Microvascular corrosion casting of normal tissue, transitional mucosa and adenocarcinoma in the human colon.

The microcirculatory architecture of normal tissue, transitional mucosa and adenocarcinoma of the human colon was investigated with microvascular corrosion casting (MVCC) combined with scanning electron microscopy (SEM). The study showed that the capillaries within the normal mucosa were arranged in a regular hexagonal pattern around the mucosal glands and that the microvessels of transitional mucosa mostly had lost the typical hexagonal pattern and become slightly wider in diameter. The microvessels in the tumor periphery were increased in number and disorganized, and presented large variation in morphology with claw-like formations, widened sinuses, diverticula and appendixoid patterns. Microvessels were lacking in the central areas of tumors. These morphological alterations may serve as additional indicators of tumor development.     

T cell adhesion to extracellular matrix molecules secreted by endothelial cells cultured on a substrate of type IV collagen

T cell emigrating from the bloodstream into lymphoid organs or sites of inflammation in the connective tissue must adhere to, and traverse, the subendothelial basement membrane (BM). The goal of the current investigation was to develop a method to study the adhesion of T cells to endothelial cell (EC)-derived extracellular matrix (ECM) as a model for the interaction of T cells with the subendothelial BM in vivo. To be certain that we were truly measuring T cell adhesion to ECM molecules secreted by the EC, it was necessary to culture the EC on a substrate to which T cells could not attach. Non-tissue culture-treated microtiter plate wells which had been coated with type IV collagen (tIVC), a major constituent of BM in vivo, were found to be suitable for this purpose since EC, but very few T cells, adhered to such wells. After incubating the EC on a substrate of tIVC in non-treated wells for a period of 48 h, the EC were gently removed from their underlying ECM and T cell adhesion to that ECM was examined. Using this system, it was observed that approximately 15-40% of human peripheral blood T cells specifically adhered to ECM molecules produced by the EC. This method should be useful as a model for the interactions of T cells and other leukocytes with the vascular BM in vivo.     

Old pulmonary embolism causing intrabronchial bleeding

A 51-year-old man was admitted because of hemoptysis. Physical examinations and chest XP revealed no abnormal findings. Fiberoptic bronchoscopy showed pulsatile bleeding at the orifice of right B6. Right bronchial arteriography showed a markedly dilated and tortous bronchial artery and shunting to the pulmonary arterial system in the middle and lower lobes. Pulmonary arteriography showed complete obstruction of the right middle lobar and lower lobe segmental arteries (A6, 9, 10). The hemoptysis was thought to be due to increased blood flow of the right bronchial artery, which compensated for reduced right pulmonary arterial flow. Right middle and lower lobe resection was done to prevent further hemoptysis. The resected specimen revealed old thromboemboli in the right middle and lower lobe pulmonary arteries. In this case old pulmonary embolism should be considered as a cause of intrabronchial bleeding.     

A Bronchial Response Comparison of Exercise and Methacholine in Asthmatic Subjects

The authors compared the inhaled methacholine and exercise responses in 22 stable unmedicated asthmatic patients. The exercise and methacholine challenges were performed at one to three week intervals. Bronchial responsiveness to methacholine was measured in relation to the concentration of methacholine (PC₂₀M). The response to exercise was expressed as the percentage of fall in FEV₁, from the pre-exercise FEV₁ The findings showed that 21 of 22 subjects demonstrated a fall in FEV₁, of more than 20% after methacholine challenge, while only 9/22 subjects experienced a similar decrease in FEV₁. All 9 of these positive response exercise cases completed three consecutive exercise challenges prior to the methacholine challenge. Of these cases, five were refractory to the repeated exercise challenge, and the PD₂₀M at the nonexercise stage was significantly lower than the postexercise state. In fact, the methacholine challenge sensitivity actually decreased (PD₂₀ increased) after repeated exercise. The authors concluded that methacholine seems to be a more sensitive bronchial provocation test than exercise. Second, only 55.6% of the exercise test-positive subjects were refractory to the second exercise challenge. Therefore, other factors besides the release of mediators should be considered in exercise induced asthma. Third, methacholine sensitivity actually decreased (PD₂₀ increases) after repeat exercise challenge.     

Acute appendicitis—a clear-cut case in men,a guessing game in young women

Background: The aggressive surgical approach to patients suspected of having acute appendicitis for fear of perforation, and the inaccuracy of available diagnostic methods lead to an unacceptably high negative appendicectomy rate, especially in young women, in whom gynecological disorders frequently mimic appendicitis. Our objectives were to determine the value of diagnostic laparoscopy in women of child-bearing age to reduce the number of negative laparotomies and establish the correct diagnosis to allow prompt and appropriate treatment. Methods: 161 consecutive adult female patients under 50 years of age with a clinical diagnosis of acute appendicitis underwent diagnostic laparoscopy prior to the planned appendicectomy. If an inflamed appendix was found, appendicectomy was usually done through a muscle-splitting McBurney incision. Other diagnoses were treated accordingly. A normal appendix was not removed. Results were compared to a group of 42 similar patients in whom the laparoscopy was omitted for various reasons, to 23 postmenopausal women, and to all 137 male adults, directly operated by the McBurney approach. Results: After laparoscopy, 55% of the patients required appendicectomy for appendicitis while in 23% a gynecological diagnosis was made in spite of previous examination by a gynecologist. Fourteen percent had a negative laparoscopy. There were no false-negative results. The negative appendicectomy rate after laparoscopy was 5% due to two false positives and eight laparoscopy failures. In the group of fertile females who escaped laparoscopy the negative appendicectomy rate was 38%. The respective rates for postmenopausal women and men were 4% and 8%. Conclusions: All women of child-bearing age suspected of having acute appendicitis should undergo diagnostic laparoscopy prior to the planned appendicectomy, regardless of the certainty of the preoperative diagnosis. This is currently the only way to reduce the negative appendicectomy rate and establish a correct diagnosis allowing prompt and appropriate treatment. In male patients and postmenopausal women one may proceed directly to emergency appendicectomy.     

Effect of temperature in focal ischemia of rat brain studied by 31P and 1H spectroscopic imaging

³¹P, ¹H and lactate spectroscopic imaging was used to evaluate the effects of hypothermia on focal cerebral ischemia produced by middle cerebral artery occlusion. The effects on high energy phosphate metabolism, pH, lactate and NAA were investigated in 24 spontaneously hypertensive rats subjected to either permanent or transient ischemia. Under either normothermic (37.5°C) or hypothermic (32°C) conditions, with permanent 6-h occlusion, there was little difference between groups in either the NMR measurements or the volume of infarction. In animals that underwent 3 h of ischemia followed by 12 h of reperfusion, the ischemic changes in lactate, pH, NAA, and high-energy phosphate returned toward control values, and there was a protective effect of hypothermia (infarct volume of 211 ± 26 and 40 ± 14 mm³ in normothermic and hypothermic groups, respectively). Thus, hypothermia did not ameliorate the changes in lactate, pH, NAA, or high energy phosphate levels occurring during ischemia, however, during reperfusion there was an improvement in both the recovery of these metabolites and pathological outcome in hypothermic compared with normothermic animals.     

Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat--evidence of heterogeneity in distribution patterns.

The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.     

THE SCIENCES OF CLINICAL PRACTICE

The Robert Wood Johnson Commission on Medical Education focused on evidence that, in the midst of the genetic revolution in medicine, medical students all too often are not engaged by the science component of their education. Medical education is being driven by social as well as these intellectual forces to make fundamental changes. In the USA, the rich array of scientific talent can be used more effectively, and there is a new significance for the behavioural, social, probabilistic, and information sciences. The Report discusses the general changes under way in the USA and includes examples from the eight schools in the Robert Wood Johnson Foundation's Preparing Physicians for the Future: A Program in Medical Education .
Another report explores the reasons why the general changes under way in North American medical education are difficult to bring about. Educating Medical Students is the report of the Assessing Change in Medical Education: The Road to Implementation (ACME-TRI) project of the Association of American Medical Colleges. This project, funded by the Charles E. Culpeper Foundation, explored the recurring problems in medical students' education that have been reported from the 1930s. The ACME-TRI report documents that most medical schools have not solved these recurring problems, summarizes the schools' views of the barriers to solving these problems, and identifies strategies to assist schools in overcoming or minimizing the barriers they have identified.
Together, the Robert Wood Johnson Commission report and the ACME-TRI report provide a context in which to consider the complex issues facing medical education in the 21st century.     

Different effects of intracellular and extracellular TEA on voltage-dependent K currents of acutely isolated hippocampal CA1 neurons.

Tetraethylammonium (TEA) effects on K currents were examined on either side of the membrane of hippocampal CA1 neurons by means of whole-cell voltage-clamp recording and intracellular perfusion. Recording media contained ion channel blockers to allow the selective activation of voltage-dependent K currents which consisted of a rapidly decaying component (A-current) and a delayed component. Voltage protocols were applied to separate the A-current from the delayed component. Results show that 10 mM extracellular TEA suppressed 50 +/- 11% (S.D., n = 4) of the delayed current at different levels of depolarization but had little effect on the A-current. In contrast 10 mM TEA applied by intracellular perfusion suppressed the A-current by 42 +/- 10% (S.D., n = 4) in addition to inhibiting the delayed currently 55 +/- 15% (S.D., n = 4). Both the intracellular and extracellular actions of TEA on K currents showed no voltage- nor time-dependency. The results suggest that voltage-dependent transient current (A-current) is mediated through a separate group of ionic channels distinct from those that sustained the delayed current. Furthermore, the asymmetrical effects of intracellular and extracellular TEA on the transient current are similar to those described for the A-current in molluscan neurons. This observation supports the notion that the structure of the ion channel mediating the A-current is closely conserved across different species.