRT]) has been proposed as a risk reduction strategy. Among the tobacco products with less individual risk than cigarettes would be any type of tobacco without smoke (smokeless) with a low content in nitrosamines and modified cigarettes; both forms included under the PREP (Potentially Reduced Exposure Products) concept. The idea would be to promote these products among patients who cannot quit smoking or wish to reduce their risk without giving up nicotine intake. The possible effects of risk reduction strategies, including PREP, on the decreased prevalence and morbidity and mortality are reviewed, and the possible implications that this measure could have in Spain are analysed. Tobacco control measures in Spain have only been made recently and are still insufficient. Therefore, the current priority in Spain is to develop control policies that have proven to be more than effective. The marketing and advertising of new tobacco products, even with reduced potential risk, seems more a serious threat than an opportunity for developing smoking control policies.