Prospective reevaluation of risk factors in mother-to-child transmission of hepatitis C virus: high virus load, vaginal delivery, and negative anti-NS4 antibody.

Of 21,791 pregnant women screened in Tottori Prefecture, Japan, 127 (0.58%) were positive for anti-hepatitis C virus (HCV) antibody and 84 (0.39%) were positive for HCV RNA. Of 84 children followed up for at least 6 months, 7 (8%) were infected. All of them were born to 26 mothers with a high virus load (HVL; >/=2.5x106 RNA copies/mL [27%]), compared with 0 of 58 children born to non-HVL mothers (P<.001). Because all the infected children were vaginally delivered, the infection rate among 16 vaginally delivered children born to the HVL mothers was as high as 44%. The prevalence of anti-NS4 antibody in the mothers with an infectious HVL was significantly lower than that in the mothers with a noninfectious HVL (P=.048). Analysis of our results suggests that maternal HVL, vaginal delivery, and negative anti-NS4 antibody are significant risk factors for the mother-to-child transmission of HCV.

Prevalence of Japanese dialysis patients with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.

BACKGROUND: A high prevalence of an A-to-G mutation at nucleotide 3243 of the mitochondrial genome in patients with diabetes mellitus (DM) and/or deafness has been reported previously. We investigated the prevalence of this mutation in Japanese dialysis patients with associated DM and/or deafness. METHODS: We studied 106 dialysis patients with DM, 26 with DM and deafness, and 26 with deafness alone, using peripheral leucocytes to detect an A-to-G transition at nucleotide 3243 of the mitochondrial gene. RESULTS: We identified this transition in 1 of 26 patients with DM and deafness. None of the 106 DM or 26 dialysis patients with deafness but no DM was positive for this mutation. A 42-year-old male patient on continuous ambulatory peritoneal dialysis (CAPD) who carried this mutation had a 20-year history of sensory hearing loss as well as hypertrophic cardiomyopathy. CONCLUSION: We found that a mitochondrial gene mutation at nucleotide 3243 was present in one dialysis patient with NIDDM and deafness. The prevalence of this mutation was found to be below 1% in diabetic end-stage renal disease patients in Japan.

GH and zinc treatments for short stature caused by steroid treatments in a young patient with autoimmune hepatitis (type 1).

An 8-yr-old boy with autoimmune chronic active hepatitis (AiCAH) was treated with steroid hormones. Liver function improved with this treatment, but the patient's growth was severely disturbed. At the age of 10 y, GH treatment was added to the steroid therapy because of his short stature (height: -2.5 SD), but in the following 12 months, he only grew 2 cm. Oral administration of zinc (5 mg/kg/day) was also added to the patient's therapy, but his height has not improved in the 12 months of this combined therapy.

[A case of glomerulonephritis with singular high titer of anticardiolipin antibody].

We report here a case of severe membranoproliferative glomerulonephritis with a singular high titer of anticardiolipin antibody (aCL). A 19-year-old Japanese female was admitted to Tsukuba Gakuen Hospital after complaining of general edema for 5 months. She had no past history of thrombosis, thrombocytopenia, or spontaneous abortion. Laboratory findings revealed that she had nephrotic syndrome and moderate renal dysfunction. Immunological test showed a high titer of aCL with a high-normal limit of antinuclear antibody, negativity for anti-beta(2) glycoprotein I antibody and negativity for anti-DNA antibody. In the renal biopsy tissue, most glomeruli showed global sclerosis and the remaining glomeruli revealed membranoproliferative change with crescent formation. Steroid therapy with warfarin and dipyridamole was effective and her renal function improved gradually. This case lacked the typical symptoms of primary antiphospholipid syndrome and did not satisfy the criteria of SLE. In spite of these findings, the singular high titer of aCL with membranoproliferative glomerulonephritis characterized this case.

Metabolism of administered triethylene tetramine dihydrochloride in humans.

Triethylene tetramine dihydrochloride (trien 2HCl) has been used for the treatment of Wilson's disease, which is characterized by the accumulation of copper in various organs. We previously developed an HPLC system for analyzing trien, and found a trien metabolite in the urine when trien was orally given to humans. In this study, the metabolite was identified as 1-N-acetyltriethylene tetramine (acetyltrien) by FAB-MS and 1H-NMR spectroscopy. Trien and acetyltrien were capable of combining with copper, iron and zinc. However, the chelating activity of acetyltrien was significantly lower than that of trien. When trien was given to healthy adults, the amount of trien excreted in the urine was about 1% of the administered trien, whereas that of acetyltrien was about 8%. Most of the trien was excreted within the first 6 hours after the administration, while acetyltrien was excreted for over 26 hours. The urinary copper, iron and zinc levels all increased in parallel with the trien excretion.

Intravenous arginine dramatically improved hyperammonemia in a patient with late-onset ornithine transcarbamylase deficiency.

We describe a 12 year-old male patient with late-onset ornithine transcarbamylase deficiency, in whom infusion of arginine alone dramatically improved intercurrent hyperammonemia. The plasma glutamine level also decreased while the urea nitrogen level increased with arginine infusion, indicating that accumulated nitrogen was metabolized to urea in response to the arginine infusion.

Clinicopathological study of dialysis patients with lupus nephritis.

To determine the clinical characteristics and long-term prognosis of 11 Japanese systemic lupus erythematosus (SLE) patients who were starting dialysis, we studied the clinicopathological findings before dialysis and during the clinical course after dialysis. Patients were divided into three groups: Group A consisting of temporary dialysis patients (n = 5); Group B consisting of early-death patient (n = 1); and Group C consisting of maintenance dialysis patients (n = 6). At the start of dialysis, the progression pattern of renal failure in all Group A patients was either acute exacerbation of chronic renal failure (CRF) or rapidly progressive glomerulonephritis (RPGN). The pattern in Group C was mostly CRF (83%). Three patients from Group A and three from Group C were still alive at the latest follow-up (mean follow-up period was 11.0 years, ranging from 1.8 to 16.2 years) and they showed no signs of clinical or serological activity. Infection was the cause of death in 3 of the 5 patients who died. We suggest that dialysis can be discontinued in patients with SLE who receive dialysis for acute exacerbation of CRF or RPGN. After the initiation of dialysis, patients tend to show diminished SLE activity. Infection is the major contributor to the poor prognosis of SLE patients receiving dialysis.

Glomerulonephritis associated with MRSA infection: a possible role of bacterial superantigen.

We report 10 cases of glomerulonephritis following methicillin-resistant Staphylococcus aureus (MRSA) infection. The clinical features of this syndrome were an abrupt or insidious onset of rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome and occasionally purpura, following MRSA infection. The renal histologic findings showed a variety of types of proliferative glomerulonephritis with varying degrees of crescent formation; immunofluorescence revealed of glomerular deposition of IgA, IgG, and C3. Laboratory findings showed polyclonal increases of serum IgA and IgG, with high levels of circulating immune complexes (ICs). Increased numbers of DR+CD4+, and DR+CD8+T cells were observed in the peripheral circulation, with a high frequency of T cell receptor (TCR) V beta + cells. MRSA produced enterotoxins C and A and toxic shock syndrome toxin (TSST)-1, all of which are known to act as superantigens. From the above observations, we speculate that post-MRSA glomerulonephritis may be induced by superantigens causing production of high levels of cytokines, and polyclonal activation of IgG and IgA. The formation of ICs containing IgA and IgG in the circulation result in development of glomerulonephritis and vasculitis. Accordingly, microbial superantigens may play an important role in the pathogenesis of this unique syndrome of nephritis and vasculitis.

[Pharmacokinetic, bacteriological, and clinical studies on SY5555 in children].

Pharmacokinetic, bacteriological and clinical studies on SY5555 were performed in children. The results were as follows: 1. A total of 15 patients considered to have bacterial infections were treated with SY5555. Each dose, 5 mg/kg, was orally administered 3 times daily, for 4-11 days. Clinical efficacies of SY5555 in 13 patients with bacterial infections (1 with pneumonia, 2 with bronchitis, each 1 with maxillary sinusitis, 2 with otitis media, 5 with pharyngitis, 1 each with gastroenteritis and pyelonephritis) were evaluated as excellent in 10 patients and as good in 3 patients with an efficacy rate of 100%. Two patients with viral infection and malignant lymphoma were not evaluated. Thirteen causative strains in 7 species were found in 10 patients. Streptococcus pneumoniae in 1/3, Haemophilus influenzae in 2/2, Streptococcus pyogenes 4/4, Salmonella spp. in 1/1, Escherichia coli in 1/1 were eradicated. Only one patient developed mild diarrhea as an adverse reaction. Another patient showed elevated GPT (glutamate pyruvate transaminase). The abnormality was mild and the patient recovered after the cessation of SY5555 administration without specific treatment. 2. MICs of SY5555 were examined against 33 clinical isolates. SY5555 has low MICs against Enterococcus faecalis and other Gram-positive cocci. 3. Pharmacokinetic studies Peak plasma concentrations of SY5555 was 1.15 micrograms/ml at a dose level of 4.9 mg/kg orally administered at fasting. Based on the above results and the broad spectrum of the anti-bacterial activities, SY5555 appears to be a promising antibiotics that is usable as a single agent for the primary therapy of respiratory tract infections, skin soft tissue infections and urinary tract infections in children.

Plasmodium vivax malaria infection diagnosed by indirect fluorescent antibody test.

We present the diagnostically challenging case of a 51-year-old Japanese male who visited Papua New Guinea for one month. Approximately a month after returning to Japan, he experienced a high fever. Malaria was suspected and he was admitted to Tsukuba University Hospital. Although the blood smear did not reveal the malarial parasite, a diagnosis of malaria was made using an indirect fluorescent antibody test (IFAT). The patient was treated and discharged but symptoms returned three months later. This time, the blood smear was positive for malarial parasites. IFAT was useful in this case for the early diagnosis of Plasmodium vivax and for ruling out infection by Plasmodium falciparum.

An infant with pseudohypoaldosteronism accompanied by cholelithiasis.

A case of an infant with very rare concurrence of pseudohypoaldosteronism and cholelithiasis is described. Aldosterone concentration was extremely high (64.6 nmol/l; normal 0.03-4.4 nmol/l) and fludrocortisone did not have favorable effects on hyperkalemia (7.4 mEq/l) and hyponatremia (124 mEq/l). A gallstone was found using ultrasonography at age 6 months, and it was extirpated surgically. The combination has not been reported previously. The study supports the previous hypothesis that cholelithiasis is found more often in infants with dehydration or electrolyte derangement.

[HLA tissue types in patients with acute tubulointerstitial nephritis accompanying uveitis].

Four cases of idiopathic acute tubulointerstitial nephritis (TIN) associated with uveitis (so-called TINU syndrome) were experienced between 1986 and 1990. Patients' ages ranged from 14 to 42 years old and three were female and one was male. All cases showed general symptoms, such as general malaise, anorexia and weight loss. All patients had initially TIN and became ill uveitis four to eight months after the onset of TIN. All cases had mild proteinuria, mild anemia, the lower serum levels of potassium, hyper gamma-globulinemia and the reduced glomerular filtration rate with the increased beta 2-microglobulin in urine and serum. All renal biopsies specimens showed mild edema and diffuse infiltration of inflammatory mononuclear cells in the interstitium without any glomerular or vascular abnormalities. Furthermore, numerous CD4 positive cells, CD8 positive cells and CD11c positive cells were seen in the interstitium. Of four patients, three cases were treated with both oral administration and eye drop of prednisolone (PSL), another one case was therapied with eye drop PSL only. In all cases TIN had good prognosis, but two patients had recurrences of uveitis. All patients underwent tissue typing for HLA-A, B, C and DR antigens. Three patients had identical HLA-Cw3 and all four cases revealed identical HLA-A24(9). These results suggest that immunological mechanism, especially cell-mediated, and HLA system may play an important role in the occurrence of TINU syndrome.

[Pneumatosis cystoides intestinalis following steroid treatment in a nephrotic syndrome patient: report of a case].

Pneumatosis cystoides intestinalis (PCI) is a relatively rare, benign condition characterized by multiple subserosal or submucosal gas-filled cysts in the bowel wall. The cause and incidence of PCI are uncertain, but the condition is most commonly diagnosed in patients who have chronic obstructive pulmonary disease, gastrointestinal disease (e.g. Crohn's disease, peptic ulcer disease) or collagen disease (e.g. scleroderma, systemic lupus erythematosus). The report of PCI associated with nephrotic syndrome has not be known as far as we have referred. We first experienced a case of PCI with nephrotic syndrome. The patient was a 28-year-old female who had developed nephrotic syndrome in 1977. Although she had been treated by steroid since the onset of the nephrotic syndrome, she was a frequent relapser. She was hospitalized to our hospital on November 1988, due to fourth relapse of the disease. The increasing dosage of steroid (60mg/day) improved general edema and decreased urinary protein, but abdominal pain and fullness occurred seven weeks after the admission. The abdominal radiographs showed air accumulations in the wall of the intestine (probably right sided colon) and retroperitoneum. That finding was confirmed by Barium enema and abdominal computed tomography. We diagnosed the lesions as PCI from the above findings, and high flow oxygen and hyperbaric oxygen therapy improved the symptom of PCI. The etiology of PCI in this case was thought to be mainly a long term steroid treatment.

[Acute renal failure due to rhabdomyolysis--clinical investigation on our 6 cases].

Six cases of acute renal failure (ARF) due to rhabdomyolysis were experienced between 1984 and 1989. Patients' ages ranged from 33 to 92 years old (average ages 61) and all were male. The causes of rhabdomyolysis were as follows: one crush syndrome, one acute arterial occlusion, one diabetic hyperosmolar nonketotic coma and three cases of malignant syndrome due to neuroleptica (mainly haloperidol). Underlying diseases included, one case of abdominal aneurysm, two cases of diabetes mellitus, two cases of schizophrenia and one case of reactive psychosis. Dehydration was considered as an important factor in the onset of rhabdomyolysis and ARF, because it was observed in 4 of the cases in this study. In all cases, the serum levels of potassium, phosphorus and uric acid as well as myoglobin and myogenic enzymes increased markedly. In patients with myoglobinuric ARF, severe metabolic acidosis and hypocalcemia in the oliguric phase and hypercalcemia in the diuretic phase were prominent. Muscle biopsy showed myolytic degeneration in 2 of 4 cases. Five cases were treated with hemodialysis and one case was managed conservatively. All 6 cases had relatively good prognosis. However, 3 cases with malignant syndrome showed outcomes more severe than in the other 3 cases without such syndrome.