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Biomedical subjects

N M Brown

Publications and source records attributed to N M Brown.

At least 19 recordsLinked to original sources
PubMed1998

The pharmacokinetics and toxicity of once-daily tobramycin therapy in children with cystic fibrosis.

The pharmacokinetics and toxicity of once-daily intravenous tobramycin were studied prospectively in seven children with cystic fibrosis. Mean 1 h post-dose concentrations of 21.9 mg/L (S.D. 3.0) and 40.2 mg/L (S.D. 8.1) were achieved following tobramycin doses of 8 mg/kg and 15 mg/kg, respectively. The half-life (mean 2.3 h) was unchanged at the two doses, as were the total clearance and volume of distribution. All patients responded well to therapy. No nephrotoxicity occurred, but one patient showed transient ototoxicity.

Adolescent↗
PubMed1998

Genistein alters the ontogeny of mammary gland development and protects against chemically-induced mammary cancer in rats.

Breast cancer is the most common cancer in US females and is the second leading cause of cancer death among women. By contrast, Asian women consuming a traditional diet high in soy products have a relatively low incidence of breast cancer. Asians who emigrate to the United States and adopt a Western diet lose this protection. Soy-based diets are high in phytoestrogens, and one of these components is genistein. Using the dimethylbenz(a)anthracene (DMBA) mammary cancer rodent model, we have investigated the breast cancer protective potential of genistein. Our results demonstrate that neonatal and prepubertal genistein treatments altered the ontogeny of the mammary gland and rendered the adult animals less susceptible to chemically-induced mammary cancer. Neonatal genistein treatment did not significantly alter the rate of formation and persistence of DMBA-DNA adducts in the mammary gland. While high concentrations of genistein during the neonatal period caused adverse effects on ovarian follicular development, prepubertal genistein treatment did not appear to be toxic in either the female reproductive tract or the endocrine system.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis.

Fusidic acid is metabolized and excreted by the liver. It is generally assumed that renal impairment has no effect on serum concentrations. However, there are few data on the pharmacokinetics of fusidic acid in patients with chronic renal failure, particularly in those requiring dialysis. Seven patients with chronic renal failure on haemodialysis were given 500 mg sodium fusidate orally every 8 h for the 48 h between dialysis. Seven patients on continuous ambulatory peritoneal dialysis (CAPD) were given the same dosage regimen for seven doses. Fusidic acid concentrations were measured by HPLC. Accumulation was seen, and in 12 of the 14 patients steady-state pharmacokinetics had not been achieved by the third day. In haemodialysis patients, mean (range) Cmax values for the first dose were 13.0 (2.0-25.5) mg/L and for the sixth dose were 40.5 (10.1-69.9) mg/L. Serum concentrations were not reduced by haemodialysis. In CAPD patients mean Cmax values for the first dose were 16.0 (4.8-33.8) mg/L and for the seventh dose were 33.9 (23.4-61.9) mg/L. Fusidic acid concentrations of 1.0-2.3 mg/L were detected in peritoneal dialysis fluid in six of the seven CAPD patients. In both patient groups there was a tendency towards increased T(1/2) with repeated dosing. Protein-binding of fusidic acid in patient serum samples was 87.6-94.6%.

Adult↗
PubMed1997

The pharmacokinetics of once-daily oral 400 mg ofloxacin in patients with peritonitis complicating continuous ambulatory peritoneal dialysis.

Seven patients with end-stage renal disease requiring support by continuous ambulatory peritoneal dialysis received once-daily 400 mg oral ofloxacin for 7 days for the treatment of bacterial peritonitis. Serum and peritoneal dialysis fluid (PDF) were collected for assay throughout the course of the study and for 5 days thereafter. Ofloxacin, desmethyl ofloxacin and ofloxacin-N-oxide accumulated over the course of therapy and could still be detected in serum and PDF 5 days after the end of therapy. The mean elimination half-life of ofloxacin in serum was 32 +/- 7 h, desmethyl ofloxacin 45 +/- 26 h and for ofloxacin-N-oxide 44 +/- 15 h. The total mean recovery of ofloxacin and its metabolites from the PDF was 15.4%. This regimen results in serum and PDF concentrations likely to be effective for the treatment of infection for at least 10 days.

Aged↗
PubMed1997

Ciprofloxacin treatment of bacterial endocarditis involving prosthetic material after cardiac surgery.

Two children with cyanotic congenital heart disease and Gram negative bacterial infection of prosthetic material after cardiac surgery were treated successfully with oral ciprofloxacin, initially in combination with netilmicin. The use of oral ciprofloxacin allowed prolonged outpatient treatment to be given, avoiding the need for intravenous access and early repeat surgery.

Anti-Infective Agents↗
PubMed1997

Three cases of meningococcal pneumonia.

Three cases of pneumonia due to Neisseria meningitidis are described. In all three cases the organism was isolated only from blood cultures, but in the presence of good clinical and radiological evidence of pneumonia. The isolates belonged to three different serogroups: B type 2b, C, and Y. The cases illustrate the fact that N meningitidis can cause pneumonia and that culture of blood plays an important part in the diagnosis. Clinically there is nothing to differentiate meningococcal pneumonia from other causes of community acquired pneumonia. Predisposing factors include aspiration, immunosuppression, influenza, and adenovirus infections. When diagnosed, pneumonia due to N meningitidis should be notified and prophylaxis given as for meningitis or septicaemia.

Adult↗
PubMed1996

Pancreatic adenocarcinoma cell line, MDAPanc-28, with features of both acinar and ductal cells.

CONCLUSION: We established a new human pancreatic adenocarcinoma cell line, MDAPanc-28. Studies on this new line indicate that it expressed both acinar and ductal gene products suggesting that the patterns of gene expression in the pancreatic adenocarcinoma from which this cell line arose have features similar to those of the protodifferentiated cells hypothesized by Rutter and his colleagues for the developing pancreas (1,2). BACKGROUND: The cell line arose from a tumor that, like most pancreatic adenocarcinomas, was ductal on the basis of its histological appearance. METHODS: Once the cell line was established in culture, they were subjected to cytogenetic analysis and tested for their ability to grow in nude mice. RNA from the cells was analyzed by Northern blot analysis and PCR of reverse transcribed cDNA for the expression of both acinar and duct cell gene products. DNA was analyzed for the presence of mutated K-ras at codon 12. RESULTS: The cell line expressed trypsin and ribonuclease RNA, which are considered to be acinar cell markers, and carbonic anhydrase II (CAII), which is considered to be a duct-cell markers. The histological appearance of xenografts in nude mice was similar to that of the tumor from which the cell line was established. The chromosome number varied between 46 and 60.

Adenocarcinoma↗
PubMed1996

Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats.

Genistein, a component of soy, was administered to prepubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 microgram/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c.) on days 16, 18 and 20 post-partum. At day 50 post-partum all animals were exposed to 80 microgram dimethylbenz[a]anthracene (DMBA) per g body wt. Animals treated prepubertally with genistein as compared to DMSO had reduced incidence and significantly fewer adenocarcinomas per animal. Mammary whole mount analysis showed that prepubertal genistein treatment resulted in mammary glands of 50-day-old rats developing fewer terminal end buds and more lobules II. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated prepubertally with genistein had significantly fewer cells in S-phase of the cell cycle. Serum genistein concentrations in 21- and 50-day-old females following prepubertal genistein treatment were 4.2 +/- 0.6 micromol and 102 +/- 30 nM, respectively. Animals treated prepubertally with genistein as compared to vehicle spent more time in the estrus phase of the estrus cycle, although all animals did cycle. In 50-day-old females, circulating estradiol-17 beta and progesterone concentrations were not significantly altered by the prepubertal genistein treatment. Oocyte/follicle counts and numbers of atretic follicles and corpora lutea were not significantly different between the genistein- and vehicle-treated animals. We conclude that genistein treatment during the prepubertal period can suppress the development of chemically-induced mammary cancer without significant toxicity to the endocrine/reproductive system.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Mycobacterial contamination of fibreoptic bronchoscopes.

Because of the increasing numbers of immunosuppressed patients and the general resurgence of mycobacterial infection, diagnostic bronchoalveolar lavage (BAL) using a fibreoptic bronchoscope is an important and frequent procedure. A contaminated bronchoscope may introduce spurious mycobacteria into specimens causing diagnostic confusion, infect the patient with mycobacteria, or be a vehicle for cross-infection. Bronchoscopes are difficult to disinfect adequately if they are not properly cleaned (which may include stripping down channel valves) or are damaged. Bronchoscope washers have also contributed to the problem when glutaraldehyde becomes too dilute or they become heavily contaminated with environmental mycobacteria. Future solutions to prevent contamination include the regular maintenance of bronchoscopes and washers, having adequate cleaning and disinfection protocols and ensuring that they are adhered to, improving bronchoscope and washer design, and developing alternative disinfectants or new ways of using current ones. All these will probably have considerable cost implications for hospitals.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Genistein suppresses mammary cancer in rats.

Female Sprague-Dawley CD rats were injected s.c. with 5 mg genistein, a soy phytoestrogen, or 20 microliters of the vehicle, dimethylsulfoxide (DMSO), on days 2,4 and 6 postpartum. At day 50, they were exposed to 80 micrograms dimethylbenz[a]anthracene (DMBA)/g body wt. Animals treated neonatally with genistein as compared to DMSO had increased latency and reduced incidence and multiplicity of DMBA-induced mammary adenocarcinomas. Mammary whole mount analysis showed that 50 day old female rats treated neonatally with genistein had fewer terminal end buds. Cell proliferation studies revealed that 50 day old genistein-treated rats had lower percentages and total numbers of cells in the S-phase of the cell cycle in terminal end buds, terminal ducts, lobules I and lobules II. In genistein-treated as compared to vehicle-treated female rats, vaginal openings occurred earlier, the estrus cycle was disrupted and the uterine-ovarian weights were smaller. In 50 day old genistein-treated females there were atretic antral follicles, fewer corpora lutea, and lower circulating progesterone but not estradiol-17 beta concentrations. In 21 day old rats treated neonatally with genistein, mammary glands were larger and there were more terminal end buds and terminal ducts, and more proliferative activity in all terminal ductals structures. It appears that neonatal genistein-treatment exerted its chemoprevention action by acting directly to enhance maturation of terminal ductal structures and by altering the endocrine system to reduce cell proliferation in the mammary gland.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Derivation of androgen-independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells.

A model of human prostate cancer was established to study cellular interaction between prostate cancer and bone stroma in vivo. In this model, subcutaneous co-injection of 2 non-tumorigenic human cell lines--LNCaP, a prostate cancer cell line, and MS, a bone stromal cell-line--into intact adult male mice resulted in formation of carcinomas that secreted prostate-specific antigen (PSA), a clinically useful human serum prostate cancer marker. In castrated hosts, upon cellular interaction with bone fibroblasts, we observed the progression of these tumors from an androgen-dependent (AD) to an androgen-independent state (AI). We derived 4 LNCaP cell sublines from the chimeric LNCaP/MS tumors: the M subline from intact hosts and the C4, C4-2 and C5 sublines from castrated hosts. The LNCaP sublines had chromosomal markers similar to those of the parental LNCaP cells and distinctly different from those of the MS bone stromal cell line. Although the parental and derived cell lines expressed similar steady-state levels of ornithine decarboxylase transcript, the sublines expressed 5- to 10-fold higher basal steady-state levels of PSA transcript than did the parental LNCaP cell line. The LNCaP sublines formed 13- to 26-fold more soft-agar colonies than the parental LNCaP cell line. The sublines became tumorigenic, yielding an incidence of tumors in intact athymic mice of 7-75%. The LNCaP sublines C4 and C5 (but not the parental and M cell line) formed tumors in castrated hosts when co-injected with bone fibroblasts. A second-generation LNCaP subline, C4-2, was derived from a chimeric tumor induced by co-inoculating castrated mouse with C4 cells and MS cells. We found that C4-2 subline was tumorigenic when inoculated into castrated hosts in the absence of inductive fibroblasts. Moreover, C4-2 was the only subline capable of forming soft-agar colonies when cultured in serum-free medium. In comparison with the parental LNCaP cells, the C4-2 subline expressed lower steady-state levels of androgen receptor (AR) protein and mRNA transcript and lost its androgen responsiveness in vitro. Our results suggest that certain genetic traits of prostate cancer cells may be selected or altered through an "adaptive" mechanism that involves cellular interaction with the bone stromal cells.

Animals↗
PubMed1994

Outbreak of infection with penicillin-resistant Streptococcus pneumoniae in a hospital for the elderly.

A penicillin- and trimethoprim-resistant strain of Streptococcus pneumoniae serotype 9 was isolated from sputum, pleural effusion fluid or blood collected from 10 patients with lower respiratory tract infection on three separate wards in a hospital for the elderly over a 3-week period in February, 1993. Eight of the 10 infections were hospital-acquired. Following the cessation of new admissions to wards with infected patients, and a change of antibiotic policy for the treatment of lower respiratory tract infections, there were no new isolates. The outbreak probably resulted from failure to promptly identify, and manage appropriately infection in the index case.

Aged↗
PubMed1994

The pharmacokinetics of once daily gentamicin in neutropenic adults with haematological malignancy.

Seven febrile neutropenic adults with normal renal function were treated with intravenous gentamicin 4.5 mg/kg once a day in combination with azlocillin. Gentamicin serum concentrations 1, 2, 4, 8, and 24 h after a 30 min infusion were 10.9 +/- 0.6, 7.1 +/- 0.4, 4.2 +/- 0.2, 1.8 +/- 0.1 and 0.16 +/- 0.003 mg/L respectively. The pharmacokinetics were best described by a triphasic plot including a distribution phase (about 1/2 h) and two elimination phases, an early and late.

Adolescent↗