Search PubMed⌕ Search

Biomedical subjects

W Lewis

Publications and source records attributed to W Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1994

Zidovudine causes early increases in mitochondrial ribonucleic acid abundance and induces ultrastructural changes in cultured mouse muscle cells.

BACKGROUND: Zidovudine (azidothymidine, AZT) causes a toxic mitochondrial myopathy in AIDS patients with changes in mitochondrial (mt) DNA and mitochondrial structure. To determine early subcellular events in AZT myopathy in vitro we examined C2C12 myotubes treated with AZT (0.2, 2, 10 micrograms/ml) for up to 4 weeks. We identified AZT-induced effects on muscle intracellular compartments by determining the comparative abundance of selected myotube cytoplasmic and mtRNAs and mtDNA. EXPERIMENTAL DESIGN: RNA and DNA were extracted from cultured C2C12 myotubes, blotted and probed with cDNAs specific for the mitochondrial gene products cytochrome b and cytochrome c oxidase I, nuclear-encoded sarcomeric troponin C, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase. Transmission electron microscopy was performed on parallel samples. RESULTS: After 4 weeks of AZT, cytochrome b and cytochrome c oxidase I mtRNA abundance increased to 64% and to 31% above respective control levels. No change occurred in mtDNA abundance or nuclear encoded glyceraldehyde-3-phosphate dehydrogenase mRNA compared with the nuclear encoded sarcomeric troponin C control. Transmission electron microscopy showed focal disruption of mitochondrial cristae with intramyocytic lipid droplets after 14 days of AZT treatment. CONCLUSIONS: Increased mtRNA abundance in absence of changes in mtDNA abundance suggests that early AZT toxicity to mitochondria may relate to defects in mtDNA replication or mtRNA transcription.

Animals↗
PubMed1993

Quality of life after restorative proctocolectomy with a pelvic ileal reservoir compares favorably with that of patients with medically treated colitis.

There remains some reluctance among physicians to refer patients for restorative proctocolectomy (RP). They argue that their patients would be worse off with a pouch because of the attendant problems of urgency and frequent bowel actions. The aim of this study was to compare quality of life in patients who had undergone RP with that of patients with ulcerative colitis on long-term medical treatment. A detailed questionnaire and the Hospital Anxiety and Depression (HAD) test were completed by 103 patients who had undergone RP and by 95 patients with ulcerative colitis on medical treatment and in remission attending a gastroenterology clinic. Patients with a pouch had a greater frequency of bowel action [five times per 24 hours (range, 4-7) vs. two times per 24 hours (range, 1-3); P < 0.001] but less urgency of defecation [12/103 (11.7 percent) vs. 69/95 (72.6 percent); P < 0.001] than patients with medically treated colitis. Efficiency of evacuation, discrimination between flatus and feces, use of perianal pads, and perianal soreness were similar. Use of antidiarrheal medication was more common in the pouch group [53 of 103 patients (51.5 percent) vs. 3 of 95 patients (3.2 percent); P < 0.05], whereas use of topical steroids was more common in medically treated patients [40 of 95 patients (47.1 percent) vs. 9 of 103 patients (8.7 percent); P < 0.05]. Limitation of social activity and HAD scores were significantly higher in medically treated patients. Quality of life for patients with a pouch appears to be as good as that for patients with medically treated colitis.

Adolescent↗
PubMed1993

Gross and microvascular distribution of retrograde cardioplegia in explanted human hearts.

In this report, explanted hearts from transplant recipients with the diagnosis of idiopathic cardiomyopathy underwent a blood cardioplegia arrest and extended subatrial resection to preserve their coronary sinus venous system. The coronary sinus and left and right coronary arteries were then cannulated and warm blood cardioplegia retrograde infused at a pressure of 30 to 40 mm Hg. Effluent from the coronary arteries and thebesian veins was then collected. Hearts were subsequently fixed with retrograde glutaraldehyde perfusion and perfused retrograde with NTB-2 (an inert intracapillary marker). Histologic sections were examined from 12 separate sites. There was no significant difference in the percentage of capillaries perfused by retrograde-delivered cardioplegia between corresponding regions of the left and right ventricles. However, effluent analysis indicated that 67.2% +/- 6.4% of retrograde-delivered blood cardioplegia was shunted through thebesian veins, thereby bypassing the microvasculature, whereas 29.3% +/- 6.3% and 3.5% +/- 3.1% traversed the myocardium supplied by the left and right coronary arteries, respectively. The results indicate that all regions of both ventricles are perfused by retrograde blood cardioplegia. However, they also suggest that nutrient flow to the microvasculature of the right ventricle is minimal during retrograde cardioplegia.

Blood↗
PubMed1992

One-stage restorative proctocolectomy without temporary defunctioning ileostomy.

A temporary ileostomy has been employed routinely by most medical centers to defunction the ileal reservoir after restorative proctocolectomy. The aim of this study was to compare the clinical outcome in patients who underwent restorative proctocolectomy with and without the use of a temporary, defunctioning ileostomy. A consecutive series of 58 patients was studied. Each patient underwent restorative proctocolectomy with quadruplicated ileal reservoir and stapled pouch-anal anastomosis, without mucosectomy; 28 had a temporary, defunctioning ileostomy and 30 did not. The decision for or against an ileostomy was taken at the end of the operation. The two groups of patients were similar in age and sex distribution. There was no postoperative mortality. There were no significant differences in the incidence of pelvic sepsis, anastomotic stricture, and intestinal obstruction in patients without an ileostomy compared with patients with an ileostomy. The total length of stay in hospital after the operation was significantly reduced in the group of patients without an ileostomy (P less than 0.01). The avoidance of a temporary ileostomy did not lead to an increase in postoperative complications and was associated with a shorter length of stay in hospital after restorative proctocolectomy.

Adult↗
PubMed1992

Zidovudine induces molecular, biochemical, and ultrastructural changes in rat skeletal muscle mitochondria.

Zidovudine (AZT) inhibits HIV-1 replication in AIDS. A limiting side effect is AZT-induced toxic myopathy. Molecular changes in a rat model of AZT-induced toxic myopathy in vivo helped define pathogenetic molecular, biochemical, and ultrastructural toxic events in skeletal muscle and supported clinical and in vitro findings. After 35 d of AZT treatment, selective changes in rat striated muscle were localized ultrastructurally to mitochondria, and included swelling, cristae disruption, and myelin figures. Decreased muscle mitochondrial (mt) DNA, mtRNA, and decreased mitochondrial polypeptide synthesis in vitro were found in parallel. Mitochondrial molecular changes occurred in absence of altered abundance of cytosolic glyceraldehyde-3-phosphate dehydrogenase, or sarcomeric mitochondrial creatine kinase mRNAs. Quadriceps mitochondrial DNA polymerase gamma activity was similar in both AZT-treated and control rats. In vivo findings with rats support the hypothesis that AZT-induced inhibition of mtDNA replication has an effect of depressing the abundance of striated muscle mtDNA, mtRNA, and mitochondrial polypeptide synthesis. This experimental approach may be useful to examine mitochondrial or toxic myopathies.

Animals↗
PubMed1992

Anthracyclines selectively decrease alpha cardiac actin mRNA abundance in the rat heart.

Anthracyclines are widely used antineoplastic agents, but possess a major side effect of congestive cardiomyopathy. Previously we showed a selective effect of the most commonly used anthracycline, doxorubicin, on decreasing alpha-cardiac (alpha c) actin mRNA abundance in the rat heart. The current studies examined the effects of several anthracyclines (doxorubicin, daunorubicin, and epirubicin) to determine if doxorubicin's previously reported effect on alpha c actin mRNA abundance is: 1) a property shared by other cardiotoxic anthracyclines; 2) selective when compared with a wider spectrum of contractile protein and muscle-specific mRNAs; and 3) related to the characteristic ultrastructural alterations, such as loss of myofilaments, seen in anthracycline-induced cardiomyopathy. Results showed a major selective effect of doxorubicin, daunorubicin, and epirubicin on decreasing alpha c actin mRNA abundance when compared with other contractile protein and muscle-specific mRNAs. In addition, ultrastructural examination of myocardium showed contractile alterations, including loss of myofilaments. These results suggest that decreased expression of selected cardiac genes may relate to the molecular mechanism of clinical anthracycline-induced cardiomyopathy.

Actin Cytoskeleton↗
PubMed1991

Adult chicken alpha-globin gene expression in transfected QT6 quail cells: evidence for a negative regulatory element in the alpha D gene region.

The chicken adult alpha-globin genes, alpha A and alpha D, are closely linked in chromosomal DNA and are coordinately expressed in vivo in an approximate 3:1 ratio, respectively. When subcloned DNAs containing one or the other gene are stably transfected into QT6 quail fibroblasts, the alpha A-globin gene is expressed at measurable RNA levels, but the alpha D gene is not. The alpha A gene expression can be considerably increased by the presence of a linked Rous sarcoma virus long terminal repeat enhancer, but that of the alpha D gene remains undetectable. Transfection with subclones containing both genes, either in cis or in trans, leads to considerably reduced alpha A RNA levels and still no observable alpha D gene expression. Transfection with deleted subclones suggests that maximal expression levels in this system require the alpha A-globin gene promoter, as opposed to that of the alpha D gene, but that such expression is greatly reduced by one or more DNA sequences which lie approximately 2,000 base pairs upstream of the alpha A gene, within the body of the alpha D gene.

Animals↗
PubMed1991

Selective alterations in rat cardiac mRNA induced by doxorubicin: possible subcellular mechanisms.

Doxorubicin (Adriamycin, ADR) is an effective antineoplastic agent with a major side effect of dilated cardiomyopathy. Previously we showed ADR selectively decreased alpha cardiac (alpha c) actin mRNA in the rat heart when compared to other mRNAs examined in heart and skeletal muscle. The present study determined if this effect was selective for mRNAs within the thin filament, related to inhibitory effects on mitochondrial transcription, and modified by pretreatment with the cardioprotective chelating agent ICRF-187. Adult Sprague-Dawley rats received ADR at 8 mg/kg intraperitoneally (ip) with or without pretreatment with ICRF-187 given at 80 mg/kg ip. After 3 days, rats were killed and myocardial RNA was extracted, electrophoresed, transferred to nitrocellulose, and hybridized with the [32]cDNA probes alpha c actin, troponin C (TnC), BamHI fragment of mouse mitochondria (MM), and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Results showed a major depressive effect of ADR on rat myocardial alpha c actin mRNA. No depression of the other mRNAs examined (TnC, MM, or G3PD) was seen. ICRF-187 did not modify the effect. We conclude that the ADR-induced decrease in alpha c actin mRNA was: (1) selective within the thin filament; (2) not related to inhibitory effects on mitochondrial transcription; and (3) not related to free radical formation. Possible subcellular mechanisms are discussed.

Actins↗
PubMed1991

Mitochondrial ultrastructural and molecular changes induced by zidovudine in rat hearts.

Zidovudine (azidothymidine (AZT)) inhibits human immunodeficiency virus replication, prolongs survival, and delays progression of acquired immune deficiency syndrome. We determined AZT-induced molecular and ultrastructural changes in the rat heart. Rats (3 per group) were given drinking water with or without AZT (0.2 to 1.0 mg/ml; 29 to 102 mg/kg/day). After 21, 35, or 49 days, hearts were glutaraldehyde-fixed by abdominal aortic perfusion, processed, and examined by transmission electron microscopy. In parallel, myocardial RNA was extracted from hearts (AZT dose: 1 mg/ml; 35 days) and subjected to Northern analysis using cDNA probes for: alpha c-actin, troponin C, mitochondrial creatine kinase and malate dehydrogenase, a portion of the mitochondrial genome containing cytochrome b coding region (pMM26), and glyceraldehyde-3-phosphate dehydrogenase. Results showed marked and widespread cardiac mitochondrial swelling with fractured and disrupted cristae after 35 days of 1 mg/ml AZT. After a 14-day recovery, these ultrastructural defects did not reverse. Changes were not present in myocardium after 21 days of AZT nor after 35 days of lower dose AZT (0.2 mg/ml). Mitochondrial cytochrome b mRNA expression was depressed in AZT-treated rat hearts (35 days; 1 mg/ml AZT). mRNAs encoding glyceraldehyde-3-phosphate dehydrogenase, alpha c-actin, troponin C, mitochondrial creatine kinase, malate dehydrogenase, and mitochondrial ribosomal RNAs remained unchanged. AZT disrupts cardiac mitochondrial ultrastructure and expression of mitochondrial cytochrome b mRNA in a dose- and time-dependent fashion. The mechanism of AZT cardiotoxicity may relate to inhibition of mitochondrial DNA replication (at the level of DNA polymerase gamma) as postulated by others.

Animals↗
PubMed1991

Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome.

In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Comparison of culture for group B streptococcus versus enzyme immunoassay and latex agglutination rapid tests: results in 250 patients during labor.

Two hundred fifty women in labor were screened for vaginal colonization by group B streptococcus using standard culture and two rapid tests. This primarily Hispanic population had a group B streptococcus vaginal colonization rate of 2.4% (95% confidence interval 0.9-5.2%) for the patients sampled. An enzyme immunoassay and a latex agglutination test for group B streptococcus antigen both had sensitivities of 33% and had specificities of 99 and 95%, respectively, when compared with culture. Neither rapid test appeared to be clinically useful for detecting colonized women in labor, although both can be useful in excluding colonization.

Antigens, Bacterial↗
PubMed1990

Infection of the heart by the human immunodeficiency virus.

Heart muscle disease in the acquired immune deficiency syndrome (AIDS), characterized by electrocardiographic changes or congestive cardiomyopathy, is a documented clinical problem, but its pathogenesis is obscure. In AIDS the heart is known to be involved by a variety of opportunistic infections as well as Kaposi's sarcoma, but no causative relation with the development of cardiomyopathy has been established. This study reports evidence for direct infection of the heart in AIDS, not by an opportunistic pathogen but by the AIDS, not by an opportunistic pathogen but by the AIDS virus itself, the human immunodeficiency virus (HIV). For this study the technique of in situ deoxyribonucleic acid hybridization was applied to cardiac tissues obtained at autopsy from AIDS patients. Using sulfur-35-labeled ribonucleic acid probes encompassing the entire HIV genome, HIV nucleic acid sequences were detected in cardiac tissue sections from 6 of 22 patients examined who died of AIDS. The hybridization targets appeared to be cardiac myocytes, although their precise morphology was often obscured by the intensity of the signal. The myocardial cells showing a positive hybridization signal were sparse, often comprising only 1 or a few cells per section, and their number and location did not correlate obviously with any histopathologic or clinical evidence of heart muscle disease in these patients. It is conceivable that the presence of HIV nucleic acid sequences may represent a preclinical marker of impending AIDS-associated heart muscle disease. This sequela would not be recognized in many patients, including those in this series, who died rapidly of Pneumocystis carinii pneumonia, Kaposi's sarcoma and other well-documented manifestations of AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

Cosmetic leg veins: evaluation using duplex venous imaging.

The records of 305 consecutive patients who had presented with cosmetic symptoms related to varicose and/or spider veins over a 12-month period were studied. Following clinical assessment, 250 (82%) patients were referred for duplex venous imaging. A total of 500 lower limbs were evaluated; 236 (47%) were documented to have incompetence in the superficial venous system (long or short saphenous veins). Only 6 (1%) limbs had deep venous incompetence and 45 (9%) limbs were found to have perforator incompetence. Short saphenous vein incompetence was found in 59 (12%) limbs. In the long saphenous vein there was a consistent pattern of an increasing incidence of incompetence from the saphenofemoral junction down to the below-knee segment. The duplex imaging findings were applied to determine the optimal treatment, ie, whether surgery, sclerotherapy, or a combination of both would provide the best short- and long-term results. The possible etiology and pathophysiology of spider and varicose veins are discussed in relation to these results.

Adolescent↗
PubMed1990

Rapid diagnosis by buffy coat smear of disseminated Mycobacterium avium complex infection in patients with acquired immunodeficiency syndrome.

A smear of the buffy coat of peripheral blood for acid-fast bacilli was assessed for sensitivity and specificity in the diagnosis of disseminated Mycobacterium avium complex (MAC) infection in acquired immunodeficiency syndrome (AIDS) patients. Seventeen AIDS patients with blood cultures positive for MAC had simultaneous quantitative blood cultures and buffy coat smears performed, as did 4 patients later proven not to have disseminated MAC. The sensitivity of the buffy coat smear for the detection of MAC was 35%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 22%. We conclude that the buffy coat smear is a rapid, simple, and specific method of diagnosis of disseminated MAC infection in AIDS patients, although it is not very sensitive.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Fitness, performance and anthropometric characteristics of 19,185 Canadian Forces personnel classified according to body mass index.

The Canadian Forces (CF), concerned with the possible adverse effects of obesity on military performance and image, recently adopted the body mass index (BMI) to monitor excess weight among its personnel. Subsequently, the records of 17,098 CF men (32.0 +/- 8 years) and 2,087 CF women (26.2 +/- 5 years) were examined. Approximately 50% of the men and 25% of the women had a BMI greater than 25 kg/m2, while 26% of the men and 12% of the women had a BMI greater than 27 kg/m2. Except for grip strength, both men and women in higher BMI zones typically demonstrated significantly lower fitness and performance scores than those in lower BMI zones. For men and women, increasing BMI was associated with progressive and significant increases in body weight, chest girth, waist girth, gluteal girth, thigh girth, waist-to-hip ratio, and waist-to-height ratio, and decreases in difference between chest-minus-waist girths. Waist girth increased proportionately more than other circumferences with increasing BMI, thus indicating a greater relative deposition of body fat in the abdominal region. In view of the relationship between high BMI and compromised fitness, appearance, and health observed in this population, the CF would benefit from continued educational and clinical efforts to reduce the prevalence of obesity. The BMI would serve as a useful epidemiologic standard to help monitor progress in these areas.

Adult↗