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Biomedical subjects

A Lewin

Publications and source records attributed to A Lewin.

At least 19 recordsLinked to original sources
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↗
PubMed1998

A birth in non-mosaic Klinefelter's syndrome after testicular fine needle aspiration, intracytoplasmic sperm injection and preimplantation genetic diagnosis.

Non-mosaic Klinefelter patients are generally azoospermic due to primary testicular failure. Nevertheless, in some cases, testicular spermatozoa may be recovered and utilized to fertilize oocytes via intracytoplasmic sperm injection (ICSI). As the risk for an increased number of gonosomes in these spermatozoa is unclear, preimplantation genetic diagnosis (PGD) may be attempted in the resulting embryos. In the present study, we report our experience with the combined approach of sperm retrieval by testicular fine needle aspiration (FNA), ICSI and PGD in seven consecutive non-mosaic Klinefelter individuals. In four patients, between one and five spermatozoa were retrieved in five out of nine consecutive attempts. In a fifth patient, only 10 round spermatids could be isolated. Mature spermatozoa were injected into a total of 16 metaphase-II oocytes, of which 11 (69%) remained intact. Two distinct pronuclei (2PN) were observed in four oocytes (36%) while a single pronucleus (1PN) was documented in two oocytes. Five cleavage stage embryos developed from the oocytes of two couples. Upon the request of one couple, their three embryos (two derived from 1PN oocytes) were transferred without PGD but pregnancy was not achieved. PGD by fluorescence in-situ hybridization (FISH) was performed in the two embryos of the other couple which were derived from normal fertilization. PGD results of one embryo were 18,18,X,X,Y, the embryo was not transferred and FISH analysis of the remaining blastomeres identified variable chromosome numbers in the nuclei. The second embryo was diagnosed as normal and was transferred, resulting in a successful pregnancy and birth. In conclusion, the results of this report indicate that a pregnancy and birth may be attained in azoospermic non-mosaic Klinefelter individuals by testicular FNA combined with ICSI. Due to the unknown risk of gonosomes aneuploidy in embryos from Klinefelter patients, PGD or prenatal diagnosis should be recommended.

Adult↗
PubMed1998

Intracytoplasmic sperm injection allows fertilization and development of a chromosomally balanced embryo from a binovular zona pellucida.

A binovular zona pellucida was found in two in-vitro fertilization (IVF) treatment cycles. In both cases, two oocytes of slightly unequal size were enclosed within a single zona pellucida, the larger oocyte appearing as a metaphase II oocyte while the smaller one as an immature oocyte with a germinal vesicle. Intracytoplasmic sperm injection performed in the mature oocyte of each pair led to normal fertilization and embryonic development in both cases. Results of genetic analysis performed by fluorescence in-situ hybridization in one of the two treatment cycles were consistent with a diploid chromosomal status of both the non-injected immature oocyte as well as the embryo which developed following the microinjection. These results indicate that, in this case, the binovular zona pellucida was most probably created when granulosa cells failed to separate two distinct oocytes during follicular formation. It may also imply that selective fertilization of a single mature oocyte in a binovular zona pellucida by intracytoplasmic sperm injection can lead to the development of a chromosomally balanced embryo and can prevent the undesired consequences that may result if the two oocytes are fertilized in the course of standard IVF.

Adult↗
PubMed1998

Assisted reproduction for the treatment of azoospermia.

Azoospermia, the most severe form of male infertility, is caused by obstructions in the genital tract or by testicular failure. Microsurgical techniques are available for the correction of some of these obstructions but no effective treatment is available for testicular failure. In recent years, methods have been developed for direct surgical sperm sampling from either the epididymis or the testis to be used by intracytoplasmic sperm injection. The main approach proven to be effective for the retrieval of spermatozoa from the epididymis in patients with obstructive azoospermia is microsurgical epididymal sperm aspiration, although recently the retrieval of spermatozoa by fine needle aspiration was shown to be equally effective. Recovery of spermatozoa is also now performed in patients with severely deficient spermatogenesis using testicular open biopsy as well as aspiration by fine needle. The ultimate choice of sperm retrieval method in these patients will depend not only on sperm availability, but also on the physiological consequences of the different techniques on testicular function. This article summarizes the recent advances achieved in the treatment of azoospermic patients using these assisted reproduction surgical techniques.

Humans↗
PubMed1998

Inhibition of RNA synthesis as a therapeutic strategy against Aspergillus and Fusarium: demonstration of in vitro synergy between rifabutin and amphotericin B.

We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.

Amphotericin B↗
PubMed1998

Selective degradation of nonsense beta-phosphodiesterase mRNA in the heterozygous rd mouse.

PURPOSE: To investigate the molecular mechanism relating phenotype and genotype in the rd mouse, mRNA and pre-mRNA levels derived from the wild-type and position-347 nonsense mutant beta-phosphodiesterase (beta-PDE) genes were determined and compared with the corresponding gene copy ratios. METHODS: Total RNA and genomic DNA was isolated from the retinas of three heterozygous rd/+ mouse strains. For each, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the ratio of wild-type and rd beta-phosphodiesterase pre-mRNA and mature mRNA. The gene copy ratio between wild-type and rd beta-PDE was also determined by quantitative PCR. RESULTS: The pre-mRNA ratio of wild-type versus nonsense mutant was close to 1:1, whereas the corresponding mRNA ratio was greater than 3:1, even though the gene copy ratio was confirmed to be 1:1. CONCLUSIONS: The equivalence of pre-mRNA ratio level for wild-type and nonsense mutant in the rd/+ retina indicates that both genes were transcribed at similar levels. Thus, neither the nonsense mutation at position 347 nor the intron 1 retroviral insertion also present in the rd gene seem to have affected gene transcription. In contrast, the strain-independent bias favoring wild-type mature mRNA in vivo suggests a specific degradation of mutant transcript during or after pre-mRNA splicing. This allele-specific degradation serves to decrease mutant transcript levels dramatically in all rd strains, and suggests that photoreceptor cells have the capacity to reduce the level of an mRNA containing a nonsense mutation.

3',5'-Cyclic-GMP Phosphodiesterases↗