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Biomedical subjects

V Mak

Publications and source records attributed to V Mak.

At least 19 recordsLinked to original sources
PubMed2006

Incidence of cancer in a cohort of patients with primary Sjogren's syndrome.

OBJECTIVE: To compare the incidence of subsequent cancers in a cohort of patients with primary Sjögren's syndrome (pSS) with that of the general population in the same region of England. METHODS: A retrospective analysis was carried out on 112 patients who had attended the out-patients department at University College Hospital, London, from 1979 onwards. Patients were followed up from diagnosis of pSS to diagnosis of first subsequent cancer, death, loss to follow-up or 31 December 2003 (the censoring date) to determine the person-years at risk for each individual. The expected numbers of subsequent cancers were calculated from sex-/age-/period-specific rates for the general population of southeast England, derived from registrations at the Thames Cancer Registry. Standardized incidence ratios (SIRs) were then calculated as the ratio of observed to expected numbers of cancers, along with 95% confidence intervals (CIs). Separate analyses were performed for all malignant cancers combined, lymphomas and non-lymphoid cancers. RESULTS: Among the 112 patients with pSS, 25 developed cancer (either before or after development of pSS), with lymphoma occurring in 11 cases. Nine patients had two cancers. There was a significantly elevated incidence of lymphomas in pSS patients compared with the general population (SIR 37.5, 95% CI 20.7-67.6). For non-lymphoid cancer, the observed increase in incidence was small and not statistically significant (SIR 1.5, 95% CI 0.9-2.6). CONCLUSION: This study confirms that there is an increased incidence of lymphoma in patients with pSS. An increase in the incidence of other cancers was not proven but the observation that some patients developed more than one cancer raises the possibility that there may be a subgroup of patients who are at greater risk of developing cancer.

Adult↗
PubMed2002

Catalase-like and superoxide dismutase-like activities in human seminal plasma.

Human spermatozoa are highly susceptible to oxidative injury but are naturally protected from such injury by the antioxidant properties of seminal plasma. We measured catalase-like and superoxide dismutase (SOD)-like activities in the seminal plasma of fertile and vasectomized men in order to gain insight into the potential source(s) and function(s) of these antioxidants in semen. Semen samples were obtained from fertile men ( n=11) and men post-vasectomy ( n=16). Catalase-like activity was measured by the decrease in hydrogen peroxide concentration after incubation with seminal plasma. SOD-like activity was measured as the inhibition of nitroblue tetrazolium reduction due to superoxide anion generation by xanthine plus xanthine oxidase. Mean seminal catalase-like activity (+/-1SD) in the fertile group was not significantly different from that of the post-vasectomy group (389+/-163 and 325+/-119 U/ml, respectively). Similarly, mean seminal SOD-like activity in the fertile group was not significantly different from that of the post-vasectomy group (37+/-10 and 36+/-10 U/ml, respectively). Our data suggest that the testis and epididymis are not an important source of catalase-like and SOD-like activities in semen. These findings indicate that antioxidants in semen are primarily of post-testicular origin and probably serve to protect ejaculated spermatozoa from oxidative stress such as that which occurs in the female reproductive tract.

Adult↗
PubMed2001

Effect of selective lipid extraction from different body regions on epidermal barrier function.

PURPOSE: To assess the effects of selective lipid extraction and tape stripping on transepidermal water loss (TEWL) at three body regions in the pig. METHODS: Lipids were extracted from the abdominal, inguinal. and back regions using three different solvent extraction procedures or cellophane tape stripping (15x) on Yorkshire pigs. Three solvent extraction stages were I, cyclohexane (5 ml for three, 1-min extractions): II, cyclohexane/ethanol (4:1) (5 ml for three, 1-min extractions): and III, cyclohexane/ethanol (1:4) (5 ml for three, 3-min extractions) extracted as follows: Site A, Stage I: Site B, Stage I and II; Site C, Stage I, II and III. Erythema, edema, and TEWL were assessed in control, tape-stripped, and extracted sites at 0, 6, and 24 h. The extracted lipids were analyzed by thin layer chromatography and quantified by densitometry for ceramide, cholesterol, cholesterol esters, fatty acids, and triglycerides. RESULTS: The change in TEWL (delta TEWL) in 14 of the 15 sites was the highest at 24 h and generally increased with each additional extraction. The greatest changes were present in the back. Each extraction stage removed specific lipids in reproducible quantities that caused the delta TEWL to increase from 0 to 24 h. Lipid removal was verified by transmission electron microscopy. The mean total lipid concentration depended on extraction solvents and body region, and was reproducible across sites and regions at equivalent stages of lipid extraction. Relative proportions of individual lipids extracted were similar across all body regions. Higher concentrations of total lipids were extracted from the back. CONCLUSIONS. These studies demonstrate that extraction of lipids increased the delta TEWL to a level similar to repeated tape stripping at all body sites in the pig. This study suggested that strategies that could biochemically alter epidermal lipid composition may increase absorption of simultaneously administered topical compounds and may be useful to enhance drug delivery.

Abdomen↗
PubMed2000

Smoking is associated with the retention of cytoplasm by human spermatozoa.

OBJECTIVES: To determine whether cigarette smoking is associated with the abnormal retention of residual sperm cytoplasm in infertile men. METHODS: Semen samples were obtained from 87 consecutive non-azoospermic men with idiopathic infertility (18 smokers and 69 nonsmokers) and from 20 men presenting for vasectomy (fertile controls). Standard semen parameters and the percentage of spermatozoa with residual cytoplasm (on Papanicolaou smears) were recorded. RESULTS: Subject age, semen volume, and sperm density, motility, and morphology were not significantly different between the two groups of infertile men. However, a significant difference was found in the mean +/- SEM percentages of sperm with cytoplasm droplets between smokers and nonsmokers (12.9% +/- 1.7% and 8.1% +/- 0.9%, respectively; P < 0.001). CONCLUSIONS: Our data suggest that cigarette smoking is associated with retention of sperm cytoplasmic droplets in infertile men, a morphologic characteristic associated with impaired sperm function.

Cytoplasm↗
PubMed2000

Influence of initial semen quality on the integrity of human sperm DNA following semen processing.

OBJECTIVE: To examine and compare the effects of density-gradient centrifugation on the integrity of sperm DNA from the semen of both fertile and infertile men. DESIGN: Prospective, observational study. SETTING: University infertility clinic. PATIENTS: Forty-four nonazoospermic, infertile men and nine fertile controls. INTERVENTIONS: Semen samples were processed by density-gradient centrifugation. Sperm motility and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa) were monitored before and after semen was processed. MAIN OUTCOME MEASURES: Sperm motility and DNA integrity. RESULTS: Following density-gradient centrifugation, mean sperm motility (+/-SEM) improved significantly compared to whole semen in samples from fertile and infertile men, respectively (71 +/- 6 vs. 49 +/- 7% and 56 +/- 3 vs. 44 +/- 3%, P<0.05). However, the percentage of sperm with denatured DNA increased compared to whole semen after processing of samples from infertile (25 +/- 3 vs. 15 +/- 2%, P<0. 01) but not fertile men (9 +/- 3 vs. 8 +/- 2%, P>0.05). CONCLUSIONS: Our data indicate that the potential detrimental effect of density-gradient centrifugation on sperm DNA integrity is related to the initial semen quality. These data urge us to examine our current sperm-processing techniques to minimize sperm DNA damage.

Acridine Orange↗
PubMed2000

Cystic fibrosis gene mutations and infertile men with primary testicular failure.

It has been proposed that the gene responsible for cystic fibrosis, called the cystic fibrosis transmembrane conductance regulator (CFTR) gene, may play an important role in the process of spermatogenesis. A group of azoospermic men with primary testicular failure underwent CFTR mutation analysis, including assessment of the intron 8 polythymidine tract (IVS8-T tract). An association was not found between CFTR mutations or the 5T variant of the IVS8-T tract and the primary testicular failure phenotype. This finding suggests that CFTR does not play a significant role in the aetiopathogenesis of primary spermatogenic dysfunction. Therefore, the abnormal testicular histological findings in some post-pubertal men with cystic fibrosis may be a result of nutritional deficiency or testicular obstruction rather than a primary defect in spermatogenesis. In addition, the decreased sperm count in oligozoospermic men with CFTR mutations may be secondary to partial reproductive tract obstruction and not abnormal spermatogenesis. Lastly, routine screening of men with primary testicular failure for CFTR gene mutations is not warranted.

Adult↗
PubMed1999

Proportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia.

CONTEXT: Infertile men with obstructive azoospermia may have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of which are rare in classic cystic fibrosis and not evaluated in most routine mutation screening. OBJECTIVE: To assess how often CFTR mutations or sequence alterations undetected by routine screening are detected with more extensive screening in obstructive azoospermia. DESIGN: Routine screening for the 31 most common CFTR mutations associated with the CF phenotype in white populations, testing for the 5-thymidine variant of the polythymidine tract of intron 8 (IVS8-5T) by allele-specific oligonucleotide hybridization, and screening of all exons through multiplex heteroduplex shift analysis followed by direct DNA sequencing. SETTING: Male infertility clinic of a Canadian university-affiliated hospital. SUBJECTS: Of 198 men with obstructive (n = 149) or nonobstructive (n = 49; control group) azoospermia, 64 had congenital bilateral absence of the vas deferens (CBAVD), 10 had congenital unilateral absence of the vas deferens (CUAVD), and 75 had epididymal obstruction (56/75 were idiopathic). MAIN OUTCOME MEASURE: Frequency of mutations found by routine and nonroutine tests in men with obstructive vs nonobstructive azoospermia. RESULTS: Frequency of mutations and the IVS8-5T variant in the nonobstructive azoospermia group (controls) (2% and 5.1% allele frequency, respectively) did not differ significantly from that in the general population (2% and 5.2%, respectively). In the CBAVD group, 72 mutations were found by DNA sequencing and IVS8-5T testing (47 and 25, respectively; P<.001 and P = .002 vs controls) vs 39 by the routine panel (P<.001 vs controls). In the idiopathic epididymal obstruction group, 24 mutations were found by DNA sequencing and IVS8-5T testing (12 each; P=.01 and P=.14 vs controls) vs 5 by the routine panel (P=.33 vs controls). In the CUAVD group, 2 mutations were found by routine testing (P=.07 vs controls) vs 4 (2 each, respectively; P=.07 and P=.40 vs controls) by DNA sequencing and IVS8-5T testing. The routine panel did not identify 33 (46%) of 72, 2 (50%) of 4, and 19 (79%) of 24 detectable CFTR mutations and IVS8-5T in the CBAVD, CUAVD, and idiopathic epididymal obstruction groups, respectively. CONCLUSIONS: Routine testing for CFTR mutations may miss mild or rare gene alterations. The barrier to conception for men with obstructive infertility has been overcome by assisted reproductive technologies, thus raising the concern of iatrogenically transmitting pathogenic CFTR mutations to the progeny.

Adult↗
PubMed1999

Potential adverse effect of semen processing on human sperm deoxyribonucleic acid integrity.

OBJECTIVE: To examine the effect of standard Percoll density-gradient centrifugation on human sperm DNA denaturation. DESIGN: Prospective, observational study. SETTING: University-based infertility clinic. PATIENT(S): Twenty-five nonazoospermic men. INTERVENTION(S): Semen samples (n = 25) were obtained from consecutively seen nonazoospermic men presenting for infertility evaluation. Samples were processed by two-layer and four-layer Percoll density gradients. Sperm motility and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa) were monitored before and after semen processing. Sperm chromatin integrity was expressed as the percentage of spermatozoa that demonstrated denatured DNA. MAIN OUTCOME MEASURE(S): Sperm motility and DNA integrity. RESULT(S): Mean sperm motility improved significantly after processing with two-layer and four-layer Percoll gradients compared with whole semen (54% and 57% motility versus 44% motility, respectively). In contrast, the percentage of sperm with denatured DNA increased after processing with two-layer and four-layer Percoll gradients compared with whole semen (34% and 32% versus 18%, respectively). CONCLUSION(S): Our data demonstrate that the improvement seen in sperm motility after Percoll processing is not associated with a similar improvement in sperm DNA integrity. These data suggest that we reexamine current sperm processing techniques to minimize sperm DNA damage and the potential transmission of genetic mutations in assisted reproductive cycles.

Acridine Orange↗
PubMed1998

Fibroblastic rheumatism: clinical and histologic evolution of cutaneous manifestations.

Correlation of the clinical manifestations of a patient with fibroblastic rheumatism with sequential skin biopsy findings revealed an early inflammatory stage with cutaneous nodules, patchy erythematous skin lesions, polyarthritis, dermal lymphomonocytic infiltrates, and fibroblastic and myofibroblastic proliferation, followed by a chronic stage with sclerodactyly, joint ankylosis, deformities and dense dermal fibrosis. Treatment of this rare disorder in its early active stages may prevent the development of incapacitating joint sequelae.

Arthritis↗
PubMed1997

Higher proportion of intact exon 9 CFTR mRNA in nasal epithelium compared with vas deferens.

The 5-thymidine (5T) variant of the cystic fibrosis transmembrane conductance regulator (CFTR) intron 8 polypyrimidine tract (IVS8-T tract) is the most frequent CFTR gene alteration identified in men with congenital bilateral absence of vas deferens (CBAVD). This alternative splicing variant gives rise to two transcripts, one normal with exon 9 intact and the other with in-frame deletion of exon 9. That CBAVD men usually have none of the other clinical signs of classical cystic fibrosis (CF) suggests less functional CFTR is produced in the reproductive tract than in other CF-associated organs. Nasal epithelia and segments of vas deferens were obtained from healthy, previously vasectomized men who presented for vasectomy reversal. Quantitative RT-PCR was performed on these specimens, with the region of CFTR cDNA spanning exon 9 amplified. For both nasal and vasal tissues, a strong positive correlation was found between the length of the IVS8-T tract and the proportion of mRNA with exon 9 intact. In addition, within the same subject, a significantly higher level of transcripts lacking exon 9 was found in vas deferens than nasal epithelia, regardless of the IVS8-T genotype. These findings suggest that the splicing of CFTR precursor mRNA is less efficient in vasal epithelia compared with respiratory epithelia. Thus, differential splicing efficiency between the various tissues which express CFTR provides one possible explanation for the reproductive tract abnormalities observed in infertile men with CFTR gene alterations but without other clinical manifestations of CF.

Alleles↗
PubMed1997

Suicide by age, ethnic group, coroners' verdicts and country of birth. A three-year survey in inner London.

BACKGROUND: Information on suicide in ethnic and immigrant groups in England and Wales is limited. METHOD: A three-year (1991-1993) survey was conducted of all unnatural deaths of residents of an urban area. 'True likely' and 'official' age-adjusted suicide rates were compared by ethnicity and, for Whites, birthplace. RESULTS: Irrespective of verdict, 329 likely suicides were identified. Relatively few ethnic minority and White immigrant suicides had received a suicide verdict. Afro-Caribbeans had relatively low, and young Indian women relatively high suicide rates. Rates of Scottish- and Irish-born residents were 2.1 to 2.9 times higher than the local base rate. Young White males' rates were higher than those of the elderly. CONCLUSIONS: Classification of suicide is biased with respect to ethnicity and national origin. Rate patterns for ethnic minority groups reflect patterns seen in attempted suicide. In this deprived area, young White male suicide rates have surpassed those among the old.

Adult↗
PubMed1996

The genetics of male infertility.

PURPOSE: We provide an up-to-date summary of the genetic aspects of male infertility. MATERIALS AND METHODS: The literature on male infertility was extensively reviewed. RESULTS: Genetic defects are associated with a variety of clinical presentations by the infertile man ranging from gonadotropin-releasing hormone deficiency to spermatogenic failure to obstructive azoospermia. Microsurgery and micromanipulation of gametes make it possible for many of these men to father children. However, with each successive breakthrough in treatment of male infertility there is an increased risk of transmitting genetic abnormalities to the progeny. CONCLUSIONS: Transmission of genetic defects through assisted reproductive techniques can have serious long-term implications. Assisted reproductive techniques should not be initiated in men with a possible or known genetic cause of infertility without prior genetic counseling and risk assessment. Clinicians and researchers involved in reproductive medicine must recognize that, although these techniques have revolutionalized the treatment of male infertility, they have the risk of passing genetic abnormalities to the progeny. Therefore, researchers must proceed cautiously with development and application of assisted reproductive technologies to avoid creating future generations of genetically abnormal individuals. The first step in accomplishing this goal is through an increased understanding of the genetic basis of male reproductive failure.

Chromosome Aberrations↗
PubMed1996

Value of magnetic resonance imaging of the lumbosacral spinal cord in patients with voiding dysfunction.

PURPOSE: We evaluated the role of magnetic resonance imaging (MRI) of the lumbosacral spinal cord in patients with voiding complaints and abnormal urodynamic findings but normal neurological and lower spine examinations. MATERIALS AND METHODS: We studied 17 women and 13 men 17 to 50 years old (mean age 32.2) who presented with voiding complaints. All patients had a completely normal neurological examination and no evidence of prostatic enlargement. Of the 30 patients 18 had incontinence (17 urge, and 1 stress and urge), 9 frequency and urgency alone, and 3 urinary retention. Seven patients had persistent enuresis (2 primary and 5 secondary). All 30 patients underwent multichannel urodynamics and MRI of the lower spinal cord. RESULTS: On urodynamic testing, 25 patients had bladder instability, 3 a hypocontractile or weak detrusor, 1 significantly decreased sensation only and 1 stress incontinence. No patient had detrusor external sphincter dyssynergia or outflow obstruction. Only 1 patient with frequency and urgency had a significant finding on MRI (tethered cord) that required surgery. CONCLUSIONS: In young adults who have voiding complaints and abnormal urodynamic findings, with normal neurological and lower spine examinations, the value of MRI of the lumbosacral spine is limited.

Adolescent↗