[Antibiotics--TAZ/PIPC, synercid, linezolid, everninomicin].

The increasing resistance among Gram-positive cocci have been accompanied by their increasing frequency as cause of severe infection. Thus new antimicrobial agents, TAZ/PIPC, synercid and linezolid, are in various stages of development. TAZ/PIPC, a combination drug of a new beta-lactamase inhibitor tazobactam and piperacillin at ratio in 1 to 4 has a broad spectrum of antimicrobial activity. Evidence from randomized clinical trials in adults in Japan has shown that TAZ/PIPC is superior to PIPC as a drug for complicated urinary tract infection. Synercid is a streptogramin antibiotic. The spectrum of activity of synercid is similar to vancomycin. Furthermore, most of E. faecium were susceptible. The efficacy of synercid in clinical trials in patients infected with VREF was 65-70%. Linezolid is a member of the oxazolidinones. The antimicrobial spectrum of linezolid is similar to that of vancomycin. In the US, patients with significant infection caused by resistant Gram-positive organisms(mostly VREF) were treated with linezolid. The efficacy of linezolid was about 75%. The clinical trials for everninomicin had been discontinued because of insufficient clinical data supporting its efficacy and safety.

Renal cell carcinoma in acquired cystic kidney disease: volume growth rate determined by helical computed tomography.

The aim of this study is to determine the growth rate and behavior of renal cell carcinoma in chronic hemodialysis patients with acquired cystic kidney disease (ACKD). Renal cell carcinomas in 17 hemodialysis patients (mean age, 52 +/- 11 years; mean hemodialysis duration, 7.2 +/- 3.3 years) with ACKD were examined with helical computed tomography (CT) for 0.5 to 6.0 years (mean, 2.1 +/- 1.9 years). The 17 renal cell carcinomas were histologically proven and graded after nephrectomy (16 patients) or autopsy (1 patient). Tumor volume was estimated by counting the number of pixels in the tumor and a 1-cm(2) area on helical computed tomographic scan using a personal computer. Estimated volume growth rates and doubling times of the carcinoma were correlated with histological grades. Fifteen of the 17 neoplasms (88%) were less than 3 cm in diameter at initial CT. The overall volume growth rate was 0.07 to 17.34 cm(3)/y (mean, 4.14 +/- 5.66 cm(3)/y), and the estimated volume-doubling time was 0. 08 to 23.31 years (mean, 5.09 +/- 6.99 years). The mean growth rate of the 3 grade 3 carcinomas was 6.01 +/- 4.50 cm(3)/y (range, 0.88 to 9.28 cm(3)/y), which was significantly greater than that of the 9 grade 1 carcinomas (0.40 +/- 0.40 cm(3)/y; range, 0.09 to 1.37 cm(3)/y) or the 5 grade 2 tumors (0.79 +/- 0.74 cm(3)/y; range, 0.12 to 2.00 cm(3)/y). Eleven of the 17 carcinomas (65%) had more than a 1-year volume-doubling time. The 3 grade 3 neoplasms and 1 of the grade 2 lesions had less than a 0.5-year doubling time.

Need for an incentive-based reimbursement policy toward quality care for dialysis patient management.

BACKGROUND: In view of the growing dialysis population and the increasing reimbursement cost in the industrialized countries, a critical evaluation of the dialysis economy is warranted. METHODS: Data for the reimbursement and dialysis patients' statistics were collected from the National Medical Care Expenditure (NMCE), 1979-1996, which was published by the Japanese government, and the article "An overview of regular dialysis treatment in Japan," 1979-1998, by the Japanese Society for Dialysis Therapy, as well as unpublished data from the Yokohama Dai-ichi Hospital and 10 affiliated urban dialysis centers. RESULTS: From 1979 to 1996, the dialysis population increased 5.2 times and the NMCE increased 2.5 times, whereas the end-stage renal disease (ESRD) payment increased only 1.8 times. Because of a drastic reduction in the dialyzer cost and the dialysis-related technical fee, both the percentage of ESRD-related payment within NMCE and ESRD payment per capita per year decreased from 5.4 to 4.1% and from 16.3 million yen to 5.6 million yen, respectively. Despite this drastic cost reduction, the patient survival and quality of life determined by the social rehabilitation rate did not decline. CONCLUSION: The Japanese health insurance policy for dialysis management achieved a successful cost cut during the 1979-1996 period by using an incentive-based payment system toward quality care. However, the forthcoming further exponential increase in the dialysis population may put the dialysis economy and hence dialysis care quality in jeopardy. Effort must be made to reduce the ESRD-related cost through prevention of the progression of kidney diseases, propagation of renal transplantation, and internationalization of continuous ambulatory peritoneal dialysis and erythropoietin cost. A reduction in dialysis reimbursement, if necessary, must be achieved through an incentive-based system toward quality patient care.

Hyperfunctional parathyroid glands with 99mTc-MIBI scan: semiquantitative analysis correlated with histologic findings.

UNLABELLED: The purpose of this study was to correlate the semiquantitative analysis of 99mTc-methoxyisobutyl isonitrile (MIBI) scan with histologic findings of hyperfunctional parathyroid glands. METHODS: Early and delayed cervical images of MIBI scans were reviewed in 31 patients who eventually underwent parathyroidectomies because of biochemically suspected hyperparathyroidism ([HPT], primary, n = 13; secondary, n = 18). The sensitivity of a scan for localizing the diseased glands was determined by comparing scan findings with pathologic findings, which were considered the gold standard. The average ratio of parathyroid-to-thyroid (P/T) count was compared between glands with large and small areas of whole gland, chief cell, oxyphil cell or cellular components. The mean areas of whole gland, chief cells and oxyphil cells were also compared between glands detected by MIBI scan and those that the scan missed. RESULTS: There were 99 resected lesions, including 9 parathyroid adenomas and 61 hyperplastic parathyroids. The sensitivity for localizing the diseased glands in patients with primary HPT (91%) was higher than that in patients with secondary HPT (83%). Significantly greater average P/T counts ratio on both early and delayed images was observed in the diseased glands with greater areas of whole gland, chief cells, oxyphil cells or cellular components. Fifty-nine MIBI-positive glands had significantly greater average areas of whole gland (P < 0.001) and chief cell (P = 0.002) than did 11 MIBI-negative glands. CONCLUSION: The uptake of MIBI in hyperfunctional parathyroid is dependent on gland size and the amount of cellular components, chief cells and oxyphil cells. However, the amount of oxyphil cells does not clearly affect the results of MIBI parathyroid scintigraphy, because it is small in most hyperfunctional glands.

Using helical CT to evaluate renal cell carcinoma in patients undergoing hemodialysis: value of early enhanced images.

OBJECTIVE: The purpose of this study was to evaluate early and delayed enhanced helical CT for revealing renal cell carcinoma in patients undergoing hemodialysis. MATERIALS AND METHODS: Over the course of 3 years, 630 chronic hemodialysis patients underwent early and delayed contrast-enhanced and unenhanced helical CT to detect renal cell carcinoma. Retrospective review showed that 23 of these patients later underwent either unilateral or bilateral nephrectomy. Two radiologists, unaware of the pathology results, independently reviewed these 23 examinations. The sensitivity and specificity of each early and delayed scan for revealing neoplasms were determined using pathology as the gold standard. The mean attenuation values of the neoplasms and parenchymas of end-stage kidneys on both early and delayed enhanced images were also compared. RESULTS: Helical CT revealed 225 lesions, 24 of which were found to be renal cell carcinomas at pathology. Delayed enhanced helical CT failed to detect one papillary carcinoma in an end-stage kidney with acquired cysts. Three nonpapillary carcinomas were not detected on delayed scans, and one was missed on an early scan of a patient without acquired cysts. The sensitivity and specificity of early enhanced CT for revealing renal cell carcinoma were 96% and 95%, respectively. In contrast, delayed enhanced CT achieved a sensitivity of 83% and a specificity of 94%. A significant difference in mean attenuation values between carcinomas and renal parenchymas was observed on the images with early enhancement but not on those with delayed enhancement (p < .0001). CONCLUSION: Early enhanced helical CT is superior to delayed enhanced helical CT for revealing renal cell carcinoma in end-stage kidneys.

Cloning of capsulin, a basic helix-loop-helix factor expressed in progenitor cells of the pericardium and the coronary arteries.

The basic helix-loop-helix (bHLH) class of transcription factors have been linked to a variety of cellular differentiation processes, including myogenesis, neurogenesis and hematopoiesis. Here we report the cloning of a new member of this family of factors, capsulin. Capsulin was shown to be expressed as early as 9.5 days of mouse development, with expression in mesodermal cells that are progenitors of the epicardium and the coronary arteries. At later stages of development, expression is seen in mesenchymal cells that are closely associated with the epithelium of the developing lung, gut and kidney. In the proepicardial organ, and in the organs where it is expressed in later development, capsulin is expressed in cells that give will give rise to smooth muscle. Given the likely expression of capsulin in smooth muscle cell progenitors, and significant sequence similarity through the bHLH domain, capsulin may be a functional ortholog of a Drosophila gene that is expressed in cells that give rise to the longitudinal visceral muscle. Capsulin alone or in combination with other bHLH proteins, was shown to function as a transcription factor by its ability to transactivate both a synthetic and a native promoter, each of which contains multiple E-boxes. These studies extend the growing family of bHLH factors that are expressed in the early mesoderm, and suggest that capsulin may have a functional role in development of the coronary vasculature and organs containing epithelial lined tubular structures.

Percutaneous autotransplantation of parathyroid tissue into the forearm muscles.

We developed a simple and easy nonsurgical percutaneous method for autografting parathyroid tissue into the forearm muscles. This method was applied to 30 patients suffering from secondary hyperparathyroidism who were then refractory to medical treatment. The operative results were then compared with 16 patients who underwent treatment using Wells' method. The graft "take," judged by a significant intact parathyroid hormone (PTH) ratio (> 1.5) between grafted and nongrafted arm vein blood, was 82% for the percutaneous method group and 75% for the Wells' method group, respectively. The percentage of recurrent hyperparathyroidism necessitating a subtotal removal of the autograft was equal in the two groups. No complications were noted for either method. Wells' method can thus be replaced by this simple and easy nonoperative method.

Can recovered protein from the CAPD patient's own dialysis effluent substitute for dextrose?

Albumin has been evaluated as an osmotic agent for peritoneal dialysis as being physiologically safe and having modest colloidal osmotic pressure. However its extremely high cost inhibits clinical applications, and hypoalbuminemia is often seen in continuous ambulatory peritoneal dialysis (CAPD) patients, especially those with high peritoneal equilibration test (PET) values and who lose a large quantity of albumin everyday. This study aims at recovering protein from CAPD effluent and reusing it safely at reasonable cost as a substitute for dextrose. The dialysis effluent was collected and concentrated with a semipermeable membrane. Uremic toxins and low-molecular-weight solutes were removed by repeated filtration and water dilution. The concentrate was acidified with hydrochloric acid down to pH 2, thence de-acidified with water dialysis up to pH 5. At this point, the isoelectric point of albumin, at which precipitate was deposited, the precipitate was separated from the supernatant and re-dissolved into electrolyte solution. The acidified concentrate exhaled an unpleasant odor, like that of decayed food. The precipitate solution, however, did not smell at all. The initial ultrafiltration rate of the recovered protein solution was measured and compared with that of dextrose and dextran by using a high-sensitivity differential manometer, one end of which was connected with the test solution cell, and the other with the serum cell. The ends were separated by a semipermeable membrane. The recovered protein solution at 20 g/dL concentration was almost equivalent in initial ultrafiltration rate to the 2.0 g/dL dextrose solution and to 20 g/dL dextran (MW: 75,000 dalton) solution.

Bilateral chromophobe cell renal carcinoma in tuberous sclerosis complex.

We report on a patient with tuberous sclerosis complex and polycystic kidney disease who developed bilateral chromophobe cell renal carcinoma. We discuss the tuberous sclerosis complex, associated bilateral renal cell carcinoma, polycystic kidney disease and chromophobe cell renal carcinoma; a recently established subtype with a rather favorable prognosis. In a patient with tuberous sclerosis complex and multiple space-occupying lesions, a diagnosis of angiomyolipoma should be considered first but bilateral and/or multifocal renal cell carcinoma is a likely diagnosis.

Genomic organization and chromosomal localization of the gene TCF15 encoding the early mesodermal basic helix-loop-helix factor bHLH-EC2.

bHLH-EC2 is a recently characterized member of a growing family of basic helix-loop-helix transcription factors. This family includes bHLH factors such as twist, which appear to be primarily involved in early mesodermal differentiation, and bHLH factors such as TAL-1, which have been characterized through their association with chromosomal breakpoints associated with T-cell leukemias. To provide for studies aimed at understanding the genetic regulation of bHLH-EC2, we have characterized the organization of this gene and conducted preliminary studies of the transcriptional activity of the upstream promoter region. The mouse bHLH-EC2 gene was found to consist of two exons separated by a 5-kb intron, an organization pattern similar to the mouse twist gene. The transcription initiation site was identified by RNase protection assay and primer extension analysis. Linked promoter-reporter gene transfection experiments in cultured cells indicated that while the identified upstream sequence can function to promote transcription, it does not function in a cell-specific fashion. To investigate the possible association of bHLH-EC2 with hematological malignancy, the chromosomal location of this gene in the human was mapped by fluorescence in situ hybridization and assigned to chromosome band 20p13.

Mutations of the p53 gene in myelodysplastic syndrome and overt leukemia.

We analysed p53 mutations in 24 patients with myelodysplastic syndrome (MDS) and overt acute myeloid leukaemia after a period of MDS, using polymerase chain reaction-single strand conformation polymorphism analysis. In exons 5 to 8, mobility shifts were detected in five of the 24 patients. Sequence analysis was subsequently performed, and four missense mutations (16.7%) and one silent nucleotide substitution were identified. Patients harbouring mutations were characterized as having advanced disease. Loss of the wild type allele was observed in three of the four patients with missense mutations. No mobility shifts of the N-ras or FMS gene were detected in these four patients. We next analysed the correlation of the p53 mutations with the progression of MDS in three patients. The mutation was accompanied by the progression in two of the three patients. These findings suggest that mutations of the p53 gene are associated with progression in some cases of MDS, while being compatible with stable disease or clonal evolution in others.

Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites.

Basic helix-loop-helix (bHLH) heterodimer protein complexes regulate transcription of genes during the processes of differentiation and development. To study the molecular basis of early mesodermal differentiation, we sought to identify bHLH proteins from cells of mesodermal origin. By using an interaction cloning strategy with a radiolabled recombinant bHLH protein, E12, a clone encoding a potential heterodimer partner was isolated from an endothelial cell library. This gene (bHLH-EC2) is most homologous to Twist but shares similarity within the bHLH domain with TAL1 and other members of this family. bHLH-EC2 is expressed in cultured endothelial cells and in embryonic stem cell, erythroleukemia, and muscle cell lines in a differentiation-dependent manner. In situ hybridization studies of mouse embryos reveal that bHLH-EC2 is expressed throughout the primitive mesoderm as early as 7.5 days postcoitum. Expression then becomes restricted to the paraxial mesoderm and to the dermamyotome of the developing somite. Expression of bHLH-EC2 in cells destined to become myoblasts thus predates expression of myogenic bHLH factors. bHLH-EC2 is expressed in early endothelial and hematopoietic cells in vivo, as shown by RNA studies of embryonic yolk sac and cultured cells derived from yolk sac explants. These findings suggest that bHLH-EC2 plays a role in the development of multiple cell types derived from the primitive mesoderm.

[Is there any correlation between urea kinetics and the clinical outcomes in CAPD patients?].

Urea kinetic modeling was applied to 19 CAPD patients followed in our outpatient clinics. Serum beta 2-microglobulin was also measured as a marker of large molecular weight substances. Clinical conditions of patients were assessed by both doctors and patients. Patient's assessment were done by the questionnaire. Indices of urea kinetics (KT/V, PCR) and biochemical parameters were compared between well-treated and not well-treated patients judging from patient's and doctor's assessment scores. The rate of peritonitis was significantly higher in the latter group. None of the parameters were different between 2 groups except for serum albumin. There was a significant correlation between serum concentration of albumin and doctor's assessment score (gamma = 0.52). In conclusion, urea kinetic parameters is not a good indicator for adequacy of dialysis in our CAPD population. Serum albumin seems to be one of the indices for adequate dialysis. However, clinical symptoms and signs are more valuable than biochemical parameters for the assessment of adequacy of dialysis.

[Ectopic production of human chorionic gonadotropin by poorly differentiated transitional cell carcinoma of the renal pelvis].

Herein we report a case of ectopic production of hCG by poorly differentiated transitional cell tumor of the renal pelvis. The patient was a 55-year-old male who had been diagnosed at another hospital as having giant hydronephrosis and renal stones and was referred to our hospital. The plain abdominal CT showed a low-density mass at the lower pole of the right kidney. His serum hCG level was as high as 120 mIU/ml. Transperitoneal nephrectomy was performed on July 7, 1987. Histopathological examinations showed the presence of squamous metaplasia within a high-grade transitional cell carcinoma, and immunohistochemical studies revealed the presence of chorionic gonadotropin in some giant cells. Two courses of combination chemotherapy with methotrexate, vinblastine, adriamycin and cisplatin (M-VAC regimen) were given to him from the third week after the operation. However, he died of debility with distant metastasis 6 months after the operation. As far as we know, this is the third reported case in Japan.