Distribution of type II diabetes in nuclear families

Type II diabetes has a substantial genetic component, but the mode of inheritance and the molecular basis of this inheritance are uncertain. This study documents the familial distribution of the disease in the parents and siblings of a consecutive series of type II diabetic subjects. We studied 66 first-degree relatives of 20 white subjects with type II diabetes and both parents alive. They were tested with a continuous infusion of glucose (5 mg.kg IBW-1.min-1) (n = 49) or FPG and hemoglobin A1c (n = 17). Seven probands had neither parent affected with diabetes or IGT, 10 had one parent affected (6 with diabetes and 4 with IGT), and 3 had both parents affected. The probands with affected and those with unaffected parents were phenotypically similar. These findings indicate that a sizable subgroup of type II diabetic subjects may have neither parent affected with a demonstrable abnormality of glucose tolerance. The assumption of autosomal dominance with complete penetrance is not supported, although it remains possible that a dominant gene of low penetrance may play a role in some pedigrees. Polygenic inheritance would appear likely, and genetic heterogeneity may occur. The inheritance of diabetic traits from phenotypically normal parents needs to be considered in the analysis of genetic linkage with type II diabetes.     

George Washington Crile, anoci-association, and pre-emptive analgesia

We report a case of myasthenia gravis in a young Melanesian woman. It is only the second case described from Papua New Guinea and the first in which antibodies to the acetylcholine receptor have been demonstrated. The patient's complaint of occasional dysarthria was initially dismissed as hysterical in nature due to her apparent normal speech on conversation. The true nature of her problem only became apparent when she was asked to read a prolonged monologue. Myasthenia gravis may present without involvement of the eye muscles and the diagnosis may only become apparent if muscle groups are specifically tested for fatiguability.     

Inhibition of morphine-induced tolerance and dependence by a benzodiazepine receptor agonist midazolam in the rat

We investigated whether midazolam administration influenced morphine-induced antinociception and tolerance and dependence in the rat. Antinociception was assessed by the tail-flick (TF) and the hot-plate test (HP 52 degrees C). Morphine tolerance developed after daily single injections of morphine for 11 days. The effect of midazolam on morphine-induced antinociception and tolerance was assessed by giving daily injections of various doses of midazolam for 11 days. The first injection of saline or midazolam was given intraperitoneally and 30 min later morphine (10 mg/kg body weight) was administered subcutaneously. Antinociception was monitored by measuring TF and HP latencies 60 min after the second injection. Midazolam was injected at four different concentrations: 0.03, 0.1, 0.3, and 3 mg/kg body weight. Chronic administration of morphine resulted in the development of tolerance to antinociception in both TF and HP tests, with rats exhibiting baseline antinociception on Day 9. Animals treated with midazolam alone showed little antinociception on Days 3-9. However, midazolam administration in morphine-treated animals attenuated morphine-induced tolerance to antinociception on Days 1-11 as measured by the tail-flick test. Midazolam also decreased the jumping behavior following naloxone injections in morphine-dependent rats. These results suggest that midazolam may prolong the effects of morphine by delaying morphine-induced development of tolerance to antinociception. Midazolam also attenuated a decrease in weight gain induced by chronic injections of morphine.     

Popliteal venous aneurysm: report of two cases and review of the world literature

Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.     

Induction of the cell cycle in baby rat kidney cells by adenovirus type 5 E1A in the absence of E1B and a possible influence of p53

From previous studies on the induction of DNA synthesis in quiescent primary baby rat kidney cells by adenovirus type 5 (Ad5) E1A deletion mutants, we concluded that induction is prevented only when cellular proteins p300 and pRb are both uncomplexed with E1A (J.A. Howe, J.S. Mymryk, C. Egan, P.E. Branton, and S.T. Bayley, Proc. Natl. Acad. Sci. USA 87:5883-5887, 1990). We have now examined induction by these same mutants in virus lacking the E1B region, so that cellular p53 was no longer complexed to the E1B 55-kDa protein. E1A mutants that fail to bind pRb induced DNA synthesis at a significantly lower level in Ad5 lacking E1B than in Ad5 containing E1B. Apparently, therefore, uncomplexed p53 can partially replace p300 in cooperating with pRb to suppress DNA synthesis in baby rat kidney cells.     

Are there structural and functional modules in the vertebrate olfactory bulb?

Each of twelve volunteers, at 2 week intervals, received 1 g of antipyrine, a test drug, and were exposed for 4 h either to toluene (375 mg/m3) or xylene (435 mg/m3) singly or in combination with ethanol (0.45 g/kg body wt. before the onset of exposure and 0.15 g/kg thrice every 1 h during exposure to maintain a steady level of ethanol in blood approximately 11 mmol/dm3). No significant differences were found in salivary antipyrine half-life (T1/2 approximately 12 h); and clearance (ClAP approximately 0.83 cm3/s) between control and groups exposed to solvents and/or ethanol. Nevertheless, a tendency to increase the metabolic rate of antipyrine in xylene-exposed group (T1/2 approximately 6.8 h; ClAP approximately 1.40 cm3/s) and counteraction of ethanol (T1/2 approximately 15 h; ClAP approximately 0.63 cm3/s) should be noted. The stimulation of lipid peroxidation in the serum as a biological effect of combined exposure to ethanol and toluene/xylene was observed.     

Benzodiazepine withdrawal reaction in two children following discontinuation of sedation with midazolam

OBJECTIVE: To report the occurrence of recurrent benzodiazepine withdrawal reactions in two very young children following discontinuation of sedation with midazolam. CASE SUMMARY: A 15-month-old boy with apneic episodes was sedated with midazolam for 12 days with constant infusion. Half a day after discontinuation of the midazolam the boy became restless, tachycardic, and hyperpyrexic. When midazolam was readministered, all symptoms disappeared. Four days later midazolam was again discontinued and within 12 hours the same signs and symptoms reappeared. Midazolam infusion was restarted, and the signs and symptoms disappeared for the second time. After thoracotomy, a 14-day-old boy received intravenous midazolam for sedation for 29 days. Within 12 hours after discontinuation of midazolam he became restless, developed a bulging stomach secondary to aerophagia, and was vomiting. Midazolam therapy was reinstituted and continued for another 2 months by constant infusion. Thereafter, the boy was successfully weaned from artificial ventilation in 5 days under sedation with midazolam. About 12 hours after discontinuation of midazolam the boy became restless, tachycardic, again developed a bulging stomach because of aerophagia, and vomited. When the child was sedated with clorazepate by continuous infusion, the signs and symptoms disappeared. DISCUSSION: Case reports describing benzodiazepine withdrawal reaction upon discontinuation of midazolam were reviewed and compared. The symptoms observed in the children we present resemble those mentioned in the three children and two adults reported previously. Unique in the very young children in this article is the occurrence of gastrointestinal symptoms, which most likely are the result of air being swallowed secondary to severe agitation. CONCLUSIONS: Midazolam withdrawal reactions in adults and children, particularly in an intensive care unit, can be significant. Considerable caution must be taken with relatively long-term administration and abrupt discontinuation of midazolam.