A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension

Summary The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n=6), and patient with hypertension (n=3), diabetes mellitus (n=8), and diabetes with hypertension (n=8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.     

Linkage guide for rotational alignment during total knee arthroplasty

A linkage guide was devised for use in conjunction with knee arthroplasty instruments to achieve proper component rotation. The femoral component was rotationally aligned to the surgical epicondylar axis using one guide. The other guides were used after all bone surfaces were cut and soft tissue balancing was completed. A Kirschner wire was guided into the proximal tibial aspect parallel to the sagittal plane of the femoral component with the patella in its normal position and the knee in full extension. The wire was used as a reference to determine tibial component rotation. The relative rotational alignment of 21 knees in 19 patients who had undergone cruciate-retaining total knee arthroplasty utilizing this guide was assessed using the modified Eckhoff method. The results of radiographic analysis were compared with those in a control group of 25 knees where the guide was not employed. The external rotation of the femoral component relative to the tibial component was 1.3° ± 2.0° (mean ± SD) in the guided group and 1.1° ± 4.4° in the control group. The relative rotational angle was significantly more consistent using the guide. Implant malrotation can be reduced using our technique.     

Conversion of pyridoxine into 6-hydroxypyridoxine by food components, especially ascorbic acid

In experiments designed to examine interactions between pyridoxine (PN) and food components, PN was found to be converted into an unidentified compound in the presence of the homogenates of various plant foods under mild conditions. The formation of the compound tended to be higher when food samples had a higher ascorbic acid (AsA) content. The reaction was neither thermal decomposition nor photodecomposition. This compound was also formed by incubating PN with AsA in the dark. Conversion of PN into the compound proceeded with oxidation of AsA, and was negligible under anaerobic conditions. The pH optimum for the reaction was between 4 and 7, and the temperature optimum was between 30 and 50 degrees C. The compound was purified by ion-exchange chromatography, isolated as colorless needles, and identified as 6-hydroxypyridoxine from UV, PMR, IR and MS spectral data. 6-Hydroxypyridoxine had neither vitamin B6 nor antivitamin B6 activity for Saccharomyces carlsbergensis 4228 (ATCC 9080). From these results, we inferred that hydroxylation of PN in the presence of food components, especially AsA, caused loss of vitamin B6 in plant foods during food processing, storage and cooking.     

Effects of methylprednisolone on cortical neural activity, blood flow, and water content in air exposure-induced cerebral edema

The correlation of changes in cortical neuron activity with water content and local cerebral blood flow was investigated in cats with brain edema produced by air exposure. The further effect of high-dose methylprednisolone on these factors was studied. Six hours after exposure of the brain surface to air, the water content of the white matter significantly increased. The local blood flow of the cortex and white matter significantly decreased with significant suppression of cortical neural activity (direct cortical response), indicating that ischemia was responsible for neural suppression. A single, large dose of methylprednisolone (30 mg/kg, i.v.) at the beginning of air exposure significantly reduced brain edema of the cortex and white matter 12 h after air exposure and improved the local blood flow of the cortex. Methylprednisolone also caused a remarkable improvement in cortical neural activity. This steroid effect on cortical neural function may play a role in the rapid neurologic improvement observed with their use in addition to the effect on brain edema.     

Protective genes expressed in endothelial cells of second hamster heart transplants to rats carrying an accommodated first graft

Abstract: Accommodation refers to survival of a xenograft despite the presence of anti-donor organ antibodies and complement. We have recently shown that accommodation of a hamster heart transplanted to a rat receiving short-term cobra venom factor (CVF) and continuing cyclosporine A (CyA) therapy is associated with i) the expression in the endothelial cells (EC) and smooth muscle cells of the graft of a number of "protective" genes, ii) a prominent intragraft Th2 cytokine profile, and iii) the relatively heavy deposition of IgG2c antibodies on the EC of the graft. In contrast, rejecting grafts do not express the protective genes, have a Th1 cytokine profile, and apparently have lesser amounts of IgG2c. These findings are consistent with host factors (Th2 cytokines and IgG2c) contributing to xenograft accommodation. To test whether these host factors may predispose to the development of accommodation, we placed a second hamster heart into each of 12 rats carrying a surviving first heart; recipients were, at the time, receiving only CyA. Whereas first grafts transplanted to rats receiving only CyA survive for 3 to 4 days, 11 out of 12 second transplants survived more than 20 days, and the other survived for 7 days. Nine of the twelve were not rejected: of these, four were removed between day 35 and 132 for study, and the remainder are still beating at 35 to 52 days. The surviving second hearts we studied had accommodated in that the picture on immunopathology was the same as for surviving first hearts. We suggest that the Th2 cytokines and perhaps the IgG2c response are factors in allowing prolonged survival of the second grafts and, further, that these factors contribute to the expression in the EC and smooth muscle cells of the surviving second hearts of the protective genes.     

Immunohistochemical localization and dynamics of paraquat in the stomach and esophagus of rats

Summary The dynamics of paraquat in the stomach and esophagus of rats were demonstrated using immunohistochemical techniques. The Rats were killed 3 h, 12 h, 24 h, 3 days, 7 days and 10 days after intravenous administration of paraquat. In the stomach, paraquat was localized in the epithelial cells between 24h and 10 days after injection, whereas in the esophagus, paraquat was localized in epithelial cells and the lamina propria mucosa between 12 h and 10 days after administration. Although these findings were similar to those observed in the intestine of rats, no clear changes in the distribution of paraquat with time were observed; suggesting that the stomach and esophagus are important reservoirs for the redistribution of paraquat.     

Kupffer cell activation in the survival discrepancy between liver grafts from enterally and parenterally fed donors

Abstract This study was designed to investigate the effects of differences in the route of nutritional support of the donor on cold ischemia/reperfusion injury. Participation of Kupffer cells in these effects, based on the analysis of hepatic energy metabolism in early phases of reperfusion was also investigated. Orthotopic liver transplantation was performed between Large-White pigs weighing 20–30 kg after a 4-h cold preservation of the graft in Euro-Collins solution at 4°C. One group was fed orally with a standard laboratory diet (FED group, n = 5), a second group was fasted and given 20% glucose intravenously (12 kJ/kg per day) (PEF group, n = 5), and a third group was fed orally with a standard laboratory diet and given GdCI₃ (10 mg/kg) intravenously 24 h before operation (FEDGD group, n = 5). These treatments were given for 7 days prior to harvesting. The survival time was significantly longer in the PEF (34.8 ± 5.5 days) and FEDGD (28.0 ± 11.9 days) groups than in the FED (9.8 ± 2.0 days) group ( P < 0.05). The serum hyaluronic acid elimination rate determined from 1 to 2 h after reperfusion was significantly lower in the FED group than in the other two groups ( P < 0.001). The glycogen content of the livers 1 h after reperfusion in all three groups had been consumed rapidly, but the ATP content of the livers was significantly reduced in the FED group alone ( P < 0.01). Hepatic FFA clearance (C_FFA) was moderately increased in all three groups in the early phase after reperfusion, but it was higher in the FED group than in the other two groups, with significant differences 1 and 2 h after reperfusion ( P < 0.05). In conclusion, parenteral nutrition of the donors reduced cold ischemia/reperfusion injury which is related to Kupffer cell activation and, thus, was better than enteral nutrition for donor management.     

Tracheal dilatation by halothane and enflurane in man

The effect of halothane and enflurane on tracheal tone were studied in 21 patients during the induction of anesthesia. Endotracheal tube cuff pressure was used to measure tracheal tone. Anesthesia, maintained by nitrous oxide 70% in oxygen, was supplimented with succinylcholine drip infusion to immobilize the patient. Ventilation was controlled by a Volume-preset ventilator. In the halothane group, the initial cuff pressure was 14.8 ± 1.3 (mean ± SE) cmH₂O but 10min after 0.15mg/kg of pancuronium injection, it increased to 21.7 ± 2.3cmH₂O (control). Ten min after inhalation of 0.75% of halothane, cuff pressure decreased to 14.7 ± 2.3cmH₂O (34 ± 11% decrease from the control value). In the enflurane group, the initial cuff pressure was 17.6 ± 1.8cmH₂O and it increased to 21.0 ± 1.7cmH₂O (control) 10min after pancuronium injection. Ten min after 1.7% of enflurane inhalation, cuff pressure decreased to 17.1 ± 2.3cmH₂O (23.9 ± 6% decrease from the control value). Halothane and enflurane produced similar tracheal dilatation in healthy individuals.(Yasuda I, Irimada M, Hirano T et al.: Tracheal dilatation by halothane and enflurane in man. J Anesth 2: 46–49, 1988)     

Effects of flunarizine therapy on intractable epilepsy

In an open trial the antiepileptic effects of flunarizine were studied in 64 patients with intractable epilepsy, and the following results were obtained: 1. Seizures disappeared completely in 2 cases, with a 50% decrease in 6 cases. 2. Of the 25 patients who had accompanying psychiatric symptoms 8.0% showed an improvement in these symptoms. 3. While no marked side-effects were observed, some cases showed an increase in frequency of seizures and the trial was stopped for 8 cases. 4. "Global evaluation" showed an overall improvement rate of 9.4%. In 47 cases, in which changes in frequency of seizure were confirmed and dosage of flunarizine was subsequently changed, improvement rate was 12.8%. 5. The above results suggest that the effectiveness of flunarizine in this open trial was very low.