Raising plasma phosphorus levels by phosphorus-enriched, bicarbonate-containing dialysate in hemodialysis patients

In 6 hemodialysis patients, enriching the "base concentrate" of a bicarbonate-containing dialysate-generating system with phosphorus succeeded in raising plasma phosphorus levels.     

A seven year experience of medical emergencies in the assessment unit.

AIMS: To analyse retrospectively all referrals to the assessment unit during a seven year period, to determine their sources and destination. METHODS: All referrals over the seven year period were analysed. Parental satisfaction was determined using a questionnaire in some of the patients. The disease pattern and the investigations performed were determined. The community nurses' working hours and type of work done were analysed. RESULTS AND CONCLUSIONS: A total of 43 496 children were seen in the unit. Over 65% of the patients were referred by the general practitioners; 13 517 (34.2%) of those referred to the unit were discharged directly from the unit. Respiratory disorders and gastrointestinal problems were commonly seen. The children discharged from the unit did not have significantly more tests done on them. Most of the parents whose children were discharged from the unit were happy to be managed at home. The community nurses attended many children who needed intravenous therapy and advice on fluid rehydration. Community nurses reduce admission to the wards by working with other members in the assessment unit. This in turn provides a single point of entry and bridges the gap between primary and secondary care. We suggest recommendations on setting up such a unit.     

Skeletal muscle involvement in infantile systemic hyalinosis

Infantile Systemic Hyalinosis is a rare autosomal recessive entity, characterised by deposition of hyaline material in skin and bone, often complicated by visceral involvement. The characteristic features are marked delay in motor milestones attributed to severe progressive flexion contractures of proximal and distal joints, and skin and mucosal hypertrophy and thickening, followed by failure to thrive. Pain secondary to osteolytic lesions is also a predominant feature. We report a patient with Infantile Systemic Hyalinosis, confirmed by the clinical findings, who also displayed clear evidence of proximal muscle weakness. Muscle biopsy revealed myopathic changes, which have not been reported previously. We suggest that skeletal muscle is involved in Infantile Systemic Hyalinosis and contributes to the characteristic poor outcome of these patients.     

Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.

OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.     

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer.

PURPOSE: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval. EXPERIMENTAL DESIGN: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles. RESULTS: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue. CONCLUSIONS: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit.     

Effects of transforming growth factor beta-1 and all-trans-retinoic acid on androgen-induced development of neonatal mouse bulbourethral glands in vitro

Effects of transforming growth factor beta-1 (TGF-beta1) and all-trans-retinoic acid (All-trans-RA) on development of bulbourethral glands (BUGs) of neonatal mice were investigated in vitro. BUGs from 0-day-old male mice were cultured for 6 days in serum-free, chemically defined medium containing transferrin and bovine serum albumin, supplemented with 5alpha-dihydrotestosterone (DHT; 10-8 M) and insulin (10 microg/mL) alone or in combination. Prior to culture, BUGs from 0-day-old mice consisted of a simple epithelial rudiment encapsulated by mesenchyme. Epithelial growth and ductal branching occurred in BUGs cultured in medium containing DHT and insulin or DHT alone, but epithelial branching did not occur in BUGs cultured in the presence of insulin alone. Addition of TGF-beta1 at concentrations of > 5 ng/mL (0.2 x 10-9 M) to medium containing both insulin and DHT, inhibited the expected increase in overall size of BUGs, epithelial area and ductal branching in a dose-dependent manner. TGF-beta1 also decreased [3H]-thymidine labelling indices of both epithelium and mesenchyme. TGF-beta1 at 10 ng/mL elicited these inhibitory effects on BUGs cultured in medium containing DHT alone. Addition of All-trans-RA (10-8 to 10-6 M) to the medium containing DHT plus insulin, or DHT alone did not exert significant effects on either overall size of BUGs or epithelial growth and ductal branching. All-trans-RA at 10-6 M decreased the [3H]-thymidine labelling index of mesenchyme of BUGs cultured in medium with DHT plus insulin or DHT alone, but did not decrease the [3H]-thymidine labelling index of epithelium. The present results indicate that TGF-beta1 inhibits androgen-induced epithelial and mesenchymal growth as well as epithelial morphogenesis of BUGs from neonatal mice. Such an inhibitory effect of TGF-beta1 is not mimicked by All-trans-RA at physiological concentrations.     

Anorectal avulsion: an unusual rectal injury

Traumatic injuries to the rectum although uncommon can result in virulent complications and even death. Diverting colostomy, presacral drainage, distal wash out and rectal repair, when feasible, have become the standard treatment for rectal injuries. We report an unusual case of rectal injury resulting in anorectal avulsion from skin and surrounding tissues.     

Rates of, and the factors affecting, cycle helmet use among secondary schoolchildren in East Sussex and Kent

Objectives—To assess the level of cycle helmet wearing among young people in two counties in the South East of England in 1994, and to identify the factors associated with helmet wearing.     

A missense mutation in the BRCA2 gene in three siblings with ovarian cancer.

Inherited susceptibility to ovarian cancer has been associated with germline defects at several loci. The major known ovarian cancer susceptibility gene is BRCA1 on chromosome 17q, which confers a risk of approximately 60% by the age of 70 years. Truncating mutations in BRCA2 on chromosome 13q also predispose to ovarian cancer, although they confer a lower risk than mutations in BRCA1. We have studied the molecular basis of ovarian cancer predisposition in a Finnish family with three affected sisters. Analysis of polymorphic markers provided evidence against linkage to BRCA1, but the sibship was consistent with linkage to BRCA2. Conformation-sensitive gel electrophoresis was used to screen the entire coding sequence of BRCA2. A G to A transition at nucleotide 8702 was observed, which is predicted to convert glycine 2901 to aspartate in the encoded protein. This sequence variant was not detected in 220 cancer-free Finnish control individuals, or in several hundred cancer families of many nationalities previously screened for BRCA2 mutations. Taken together with the fact that this amino acid residue and the surrounding region of BRCA2 is identical in mouse and chicken, the data suggest that this alteration is a disease-causing BRCA2 missense mutation. Previously published data indicate that the risks of breast and ovarian cancer conferred by BRCA2-truncating mutations varies with the position of the mutation in the gene. The missense mutation reported here suggests that the BRCA2 domain including and surrounding glycine 2901 may be more important in preventing neoplastic transformation in ovarian epithelium than in breast epithelium.