How long are oral antidiabetic drugs effective?

Dopamine-beta-hydroxylase (DBH), the enzyme responsible for the biosynthesis of norepinephrine from dopamine was assayed in the blood serum of 23 normal adults, 16 patients with congestive heart failure, 19 patients with asymptomatic ischemic heart disease, 4 patients with angina pectoris at rest, 15 patients with essential hypertension, 8 patients with essential hypotension, 5 patients with neurocirculatory asthenia, and 9 normal adults before and after the exercise test. The serum DBH activity varied within a wide range in the control population. The DBH activity increased about 16% after the exercise stress. A tendency to increase DBH activity was shown in the patients with congestive heart failure. There was no significant difference between asymptomatic ischemic heart disease, essential hypertension and normal controls. A lower value was observed in the patients of angina pectoris at rest, while a higher DBH activity was demonstrated in the patients with essential hypotension. There was no significant difference between the neurocirculatory asthenia group and the normal control group.     

Pelvic fractures: an anatomic guide to severity of injury. Review of 100 cases

A series of 100 cases of pelvic fracture secondary to violent trauma were reviewed and divided into two anatomic groups, those with pure anterior arch fractures (57 patients) and those with posterior fractures (43 patients). By this classification, mortality and associated injury are shown to be markedly increased in those patients with posterior fractures. A detailed study of the major complications has shown that a conservative approach to these injuries is probably the safest for the patient. Major blood loss is the rule rather than the exception and restoration of an adequate circulating volume by transfusion should precede operative attempts to control continuing retroperitoneal hemorrhage.     

Binding of insulin analogs to partially purified insulin receptor from rat liver membrane (author's transl)

The insulin binding fraction was solubilized from rat liver membrane vesicles by triton and partially purified up to the specific binding activity of 2.1 pmol/mg. A further characteristic of the partially purified soluble receptor is a decrease in irreversible binding to 0.36% (+/- 0.28) with regard to total iodine insulin and to (+/- 1.8) in comparison to reversible binding. From Scatchard plots a high affinity binding site (KD = 5 X 10(-10)M) with low capacity (5 pmol/mg) and a low affinity binding site (KD = 3 X 10(-8) M) with high capacity (30 pmol/mg) can be seen. With carefully prepared liver membrane vesicles, the dissociation constant of the high affinity binding site from Scatchard plot is only 2 X 10(-9)M. With liver membrane vesicles, isolated for preparative purification procedure, the high affinity binding site could not be demonstrated. Displacement studies with insulin analogs were performed with [A1-D-alanine] insulin, [A1-L-alanine] insulin, [des-Gly-A1, NB1, NB29-(Msc)2]-insulin, proinsulin and [desoctapeptid B23-B30]-insulin. Results of binding measurements are presented in half-maximal iodo-insulin binding, in determination of inhibitor- and dissociation constants from Dixon-, Scatchard- and Lineweaver-Burk plots. There are equal relative binding potencies of analogs, observed with crude membrane vesicles and partially purified soluble receptor, although there is a 50-fold difference in specific binding activity. Biologically active insulins are characterized by strong binding to the high affinity binding site. The binding to the low affinity binding site is not correlated to the biological activity of the insulin analog. With insulin and biologically responsive analogs a non-linear curve in the double-reciprocal Lineweaver-Burk plot can be observed. Analogs with low biological activity show a linear dependency. Functional interactions of insulin with the receptor can be demonstrated in a high affinity binding with the first binding site of the Scatchard plot and in a non-linear hyperbolic Lineweaver-Burk plot.     

Yersinia enterocolitica infection in a 4-month-old infant associated with infection in household dogs

Colon atresia is a rare cause of intestinal obstruction in the neonate and requires early diagnosis and prompt surgical treatment. It is impossible in the neonate to differentiate colon atresia from other forms of obstruction at the time of initial presentation. The diagnosis is confirmed roentgenographically, including views of the abdomen and contrast barium enema series. Lesions proximal to the splenic flexure are treated with initial resection of the atretic segment and a primary anastomosis. Those lesions distal to the splentic flexure are managed initally with a diverting loop colostomy with subsequent staged resection and anastomosis.     

Phospholipid membrane stabilization by dimethylsulfoxide and other inducers of Friend leukemic cell differentiation

A large number of low molecular weight polar cryoprotective agents have recently been found to induce erythroid differentiation of Friend leukemic cells in vitro. The effect of these agents on membrane fluidity in phospholipid vesicles was studied by determining the solid-to-liquid crystalline phase transition using differential scanning calorimetry. Some of the inducing agents studies were found to raise the normal transition temperature (Tc) by a few degrees. All of these agents were found to produce a separate transition at a much higher temperature. Changes in the head group of the phospholipid, the pH, the presence of divalent cations, and the addition of other membrane-active compounds were found to significantly influence the inducing agent's effects on the Tc of phospholipid membranes. The ability of the different agents to produce a new transition at a high temperature was found to correlate well with their ability to induce Friend leukemic cell differentiation. The possible mechansims of action of the chemical inducers, and the significance of the observed membrane effects on differentiation and malignancy are discussed. It is concluded that inducing agents decrease the fluidity and stabilize phospholipid membranes, and that their effects in cell differentiation might be initiated by a similar change in the properties of cell membranes.     

Effects of dextran, gelatine and homologous plasma on circulation in shock caused by severe anemia in the dog

Irreversible shock is produced in 28 anaesthetized mongrel dogs by withdrawal of erythrocytes and substitution by dextran, gelatine or plasma to an average Hb of 4.5g%. In contrast to other shock models cardiac output and perfusion pressure are not decreased by this preparation. In order to maintain arterial blood pressue above 90 mm Hg significantly more gelatine than dextran or serum has to be infused. There is no difference in hemodynamic responses after treatment with dextran or gelatine respectively. Both groups treated with colloidal solutions have the same survival rate of 38%. In the serum substituted dogs, however,survival rate is significantly greater (83%). Very likely this is due to a greater buffer capacity preventing severe acidosis, which is observed in the animals treated with colloidal solutions.     

Evaluation of nefazodone as a serotonin uptake inhibitor and a serotonin antagonist in vivo

Nefazodone (2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl- 2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one) has been reported to be effective in the treatment of depression. Antagonism of serotonin type 2A (5HT2A) receptors, as well as inhibition of the serotonin (5HT) uptake carrier, has been suggested to contribute to the antidepressant action of nefazodone in vivo (Eison et al., 1990). Nefazodone weakly antagonized the quipazine-induced rise in rat serum corticosterone levels and the quipazine-induced increase in rat hypothalamic 3-methoxy-4-hydroxy-phenylglycol sulfate, suggesting blockade of 5HT2A receptors in vivo. Nefazodone, however, failed to antagonize the p-chloroamphetamine-induced depletion of mouse or rat brain 5HT, displaying a lack of effect on the 5HT uptake carrier. These data extend previous in vitro and in vivo data (Eison, et al. 1990) reporting nefazodone to be an antagonist at 5HT2A receptors, but fail to show inhibition of the 5HT uptake carrier in the same dose range.     

A computer-controlled spraying-freezing apparatus for millisecond time-resolution electron cryomicroscopy

The application of gene therapy techniques to the clinical problem of coronary restenosis has generated tremendous attention and enthusiasm. Use of gene transfer technology to prevent a common intractable illness would represent a watershed event for human gene therapy. However, the time is not yet right to initiate gene therapy trials for restenosis. The biology of restenosis is incompletely understood, catheter-based gene delivery is poorly adapted to the coronary circulation, and current gene transfer vectors are ill-suited for safe and effective gene delivery to the coronary artery wall. Basic research designed to overcome these obstacles is currently more appropriate than the initiation of clinical trials.     

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