Anti-inflammatory therapy reduces wheezing after bronchiolitis.
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Biomedical subjects
Publications and source records attributed to A Hakim.
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Neuroanatomical methods have been used to study selective vulnerability after global brain ischemia. A consistent pattern of ischemic neuronal damage is found in the rodent hippocampus with loss of CA1 neurons and of some cells in the hilus of the dentate gyrus. Very little is known about plastic changes that would be expected in ischemia-resistant areas such as CA3 neurons and granule cells. Neuronal plasticity after lesions may be indicated by changes in labeling with antibodies to the growth-associated protein 43 (GAP-43). Expression of GAP-43 as a marker for neuronal plasticity was studied here in the hippocampus after global brain ischemia. Halothane-anesthetized rats were subjected to 20 min of transient forebrain ischemia using four-vessel occlusion. In situ hybridization was used to study GAP-43 mRNA at 1, 3, 6, and 12 h and at 1, 3, and 7 days after ischemia. Immunostaining was carried out with two different antibodies to GAP-43 in brains which were perfusion-fixed after 1, 2, 4, and 7/8 days. In the control hippocampus, GAP-43 mRNA was localized to CA1-CA3 and the hilus. Moderate increases in cellular signals were seen in hilar cells and granule cells early after ischemia, and some changes occurred in CA3 at late stages. Hybridization was lost in CA1 due to cell death. With immunostaining, GAP-43 was not seen in the cytoplasm of neurons, whereas dense labeling occurred in a differentiated pattern in the axonal and dendritic layers. At 1 day after ischemia, neurons in the hilus of the dentate gyrus and in the stratum pyramidale and lucidum of CA3 showed strong cytoplasmic labeling for GAP-43. Few cells were labeled in these regions at 2 days, and none at later stages. Pyramidal cells in CA1 and CA3 areas and granule cells were never labeled. These studies demonstrate a transient expression of GAP-43 mRNA and protein in a subset of vulnerable neurons after transient brain ischemia. The cytoplasmic localization in hilar neurons could be due to increased synthesis of GAP-43 or to changes in axoplasmic transport. It is suggested that axonal damage occurs in hilar cells which stimulates GAP-43 expression. The increased production of trophic factors after ischemia in granule cells could also cause plastic changes in hilar cells. Since hilar neurons are in a strategic position to control the excitability of the dentate area, increased expression of GAP-43 may indicate an important pathophysiological process. In seizure experiments, strong expression of GAP-43 mRNA in granule cells was associated with abnormal mossy fiber sprouting and development of chronic epilepsy. The relevance of the minor GAP-43 mRNA upregulation after ischemia must be considered. The changes in CA3 neurons at several days after ischemia might represent a plastic response to a loss of CA1 neurons.
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Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits lipopolysaccharide-induced tumor necrosis factor production. We determined the plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock and in 11 patients with circulatory shock of nonseptic origin. In septic shock, interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma levels also increased during the first 24 h but to a lesser extent (median: 17 pg/ml). In septic shock patients, interleukin-10 plasma levels were positively correlated with tumor necrosis factor (r = 0.8, p = 0.01) and with parameters of shock severity including lactate levels (r = 0.56, p < 0.05) and correlated negatively with blood platelet counts (r = -0.65, p < 0.05). The decreased production of tumor necrosis factor-alpha and interleukin-6 after in vitro incubation of whole blood from septic shock patients with lipopolysaccharide was not influenced by in vitro neutralization of interleukin-10. We conclude that interleukin-10 is produced in patients with circulatory shock of septic and nonseptic origin and that the production of this anti-inflammatory cytokine during septic shock correlates positively with the intensity of the inflammatory response.
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We studied the role of ultrasound assessment of the thyroid gland in detecting amyloid deposition in 9 patients confirmed to have renal amyloidosis because the thyroid gland is a readily accessible organ. Ultrasound examination of the thyroid gland showed a distinctive abnormal appearance in 7 patients. There was enlargement of one or both lobes of the thyroid, a high echogenicity approaching that of the surrounding connective tissue, and a very fine homogeneous echotexture similar to ground glass appearance. Four patients showed dilated follicles in the thyroid gland. The other two patients had normal ultrasound findings. Open wedge biopsy of the thyroid gland in 4 patients, (3 with abnormal ultrasound findings and 1 with normal ultrasound findings) showed amyloid deposits in the 3 patients with abnormal echo findings and no amyloid deposits in the 1 patient with normal findings. In 10 healthy individuals, 10 patients who were just initiated on maintenance hemodialysis and another 10 patients on dialysis for more than 1 year, the thyroid gland was of normal size and appearance in the ultrasound examination. We conclude that ultrasound examination by an experienced radiologist is a useful tool in the diagnosis of thyroid amyloidosis.
Data on end-stage renal disease (ESRD) patients in Kuwait were collected retrospectively and prospectively starting in mid-1988. The study period covered 4 1/2 years from 1 January 1986 to 30 June 1990. Epidemiological characteristics of ESRD patients and their disposal by dialysis and transplantation were analysed and compared with previous reports from Kuwait, neighbouring countries, Europe, and USA. A total of 647 patients received renal replacement therapy (RRT) in Kuwait during the study period. This gave an incidence rate of 72 patients per year per million of population. The prevalence rate for patients on maintenance dialysis was 80.6 per million population in mid-1988. Nearly one-fifth of total patients (19.6%) were older than 60 years of age and one-third (30.8%) were identified as 'high risk' category. As for Kuwaiti nationals alone on RRT 29.7% were above 60 years of age and 44.2% were high-risk patients. We have noticed a steady decline in the number of patients who accepted continuous ambulatory peritonial dialysis (CAPD) for dialytic support. Chronic tubulointerstitial disease resulting from atrophic pyelonephritis was the leading cause of ESRD amongst both Kuwaiti nationals and expatriates. Though diabetic nephropathy was only the third leading cause of ESRD (14.7%) in the total population, it was more frequent (21.2%) among Kuwaitis. The gross mortality rate on dialysis was 14.7%. The major causes of death were related to cardiovascular diseases (60%) and sepsis (24.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
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Erythropoietic response to exogenously administered recombinant human erythropoietin (rHuEpo) was examined in 11 maintenance haemodialysis patients with iron overload (IO). All had required numerous blood transfusions earlier (> 12 units/year). Diagnosis of IO was established by high serum ferritin (SF) levels (> 1,100 micrograms/l), high hepatic CT density (> 70 Hounsfield units; HU) and excessive iron stores in bone marrow aspirate (grade 6). None of the patients had osteitis fibrosa cystica, aluminium intoxication, haemoglobinopathy or haemochromatosis alleles (HLA A3, B7 and B14). All patients responded to rHuEpo treatment (target haemoglobin level of 9-10 g/dl). None of the patients required iron supplementation or developed 'functional anaemia'. During 30 +/- 3 months of therapy, the initial maintenance dose of rHuEpo (103 +/- 12 units/kg/week) and median SF levels (2,250 micrograms/l) fell (50 +/- 8 units/kg/week and 1,060 micrograms/l, respectively) (p = 0.0003 and 0.0007). The initial and final rHuEpo doses correlated well with the respective SF levels (r = 0.89, p < 0.001). The maintenance dose of rHuEpo required for patients with IO at the start of the treatment period was significantly higher than that (50 +/- 5 units/kg/week) required by a control group of patients with adequate iron stores (SF = 100-600 micrograms/l) who were matched for age, sex and frequency of previous blood transfusions (p = 0.002). The findings suggested that excessive IO caused relative resistance to erythropoiesis on exogenous administration of rHuEpo and that iron supplementation was not warranted during rHuEpo therapy in those patients.
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Mycobacterial peritonitis is rare among patients undergoing peritoneal dialysis. It is usually caused by group IV environmental mycobacteria. We report three such cases and review the literature on this subject. Negative results in routine bacterial cultures and persistent peritonitis may be the only clues indicating the presence of mycobacterial infection. The lack of specific symptoms and signs as well as inadequate culture techniques may delay diagnosis. Multiple cultures of centrifuged dialysis fluid may be required for isolation of the organism. Peritoneal biopsy may yield additional diagnostic information. Management frequently entails removal of the dialysis catheter in addition to antimicrobial therapy. Significant morbidity may ensue if treatment is delayed. Amikacin--with or without another antibiotic--provides adequate coverage.