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Biomedical subjects

A Lewin

Publications and source records attributed to A Lewin.

At least 19 recordsLinked to original sources
PubMed2005

Prophylactic administration of abatacept prevents disease and bone destruction in a rat model of collagen-induced arthritis.

Abatacept is the first in a new class of agents that selectively modulates T-cell activation by attenuating CD28-mediated co-stimulation. This study examined the effects of abatacept on disease development in a rat model of collagen-induced arthritis (CIA). The rats were treated with either abatacept (1mg/kg) or control IgG beginning at the time of induction of CIA. By day 16, significant paw swelling was observed in IgG-treated control animals that continued to increase, reaching a plateau on day 21. Prophylactic treatment with abatacept completely abrogated paw swelling throughout the study. Histopathology demonstrated a significant reduction in inflammation, cartilage destruction, bone resorption and pannus formation. Abatacept treatment resulted in 90% inhibition of circulating collagen-specific antibodies and decreased the serum expression of many cytokines and chemokines that were upregulated in diseased animals. Immunohistochemical analysis of the ankle joints demonstrated that interleukin-6 production was reduced in the tissues and the numbers of osteoclasts present in the joints were also decreased. Ankle microcomputer tomography (micro-CT) analyses dramatically demonstrated the protective effects of abatacept on bone destruction in these animals. Data presented here demonstrate that prophylactic administration of abatacept significantly inhibits the onset and progression of disease in a rat CIA model, with reductions in inflammation, inflammatory mediators, and bone and joint destruction.

Abatacept↗
PubMed2005

[Slow growth rate of mycobacteria. Possible reasons and significance for their pathogenicity].

A characteristic feature of mycobacteria is their slow growth rate, which in addition strongly varies in different species of the genus. All highly pathogenic species such as M. tuberculosis and M. leprae causing tuberculosis and leprosy, respectively, belong to the slow growing mycobacteria, while the apathogenic and opportunistic species are members of the fast growing mycobacteria. This suggests that the question be posed whether there is causality between mycobacterial growth rate and virulence. We discuss possible reasons for the slow and variable growth rates of mycobacteria and the current state of knowledge concerning the significance of slow growth for mycobacterial pathogenicity.

Animals↗
PubMed2005

Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients.

AIM: In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD-treated T2DM patients. METHODS: This was a randomized, double-blind, parallel group, multicentre study in T2DM patients, 30-75 years of age, who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l (100 mg/dl) prior to study entry. Other antidiabetic medications were also allowed. Following 6 weeks of open-label simvastatin 20 mg/day, patients were randomized to the addition of either blinded ezetimibe 10 mg/day (n = 104) or an additional blinded simvastatin 20 mg/day (total simvastatin 40 mg/day; n = 110) for 24 weeks. Patients were stratified according to TZD type and dose (pioglitazone 15-30 vs. 45 mg/day; rosiglitazone 2-4 vs. 8 mg/day). RESULTS: LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (-20.8%) than by doubling the dose of simvastatin to 40 mg (-0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated. CONCLUSIONS: Co-administration of ezetimibe with simvastatin, a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption, is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs.

Adult↗
PubMed2004

Twin delivery following 12 years of human embryo cryopreservation: case report.

It is uncertain how long IVF units can keep frozen embryos. Few data exist on success of embryo transfer for embryos that have been cryopreserved for many years. We report the delivery of healthy twins following the transfer of embryos cryopreserved for 12 years. To the best of our knowledge, this is the longest reported successful human embryo freezing.

Adult↗
PubMed2003

Use of a quantitative TaqMan-PCR for the fast quantification of mycobacteria in broth culture, eukaryotic cell culture and tissue.

The quantification of slow-growing mycobacteria such as Mycobacterium tuberculosis or M. bovis from in vitro and in vivo samples is complicated by their long generation time, their ability to form aggregates, and their capacity to persist in a state of dormancy. We compared different methods for the establishment of growth curves for broth cultures of M. bovis bacille Calmette-Guérin (BCG). A quantitative TaqMan-PCR yielded results comparable with those obtained by protein quantification and measurement of the ATP content of the cultures. The quantitative TaqMan-PCR furthermore turned out to be particularly suitable for the measurement of multiplication of BCG within eukaryotic cells. Furthermore, it is a fast method allowing an estimation of the mycobacterial load in tissue long before colony counts can be obtained.

Animals↗
PubMed2002

Cancer risks in populations living near landfill sites in Great Britain.

Previous studies have raised concerns about possible excess risks of bladder, brain and hepatobiliary cancers and leukaemias near landfill sites. Several cancers have been implicated, but no consistent pattern has emerged. We present a large nationwide analysis of selected cancers near landfill sites in Great Britain. The base population comprised people living within 2 km of 9565 (from a total of 19 196) landfill sites that were operational at some time from 1982 to 1997, with populations living more than 2 km from a landfill as reference. Risks of cancers at the above sites were computed with adjustment for age, sex, year of diagnosis, region and deprivation. National post-coded registers provided a total of 341 856 640 person-years for the adult cancer analyses and 113 631 443 person-years for childhood leukaemia. There were 89 786 cases of bladder cancer, 36 802 cases of brain cancer, 21 773 cases of hepatobiliary cancer, 37 812 cases of adult leukaemia and 3973 cases of childhood leukaemia. In spite of the very large scale of this national study, we found no excess risks of cancers of the bladder and brain, hepatobiliary cancer or leukaemia, in populations living within 2 km of landfill sites. The results were similar if the analysis were restricted to landfill sites licensed to carry special (hazardous) waste. Our results do not support suggestions of excess risks of cancer associated with landfill sites reported in other studies.

Child↗
PubMed2002

A high predictive value of the first testicular fine needle aspiration in patients with non-obstructive azoospermia for sperm recovery at the subsequent attempt.

BACKGROUND: The objective of this retrospective study, which included 51 men with non-obstructive azoospermia, was to evaluate the predictive value of the results of the first sperm recovery attempt on the probability for sperm recovery in a second attempt. METHODS AND RESULTS: A positive testicular fine needle aspiration (TEFNA) was defined as the recovery of any number of mature sperm. At the first and second TEFNA attempts, mature sperm were recovered in 33 (64.7%) and 25 (49%) of 51 patients respectively. In 23 of the 33 (69.7%) patients with a positive first TEFNA, sperm were recovered at both attempts, whereas in only two of 18 (11.1%) with a negative first TEFNA, sperm were recovered at the second attempt. Our analysis revealed a high predictive value of the first TEFNA for sperm recovery at the subsequent attempt, with a mean positive predictive value of 69.7%, with the highest probability being 90.9% in hypospermatogenesis, 72.7% in Sertoli cell-only pattern, 75% in tubular hyalinization, and the lowest being 28.6% in maturation arrest. The mean negative predictive value was 88.9%, which was high in all categories (80% in Sertoli cell-only pattern and 100% in maturation arrest and tubular hyalinization). CONCLUSION: A second TEFNA attempt should be offered to all non-obstructive azoospermic patients with a positive first TEFNA. Patients with a negative first TEFNA may undergo a repeated attempt, but a donor sperm back-up is strongly advised.

Adult↗
PubMed2002

Simplified artificial endometrial preparation, using oral estradiol and novel vaginal progesterone tablets: a prospective randomized study.

There are various successful protocols for artificial endometrial preparation, comprising induction of endometrial proliferation with estrogens and secretory transformation with progestins. The aim of this prospective randomized study was to evaluate a simplified approach for endometrial preparation, comparing two constant doses of oral estradiol combined with a novel low-dose vaginal natural progesterone preparation (100 mg Endometrin tablets). Twenty-nine patients were enrolled in the study and divided randomly into two groups. Both groups received oral estradiol tablets from the beginning of menstruation, group A (15 patients) receiving 4 mg/day divided into two doses of 2 mg each, and group B (14 patients) receiving 6 mg/day divided into three doses. Serum estradiol and progesterone and sonographic thickness of the endometrium were measured on the 1st day of menstruation and on the 6th, 11th, 16th and 21st days of the artificial cycle. Following the first 12 days of estradiol priming, with an endometrial thickness of > or = 8 mm, Endometrin vaginal tablets 100 mg were added twice a day for 10 days. On the 21st cycle day, an endometrial biopsy was taken from all patients using Pipelle. In all 29 patients, appropriate changes in estradiol, progesterone and endometrial thickness were observed. Estradiol levels were significantly higher in the 6 mg/day group on days 6 and 11, but no significant difference was noted in serum progesterone level and endometrial thickess between groups. Histological evaluation of endometrial biopsies, on the 21st day, revealed adequate late-secretory endometrium in 14/15 (93.3%) patients of group A and in 13/14 (92.9%) patients of group B. In conclusion, our results demonstrate that an appropriate endometrial secretory transformation may be induced using an economical regimen of fixed low-dose oral estradiol (4 mg/day) and low-dose vaginal progesterone tablets (Endometrin 100 mg twice daily).

Administration, Intravaginal↗
PubMed2001

Soluble ICAM-1 and E-selectin levels correlate with clinical and biological aspects of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess the potential involvement of the soluble endothelial cell-leukocyte adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathophysiology of capillary hyperpermeability in the ovarian hyperstimulation syndrome (OHSS). DESIGN: Controlled clinical study. SETTING: Women hospitalized for severe OHSS after ovulation induction for IVF at two tertiary medical centers. PATIENT(S): Eleven patients with severe OHSS undergoing IVF and 20 controls who had received a similar ovulation induction regimen and did not develop OHSS. INTERVENTION(S): Serial serum samples were obtained from all patients with OHSS from admission until discharge. Ascitic fluid was obtained from all patients by therapeutic paracentesis. Serum was obtained from all controls 4-8 days after ET. MAIN OUTCOME MEASURE(S): Samples were assayed for soluble E-selectin and soluble ICAM-1 by using enzyme-linked immunosorbent assay and results were correlated with clinical and biological aspects of OHSS. RESULT(S): Compared with controls, patients with severe OHSS had higher levels of soluble ICAM-1 and lower levels of soluble E-selectin detected in serum and ascites. Serum levels of soluble ICAM-1 decreased, while soluble E-selectin levels increased along with clinical and biological improvement. Serum soluble ICAM-1 showed significant positive correlation and serum soluble E-selectin showed significant negative correlation with clinical and biological aspects of severe OHSS. CONCLUSION(S): Soluble ICAM-1 and soluble E-selectin seem to be involved in the pathophysiology of capillary hyperpermeability in severe OHSS.

Adult↗
PubMed2001

Efficacy and safety of omapatrilat with hydrochlorothiazide for the treatment of hypertension in subjects nonresponsive to hydrochlorothiazide alone.

This multicenter, double-blind study evaluated efficacy and safety of the vasopeptidase inhibitor omapatrilat, which simultaneously inhibits neutral endopeptidase and angiotensin converting enzyme, when given in conjunction with hydrochlorothiazide (HCTZ) to subjects nonresponsive to HCTZ alone. The study enrolled 657 subjects with mild to severe hypertension. After a 2-week placebo lead-in period and a 4-week HCTZ phase, 274 subjects were randomized to receive omapatrilat (10 or 20 mg, electively titrated to 20 or 40 mg, respectively, at week 4 if seated diastolic blood pressure [SeDBP] was > or =90 mm Hg) or matching placebo in addition to 25 mg of HCTZ as continuing therapy. The primary outcome measure was change in SeDBP from baseline to week 8. At week 8, placebo plus HCTZ-adjusted additional reductions in SeDBP in the omapatrilat 10/20 mg and 20/40 mg treatment groups (4 and 5 mm Hg, respectively) were significant (P < .001), as were changes in seated systolic blood pressure in both omapatrilat-treated groups (7 and 10 mm Hg, respectively; P < .001). Seated diastolic blood pressure was normalized (<90 mm Hg) in 38% of subjects in the placebo group compared to 59% and 64% of subjects in the omapatrilat groups (P < or = .008). Adverse events, serious adverse events, and discontinuations attributed to adverse events were infrequent. There were no clinically relevant changes in serum creatinine or potassium. Omapatrilat was effective and well tolerated when added to HCTZ in subjects whose blood pressure was not controlled with HCTZ alone.

Adult↗
PubMed2000

Seasonal variability in fertilization and embryo quality rates in women undergoing IVF.

OBJECTIVE: IVF-ET provides unique controlled conditions for the study of seasonal influences on the human reproductive process. This study was designed to evaluate the effects of seasonality on fertilization rate, embryo quality, and conception rates. DESIGN: A retrospective observational cohort study. A chart review of all individuals undergoing IVF-ET from 1988 to 1991 at our institution was performed. SETTING: An assisted reproduction unit at a university-based tertiary medical center. PATIENT(S): 657 women, for a total of 1074 IVF-ET treatment cycles, were evaluated. From this population, we chose 305 women undergoing their first IVF-ET cycle for reasons of pure mechanical infertility. INTERVENTION(S): IVF-ET cycles. MAIN OUTCOME MEASURE(S): Seasonal variability in fertilization rates and quality-A embryo rates, and the correlation with the absolute number of light hours, as well as the influence of temperature, humidity, and other environmental parameters. RESULT(S): A significant seasonal variability in the fertilization rate and the quality-A embryo rate was demonstrated. The highest fertilization and quality-A embryo rates were observed during the spring and the lowest in the autumn. These changes correlated with the absolute number of light hours and its increment over time, but not with the temperature, humidity, or other environmental parameters. CONCLUSION(S): Seasonality seems to have a significant influence on the fertilization process and on the quality of the human embryos that are obtained in vitro, possibly because of the light/dark variations over time. If this finding is confirmed, these seasonal changes should be taken into account when evaluating infertility data and in everyday clinical practice.

Adult↗
PubMed2000

Systematic screening of Anopheles mosquito genomes yields evidence for a major clade of Pao-like retrotransposons.

We developed a degenerate PCR procedure to simultaneously amplify products from divergent retrotransposon families within the genomes of Anopheles mosquitoes. The procedure required cloning of multiple PCR products, but more than half of the clones subsequently sequenced were of retrotransposon origin. These included Copia-like and LINE retrotransposons, as well as the first Gypsy-like retrotransposons reported from mosquitoes. Furthermore, some Anopheles retrotransposon sequences showed similarity to the divergent Pao element from the silkmoth Bombyx mori. Phylogenetic analyses provided consistently strong bootstrap support (> 95%) for a major clade of Pao-like retrotransposons, which includes five mosquito sequences and the recently discovered Drosophila retrotransposons BEL and ninja. This appears to represent a new family of Pao-like LTR-retrotransposons distinct from the Copia and Gypsy families.

Amino Acid Sequence↗
PubMed2000

A highly homologous 68 kbp plasmid found in Vibrio vulnificus strains virulent for eels.

Vibrio vulnificus serovar E (biotype 2) strains are virulent for eels and have also been reported to cause illness in humans. Studies on the plasmid content of serovar E strains revealed the existence of a plasmid of approximately 70 kbp present in most of these strains. In this study we characterized the 70 kbp plasmids of seven biotype 2 strains isolated from seawater, diseased eels and wound infections in humans. We determined the exact size of the high molecular weight plasmids to be 68 kbp. A comparison of the plasmids of the seven strains by restriction length polymorphism and hybridization analysis showed them to be almost identical.

Animals↗
PubMed1999

Plasma immunoglobulins in patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess immunoglobulin (Ig) concentrations in plasma and ascitic fluid of patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Controlled clinical study. SETTING: Tertiary medical center. PATIENT(S): Ten patients with severe OHSS after ovulation induction for IVF and 10 controls who had undergone similar ovulation induction and did not develop OHSS. INTERVENTION(S): Three blood samples were obtained from each OHSS patient: one at the time of hospitalization for severe OHSS, one when significant clinical improvement was evident, and one at the first follow-up visit after discharge from the hospital. Blood samples were drawn from control patients 6-8 days after ET. Ascitic fluid was obtained from all patients with OHSS by therapeutic paracentesis. MAIN OUTCOME MEASURE(S): Immunoglobulin concentrations were assayed by radial immunodiffusion. RESULT(S): Significantly lower levels of gamma-globulins, specifically IgG and IgA, were detected in the plasma of patients with severe OHSS, whereas alpha- and beta-globulin levels as well as IgM levels were not significantly different from those in controls. Both IgG and IgA levels increased as patients clinically improved. Ascitic fluid contained high IgG, moderate IgA, and negligible IgM levels. CONCLUSION: Severe OHSS is characterized by hypogammaglobulinemia, attributed to leakage of medium-molecular-weight immunoglobulins such as IgG and IgA to the peritoneal cavity.

Adult↗
PubMed1999

Testicular fine needle aspiration: the alternative method for sperm retrieval in non-obstructive azoospermia.

The objective of this prospective open study was to determine the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by testicular fine needle aspiration (TEFNA) in men diagnosed with non-obstructive azoospermia. TEFNA consisted of a mean of 15 punctures and aspirations in each testis, using 23 gauge butterfly needles, connected to a 20 ml syringe with an aspiration handle. Patients (n = 85) underwent 111 TEFNA cycles. Mature testicular spermatozoa were recovered in 65 (58.5%) cycles from 50 (58.8%) patients. The sperm recovery rate by testicular histology was 14 out of 29 (48.3%) in patients with Sertoli cell-only, 13 out of 28 (46.4%) in patients with maturation arrest, 19 out of 20 (95%) in patients with hypospermatogenesis, four out of six (66.6%) in patients with tubular hyalinization due to non-mosaic Klinefelter's syndrome. No spermatozoa were found in two cases with post-irradiation fibrosis. ICSI was performed in all 65 cycles. In 58 cycles in which only the husbands' spermatozoa were used, 406 mature oocytes were injected, and 154 (37.9%) were normally fertilized. Of the 143 embryos that developed (92.8%), 119 were transferred in 42 cycles resulting in 18 clinical pregnancies (42. 8%), with 31 gestational sacs, providing an implantation rate of 26%. One abortion of a singleton pregnancy occurred (5.6%). No major side-effects, such as haematoma or infection were recorded. In conclusion, we have found TEFNA to be efficient, easy to learn, safe and well tolerated by all patients. In our opinion, TEFNA should be considered the first choice whenever sperm recovery is attempted in patients with non-obstructive azoospermia.

Adult↗
PubMed1998

Multiple hemopoietic defects and lymphoid hyperplasia in mice lacking the transcriptional activation domain of the c-Rel protein.

The c-rel protooncogene encodes a member of the Rel/nuclear factor (NF)-kappaB family of transcriptional factors. To assess the role of the transcriptional activation domain of c-Rel in vivo, we generated mice expressing a truncated c-Rel (Deltac-Rel) that lacks the COOH-terminal region, but retains a functional Rel homology domain. Mice with an homozygous mutation in the c-rel region encoding the COOH terminus of c-Rel (c-relDeltaCT/DeltaCT) display marked defects in proliferative and immune functions. c-relDeltaCT/DeltaCT animals present histopathological alterations of hemopoietic tissues, such as an enlarged spleen due to lymphoid hyperplasia, extramedullary hematopoiesis, and bone marrow hypoplasia. In older c-relDeltaCT/DeltaCT mice, lymphoid hyperplasia was also detected in lymph nodes, liver, lung, and stomach. These animals present a more severe phenotype than mice lacking the entire c-Rel protein. Thus, in c-relDeltaCT/DeltaCT mice, the lack of c-Rel activity is less efficiently compensated by other NF-kappaB proteins.

Animals↗
PubMed1998

Is natural genetic transformation a mechanism of horizontal gene transfer in Yersinia?

We investigated the capacity of different Yersinia strains with emphasis to Yersinia enterocolitica to take up and incorporate DNA by natural genetic transformation. Our studies were initiated by the observation of partial homology between the virulence plasmid of a pathogenic Y. enterocolitica strain (O: 3, biovar 4) and plasmids indiginous to different a pathogenic Y. enterocolitica biovar 1A strains revealed by hybridization studies. Furthermore, an observation of natural genetic transformation in a strain of Y. enterocolitica has been published by CALLAHAN and KOROMA (1979). To detect an uptake and incorporation of DNA, we incubated potential recipient strains with naked DNA under varying experimental conditions. The parameters tested were--the recipient strain,--the markers used to detect a DNA transfer,--the condition of the transforming DNA,--the nutrient availability,--the temperature,--the growth phase, and--the influence of stress. In our experiments, we could not identify conditions under which Y. enterocolitica could be naturally transformed. We thus conclude that natural transformation is unlikely to be an important mechanism for horizontal gene transfer in Yersinia.

Electroporation↗