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Biomedical subjects

R Metcalf

Publications and source records attributed to R Metcalf.

17 recordsLinked to original sources
PubMed1998

A multifaceted study of human papillomavirus and prostate carcinoma.

BACKGROUND: The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS: The cases were comprised of 51 African-American (men at high risk for prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/ GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be 1 HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS: All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS: The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men.

Aged↗
PubMed1997

Caval thrombectomy for severe staphylococcal osteomyelitis.

Two children are presented in whom thrombosis of the inferior vena cava developed in association with an acute staphylococcal osteomyelitis. One case involved the left femur and the other the left ileum. Both children had diffuse bilateral staphylococcal pneumonia from presumed septic embolization. There were close similarities between their illness and management, except that the child who survived underwent a caval thrombectomy in the acute phase of her illness. It is hypothesized that the thrombectomy played an important role in her recovery.

Acute Disease↗
PubMed1997

The use of breastmilk in a neonatal unit and its relationship to protein and energy intake and growth.

OBJECTIVE: A nutritional audit was performed to determine whether current feeding regimes were achieving nutritional goals and to evaluate the use of breastmilk (BM) in a neonatal unit (NNU). METHODS: All fluid consumed or infused daily was documented with daily weight and weekly length and head circumference measurements in 90 preterm infants (gestational age 30.1 +/- 2.6 weeks) while in the NNU for 60 +/- 27 days. Daily protein and energy intakes were calculated using values for South Australian preterm BM. RESULTS: Parenteral nutrition provided 85% of the daily energy in week 1 falling to 11% by week 6. Ninety per cent of infants received some of their mother's BM and 62% were discharged at least partially breastfed. Protein and energy intakes were 1.03 +/- 0.35 g and 55 +/- 10 kcal/kg/day in week 1, increasing to 2.52 +/- 0.60 g and 109 +/- 15 kcal/kg per day by week 4. Protein intake correlated with weight gain (r2 = 0.39). Weight gain was 14.0 +/- 2.0 g/kg per day and z-scores for weight declined from -0.25 on admission to -1.22 on discharge, P < 0.0001. When infants were divided into two groups comprising those who received BM or formula as their predominant enteral feed, growth and protein intake (but not energy intake) were lower in the BM-fed infants. However, enteral feeds were tolerated earlier and more quickly in those infants receiving predominantly BM. CONCLUSION: Energy requirements were readily met using current feeding regimes for preterm infants but protein intakes were marginal. Mothers of preterm infants had similar breastfeeding rates to mothers of term infants in South Australia. The long-term effects of the lower growth rates of preterm infants fed predominantly BM compared with those fed predominantly formula are unknown and need be balanced against the benefits of BM.

Analysis of Variance↗
PubMed1994

P53 gene mutations in women with breast cancer and a previous history of benign breast disease.

Mutations of the p53 tumour suppressor gene are the most common genetic lesions in human cancers and have been reported in breast cancer as part of the Li-Fraumeni syndrome. In the present study, we determined frequencies and types of the p53 mutations in breast cancer tissues in women with a history of benign breast disease (BBD) identified in Florence, Italy, with (n = 6) or without (n = 10) a family history of breast cancer. Among the cases with a family history of breast cancer and BBD, 2 out of 6 had p53 gene mutations in cancer samples. 1 patient had a mutation at codon 248 and the other had double mutations at codons 243 and 241. In these cases, the p53 gene was also analysed in the tissue samples from previous BBD lesions; however, no mutations were observed (0 out of 6). These results suggest that the p53 mutations occur during advanced stages of tumour progression. In sporadic breast cancer cases with a history of BBD, p53 point mutations were observed of tumour progression. In sporadic breast cancer cases with a history of BBD, p53 point mutations were observed in four samples (4 out of 10). Two of these mutations turned out to be silent changes and one of the samples showed triple mutations at amino acid positions 267, 277 and 296. No p53 gene mutations were found in the breast tumour tissues of 10 additional women from the same area with a family history of breast cancer, but no previous BBD (0 out of 10). Family history of breast cancer does not appear to affect the frequency of p53 mutations in women with a previous history of BBD.

Base Sequence↗
PubMed1994

How appropriate are commercially available human milk fortifiers?

A preliminary investigation was made into the effectiveness of two breastmilk fortifiers on the Australian market (FM-85 [Nestlé, Vevey, Switzerland] and Enfamil Human Milk Fortifier [EHMF; Mead Johnson, Evansville, IN, USA]). Infants < 1800 g and < 34 weeks gestation at birth, who were receiving breast milk, were randomized to receive either of the fortifiers (n = 14 for FM-85, n = 10 for EHMF), until a weight of 2 kg was reached. Infants not receiving breast milk (n = 9) were fed a preterm formula (Prenan, Nestlé). The two fortifier groups were similar in most parameters examined: (i) weight gain (17.9 +/- 3.0 vs 17.4 +/- 3.5 g/kg per day); (ii) head circumference growth (1.02 +/- 0.28 vs 1.03 +/- 0.25 cm/week); (iii) arm muscle area growth (32.6 +/- 20.0 vs 33.5 +/- 13.7 mm2/week); (iv) arm fat area growth (14.0 +/- 8.7 mm2/week); (v) plasma calcium (2.52 +/- 0.08 vs 2.58 +/- 0.15 mmol/L); (vi) plasma phosphate (2.02 +/- 0.21 vs 2.13 +/- 0.32 mmol/L); (vii) plasma copper (5.28 +/- 2.83 vs 5.66 +/- 3.07 mumol/L); and (vii) plasma zinc (13.3 +/- 5.5 vs 15.8 +/- 9.2 mumol/L). The FM-85 group had a higher alkaline phosphatase level (355 +/- 110 vs 231 +/- 70 iu/L) than the EHMF group; however, no values were outside the normal range. The Prenan group had a higher rate of weight gain (23.6 +/- 3.3 g/kg per day) and higher arm fat area growth rate (25.2 +/- 7.6 mm2/week) than the fortifier groups while all other parameters were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Invasive tumors derived from xenotransplanted, immortalized human cells after in vivo exposure to chemical carcinogens.

Several chemicals that are found in cigarette smoke or diesel oil engine exhausts, such as benzo[a]pyrene (B[a]P) and 1,6-dinitropyrene (DNP) are carcinogenic in experimental animal models. In the present study, we have exposed in vivo the xenotransplanted immortalized human bronchial epithelial cell line BEAS-2B to the ultimate carcinogen of B[a]P, benzo[a]pyrene diolepoxide (BPDE), to DNP or to the benzo[e]pyrene, a less active compound that has tumor-promoting abilities in mouse skin carcinogenesis bioassays. All three compounds were administered using slow-release beeswax pellets. After a 6 month exposure, BPDE produced two tumors in seven transplants, four tumors were seen in 10 transplants treated with DNP and one tumor was observed in five tracheal grafts exposed to B[a]P. All the neoplasms were well-differentiated invasive adenocarcinomas. Tracheal transplants exposed to beeswax without carcinogen did not show any evidence of neoplastic growth, and their luminal surfaces were lined by a single or double layer of cuboidal cells. All lines derived from the adenocarcinomas showed increased in vitro resistance to serum-induced terminal differentiation, gelatinolytic activity, s.c. tumorigenicity and invasive growth in an in vivo assay. When these cell lines were compared with previously described tumor cell lines derived from xenotransplants exposed to cigarette smoke condensate, it became clear that the latter exhibited a more aggressive invasive behavior. Nevertheless treatment with the three chemicals gave rise to tumor cell lines that exhibited a similar invasive behavior in vivo, and were able to penetrate early into the wall of the tracheal transplants in which they were seeded. These data indicate that this system based on xenotransplanted bronchial epithelial cells is a very relevant model to identify human carcinogens and to study mechanisms of bronchogenic cancer pathogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

A tobacco-specific N-nitrosamine or cigarette smoke condensate causes neoplastic transformation of xenotransplanted human bronchial epithelial cells.

Using a xenotransplantation system in which immortalized nontumorigenic human bronchial epithelial cells (BEAS-2B cells) are grown in deepithelialized rat tracheas that are subcutaneously transplanted into athymic nude mice, we exposed BEAS-2B cells either to cigarette smoke condensate or to the tobacco-specific N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1- butanone. After 6 mo the carcinogen-exposed BEAS-2B cells were neoplastically transformed to invasive adenocarcinomas. Cell lines obtained from xenografts exposed in vivo to chemicals exhibited several features typical of malignant lung cancer cells, such as increased in vivo invasiveness that correlated well with enhanced type IV collagenolytic activity, resistance to serum-induced growth inhibition, and increased expression of transforming growth factor alpha and its cellular-membrane receptor. Invasiveness, similar to that seen after exposure to phorbol esters, was also detected after in vitro exposure of BEAS-2B cells to cigarette smoke condensate. Collectively, these data indicate that cigarette smoke condensate and N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone induce in vivo phenotypic changes in BEAS-2B cells similar to the progressive changes that occur during human lung carcinogenesis.

Animals↗
PubMed1990

Mesalazine: an overview of key preclinical studies.

Studies were undertaken to evaluate the clinical relevance of toxicologic assessments of mesalazine and to establish mesalazine pharamcokinetics. In the toxicology studies groups of rats and dogs received various doses of mesalazine, ranging from 40 to 320 mg/kg of body weight, for 6 or 12 months. Evidence of renal papillary necrosis was found at 60 or 100 mg/kg in dogs and 320 mg/kg in rats. Data are presented to show that drug absorption after the clinical doses of mesalazine given to human patients is much lower than after the potentially nephrotoxic doses given to experimental animals. In the pharmacokinetic studies plasma from rats and dogs given various doses of mesalazine was analysed for mesalazine and its major metabolites. The results demonstrated that mesalazine in pharmaceutic preparations is not likely to present a nephrotoxic risk to patients, given the low systemic exposure achieved. After 12 months of mesalazine administration to dogs, many showed an ocular condition diagnosed as keratoconjunctivitis sicca. Experimental and epidemiologic evidence demonstrates that this condition is peculiar to dogs, and there are no reports of untoward ocular effects in patients receiving long-term therapy with mesalazine.

Administration, Oral↗
PubMed1988

The metabolism of 5-(4-acetamidophenyl)pyrazin-2(1H)-one in rat, dog and cynomolgus monkey.

1. The metabolism and disposition of 14C-acetamidophenyl pyrazinone has been studied in rat, dog and cynomolgus monkey. The compound was well absorbed and rapidly excreted in urine and faeces by all three species. 2. Distribution of 14C-pyrazinone was rapid and extensive with the exception of the central nervous system where concentrations were at, or below, the limit of detection. 3. Whereas, in in vitro studies, metabolites (but not the parent compound) weakly inhibited some activities of the cytochrome P-450 system, there was evidence from in vivo studies in the rat that the compound and/or its metabolite(s) are weak selective inducers of cytochrome P-450. 4. Metabolite patterns were similar in all three species. The major route of metabolism was glucuronidation at the oxygen of the pyrazinone ring. Other metabolites originated from metabolism by gut microflora with subsequent hepatic metabolism.

Animals↗
PubMed1987

Neurotoxicity of quinolinate in the rat nucleus basalis magnocellularis.

Injections of quinolinic acid (QUIN) alone or combinations of QUIN with dipicolinic acid, Mg2+ or 3,4-diaminopyridine were made into the nucleus basalis magnocellularis of the rat. Choline acetyltransferase activity in the cortex decreased following injections of QUIN and this was antagonized by co-injections of QUIN with dipicolinic acid or Mg2+. Co-injections of QUIN with 3,4-diaminopyridine increased the neurotoxicity of quinolinic acid, while diaminopyridine alone was not toxic.

4-Aminopyridine↗
PubMed1977

Chronic arthropathy associated with rubella vaccination.

Eleven children suffered recurrent ipisodes of knee stiffness ("catcher's crouch syndrome") after receiving HPV-77DK12 rubella vaccine. One was evaluated by arthroscopy and the synovium was found to be hypertrophied posteriorly and to protude in folds into the intercondylar notch and lateral joint space. Culture for rubella virus was unsuccessful. The author's observations provide evidence that "catcher's crouch syndrome" is a synovial disease and that chronic joint disease can be a sequela of rubella immunization.

Child↗
PubMedDate not supplied

Shared governance in the endoscopy department.

Studies have indicated that active participation by employees improves job satisfaction and performance. There is a sense of pride and accountability that is demonstrated in the work environment when staff are involved in the decision-making process. Recent emergence of a relatively new philosophy for management that promotes employee ownership is shared governance. This type of leadership allows individuals who are at the center of the work place to participate in the decisions that actively reflect their needs. In this article, the authors describe the process of implementing shared governance in an Endoscopy Department. The effectiveness of shared governance is evidenced by the renewed enthusiasm and energy demonstrated by the staff.

Decision Making, Organizational↗
PubMedDate not supplied

Front line workers in long-term care: the effect of educational interventions and stabilization of staffing ratios on turnover and absenteeism.

OBJECTIVE: Front line workers in long-term care play a crucial role in helping residents achieve their highest possible functional level. High turnover (rates in excess of 100% are common) and absenteeism threaten the ability of long-term care providers to meet this goal. The purpose of this study was to determine the effect of a formalized certified nursing assistant (CNA) education program and stabilization of staffing ratios on turnover and absenteeism. DESIGN AND SETTING: This study was a 12-month prospective, nonrandomized trial involving two long-term care facilities providing traditional intermediate and skilled care serving as study sites and a similar facility serving as a control. For historical comparisons, each facility served as its own control using data from the year before the interventions. INTERVENTIONS: An in-house educational program based on the State of North Carolina core curriculum for CNAs was instituted in each study site. During the study period, efforts were made to achieve stable staffing ratios of 1 CNA:8 residents for days, 1:10 for evenings, and 1:15 for nights. Traditional quality of care indicators and resident/surrogate satisfaction were tracked during the study period. RESULTS: Both study facilities showed a decline in turnover, with the decline reaching statistically significant levels at Facility B (134% to 41%, P = 0.0001). Absenteeism rates did not change significantly during the study period. Resident/surrogate satisfaction with nursing care was improved significantly at Facility B (P = 0.02). CONCLUSION: A formal education program in conjunction with stabilization of staffing ratios can result in lower turnover rates for CNA's and improved resident/surrogate satisfaction.

Journal Article↗
PubMedDate not supplied

The disposition and metabolism of 5-(4,5-dihydro-2-phenylbenz[e]indol-3-yl)salicylic acid (fendosal) in the rat, mouse, rabbit, do, rhesus monkey, and man.

The disposition and metabolism of 5-(4,5-dihydro-2-phenylbenz[e]indol-3-yl)salicylic acid (fendosal) a new salicylate-type analgesic, has been studied in the rat, mouse, rabbit, dog, rhesus monkey, and man. Animals were given single oral or parenteral doses at levels of 5, 10, or 50 mg/kg; human volunteers received 200 mg orally. In all species, virtually all radioactivity was excreted in the feces. Biliary excretion accounted for approximately 50% of an oral dose in the rat and dog. Enterohepatic circulation was demonstrated in the rat. The compound was fairly rapidly absorbed in all species except the rhesus monkey. The principal excretion products found in all species were unchanged fendosal and a monohydroxylated metabolite, the latter being present both in the free state and as a glucuronide. A minor metabolite, present only in man and rhesus monkey, was tentatively identified as a dihydroxylated metabolite. These compounds were, however, detected only in unpurified samples. During the isolation and purification procedure, oxidation occurred, resulting in the production of the corresponding dehydrogenated derivatives, which were the actual materials whose structures were elucidated.

Adult↗