Anorectal Melanoma

Malignant melanoma is an aggressive disease. The anorectal region is the most common site of primary gastrointestinal malignant melanoma. Due to its low incidence, the diagnosis is often delayed. The most characteristic clinical feature of this tumor is its brown-black appearance due to the melanin pigment. However, the pigmentation may be absent in up to 20% cases. Timely diagnosis and treatment are crucial for achieving good long-term outcomes. Surgical excision remains the treatment of choice for localized disease. However, the extent of surgery has been a matter of debate. Anorectal melanoma is a highly malignant disease, and more than 50% cases have metastasis at the time of diagnosis. Targeted therapies especially immune check point inhibitors have brought about a paradigm shift in the management of cutaneous melanoma. They are being increasingly used for mucosal melanomas, and their role in anorectal melanoma is being investigated in various clinical trials

No association of androgen receptor GGN repeat length polymorphism with infertility in Indian men

Androgens, acting through the androgen receptor (AR), play a role in secondary sexual differentiation from the prenatal stage to adulthood, including spermatogenesis. The AR gene has 2 polymorphic trinucleotide repeats (CAG and GGN) in exon 1. The CAG repeat length polymorphism has been well studied in a variety of medical conditions, including male infertility. Many of these studies have shown an association of the expanded CAG repeats with male infertility, although this is not true for all populations. The GGN repeat, in contrast, has been less thoroughly studied. Thus far, only 4 reports worldwide have analyzed the GGN repeat, alone or in combination with the CAG repeat, in male infertility cases. No such study has been undertaken on infertile Indian men. Therefore, we have analyzed AR-GGN repeats in a total of 595 Indian males, including 277 azoospemric, 97 oligozoospermic, and 21 oligoteratozoospermic cases, along with 200 normozoospermic controls. The analysis revealed no difference in the mean number or the range of the repeat between cases (mean=21.51 repeats, range 15-26 repeats) and controls (mean 21.58 repeats, range 15-26 repeats). Furthermore, no difference was observed when azoospermic (mean=21.53 repeats, range 15-26 repeats), oligozoospermic (mean=21.46 repeats, range 15-26 repeats), and oligoteratozoospermic cases (mean=21.48, range 19-26 repeats) were compared individually with the controls

Male infertility: no evidence of involvement of androgen receptor gene among Indian men

Spermatogenesis is collaboratively controlled by testosterone and follicle stimulating hormone. Testosterone and its immediate metabolite dihydrotestosterone affect their roles through the androgen receptor (AR). Mutations in the AR gene have been shown to cause partial to complete androgen insensitivity or infertility in otherwise normal males. The dependence of germ cells upon Sertoli and Leydig cells for their differentiation into sperms and deletion studies of the AR gene in animal models indicate a direct or indirect role of the AR gene in spermatogenesis. Although a few studies worldwide have reported AR mutations in male infertility, no similar study has been conducted on Indian populations. Therefore, we undertook this study to look at the contribution of AR mutations in male infertility among Indian men. We have sequenced the complete coding region of the AR gene in a total of 399 infertile samples, comprising 277 azoospermic, 100 oligozoospermic, and 22 oligoteratozoospermic samples. A total of 100 healthy males with proven fertility and the same ethnicity as the experimental group served as controls. Sequence analysis revealed no mutation in any of these samples. Our study suggests that mutations in the AR gene are less likely to cause azoospermia and oligozoospermia; however, it was difficult to rule out its effect in oligoteratozoospermia, as the sample size was small

APOB gene signal peptide deletion polymorphism is not associated with infertility in Indian men

Apolipoprotein B (APOB) plays a key role in lipoprotein metabolism and plasma lipid transport. It has been shown that about two-thirds of male mice heterozygous for ApoB were infertile. Moreover, a 3-codon deletion polymorphism (rs11279109) in the signal peptide region of the APOB gene has been shown to be a risk factor for infertility in Slovenian men, but its association with infertility in Indian men has not been evaluated to date. Hence, in the present study, we have genotyped this polymorphism in 545 Indian men, including 294 infertile and 251 fertile men. Our results show that the distribution of this deletion polymorphism was consistent with the Hardy-Weinberg equilibrium in both infertile and fertile men. No statistically significant difference was observed in the distribution of the APOB signal peptide deletion polymorphism between infertile and fertile men (χ2=0.156, P=.925 for genotypes; χ2=0.015, P=.903 for alleles). Moreover, no significant difference was observed when infertile and fertile men were categorized on the basis of presence (D/D and D/W genotypes) or absence (W/W genotypes) of deletion (odds ratio, 0.955; 95% confidence interval, 0.644-01.418; P=.820). Our study concludes that the APOB gene deletion polymorphism is not a risk factor for the development of infertility in Indian men

Y chromosome deletions in azoospermic men in India

Genetic factors cause about 10% of male infertility. Azoospermia factors (AZFa, AZFb, AZFc) are considered to be the most important for spermatogenesis. We therefore made an attempt to evaluate the genetic cause of azoospermia, Y chromosome deletion in particular, in Indian men. We have analyzed a total of 570 men, including 340 azoospermic men and 230 normal control subjects. DNA samples were initially screened with 30 sequence-tagged site (STS) markers representing AZF regions (AZFa, AZFb, AZFc). Samples, with deletion in the above regions were mapped by STS walking. Further, the deletions were confirmed by Southern hybridization using the probes from both euchromatic and heterochromatic regions. Of the total 340 azoospermic men analyzed, 29 individuals (8.5%) showed Y chromosome deletion, of which deletion in AZFc region was the most common (82.8%) followed by AZFb (55.2%) and AZFa (24.1%). Microdeletions were observed in AZFa, whereas macrodeletions were observed in AZFb and AZFc regions. Deletion of heterochromatic and azoospermic regions was detected in 20.7% of the azoospermic men. In 7 azoospermic men, deletion was found in more than 8.0 Mb spanning AZFb and AZFc regions. Sequence analysis at the break points on the Y chromosome revealed the presence of L1, ERV, and other retroviral repeat elements. We also identified a 240-kb region consisting of 125 bp tandem repeats predominantly comprised of ERV elements in the AZFb region. Histological study of the testicular tissue of the azoospermic men, who showed Y chromosome deletion, revealed complete absence of germ cells and presence of only Sertoli cells

The profile and treatment outcomes of the older (aged 60 years and above) tuberculosis patients in Tamilnadu, South India

Background: With changing demographic patterns in the context of a high tuberculosis (TB) burden country, like India, there is very little information on the clinical and demographic factors associated with poor treatment outcome in the sub-group of older TB patients. The study aimed to assess the proportion of older TB patients (60 years of age and more), to compare the type of TB and treatment outcomes between older TB patients and other TB patients (less than 60 years of age) and to describe the demographic and clinical characteristics of older TB patients and assess any associations with TB treatment outcomes. Methods: A retrospective cohort study involving a review of records from April to June 2011 in the 12 selected districts of Tamilnadu, India. Demographic, clinical and WHO defined disease classifications and treatment outcomes of all TB patients aged 60 years and above were extracted from TB registers maintained routinely by Revised National TB Control Program (RNTCP). Results: Older TB patients accounted for 14% of all TB patients, of whom 47% were new sputum positive. They had 38% higher risk of unfavourable treatment outcomes as compared to all other TB patients (Relative risk (RR)-1.4, 95% CI 1.2–1.6). Among older TB patients, the risk for unfavourable treatment outcomes was higher for those aged 70 years and more (RR 1.5, 95% CI 1.2–1.9), males (RR 1.5, 95% CI 1.0–2.1), re-treatment patients (RR 2.5, 95% CI 1.9–3.2) and those who received community-based Direct Observed Treatment (RR 1.4, 95% CI 1.1–1.9). Conclusion: Treatment outcomes were poor in older TB patients warranting special attention to this group – including routine assessment and recording of co-morbidities, a dedicated recording, reporting and monitoring of outcomes for this age-group and collaboration with National programme of non-communicable diseases for comprehensive management of co-morbidities