Search PubMed⌕ Search

Biomedical subjects

J Sloan

Publications and source records attributed to J Sloan.

At least 19 recordsLinked to original sources
PubMed2001

Phase I trial of gemcitabine and CPT-11 given weekly for four weeks every six weeks.

BACKGROUND: Our previous studies have shown that the in vitro cytotoxicity of gemcitabine and SN-38, the active metabolite of irinotecan (CPT-11), is synergistic in human tumor cell lines. PATIENTS AND METHODS: Twenty-four patients with solid tumors, refractory to standard chemotherapy or for whom no effective therapy existed (age range 31-74; 7 female, 17 male; ECOG PS 0 = 12, 1 = 11, 2 = 1), received gemcitabine and CPT-11 weekly for four weeks out of every six weeks. Fifty courses of treatment (median 2, range 1-8) were given through five dose levels of gemcitabine/CPT-11 (600/75, 800/75, 800/100, 1000/100, 1000/125 mg/m2). RESULTS: Grade 3 and 4 neutropenia occurred in eight and two patients, respectively. Grade 3 and 4 thrombocytopenia occurred in one and three patients, respectively. Hematologic toxicity resulted in > or = 2 missed doses of treatment in two out of six patients and was therefore dose limiting at gemcitabine 1000 mg/m2 and CPT-11 125 mg/m2. Grade 3 and 4 diarrhea occurred in two and one patients, respectively. Other moderate non-hematologic toxicities included alopecia, anorexia, fatigue, nausea, vomiting, and weight loss. CONCLUSIONS: The maximum tolerated dose for this study recommended for phase II testing is gemcitabine 1000 mg/m2 and CPT-11 100 mg/m2. A partial response was seen in transitional cell carcinoma.

Adult↗
PubMed2001

Phase I trial of sequential administration of raltitrexed (Tomudex) and 5-iodo-2'-deoxyuridine (IdUrd).

Raltitrexed (Tomudex) is a specific inhibitor of thymidylate synthase with clinical activity in colorectal cancer. The combination of raltitrexed and 5-iodo-2'-deoxyuridine (IdUrd, a cytotoxic pyrimidine analog) resulted in increased IdUrd incorporation into DNA and exhibited in vitro synergism against colon and bladder human carcinoma cell lines. We designed a phase I trial to determine the MTD, pharmacokinetics, and biologic effects of escalating doses of the combination of IdUrd given as a 24-hour infusion after a raltitrexed 15-minute infusion every three weeks. Thirty-four patients received 95 courses of raltitrexed and IdUrd at doses ranging from raltitrexed 1 mg/m2 and IdUrd 750 mg/m2 to raltitrexed 2.5 mg/m2 and IdUrd 10,400 mg/m2. The median number of cycles administered was 2 (range 1-10). Dose limiting hematologic toxicity occurred at doses of raltitrexed 2.5 mg/m2 and IdUrd 10,400 mg/m2. In addition, we determined the mean plasma concentrations C(SS) of IdUrd, the iodouracil level at 22 hours and the IdUrd clearance. Raltitrexed did not appear to affect the pharmacokinetics of IdUrd in the dose range tested. The recommended phase II dose is raltitrexed 2 mg/m2 and IdUrd 10,400 mg/m2 repeated every three weeks. Evidence of potential antitumor activity was observed: 1 patient (with colon cancer) had a partial response while 15 others had stable disease.

Adult↗
PubMed2000

Discrete atom imaging of one-dimensional crystals formed within single-walled carbon nanotubes

The complete crystallography of a one-dimensional crystal of potassium iodide encapsulated within a 1.6-nanometer-diameter single-walled carbon nanotube has been determined with high-resolution transmission electron microscopy. Individual atoms of potassium and iodine within the crystal were identified from a phase image that was reconstructed with a modified focal series restoration approach. The lattice spacings within the crystal are substantially different from those in bulk potassium iodide. This is attributed to the reduced coordination of the surface atoms of the crystal and the close proximity of the van der Waals surface of the confining nanotube.

Journal Article↗
PubMed2000

Evolution of a glucose-regulated ADH gene in the genus Saccharomyces.

To determine when a glucose-repressed alcohol dehydrogenase isozyme and its regulatory gene, ADR1, arose during evolution, we surveyed species of the genus Saccharomyces for glucose-repressed ADH isozymes and for ADR1 homologues. Glucose-repressed ADH isozymes were present in all species of Saccharomyces sensu strictu and also in Saccharomyces kluyveri, the most distant member of the Saccharomyces clade. We cloned and characterized ADH promoters from S. bayanus, S. douglasii, and S. kluyveri. The ADH promoters from S. bayanus and S. douglasii had conserved sequences, including upstream regulatory elements, and an extended polydA tract. The expression of a reporter gene driven by the S. bayanus promoter was glucose-repressed and dependent on the major activator of transcription, ADR1, when it was introduced into S. cerevisiae. One S. kluyveri promoter was also glucose-repressed and ADR1-dependent in S. cerevisiae. The other S. kluyveri ADH promoter was expressed constitutively and was ADR1-independent. Although showing little sequence conservation with the S. cerevisiae ADH2 promoter, the glucose-repressed S. kluyveri promoter contains numerous potential binding sites for Adr1. The glucose-repressed ADH from S. kluyveri is a mitochondrial isozyme most closely related to S. cerevisiae ADHIII. ADR1 homologues from S. douglasii and S. paradoxus contain a trinucleotide repeat encoding polyAsn that is lacking in S. cerevisiae and S. bayanus. No ADR1 homologue could be detected in S. kluyveri, suggesting that the potential for Adr1 regulation may have arisen first, before ADR1 evolved.

Alcohol Dehydrogenase↗
PubMed2000

An examination of psychometric properties of the mini-mental state examination and the standardized mini-mental state examination: implications for clinical practice.

The Mini-Mental State Examination (MMSE), as developed by Folstein, Folstein, and McHugh (1975), is the most widely used of cognitive screening tools. An examination of the psychometric properties of the MMSE seems warranted because the accurate and comprehensive assessment of mental status can yield profound implications for the quality of life of cognitively impaired older adults (Danner, Beck, Heacock, & Modlin, 1993). In clinical practice, nurses must not only use a valid and reliable screening tool for assessing cognitive impairment, but they must also assess the physical disabilities that may affect client performance and, hence, the cognitive impairment score. The purpose of this study is to examine the psychometric properties of the MMSE in comparison to a more standardized tool and to identify implications of the tool for clinical practice.

Aged↗
PubMed1999

The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames.

Molybdoenzymes are ubiquitous and require a prosthetic group called the molybdenum cofactor for activity. We provide evidence here that the two heteromeric subunits (MOCO1-A and MOCO1-B) of human molybdopterin synthase, which is involved in the conversion of precursor Z to molybdopterin in the molybdenum cofactor biosynthetic pathway, are spe-cified by a single bicistronic mRNA with overlapping reading frames. The transcript is in low abundance and shows variable tissue distribution. We propose that leaky scanning of the first translational initiation codon for MOCO1-A by 40S ribosomal subunits occurs, allowing recognition of the AUG for the downstream MOCO1-B reading frame. Such a genetic arrangement may result in a constant ratio and close proximity of lowly expressed enzyme subunits which should, a priori, be especially advantageous for assembly in complex mammalian cells. The MOCO1 locus resides on human chromosome 5.

Adult↗
PubMed1999

Pilot evaluation of venlafaxine for the treatment of hot flashes in men undergoing androgen ablation therapy for prostate cancer.

PURPOSE: Hot flashes may be a significant clinical problem in men undergoing androgen deprivation therapy with gonadotropin releasing hormone analogues, oral antiandrogens and/or surgical bilateral orchiectomy. Anecdotal information suggests that a low dose of the relatively new antidepressant venlafaxine may abrogate this clinical problem. We developed the current pilot trial to investigate further whether venlafaxine alleviates hot flashes in such men. MATERIALS AND METHODS: The study included men in whom substantial hot flashes were associated with androgen deprivation therapy. Hot flash data were collected by daily diary questionnaires during a 1-week baseline period when no therapy was given for hot flashes, as well as for the next 4 weeks when study participants received 12.5 mg. venlafaxine orally twice daily. Questionnaires completed during the 4 weeks ofvenlafaxine therapy also documented data on potential drug toxicity. RESULTS: Of the 16 evaluable patients who completed the study 10 (63%) had a greater than 50% decrease in hot flash score, as determined using the formula, frequency x severity, by week 4 of treatment versus the baseline week. Median weekly hot flash scores decreased 54% from baseline during week 4 of venlafaxine therapy. Average incidence of severe and very severe hot flashes was reduced from 2.3 daily at baseline to 0.6 daily at study end (p = 0.003). Therapy was generally well tolerated. CONCLUSIONS: Venlafaxine hydrochloride appears to represent an efficacious new method for alleviating hot flashes in men undergoing androgen ablation therapy. Further evaluation of this compound for alleviating hot flashes is indicated.

Aged↗
PubMed1999

Doctor's assistants--do we need them?

OBJECTIVE: To investigate the potential for the doctor's assistant role within an accident and emergency (A&E) department in relation to consultant workload. METHODS: A time and motion evaluation of the activities of four A&E consultants before and after a doctor's assistant was established as a team member within our department. A review of the literature was undertaken to allow comparisons with the American model of the physician assistant within the emergency department. RESULTS: The initial evaluation indicated that over 20% of the consultant's time could have been saved if an assistant were available to perform a variety of non-medical tasks. The restudy performed once the assistant was in post indicated less time was spent by the doctors in "medical" clerical duties (6.7% v 11.5% time), telephone use (5.6% v 7.7%), and venepuncture/cannula insertion (0.4% v 2.1%), and more time was spent on consultation over cases (15.3% v 11.3%) and supervision of other staff (9.3% v 4.1%). These five areas changed significantly (p = 0.005 by paired t test). CONCLUSIONS: The doctor's assistant may have a role in reprofiling the workload of senior doctors in A&E departments in the UK. They may also have a role in reducing the pressure on junior doctors, though this effect was not evaluated.

Data Collection↗
PubMed1998

The Aspergillus nidulans cnxF gene and its involvement in molybdopterin biosynthesis. Molecular characterization and analysis of in vivo generated mutants.

The product of the Aspergillus nidulans cnxF gene was found by biochemical analysis of cnxF mutants to be involved in the conversion of precursor Z to molybdopterin. Mutants cnxF1242 and cnxF8 accumulate precursor Z, while the level of molybdopterin is undetectable. The DNA sequence of the cnxF gene was determined, and the inferred protein of 560 amino acids was found to contain a central region (residues around 157 to 396) similar in sequence to the prokaryotic proteins MoeB, which is thought to encode molybdopterin synthase sulfurylase, ThiF, required for thiamine biosynthesis, and HesA, involved in heterocyst formation, as well as eukaryotic ubiquitin-activating protein E1. Based on these similarities, a possible mechanism of action is discussed. Sequence comparisons indicate the presence of one and possibly two nucleotide binding motifs, Gly-X-Gly-X-X-Gly, as well as two metal binding Cys-X-X-Cys motifs in this central region of the CnxF protein. Seven in vivo generated A. nidulans cnxF mutants were found to have amino acid substitutions of conserved residues within this central region of similarity to molybdopterin synthase sulfurylase, indicating that these seven amino acids are essential and that this domain is crucial for function. Of these seven, the cnxF1285 mutation results in the replacement of Gly-178, the last glycine residue of the N-proximal Gly-X-Gly-X-X-Gly motif, indicating that this motif is essential. Mutation of the conserved Arg-208, also probably involved in nucleotide binding, leads to a loss-of-function phenotype in cnxF200. Alteration of Cys-263, the only conserved Cys residue (apart from the metal binding motifs), in cnxF472 suggests this residue as a candidate for thioester formation between molybdopterin synthase and the sulfurylase. Substitution of Gly-160 in two independently isolated mutants, cnxF21 and cnxF24, results in temperature-sensitive phenotypes and indicates that this residue is important in protein conformation. The C-terminal CnxF stretch (residues 397-560) shows substantial sequence conservation to a yeast hypothetical protein, Yhr1, such conservation between species suggesting that this region has function. Not inconsistent with this proposition is the observation that mutant cnxF8 results from loss of the 34 C-terminal residues of CnxF. There is no obvious similarity of the CnxF C-terminal region with other proteins of known function. Two cnxF transcripts are found in low abundance and similar levels were observed in nitrate- or ammonium-grown cells.

Amino Acid Sequence↗
PubMed1998

Coeliac disease detected by screening is not silent--simply unrecognized.

Coeliac disease (CD) is associated with a wide spectrum of clinical presentation and may be overlooked as a diagnosis. There is some evidence that untreated CD is associated with a doubling of mortality, largely due to an increase in the incidence of malignancy and small intestinal lymphoma, which is decreased by a strict gluten-free diet. We studied the clinical features of screening-detected coeliacs compared to age- and sex-matched controls as a 3-year follow-up to a population screening survey, and followed-up subjects who had had CD-associated serology 11 years previously to determine whether they have CD or an increased mortality rate compared to the general population. Samples of the general population (MONICA 1991 and 1983) were screened for CD-associated serology and followed-up after 3 and 11 years, respectively, and assessed by a clinical questionnaire, screening blood tests and jejunal biopsy. Mortality rates for 'all deaths' and 'cancer deaths' were compared in subjects with positive serology in 1983 with reference to the general population. Thirteen coeliacs were diagnosed by villous atrophy following screening, compared to two patients with clinically detected CD, giving a prevalence of 1:122. Clinical features or laboratory parameters were not indicative of CD compared to controls. Subjects with positive serology followed up after 11 years did not have an excess mortality for either cancer deaths or all causes of death. Screening-detected CD is rarely silent and may be associated with significant symptoms and morbidity. In this limited study with small numbers, there does not appear to be an increased mortality from screening-detected CD, although the follow-up may be too short to detect any difference.

Adult↗
PubMed1997

Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy.

PURPOSE: Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention. PATIENTS AND METHODS: A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS: There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm. CONCLUSION: The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis.

Anti-Ulcer Agents↗
PubMed1997

Development and testing of the Primary Health Care Questionnaire (PHCQ): results with students and faculty in diploma and degree nursing programs.

Primary health care (PHC) has been proposed as a key strategy for improving the health of the world community, and nurses are acknowledged as key health-care professionals in meeting this goal. Efforts to have nurses implement PHC policies presuppose that they are knowledgeable about this approach to health care and have positive attitudes. The underlying aim of this study was to develop a measure of knowledge, attitudes, and practices in PHC and to assess the reliability and validity of the measure with a sample of student nurses and faculty in degree and diploma programs. The Primary Health Care Questionnaire (PHCQ) is a three-part self-report measure that provides quantitative data on knowledge and attitudes and qualitative data on practices of PHC. The instrument was developed from a rigorous review of the literature and systematic feedback from two panels (local and national) expert in PHC. Data were collected from 457 students and faculty in one four-year degree program (three sites), one post-diploma degree program, and three diploma programs, in a western Canadian province. Internal consistency reliability estimates using Cronbach's alpha were .76 (knowledge) and .85 (attitudes). Test-retest reliability at two weeks was r = .67 (knowledge) and .76 (attitudes). Content validity was enhanced through a systematic review of the instrument by a two-phase local and a national expert panel. Findings indicated greater knowledge and more positive attitudes among senior compared to junior students, degree compared to diploma students, and faculty compared to students. These findings lend support to the validity of the measure. The qualitative data revealed that learning opportunities related to PHC were built into both the diploma and the degree program through classroom teaching, clinical practice, and written assignments.

Canada↗
PubMed1996

Analysis of isoniazid-resistant transposon mutants of Mycobacterium smegmatis.

The emergence of multidrug-resistant tuberculosis has renewed interest in the study of drug resistance in mycobacteria with the objective of improved chemotherapy. The genetic basis of isoniazid resistance in a model mycobacterium was studied. Eleven isoniazid-resistant mutants of Mycobacterium smegmatis were created using transposon mutagenesis. Genetic and enzymatic characterisation of the mutants showed that katG, encoding T-catalase, was inactivated. The nucleotide sequence of M. smegmatis katG was determined and the mutation sites mapped demonstrating that both the amino and carboxyl halves of T-catalase are important for enzymatic activity.

Bacterial Proteins↗