Expression of Cyclin D1 in Urothelial Carcinoma of Urinary Bladder and its Association with Tumour Grade.

Urothelial carcinoma (UC) is the most common malignancy of urinary bladder. It is the 9th leading cause of death worldwide and second most common genitourinary malignancy among male. Incidence is increasing in developing countries like Bangladesh. About 80% of patients are found between 50 to 80 years of age. It is 3-4 times more common in male than in female. Determination of therapeutic strategy and prediction of progression of urothelial carcinoma is a major clinical challenge. Treatment of urothelial carcinoma still now mostly depends on pathological stages. Amplification or genomic alteration of Cyclin D1 (a proto-oncogene) may cause protein overexpression which is frequently realized as a clonal pathology in various human neoplasms including bladder cancer. Evaluation of Cyclin D1 expression is promising for guiding therapeutic strategies, risk stratification and prediction of tumor progression. The aim of the study was to determine the expression of Cyclin D1 in urothelial carcinoma of urinary bladder and its association with tumour grade. This cross-sectional observational study was conducted in Department of Pathology, Dhaka Medical College, Dhaka, Bangladesh from July 2019 to June 2021. Histomorphologically diagnosed 51 urothelial carcinomas were included. Sections were stained with hematoxylin and eosin. Immunostaining with Cyclin D1 antibody was also done. Relevant information was collected and recorded in a predesigned data sheet. Statistical analysis was carried out as required. Mean age ±SD was 57.8±10.55 years. Male female ratio was 4.6:1. In this study 39(76.5%) patients were smoker. Regarding clinical presentations 36(70.6%) patients presented with painless hematuria alone. Lateral wall (64.7%) was the most frequent tumor location. Among 51 cases, 38(74.5%) cases were high grade urothelial carcinoma (HGUC) and 13(25.5%) cases were low grade urothelial carcinoma (LGUC). Considering Cyclin D1 expression, most of the LGUC cases showed high level of expression by both percentage (84.6%) and intensity (84.6%). Most of the HGUC cases showed low level of expression by both percentage (63.2%) and intensity (60.5%). Cyclin D1 showed significant inverse association with HGUC (p<0.05). In urothelial carcinoma of urinary bladder, Cyclin D1 expression was decreased with increasing grade of the tumor. Cyclin D1 expression was inversely associated with tumour grade.

Laparoscopic Adrenalectomy: Two Years Experience at Bangabandhu Sheikh Mujib Medical University.

Laparoscopic surgery has become an efficient tool for many complex surgical procedures. In last decades, laparoscopic adrenalectomy has become a more viable option for removal of adrenal pathology, with many surgeons preferring it to the conventional open technique. This study was done to evaluate the outcomes of lateral transperitoneal adrenalectomy (LTA) in our department and evaluate the feasibility of lateral transperitoneal adrenalectomy (LTA) in our perspective. This study is case series observational study carried out at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from March 2015 to May 2017. Suspected primary adrenal malignancies were excluded. Seventeen (17) patients (10 male and 7 females with mean age of 35.29 years) underwent 18 adrenalectomy (one bilateral). Seventeen (17) adrenal tumours were resected through laparoscopy and one adrenal tumour is resected through open approach due to conversion. All the patients underwent hormonal evaluation, ultrasonogram and computed tomography of whole abdomen. Ten (10) patients (58.82%) had hormonal active adrenal mass. Seven (7) patients (41.18%) were asymptomatic of which 2 had associated cholelithiasis, 7 patients had generalized weakness, 3 had weight gain with Cushing syndrome (one drug induced) and one had Hirsutism with musculanizing effect. Nine (9) patients had hypertension and 6 patients had diabetes mellitus. Eight (8) right, 8 left and 1 bilateral LTA were performed. The mean age of the patients were 35.29 years, adrenal tumour size ranges from 15-65mm and operation time ranges from 75-120 minutes for unilateral adrenalectomies and 220 minutes for bilateral adrenalectomy. Estimated blood loss ranges from 30 to 130 ml in 16 cases and in one case it was 220 ml in which conversion was done. Mean post operative stay in hospital was 3.94 days. In 16 cases no major or minor complications were observed but in one case due to haemorrhage and infiltration of the tumour to kidney conversion are done in the form of right adrenalectomy with upper partial nephrectomy (Histopathology revealed angiomyolipoma). In pathological examination 9 patients (52.94%) had adrenocortical adenoma, 2 patients (11.76%) had phaeochromocytoma including bilateral one, 2 patients (11.76%) had myolipoma of which one converted to open, 2 patients (11.76%) had adrenocortical hyperplasia, one patient (5.88%) had adrenal cyst and one patient (5.88%) had haemorrhagic cyst. LTA is a safe and efficient minimally invasive treatment options for both secreting and non secreting adrenal masses. The procedure has a learning curve and should be performed by a surgeon experienced in both open and laparoscopic adrenal surgery.

Nodular Mucinosis of Male Breast: A Rare Case Report.

Multinodular accumulation of stromal mucin in breast known as nodular mucinosis is an extremely rare condition of breast. Alternatively it is known as myxoma or nerve sheath myxoma of breast. This benign lesion is confined to only nipple and areola region presenting as slow growing, soft and non tender lobulated mass. Histopathologically it reveals well circumscribed non-encapsulated myxoid/mucinous lesion with few infiltration of spindle cells within a collaginized stroma. The mucinous substance is stained positively with Alcian blue. Mucinous carcinoma or phylloids tumour are important differential diagnosis of nodular mucinosis of breast. Here we report a case of nodular mucinosis of male breast with clinical, radiological and pathological findings with differential diagnosis and treatment modalities.

Malignancy in Solitary Thyroid Nodule.

This prospective study was done to find out the relative frequency of the malignancy in cold solitary thyroid nodules with other solitary thyroid nodules (hot and warm). This study was carried out in the Department of General Surgery and Otolaryngology-Head & Neck Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2011 to February 2012. One hundred (100) patients with clinically and ultrasonographically diagnosed as solitary thyroid nodules were included. Out of them, 52% of patients were in the third and fourth decades of life and 26% were in the second decade of life. In sex distribution, females were more affected than males and female: male ratio was 2.1:1. All patients presented with neck swelling, which moved with deglutition and 18% presented with palpitation. Solitary nodule was present in about 60% in the right lobe and 32% in the left lobe. In 72% patients, radioiodine uptake was low; in 25% patient's radioiodine uptake was normal. The thyroid scan revealed 72% cold nodule, in 25% patients radioiodine uptake was normal. On Ultrasonographic study, 60% were solid, 28% cystic and others mixed. Each and every patient of this series was treated surgically. Mostly (73%) lobectomy was done. Total thyroidectomy was done in 16% cases. On histopathology, 56% were colloid nodule, 28% were adenoma and 16% were carcinoma. Among the 16% malignant patients, majority of the patients had their age between 21-48 years. Histopathological types were mostly papillary (50%). Complications of surgery were mostly hoarseness of voice (5%), hematoma (4%), infection (2%) and hypoparathyroidism (3%). In this study, more malignant cases (20.83%) were found in cold solitary nodules.

Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.

BACKGROUND: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. METHODS: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014. RESULTS: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/µl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. CONCLUSIONS: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.

Parathyroid Carcinoma in a 10 Years Old Female Child.

Parathyroid carcinoma (PC) is a rare cause of hypercalcaemia in children. Only 7 cases of PC have been reported so far in the world journal. The authors report the 8th case of parathyroid carcinoma in children less than 16 years of age. A 10 year old girl presented with difficulty in walking, dorsiflexion and ulnar deviation of both wrist joints and occasional pain in the central abdomen of about two years duration. Biochemical investigations revealed serum calcium 12.2 mg/dL (normal 9-11 mg/dL), serum alkaline phosphate 4992 U/L (normal 50-136 U/L), PTH (parathyroid hormone) 2217 pg/ml (normal 9-80 pg/ml). Parathyroid scintigraphy localized the lesion in the left parathyroid gland. X-ray showed bilateral coxa vera, genu valgus deformity and multiple stress fractures in both wrist joints. Histopathology confirmed PC with capsular and vascular invasion.

Primary malignant melanoma of the penis with secondary to adrenal.

Primary malignant melanoma of penis with secondaries to the adrenal gland is rare. Here we report a case of malignant melanoma of penis in a 60 years old man who presented with intermittent gross, episodic haematuria of 11 months duration and a hard indurated pigmented fungating lesion over the glans penis. Following an initial tissue biopsy from the penile growth which revealed malignant melanoma the patient underwent partial Panectomy. Few days after recovery the patient underwent laparotomy and incisional biopsy from adrenal mass revealed metastatic malignant melanoma histopathologically.

Improved survival in multidrug-resistant tuberculosis patients receiving integrated tuberculosis and antiretroviral treatment in the SAPiT Trial.

BACKGROUND: The therapeutic effects of antiretroviral treatment (ART) in patients with multidrug-resistant tuberculosis (MDR-TB) and human immunodeficiency virus (HIV) infection have not been established. OBJECTIVE: To assess therapeutic outcomes of integrating ART with treatment for MDR-TB. DESIGN: A subgroup of MDR-TB patients from a randomised controlled trial, the SAPiT (Starting Antiretroviral Therapy at Three Points in Tuberculosis) study, conducted in an out-patient clinic in Durban, South Africa, from 2008 to 2012. METHODS: Clinical outcomes at 18 months were compared in patients randomised to receive ART within 12 weeks of initiating standard first-line anti-tuberculosis treatment with those who commenced ART after completing anti-tuberculosis treatment. RESULTS: Mycobacterium tuberculosis drug susceptibility results were available in 489 (76%) of 642 SAPiT patients: 23 had MDR-TB, 14 in the integrated treatment arm and 9 in the sequential treatment arm. At 18 months, the mortality rate was 11.9/100 person-years (py; 95%CI 1.4-42.8) in the combined integrated treatment arm and 56.0/100 py (95%CI 18.2-130.8) in the sequential treatment arm (hazard ratio adjusted for baseline CD4 count and whether MDR-TB treatment was initiated: 0.14; 95%CI 0.02-0.94, P = 0.04). CONCLUSION: Despite the small sample size, the 86% reduction in mortality due to early initiation of ART in MDR-TB patients was statistically significant.

Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults.

On the basis of positive preclinical data, we evaluated the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine (AVX101), expressing a nonmyristoylated form of Gag, in two double-blind, randomized, placebo-controlled clinical trials in healthy HIV-1-uninfected adults. Escalating doses of AVX101 or placebo were administered subcutaneously to participants in the United States and Southern Africa. Because of vaccine stability issues, the first trial was halted prior to completion of all dose levels and a second trial was implemented. The second trial was also stopped prematurely due to documentation issues with the contract manufacturer. Safety and immunogenicity were evaluated through assessments of reactogenicity, reports of adverse events, and assessment of replication-competent and Venezuelan equine encephalitis (VEE) viremia. Immunogenicity was measured using the following assays: enzyme-linked immunosorbent assay (ELISA), chromium 51 ((51)Cr)-release cytotoxic T lymphocyte (CTL), gamma interferon (IFN-γ) ELISpot, intracellular cytokine staining (ICS), and lymphoproliferation assay (LPA). Anti-vector antibodies were also measured. AVX101 was well tolerated and exhibited only modest local reactogenicity. There were 5 serious adverse events reported during the trials; none were considered related to the study vaccine. In contrast to the preclinical data, immune responses in humans were limited. Only low levels of binding antibodies and T-cell responses were seen at the highest doses. This trial also highlighted the difficulties in developing a novel vector for HIV.

Malignancy in solitary solid cold thyroid nodule.

Solitary thyroid nodule is a common endocrine problem. The main concern of solitary thyroid nodule lies in excluding the malignancy & to operate on as few patients as possible. Other than history & clinical examination, hormone assessment, USG of thyroid gland, radionuclide scan & FNAC were used to differentiate malignant nodules from benign ones. In this study 127 cases with solitary thyroid nodule of all age group & both sexes were included from Endocrine & Thyroid clinic of BSMMU. They were clinically & biochemically euthyroid & had cold nodule on radionuclide scan. USG & FNAC were done & subsequently they underwent surgical procedure. On the basis of postoperative histopathological report the specimens were divided into benign & malignant groups. All the nodules were cold among which 104 were solid & 23 were mixed in consistency. Of the 104 solid cold nodules histopathology revealed 36(34.6%) malignant & 68(65.4%) benign cases. From the 23 mixed cold solitary nodule 5(21.7%) appeared malignant & 18(78.3%) were benign. So malignancy was higher in solid cold group than the mixed cold one but this was not statistically significant (p=0.673). FNAC was done & it revealed that 83(65.5%) cases were benign, 10(7.8%) cases were suspicious & 34(26.7%) were malignant. Finally histopathology showed 41(32.3%) cases were positive & 86(67.7%) cases were negative for malignancy.

Screening for 'window-period' acute HIV infection among pregnant women in rural South Africa.

OBJECTIVES: The aim of this study was to evaluate the HIV-1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the 'window period' of acute HIV infection (AHI) in rural South Africa. METHODS: In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV-1 RNA pooled NAAT was performed on HIV antibody-negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence. RESULTS: The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3­41.3]. Of the 467 HIV antibody-negative samples, four (0.9%) were HIV-1 RNA-positive. The mean viral load in the four samples was 386 260 HIV-1 RNA copies/mL (range 64 200­1 228130). The HIV incidence was 11.2%per year (95% CI 0.3­22.1) and all women with AHI were 21 years of age. CONCLUSIONS: Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.

Human TRIM5alpha expression levels and reduced susceptibility to HIV-1 infection.

BACKGROUND: Human TRIM5alpha (TRIM5alphahu), a member of the tripartite motif protein family, displays some anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro, although it is substantially less potent than its rhesus monkey counterpart (TRIM5alpharh). The effects of levels of TRIM5alphahu on prevention or control of HIV-1 infection in vivo are unknown. METHODS: We used a quantitative real-time polymerase chain reaction (PCR) assay to measure levels of TRIM5alphahu expression in peripheral blood mononuclear cells (PBMCs) obtained from a cohort of individuals at high risk for HIV-1 infection in Durban, South Africa. Samples were available from 38 infected subjects (with all these samples obtained within 1 year of infection) and from 57 uninfected persons. Matched preinfection and postinfection samples were available from 13 individuals. RESULTS: TRIM5alphahu messenger RNA levels were lower in the PBMCs of HIV-1-infected subjects than in those of uninfected subjects (P <.001). Seroconverters had lower preinfection levels of TRIM5alphahu than did nonseroconverters (P<.001). TRIM5alphahu levels did not change significantly after infection. There was no correlation between TRIM5alphahu levels and viral loads or CD4(+) T cell counts. CONCLUSIONS: High expression of TRIM5alphahu is associated with reduced susceptibility to HIV-1 infection. Furthermore, infection is not associated with disregulation of TRIM5alphahu. TRIM5alphahu expression levels do not contribute to the control of primary HIV-1 viremia.

Opportunities for treating sexually transmitted infections and reducing HIV risk in rural South Africa.

AIM: This paper is a report of a study to determine the aetiological distribution of sexually transmitted infections and prevalence of human immunodeficiency virus infection in selected primary health care clinic attendees. BACKGROUND: South Africa has a high prevalence of human immunodeficiency virus and other sexually transmitted infections. Sexually transmitted infections are managed syndromically in the public sector as part of the essential nurse-driven primary care services provided at no cost to the client. METHOD: This cross-sectional study was conducted in a rural community in South Africa between September and November 2002. A total of 277 consenting women were recruited. Vulvo-vaginal swabs were collected for screening for Neisseriae gonorrheae, Chlamydia trachomatis and Trichomonas vaginalis using DNA amplification methods and Gram stain with Nugent's score for the diagnosis of bacterial vaginosis. Seroprevalence of syphilis and human immunodeficiency virus infection were determined. FINDINGS: The overall prevalence of human immunodeficiency virus in the study was 43.7% (95% confidence interval 37.6-50.0) with the prevalence in family planning clinic attendees 45.5% (95% confidence interval 38.9-52.3) and antenatal clinic attendees 33.3% (95% confidence interval 19.6-50.3). The prevalence of sexually transmitted infections amongst both the antenatal clinic and family planning attendees accounted for at least 70% of cases. Fifty per cent of women had one recognized sexually transmitted infection with 17.9% of the family planning and 14.5% of the antenatal clinic attendees having infections from two recognized pathogens. All infections were asymptomatic. CONCLUSION: Nurse-driven antenatal and family planning services provide a useful opportunity for integrating reproductive health services, human immunodeficiency virus voluntary counselling and testing and treatment of sexually transmitted infections.

Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection.

The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.

TB treatment outcomes following directly-observed treatment at an urban outpatient specialist TB facility in South Africa.

The treatment of 450 consecutive new patients with pulmonary TB was evaluated to determine outcome following directly-observed treatment. In all, 176 (39.1%) patients were cured, 23 (5.1%) completed treatment, 80 (17.8%) defaulted treatment, 24 (5.3%) died, 54 (12.0%) were lost to follow-up and 93 (20.7%) were transferred out. Increasing age was significant for death. Males were more likely to default and those with negative pretreatment sputum smears and those who were unemployed were more likely to be lost to follow-up. The overall treatment success rate remains low. Our data suggests that greater emphasis is needed to improve TB treatment success.

Impact of on-site testing for maternal syphilis on treatment delays, treatment rates, and perinatal mortality in rural South Africa: a randomised controlled trial.

BACKGROUND: Syphilis remains a significant cause of preventable perinatal death in developing countries, with many women remaining untested and thus untreated. Syphilis testing in the clinic (on-site testing) may be a useful strategy to overcome this. We studied the impact of on-site syphilis testing on treatment delays and rates, and perinatal mortality. METHODS: We conducted a cluster randomised controlled trial among seven pairs of primary healthcare clinics in rural South Africa, comparing on-site testing complemented by laboratory confirmation versus laboratory testing alone. Intervention clinics used the on-site test conducted by primary care nurses, with results and treatment available within an hour. Control clinics sent blood samples to the provincial laboratory, with results returned 2 weeks later. RESULTS: Of 7134 women seeking antenatal care with available test results, 793 (11.1%) tested positive for syphilis. Women at intervention clinics completed treatment 16 days sooner on average (95% confidence interval: 11 to 21), though there was no significant difference in the proportion receiving adequate treatment at intervention (64%) and control (69%) clinics. There was also no significant difference in the proportion experiencing perinatal loss (3.3% v 5.1%; adjusted risk difference: -0.9%; 95% CI -4.4 to 2.7). CONCLUSIONS: Despite reducing treatment delays, the addition of on-site syphilis testing to existing laboratory testing services did not lead to higher treatment rates or reduce perinatal mortality. However on-site testing for syphilis may remain an important option for improving antenatal care in settings where laboratory facilities are not available.

A randomized controlled trial of azithromycin versus doxycycline/ciprofloxacin for the syndromic management of sexually transmitted infections in a resource-poor setting.

A randomized controlled trial was carried out to assess the effectiveness of azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the treatment of sexually transmitted infections in a resource-poor environment. Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting in three treatment failures. Gonorrhoea was cured in 55/56 (98.2%) women, with one treatment failure in a patient with concomitant C. trachomatis infection. These results indicate that a single oral dose of azithromycin may prove to be a more effective and convenient treatment for sexually transmitted infections in women in a resource-poor environment

Characterization of full-length HIV type 1 subtype C sequences from South Africa.

Four full-length genome subtype C sequences from South Africa, three of which are being used for vaccine development, were characterized. Three isolates were obtained from recently infected individuals in KwaZulu/Natal: Du151, Du422, and Du179. A fourth isolate, CTSc2, was obtained from an individual residing in Cape Town. All four strains used the CCR5 coreceptor, although Du179 also used CXCR4. The four isolates clustered within subtype C, but the three Du isolates formed a subcluster with a bootstrap value of 100%, with CTSc2 outside the subcluster. None of the strains showed evidence of intersubtype recombination, as expected from the predominance of subtype C in South Africa. All 4 isolates had a 16-amino acid truncation on the 3' end of the Rev protein, identified in other subtype C isolates. Like many other subtype C strains, Du151, Du422, and Du179 had three NF-kappa B-binding sites in the LTR; however, CTSc2 had only two.