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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Epidemiology of erectile dysfunction: a community-based study in rural New York State.

PURPOSE: Few published population-based studies that deal with the prevalence of erectile dysfunction (ED) involve rural populations. This study determined the prevalence and determinants of ED among a rural population. It also evaluated the relevance of some major predictors of help-seeking decisions. METHODS: A self-administered survey was conducted by mail among 5198 randomly selected men 50-76 years old, living in four rural counties in Central New York State. RESULTS: The response rate was 44.7% and the participation rate among respondents was 71.0%. Mean ages of men reporting and those not reporting ED were 64.5 7.2 and 59.8 7.2 years respectively. The mean duration of self-reported ED was 4.9 4.6 years. The overall prevalence of ED was 46.3% while the minimum prevalence was estimated as 21.3%. Age-specific prevalence was 26.0%, 34.9%, 46.9%, 57.8% and 69.4% among men 50-54, 55-59, 60-64, 65-69, and 70-76 years old respectively. There was a statistically significant relationship between age, socio-economic status, perceived state of health and erectile function status (p < 0.001). However, socio-economic status, marital status, perceived state of health and age were not significant predictors of help-seeking decisions. CONCLUSIONS: The prevalence of ED among men 50-76 years old in rural Central New York State is at least 21.3% and may be as high as 46.3%. Age, perceived state of health and socio-economic status were found to be important determinants of erectile dysfunction among this population. For purposes of comparative analyses, future epidemiological studies should report both the overall and minimum rates among men with clinically relevant erectile dysfunction.

Aged↗
PubMed2000

Stability and haplotype analysis of the FRAXE region.

FRAXE full mutations are rare and appear to be associated with mild mental retardation. As part of a screening survey of boys with learning difficulties to determine the frequency of full and premutations, we have collected data on the frequency of instability at FRAXE for about 4000 transmissions and the haplotype for over 7000 chromosomes. The distribution of FRAXE repeats was similar to other English populations but differed from two North American Caucasian series. Observed instability at FRAXE was rare but increased with increasing repeat number, and there were no expansions into the full mutation range, except in pedigrees ascertained through a full mutation. Haplotype analysis suggested division into five groups with each group having a characteristic distribution of FRAXE repeats. Fourteen of the 15 full mutations occurred on a single haplotype and this haplotype also had a significant excess of intermediate-sized alleles, suggesting that full mutations originate from large normal alleles. However, a related haplotype also had a significant excess of intermediates but we observed no full mutations on this haplotype, suggesting either loss or gain of stability determinants on it. We suggest that whilst triplet repeat size is a significant predisposing factor for expansion at FRAXE other genetic determinants are also likely to be important.

Alleles↗
PubMed2000

The macrophage - a novel system to deliver gene therapy to pathological hypoxia.

The use of activated macrophages in the treatment of cancer has been largely ineffectual. By 'arming' these cells with the ability to express a therapeutic gene we demonstrate significant advances in the efficacy of this approach. We have used a hypoxia-regulated adenoviral vector to transduce human macrophages with either a reporter or a therapeutic gene encoding human cytochrome P4502B6 (CYP2B6). Infiltration of transduced macrophages into a tumour spheroid results in induction of gene expression. We demonstrate significant tumour cell killing only in the presence of cyclophosphamide via activation by P4502B6 and show that this can be further targeted to tumours through hypoxia regulated gene expression. Gene Therapy (2000) 7, 255-262.

Adenoviridae↗
PubMed2000

A phase II trial of paclitaxel and epirubicin in advanced breast cancer.

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0-2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m(-2) followed by a 3-h infusion of paclitaxel 175 mg m(-2) repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of > or =20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m(-2) and epirubicin 75 mg m(-2) is a well tolerated, promising regimen for the treatment of advanced breast cancer.

Adult↗
PubMed2000

Higher brain blood flow at amygdala and lower frontal cortex blood flow in PTSD patients with comorbid cocaine and alcohol abuse compared with normals.

Posttraumatic stress disorder (PTSD) patients with histories of cocaine and alcohol abuse (CA-PTSD) were compared with normal volunteers. Positron emission tomography (PET) scans with 15O-butanol were used to compare regional cerebral blood flow (rCBF) between the groups during rest and during an auditory continuous performance task (ACPT). CA-PTSD patients had significantly higher rCBF in right amygdala and left parahippocampal gyrus than normals during the ACPT. Normals had higher rCBF at frontal cortex during the resting scan and during the ACPT. The role of the amygdala in attention and fear conditioning suggests that increased amygdala rCBF may be related to clinical features of PTSD. Cocaine use may be associated with increased amygdala rCBF in PTSD patients. Amygdala and frontal cortex attention system components may be reciprocally related and their relative contributions to processing of neutral stimuli perturbed in CA-PTSD.

Adult↗
PubMed2000

Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in self-diagnosed individuals, dosage effect, and sibling risk.

BACKGROUND: Celiac disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten. Traditionally, diagnosis is made by intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the serum also is used for diagnosis. Biopsy and serology revert to normal with adherence to a gluten-free diet. Often, after an index case is diagnosed, siblings with symptoms adhere to a gluten-free diet without biopsy or serologic confirmation. More than 90% of patients with celiac disease have the human leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have been implicated. METHODS: One hundred ninety-five individuals with confirmed or suspected celiac disease were identified in 73 families affected by the disease. IgA endomysial antibody testing was performed for all symptomatic family members who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276 and the HLA class II loci DQA and DQB. RESULTS: At the time sampling was begun in families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology) had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69) of cases self-diagnosed (adherence to gluten-free diet without confirmation) had at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is estimated that the HLA association and other unlinked genes contribute approximately equally to the sibling risk of celiac disease. CONCLUSIONS: A dosage effect of DQB1*0201 may be associated with an increased risk of celiac disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in families in the United States. Diagnosis of celiac disease on the basis of clinical response to gluten restriction is inaccurate. With long-term adherence to a gluten-free diet, serologic test results are likely to be negative. Based on HLA genotype, approximately one third of self-diagnosed individuals are unlikely to have celiac disease. However, it is not possible to determine which individuals consuming a gluten-free diet have the disease. Therefore, before starting a gluten-free diet, serologic screening and biopsy confirmation are necessary.

Biopsy↗
PubMed2000

EMCyberSchool: an evaluation of computer-assisted instruction on the Internet.

OBJECTIVES: To test the hypothesis that integration of the EMCyberSchool, a computer-assisted instruction (CAI) tool available on the Internet, into the curriculum of a senior medical student subinternship in emergency medicine (EM) would improve exam scores and course satisfaction. METHODS: Students were prospectively randomized, by four-week blocks, into a CAI group and a no-CAI group. All students were surveyed on previous computer experience and their use and opinion of the EMCyberSchool. RESULTS: Completed data were obtained from 100 of 120 students. Sixty-five percent of the students said they wanted CAI as an adjunct to their course curricula; only 28% actually used the educational tool. The students who used the site rated it useful (4.2/5), easy to use (4.4/5), and easy to access (4.1/5). Of the students who had access, and chose not to use the EMCyberSchool, 77.8% reported not having enough time as the reason for not using the site. The mean exam scores were 72.8% for the students in the CAI group and 68.2% for those in the no-CAI group (p = 0.058). In the CAI group, 77.5% (31/40) of the students rated the course as outstanding or excellent; compared with 66% (33/50) in the no-CAI group (p = 0.23). CONCLUSIONS: Although desired, it remains unclear whether CAI on the Internet is a useful adjunct for teaching EM to medical students.

Clinical Clerkship↗
PubMed2000

FRAXA and FRAXE: the results of a five year survey.

We report the results of a five year survey of FRAXA and FRAXE mutations among boys aged 5 to 18 with special educational needs (SEN) related to learning disability. We tested their mothers using the X chromosome not transmitted to the son as a control chromosome, and the X chromosome inherited by the son to provide information on stability of transmission. We tested 3738 boys and 2968 mothers and found 20 FRAXA and one FRAXE full mutations among the boys and none among the mothers. This gives an estimated prevalence of full mutations in males of 1 in 5530 for FRAXA and 1 in 23 423 for FRAXE. We found an excess of intermediate and premutation alleles for both FRAXA and FRAXE. For FRAXA this was significant at the 0.001 level but the excess for FRAXE was significant only at the 0.03 level. We conclude that the excess of intermediate and premutation sized alleles for FRAXA may well be a contributing factor to the boys' mental impairment, while that for FRAXE may be a chance finding. We studied approximately 3000 transmissions from mother to son and found five instabilities of FRAXA in the common or intermediate range and three instabilities of FRAXE in the intermediate range. Thus instabilities in trinucleotide repeat size for FRAXA and FRAXE are rare, especially among alleles in the common size range.

Adolescent↗
PubMed2000

Defenselike patterns of spinal sympathetic outflow involving the 10-Hz and cardiac-related rhythms.

Frequency- and time-domain analyses were used to compare the effects of stimulation of the defense region of the midbrain periaqueductal gray (PAG) on the 10-Hz and cardiac-related discharges of sympathetic nerves with different cardiovascular targets. In baroreceptor-denervated cats anesthetized with urethan, PAG stimulation at frequencies equal to or higher (up to 25 Hz) than that of the free-running 10-Hz rhythm produced an immediate and sustained decrease in vertebral sympathetic nerve (VN) 10-Hz activity but increased the 10-Hz discharges of the inferior cardiac (CN) and renal (RN) nerves. In baroreceptor-innervated cats, VN cardiac-related activity was initially unchanged by high-frequency (25-Hz) PAG stimulation, or it increased along with that in the CN and RN. Later, during high-frequency PAG stimulation, when the rise in blood pressure approached its peak, VN cardiac-related activity usually was reduced below control level. At this time, the increases in CN and RN cardiac-related discharges were largely sustained. The cardiac-related discharges of the three nerves were unaffected by PAG stimulation at frequencies just below or just above that of the heartbeat. We conclude that the defenselike pattern of spinal sympathetic outflow involving the 10-Hz rhythm is different in mechanism and character from that involving the cardiac-related rhythm.

Animals↗
PubMed2000

No better time.

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American Hospital Association↗
PubMed1999

Diurnal differences in amphetamine sensitization.

A computerized motor activity monitoring system was used to investigate the development and time dependence of sensitization to repeated exposure of amphetamine. Male Sprague-Dawley rats were acclimated for 7 days to light/dark cycle (0700 h:1900 h) in the testing room, and were then housed in the test cages for 16 days of continuous recording. The locomotor responses to s.c. administration of amphetamine (0.3, 0.6, or 1.2 mg/kg) were compared before and after five daily injections of 0.6 mg/kg of amphetamine. Different groups of rats were administered drug at either 0800 h, 1400 h, 2000 h, or 0200 h. The locomotor indices studied were total distance and vertical activity. Sensitization was more pronounced for total distance (i.e., forward ambulation) than for vertical activity (i.e., rearing), and its expression was dependent on the challenge dose. Sensitization was also time-dependent, with the strongest sensitized response occurring during the middle of the dark cycle (0200 h). Repeated administration of amphetamine (0.6 mg/kg) did not cause post-stimulant depression as has been seen at higher doses.

Amphetamine↗
PubMed1999

Human brain alpha rhythm: nonlinear oscillation or filtered noise?

The mechanism for generation of the alpha rhythm is controversial. In the current study, analysis in the time and frequency domains revealed that the alpha rhythm recorded from the scalp overlying the human occipital cortex can be entrained to the second or third harmonic of low frequency light flashes. These results support the view that the alpha rhythm is generated by a nonlinear oscillator rather than a narrow-band transmission system acting as a filter.

Adult↗
PubMed1999

Hepatitis C virus and lichen planus: A case-control study of 340 patients.

Lichen planus (LP) has been associated with liver disease, particularly hepatitis C virus (HCV) infection, in several studies to date. Most of these reports, especially the larger series, were conducted in Europe. In addition, the type of LP associated with HCV was reported to be oral LP in most studies. We conducted a case-control study in a US metropolitan population known to have a low seroprevalence of HCV infection to explore the impact of geography and endemicity of HCV on the association between cutaneous LP and HCV. The study comprised 340 patients with cutaneous LP (as case ) against 577 patients with psoriasis (as control-1 ). Hepatitis antibody titers and liver function abnormalities were our main outcome measures. Prevalence of HCV antibody among 149,756 regional volunteer blood donors (as control-2 ) was also used for comparison. Twelve (55%) of 22 patients with LP tested for HCV were antibody positive. This was significantly higher than 25% of 40 psoriasis patients tested for HCV antibody (P =.04) or than 0.17% of blood donors tested for HCV antibody (P < 10(-5)). Thus a small but significant percentage of US patients with cutaneous LP had HCV antibody. Because LP may be the first presentation of HCV infection, it is important for clinicians to actively look for such infection in patients with LP.

Case-Control Studies↗