Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.

BACKGROUND--Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS--Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS--Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS--The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.     

Allogeneic cell stimulation enhances cytomegalovirus replication in the early period of primary infection in an experimental rat model.

BACKGROUND: Cytomegalovirus (CMV) diseases commonly occur in allograft recipients in the early post-transplant period. However, factors responsible for the high incidence of CMV diseases during this period are not yet fully defined. METHODS: Wistar-Furth (WF; RT-1(u)) rats were inoculated with 10(4) plaque-forming units (PFU) of rat CMV (RCMV) intraperitoneally, and then transplanted with allogeneic lungs from Dark Agouti (DA; RT-1avl) rats or stimulated with 10(7) mitomycin C-treated spleen cells from DA rats by daily sub-cutaneous injections for 2 weeks. No immunosuppressive agent was used. Naive WF rats and WF rats grafted with syngeneic lungs or cells were used as controls. The level of RCMV replication in rats was assessed by infectious virus titers in tissues. RESULTS: The virus titers in salivary glands of allogeneic and syngeneic lung graft recipients were significantly higher than in naive WF rats. The level of RCMV replication in rats stimulated with allogeneic spleen cells was significantly higher than in the syngeneic recipient rats: virus titers in the salivary gland of allogeneic and syngeneic recipients reached 4.61 +/- 0.33 and 4.00 +/- 0.37 log(10) PFU/g tissue, respectively, at 14 days post-infection (p = 0.015). The augmented viral replication in allogeneic recipients was confirmed by an increase in the number of RCMV antigen-positive macrophages present in tissue sections of the salivary gland. CONCLUSIONS: Acute lung allograft rejection and allogeneic spleen cell stimulation enhance CMV replication in the salivary gland of rats. Various responses to allogeneic antigens occurring in the process of acute allograft rejection could be risk factors for post-transplant CMV replication and infection.     

Spontaneous mesenteric hemorrhage associated with ehlers-danlos syndrome

The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.     

beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices.

To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) on synaptic transmission and morphological integrity during glucose deprivation in rat hippocampal slices. After the depression of excitatory postsynaptic potentials (EPSPs) by 60 min of glucose deprivation, administration of 0.5-10 mM D-betaHB restored EPSPs in slices from postnatal day (PND) 15 rats but not in slices from PND 30 or 120 rats. At PND 15, adding D-betaHB to the media allowed robust long-term potentiation of EPSPs triggered by high frequency stimulation, and prevented the EPSP-spike facilitation that suggests hyperexcitability of neurons. Even after PND 15,D-betaHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-betaHB is not only able to substitute for glucose as an energy substrate but is also able to preserve neuronal integrity and stability, particularly during early development.     

Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese

The nitric oxide synthase (NOS) gene is thought to be associated with essential hypertension (EH), because NO is implicated in endothelium-mediated vasodilation. We investigated the possible association between the alleles of simple tandem repeat DNA polymorphism of the endothelial constitutive NOS (cNOS) gene and EH in Japanese subjects. In all, 100 patients with EH and 123 subjects with normal blood pressure were studied. Polymerase chain reaction was used to amplify the CA repeat site in the endothelial cNOS gene and alleles based on the CA repeat number were determined. The allele frequencies in the hypertensive group and normotensive group were then compared. Twenty-three alleles were identified in this study of Japanese subjects. The overall distributions of allele frequencies in the two groups were not significantly different. However, comparing the allele frequencies in the EH group without left ventricular hypertrophy (LVH) and the normotensive group, the overall distributions were significantly different (p = 0.019). The 33-repeat allele was found more frequently in the EH group without LVH than in the normotensive group (p = 0.000047, Odds ratio = 3.71). In conclusion, the 33-repeat allele of the endothelial cNOS gene is associated with EH without LVH, and may be a genetic marker of EH in Japanese subjects.     

A comparative clinical and pharmacokinetic study of a new slow-release versus conventional preparations of valproic acid in children with intractable epilepsy.

Thirteen children with intractable epilepsy were treated by means of three-times-daily administration of a conventional preparation of valproic acid (C-VPA) and twice-daily administration of a new slow-release preparation of VPA (SR-VPA) with the cross-over technique. The frequency of seizures, side effect and steady-state pharmacokinetics of VPA were evaluated. With the change from C-VPA tid to SR-VPA bid, four patients exhibited a significant reduction in seizure frequency. The steady-state minimum concentration (Cmin) was higher, the maximum concentration (Cmax) lower and there were less diurnal fluctuations with SR-VPA, than with the respective values obtained in the C-VPA group, all the differences being statistically significant. Furthermore, a significant difference was unexpectedly found in the area under the curve (AUC) from 0 to 24 hours, the mean AUC in the period of SR-VPA being 9% higher than that with C-VPA. Five of the nine patients under 6 years of age showed more than 10% increase, and all four patients over 6 years of age less than 10% increase or a decrease in AUC. It was concluded that with SR-VPA bid, the pharmacokinetic features were more stable, the age-related AUC value was larger and the clinical effect was better than in comparison to C-VPA tid in children with intractable epilepsy.     

Nodular fasciitis of the upper labial fascia: cytometric and ultrastructural studies

The rare case of nodular fasciitis in the upper labial fascia is reported. Light microscopic, electron microscopic and cytometric studies were performed. The histopathology corresponded to intermediate and reactive types in the Price and Bernstein classification. Cytometric study of evaluating DNA of fibroblasts revealed a high distinct peak in myxoid and inflammatory areas. Ultrastructurally, fibroblasts and myofibroblasts were identified in the lesion. Reported Japanese cases of orofacial nodular fasciitis are reviewed and compared with the European-American literature.     

Evaluation of renal function with dynamic Gd-DTPA-enhanced magnetic resonance imaging after shock wave lithotripsy]

It has already been reported that MR imaging is a superior imaging technique to detect minute anatomical changes in the kidney after ESWL. However, the morphological abnormalities found by MR imaging do not necessarily mean deterioration of the renal function. The purpose of this study is to assess the morphological changes in the kidney and changes in renal function after the ESWL treatment by dynamic MR imaging. A total of 16 patients underwent axial MR imaging before and after ESWL. Dynamic MR was also performed on 11 patients of them within 24 hours after ESWL, and both before and after ESWL in the remaining 5 patients. Eight kidneys showed morphological abnormalities on T1-weight images, and 4 of them showed loss of corticomedullary demarcation. Furthermore, the first MR imaging after injection of GdDTPA revealed focal areas of decreased signal intensity in only 2 of these 4 patients who showed loss of corticomedullary demarcation on previous MR images. However, the second MR imaging 6 months after ESWL showed no abnormality in either of them. The percent contrast of signal intensity increase to fat signal intensity was one minute after GdDTPA injection compared before and after ESWL in 5 of the 16 patients. The values before and after ESWL revealed no statistically significant difference, and no patient showed any remarkable decrease of signal intensity after ESWL. These results suggest that loss of corticomedullary demarcation after ESWL does not necessarily reflect damage to the renal function and that the shock-wave exposure causes no permanent damage to the renal function but only temporary impairment.     

Insulin protects brain tissue against focal ischemia in rats.

The influence of insulin on the infarct volume due to middle cerebral artery (MCA) occlusion was investigated in rats. A small dose of insulin (1 unit/kg) was injected i.p. just after MCA occlusion. The infarct areas were measured by planimetry from brains perfused with 2,3,5-triphenyltetrazolium-chloride (TTC) 48 h after the occlusion. Systemic variables were measured before and at various times after ischemia. The comparison between insulin-treated (n = 14) and control (n = 13) rats provided evidence that insulin significantly reduced the infarct volume due to MCA occlusion. As insulin minimally and transiently decreased blood glucose, the present results suggest that insulin exerts a beneficial effect directly on the central nervous system.     

Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease

BACKGROUND: Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut-off point to predict aneurysm formation is not clear. METHODS: One hundred and five patients with giant coronary aneurysms were selected from the 15th and 16th nationwide surveys of Kawasaki disease in Japan. A total of 2936 patients without Kawasaki disease were recruited from a single hospital as a control group. Odds ratios were calculated for six laboratory data with specific values as cut-off points. Receiver operating characteristic (ROC) curves were observed to determine the most appropriate laboratory tests and cut-off points. RESULTS: Hematocrit, leukocyte count, neutrophil proportion, and hemoglobin had one or more peaks of odds ratio for specific cut-off points, but they did not have a clear cut-off point for the predictor according to the receiver operating characteristic curves. Alanine aminotransferase (ALT) increased the risk of giant coronary aneurysms continuously so no clearly appropriate cut-off point was identified. Serum sodium concentration of 135 mEq/L had a peak of odds ratio, and those with <135 mEq/L had the highest odds ratio (4.78). This value seemed appropriate with a sensitivity of 78% and specificity of 57%, although the predictive positive value was as small as 5%. CONCLUSION: The author's propose that a serum sodium concentration of <135 mEq/L at the patient's first visit to hospital may be a predictor of giant coronary aneurysms due to Kawasaki disease.