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Biomedical subjects

M Schneider

Publications and source records attributed to M Schneider.

At least 145 records · Page 8Linked to original sources

Functional results after anterior cruciate ligament reconstruction using the patellar ligament bone-tendon-bone technique.

This study evaluates the outcome after surgical repair of the cruciate ligament in 129 patients (physical examination plus questionnaire) and another 49 patients (questionnaire only) after a mean interval of 3.2 years. A modified Lysholm score and the OAK score together with KT 1000 arthrometry were used. Ninety-five percent of patients evaluated the overall result as 'excellent' or 'good'. The overall OAK objective score was good or excellent in 81%. Elongation as measured by KT 1000 arthrometry was 1.0 mm (67 N) and 1.2 mm (90 N) on average compared with the contralateral knee.

Anterior Cruciate Ligament Injuries↗

Comparison between nasogastric tube feeding and percutaneous fluoroscopic gastrostomy in advanced head and neck cancer patients.

Wasting is a major complication of advanced head and neck cancer and the aim of this study was to compare nasogastric tube feeding (NG) and percutaneous fluoroscopic gastrostomy (PFG) in these patients. The goal of these two methods of nutritional support was to improve or maintain the initial nutritional status during treatment. A total of 90 patients, all stage IV oropharynx or hypopharynx tumor, were reviewed from a prospective databank. All these patients were treated by concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration. Fifty patients were managed by PFG, and the rest by NG. Mechanical failure, duration of feeding, complications, nutritional evaluation and quality of life were analysed. Mechanical failure occurred in 32 of the 40 NG patients and in seven of the gastrostomy group. In the PFG group, 80% of patients conserved their nutritional support after the end of the radiotherapy, none patient in the NG group. In the PFG group, two presented a wound infection and six had aspiration pneumonia while in the NG group, 21 had aspiration pneumonia probably due to the NG tube (gastroesophageal reflux). The feeding methods were found to be equally effective at maintaining body weight and body mass index at time 1 (3 weeks) and at time 2 (6 weeks). Advantages were associated with PFG cosmesis, mobility and quality of life. PFG is a safe and effective method of providing enteral nutrition during treatment to patients with advanced head and neck cancer and offers important advantages over NG.

Administration, Cutaneous↗

Rapid improvement of nitric oxide bioavailability after lipid-lowering therapy with cerivastatin within two weeks.

OBJECTIVES: We investigated whether improvement of endothelial dysfunction in hypercholesterolemia can be achieved with short-term lipid-lowering therapy. BACKGROUND: Impaired endothelium-dependent vasodilation plays a pivotal role in the pathogenesis of atherosclerosis and acute coronary syndromes. METHODS: In a randomized, double-blind, placebo-controlled trial, we studied 37 patients (52 +/- 11 yrs) with low density lipoprotein cholesterol > or = 160 mg/dl (196 +/- 44 mg/dl) randomly assigned to either cerivastatin (0.4 mg/d) or placebo. Endothelium-dependent vasodilation of the forearm vasculature was measured by plethysmography and intra-arterial infusion of acetylcholine (ACh 12, 48 microg/min) and endothelium-independent vasodilation by intra-arterial infusion of nitroprusside (3.2, 12.8 microg/min). RESULTS: Low density lipoprotein cholesterol decreased after two weeks of treatment (cerivastatin -33 +/- 4% vs. placebo + 2 +/- 4%, x +/- SEM, p < 0.001). Endothelium-dependent vasodilation improved after two weeks of therapy with cerivastatin compared with baseline (ACh 12 microg/min: + 22.3 +/- 5.2 vs. + 11.2 +/- 1.9 ml/min/100 ml, p < 0.01; ACh 48 microg/min: +31.2 +/- 6.3 vs. +19.1 +/- 3.1 ml/min/100 ml, p < 0.05). In contrast, changes in forearm blood flow to ACh were similar before and after therapy in the placebo group (ACh 12 microg/min: + 12.9 +/- 3.6 vs. + 9.0 +/- 1.9 ml/min/100 ml, NS; ACh 48 microg/min: +20.7 +/- 3.7 vs. 19.4 +/- 2.9 ml/min/100 ml, NS). Endothelium-dependent vasodilation improved in comparison with placebo (ACh 48 microg/min: +203 +/- 85% [cerivastatin] vs. -26 +/- 71% [placebo], p < 0.05). This improvement in endothelium-dependent vasodilation was no longer observed when the nitric oxide-synthase inhibitor N(G)-monomethyl-L-arginine was coinfused (ACh 48 microg/min + N(G)-monomethyl-L-arginine 4 micromol/min -48 +/- 85% [cerivastatin]). CONCLUSIONS: Short-term lipid-lowering therapy with cerivastatin can improve endothelial function and NO bioavailability after two weeks in patients with hypercholesterolemia.

Adult↗

The relationship of epidermal growth factor receptor levels to the prognosis of unresectable pharyngeal cancer patients treated by chemo-radiotherapy.

The aim of this study was to analyse prognostic factors for time to treatment failure (TTF) and overall survival (OS) in patients with unresectable cancer of the pharynx. A twice daily (b.i.d.) radiotherapy with concomitant cisplatin-5-fluorouracil chemotherapy was administered to 77 consecutive patients (68 males, 9 females; median age: 56 years). The studied factors were: age, gender, tumour differentiation, tumour volume, initial hemoglobin level, karnofsky index (KI), primary tumour location, T, N, epidermal growth factor receptor (EGFR) level in the tumour (fmol/mg protein). KI and EGFR level were significant predictors in a multivariate analysis for TTF (P=0.004 and P=0.0001) and OS (P=0.004 and P=0.0001). In order to select subgroups with different outcomes, a stratification of patients was performed based on the EGFR value: patients with tumour EGFR levels <35 fmol/mg protein, between 35 and 275 fmol/mg protein and >275 fmol/mg protein had 95%, 51% and 16% 3 year OS rates, respectively (log rank test; P=0.0001). Interestingly, for patients exhibiting a complete response (CR) after concomitant b.i.d. chemo-radiotherapy, patients with EGFR levels <35 fmol/mg protein were all alive at 3 years; in contrast, there was only 70 and 13% 3 year survival rates for patients with EGFR tumour levels between 35 and 275 fmol/mg protein and above 275 fmol/mg protein, respectively. EGFR determination appears to be a powerful prognostic parameter in unresectable pharyngeal cancer patients treated by concomitant chemo-radiotherapy.

Adult↗

Differences between adolescents and young adults at presentation to an eating disorders program.

OBJECTIVE: To describe differences between adolescents and adults in clinical presentation of eating disorders. METHODS: Data from the charts of 622 female patients treated for an eating disorder in a division of adolescent medicine between 1980 and 1994 were coded and computerized. General categories included demographic and family factors, weight loss and weight changes, eating-related behaviors, diagnosis and severity, and treatment issues. Differences between the 438 patients who were aged 9-19 years (adolescents) and 184 patients who were aged 20-46 years (adults) were analyzed. RESULTS: Adolescents were more likely than adults (p <.05) to have a diagnosis of "eating disorder not otherwise specified," lower global severity score, greater denial and less desire for help, weight loss > or = 3 lb/month, lower original and maximum weights, and history of fasting and elimination of junk food from their diets. Adults were more likely than adolescents (p <.05) to have >1 year of weight loss, greater total weight loss, history of binge eating and laxative use, history of diuretic and ipecac use, diagnosis of bulimia nervosa, and prior use of psychiatric medications. Adolescents and adults did not differ (p >.05) in parents' occupational level; height, weight, and percent ideal body weight at presentation; original percent ideal body weight; use of diet pills, elimination of meat and use of a low-fat diet; daily calorie intake; prior eating disorder hospitalizations; and hospitalization during the course of treatment. CONCLUSIONS: The findings in this study document and confirm that there are important differences between adolescents and adults that must be taken into account in the evaluation and treatment of patients with eating disorders.

Adolescent↗

[Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center].

PURPOSE: Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. PATIENTS AND METHODS: From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. RESULTS: Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009). CONCLUSION: These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

Adult↗

Defining premature ejaculation for experimental and clinical investigations.

Researchers investigating premature ejaculation (PE) have employed widely diverse definitions of it, thereby limiting progress in the field. This study summarizes available research on PE, notes patterns that emerge from these studies, compares patterns across several types of studies, and suggests a common model for defining PE groups to guide future research. We surveyed two bibliographic databases, identifying 45 studies employing a definition or description of a PE group. From these, we extracted a range of information, including descriptions of the participants, recruitment procedures, if PE subtypes were identified, operational criteria for PE classification, relationship and partner information, and additional inclusion/exclusion criteria. Over 50% of studies reported no criteria, or relied on simple self-identification by participants to establish the PE group. Quantifiable behavioral criteria were used in 49% of the studies, with ejaculatory latency reported most frequently. This measure was also used as a criterion more frequently in studies focusing on assessment of sexual response, whereas the number of penile thrusts was used more frequently in studies prior to 1989. Partner information was often included but seldom used as part of the assessment procedure. Progress on research and treatment of PE will continue to be limited by the absence of commonly accepted criteria for PE group membership and by a lack of identification of relevant PE subtypes and etiologies. This paper suggests a flowchart, based on data and a rational analysis of 40 years of research, for characterizing PE in ways that could assist the development of the field.

Ejaculation↗

Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer.

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m2 was weekly given by short infusion, and nolatrexed 725 mg/m2 per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA. 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.

Adult↗

Structure of transfection-active histone H1/DNA complexes.

Relationships between the structure of transfecting complexes of histone H1 and DNA and their transfection efficiency were studied. Transfection activity proved to be connected to complex aggregates. Low speed centrifugation of the complexes resulted in loss of the transfection activity. The complexes/aggregates were active with high efficiency in a broad range of weight input ratios r(i) (0.1 < r(i) < 30). Using atomic force microscopy (AFM), the complexes were imaged at negative, nearly electroneutral and positive charge conditions. Electroneutral complexes at r(i) = 1 showed a multitude of different complex forms. Fibrillar, network-like and branched structures were frequently present in one complex. Strongly positive charged complexes had a toroidal appearance. All these different forms contributed to the high transfection efficiency. Cellular uptake is supposed to be by phagocytosis.

Animals↗

Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin.

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.

Adult↗

Influence of transplantation regimen on prognostic significance of high-level minimal residual disease before allogeneic stem cell transplantation in children with ALL.

High MRD levels before transplantation in children receiving T cell-depleted unrelated grafts for relapsed ALL were associated with a 100% relapse risk. We report on two children with relapsed ALL who underwent non T cell-depleted BMT from unrelated donors. Despite a high residual tumor load pre- transplant and the occurrence of only aGVHD grade I, they are still in second complete remission 2.7 and 5.2 years after transplantation, respectively. Thus, we propose that the transplant regimens influence the prognostic significance of high MRD levels pre-BMT.

Burkitt Lymphoma↗

Identification of the beta-dystroglycan binding epitope within the C-terminal region of alpha-dystroglycan.

Dystroglycan is a receptor for extracellular matrix proteins that plays a crucial role during embryogenesis in addition to adult tissue stabilization. A precursor product of a single gene is post-translationally cleaved to form two different subunits, alpha and beta. The extracellular alpha-dystroglycan is a membrane-associated, highly glycosylated protein that binds to various extracellular matrix molecules, whereas the transmembrane beta-dystroglycan binds, via its cytosolic domain, to dystrophin and many other proteins. alpha- and beta-Dystroglycan interact tightly but noncovalently. We have previously shown that the N-terminal region of beta-dystroglycan, beta-DG(654-750), binds to the C-terminal region of murine alpha-dystroglycan independently from glycosylation. Preparing a series of deleted recombinant fragments and using solid-phase binding assays, the C-terminal sequence of alpha-dystroglycan containing the binding epitope for beta-dystroglycan has been defined more precisely. We found that a region of 36 amino acids, from position 550-585, is required for binding the extracellular region, amino acids 654-750 of beta-dystroglycan. Recently, a dystroglycan-like gene was identified in Drosophila that showed a moderate degree of conservation with vertebrate dystroglycan (31% identity, 48% similarity). Surprisingly, the Drosophila sequence contains a region showing a higher degree of identity and conservation (45% and 66%) that coincides with the 550-585 sequence of vertebrate alpha-dystroglycan. We have expressed this Drosophila dystroglycan fragment and measured its binding to the extracellular region of vertebrate (murine) beta-dystroglycan (Kd = 6 +/- 1 microM). These data confirm the proper identification of the beta-dystroglycan binding epitope and stress the importance of this region during evolution. This finding might help the rational design of dystroglycan-specific binding drugs, that could have important biomedical applications.

Amino Acid Sequence↗

Lupus-like syndrome with submassive hepatic necrosis associated with hepatitis A.

Hepatitis A is a common self-limited liver disease. However, 15% of patients may have some complications. Autoimmune hepatitis that is triggered by viral hepatitis has been reported. We hereby describe an unrecognized association of hepatitis A with a full blown lupus-like syndrome manifested by the appearance of arthralgia, exudative pleural effusion with the presence of lupus erythematosus cells and autoantibodies. All these findings disappeared after a short course of steroid treatment. The case is presented and the literature is reviewed.

Acute Disease↗

Peritoneal dialysis fluids with a physiologic pH based on either lactate or bicarbonate buffer-effects on human mesothelial cells.

Conventional lactate (Lac)-buffered peritoneal dialysis (PD) solutions have turned out to be detrimental to human peritoneal cells, especially because of a low pH. In the present study, we focus on potential differences between Lac and bicarbonate (Bic) as a buffer when adjusted to a physiological pH. All test fluids were buffered with either 40 mmol/L of Lac or 34 mmol/L of Bic, sterile filtered, and adjusted to a pH of 7.4. Osmotic agents used were 1.36% glucose (Glu), 3.86% Glu, 1% amino acids (AA), and 7.5% Glu polymer (Glupoly). Human peritoneal mesothelial cells (HPMCs) were isolated from the omentum majus, grown to confluence, and incubated after the second passage for 15 minutes (37 degrees C and 5% carbon dioxide) with the test fluids. Cytotoxicity was controlled by measuring apoptotic and necrotic cells with cytofluorometry. Aerobic cell metabolism (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay) and intracellular adenosine triphosphate (ATP) concentrations were measured to assess cell viability. Release of interleukin-6 (IL-6) from HPMCs was determined as a parameter of cellular host defense. No significant difference in apoptosis or necrosis rates was found between the solutions adjusted to normal pH. However, in the MTT assay, Bic solutions were superior to corresponding Lac pendants at an identical pH of 7.4 (P < 0.01). Intracellular ATP concentrations reflected a very similar pattern (P < 0.05). Glupoly in combination with Lac showed an impaired pattern with both the MTT and ATP assays. Regarding IL-1beta-stimulated IL-6 release, there was a small, but not significantly better, response for Bic. Differences in manifest cell cytotoxicity reflected by apoptosis and necrosis rates could not be detected comparing PD solutions buffered with Lac or Bic at a physiological pH. However, distinct parameters of cell metabolism were superior with Bic compared with Lac. Especially Glupoly was inferior in combination with Lac as a buffer.

Adenosine Triphosphate↗

[First results in an animal model on stents sheathed with a polytetrafluoroethylene membrane].

OBJECTIVES: Mechanisms of restenosis after coronary stent implantation include marked intimal proliferation as well as vascular tissue protrusion through the meshes. Thus, stent sheathed with membranes may be an alternative to improve the long-term outcome. METHODS: Seventeen cylindric serpentine shaped 316L stainless steel stents (nominal diameter 3.0 mm, length 15 mm) lined and covered by a polytetrafluoroethylene (PTFE) membrane and 10 unsheathed devices were implanted into the iliac arteries of 14 New Zealand White Rabbits for an observation period of 1 - 10, 11 - 20, and 21 - 30 weeks. After sacrificing the animals, specimens were harvested, fixed in formalin, processed in paraffin, serially sliced into 5 microm thick preparations, and stained (hematoxylin & eosin, elastica von Gieson). RESULTS: The polytetrafluoroethylene membrane stents increased the vascular lumen significantly (p < 0.04) to 1185.3 - 1620.4 microm compared with the native segments (655.6 +/- 268.8 microm). In the stainless steel stents the lumen decreased from 1873.1 microm to 719.1 microm. None of the devices penetrated the internal elastic membrane. There was no inflammatory vascular reaction. Compared to the native segments, the amount of elastic fibres was slightly less (native: 8.9 %, PTFE: 2.3 - 3.5 %, without PTFE: 1.9 - 5.5 %) whereas the collagen fibres increased marginally (native: 5.1 %, PTFE: 6 - 6.9 %, without PTFE: 6.4 - 8.4 %). CONCLUSIONS: In the rabbit iliac artery, stents sheathed with a microporous polytetrafluoroethylene membrane showed good tissue compatibility with no restenosis. These results warrant clinical trials.

Angioplasty, Balloon, Coronary↗

[MR-morphological changes of the metacarpophalangeal joints in patients with rheumatoid arthritis: Comparison of early and chronical stages].

UNLABELLED: MR-morphological changes of the metacarpophalangeal joints in patients with rheumatoid arthritis: Comparison of early and chronical stages. PURPOSE: Evaluation of MRI findings in the metacarpophalangeal (MCP) joints in patients with early (eRA) and chronical rheumatoid arthritis (cRA). MATERIAL AND METHODS: In 22 RA patients (9 with disease duration </= 1.5 years = eRA) the dominant hands were examined by MRI in coronal T(2) weighted turbo-spin-echo (TSE). T(1) weighted spin-echo (SE) sequences before and after injection of Gd-DTPA and fat-suppressed short tau inversion recovery (STIR) sequences, followed by miniarthroscopy (MA) of the MCP II joint after an interval of 24 hours. MRI and MA findings were assessed using standardised semiquantitative items of synovial and bony pathologies and a statistical comparison between eRA and cRA patients was performed. RESULTS: In MRI synovial proliferation was detected in 13/13 cRA and 8/9 eRA patients. It was statistically not significant; the degree of synovial proliferation was however lower in the eRA group. All eRA patients with synovial changes showed enhancement after administration of contrast medium, a marker which correlated with the clinical activity. In 2/13 cRA patients no uptake of contrast medium was evident. Bony erosions and strongly narrowing joint space correlated with disease duration and were documented significantly rarer in the eRA patients (1/9, 2/9) than in the cRA patients (9/13, 10/13). CONCLUSION: In RA patients, MRI of the metacarpophalangeal joints can detect specific pathological changes which are observed significantly more often in either early or chronic stages and which are associated with disease activity and duration.

Adult↗

The relationship of pregnancy to the use of highly active antiretroviral therapy.

OBJECTIVE: Public health agencies have recommended that the criteria for the use of highly active antiretroviral therapy should not be modified because of pregnancy. However, little information has been published with regard to the degree to which these recommendations are being followed. We report here the frequency of highly active antiretroviral therapy use among pregnant women in the Women's Interagency HIV Study and compare the frequencies of its use by pregnant women meeting published criteria for implementing highly active antiretroviral therapy and its use by nonpregnant women meeting the same criteria. STUDY DESIGN: From October 1994 through November 1995, a total of 2059 human immunodeficiency virus type 1-seropositive women were enrolled in a cohort study. Participants were evaluated at baseline and at 6-month intervals with standardized interview instruments. In addition to a general physical examination at each visit, patients had a urine pregnancy test performed and were asked about current pregnancies, pregnancies since the last visit, and which antiretroviral medications they had used since the last visit. Highly active antiretroviral therapy was defined according to 1997 National Institutes of Health guidelines. RESULT: At each calendar interval after October 1996, a greater proportion of nonpregnant women than pregnant women reported the use of highly active antiretroviral therapy. The use of monotherapy declined for both groups during the course of multiple calendar periods (P <.01), although the use of monotherapy remained higher among the pregnant women. In any given calendar period, pregnant women meeting published criteria for highly active antiretroviral therapy use were slightly less likely than similar nonpregnant women to receive highly active antiretroviral therapy (odds ratio, 0.28-0.98). Because of the sample size these differences reached significance in only one calendar period (P =.02). With time pregnant women did demonstrate an increase in the percentage receiving highly active antiretroviral therapy. In nearly all calendar periods a larger percentage of pregnant than nonpregnant women were receiving a regimen that included zidovudine. CONCLUSIONS: Highly active antiretroviral therapy is being received by an increasing percentage of women who meet published criteria for its use, and pregnancy is a relatively small impediment to its use. Further efforts are needed to bolster the use of highly active antiretroviral therapy by all appropriate candidates and to ensure equal access to this therapy for pregnant women. Because of the increasingly frequent use of highly active antiretroviral therapy during pregnancy, ongoing efforts are needed to monitor any long-term effects of in utero exposure to multiple antiretroviral agents.

Anti-HIV Agents↗

Protective effects of vitamins C and E on the number of micronuclei in lymphocytes in smokers and their role in ascorbate free radical formation in plasma.

Cigarette smoke is widely believed to increase free radical concentrations causing subsequent oxidative processes that lead to DNA damage and hence, to several diseases including lung cancer and atherosclerosis. Vitamin C is a reducing agent that can terminate free-radical-driven oxidation by being converted to a resonance-stabilized free radical. To investigate whether short-term supplementation with the antioxidants vitamin C and E decreases free-radical-driven oxidation and thus decreases DNA damage in smokers, we determined the frequency of micronuclei in lymphocytes in 24 subjects and monitored the electron paramagnetic resonance signal of ascorbate free radical formation in plasma. Further parameters comprised sister-chromatid exchanges and thiobarbituric acid-reactive substances. Twelve smokers and twelve non-smokers took 1000 mg ascorbic acid daily for 7 days and then 1000 mg ascorbic acid and 335.5 mg RRR-alpha-tocopherol daily for the next 7 days. Baseline concentrations of both vitamins C and E were lower and baseline numbers of micronuclei were higher (p < 0.0001) in smokers than in non-smokers. After 7 days of vitamins C and E, DNA damage as monitored by the number of micronulei was decreased in both, smokers and non-smokers, but it was more decreased in smokers as indicated by fewer micronuclei in peripheral lymphocytes (p < 0.05). Concomitantly, the plasma concentrations of vitamin C (p < 0.001) as well as the ascorbate free radical (p < 0.05) were increased. The corresponding values in non-smokers, however, did not change. Our findings show that increased ascorbate free radical formation in plasma after short-term supplementation with vitamins C and E can decrease the number of micronuclei in blood lymphocytes and thus DNA damage in smokers.

Adult↗