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Biomedical subjects

R Chetty

Publications and source records attributed to R Chetty.

At least 19 recordsLinked to original sources

Cyclin E immunoexpression in gastric cancer does not correlate with clinicopathological parameters.

AIMS: To ascertain whether cyclin E immunoexpression relates to clinicopathological characteristics of gastric cancer and is of possible routine use. METHODS AND RESULTS: One hundred and twenty-four gastrectomy specimens were assessed for age, gender, histological subtype, lymph node status and Helicobacter pylori infection. Immunohistochemistry using a commercially available antibody to cyclin E was then applied to the cases. The immunohistochemical staining was correlated with clinicopathological features. Fifty-three of 124 cases were cyclin E-positive, with 28 of these cases showing >50% of the tumour cells staining. However, no statistical significance was obtained between cyclin E immunostaining and any clinicopathological parameter, especially lymph node spread. CONCLUSIONS: We have not demonstrated any significant relationship between cyclin E immunopositivity and any of the usual clinicopathological parameters (especially lymph node involvement) and therefore cyclin E immunohistochemistry alone does not appear to have a role in the assessment of gastric cancer currently.

Adenocarcinoma↗

Plasmablastic lymphoma in HIV+ patients: an expanding spectrum.

AIM: To describe an unusual human immunodeficiency virus (HIV)-associated lymphoma in uncommon sites. Plasmablastic lymphoma is a distinctive HIV-associated tumour that was first described in the jaws and oral cavity. Only two cases (stomach and lung) have been documented in extra-oral sites. MATERIALS AND METHODS: Four cases were encountered in HIV+ patients: three in the anorectal region and one which was nasal and paranasal. The cases were routinely processed and immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue. RESULTS: The cases showed the typical morphological appearances of a high-grade, blastic non-Hodgkin's lymphoma (brisk mitotic activity and tingible body macrophages). In addition, some cells had a plasmacytoid appearance and paranuclear clearing. Immunophenotypically, the tumour cells were negative for LCA, CD20 and CD45RA. However, a small proportion of cells (5%) were immunoreactive for CD79a and the majority were positive with VS38c, indicative of plasma cell differentiation. Kappa light chain and IgG heavy chain restriction was also detected. CONCLUSIONS: Plasmablastic lymphoma may occur in extra-oral sites and has a characteristic immunophenotype including focal expression of CD31 by the neoplastic cells. Awareness of the absence of expression of conventional B-cell markers and its presence in unusual sites should facilitate the diagnosis of plasmablastic lymphoma in HIV+ patients.

Adult↗

Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol.

AIMS: Adiponectin is a 30-kDa protein secreted by adipose tissue. The aim of the present study was to compare serum adiponectin in male Indo-Asian and Caucasian subjects and examine its association with fat topography and metabolic parameters. METHODS: Diabetic and non-diabetic male subjects (n = 48) were studied. A single observer carried out blood pressure and anthropometric measurements. Serum glucose, insulin, lipid profile and adiponectin (measured by RIA) were measured on a fasting sample. RESULTS: There was no statistically significant difference in serum adiponectin between diabetic and BMI-matched non-diabetic subjects. However, serum adiponectin was lower in Indo-Asians compared with BMI-matched Caucasians, [median adiponectin (interquartile range) 3.3 (2.1-3.9) vs. 4.9 (3.5-6.6) microg/ml respectively (p = 0.016)]. Univariate analysis showed serum adiponectin to be positively associated with HDL in diabetic (p = 0.039) and non-diabetic subjects (p = 0.0098). Waist circumference (p = 0.02), saggital diameter (p = 0.04) were negatively correlated with serum adiponectin in diabetic subjects. Multiple regression analysis including waist, HDL, fasting insulin, age, diabetes and ethnicity in all subjects showed HDL to be the best predictor of serum adiponectin. CONCLUSIONS: Serum adiponectin is associated with HDL cholesterol and central obesity. Caucasians have higher serum adiponectin levels compared with Indo-Asians. Further studies are needed to explore basis for the association of adiponectin with HDL cholesterol and the reason for lower levels in Indo-Asians.

Adiponectin↗

Lymphoproliferative disorders in Oxford renal transplant recipients.

BACKGROUND: Increased cancer incidence, particularly lymphoproliferative disease, is a complication of immunosuppression in organ transplantation. Non-Hodgkin's lymphomas (NHLs) occur frequently during the first year after transplantation, more so in North America than in Europe. METHODS: This study audited and correlated the demographic, clinical, pathological, and outcome features of post-transplant lymphoproliferative disorders (PTLDs) in a large centre in Oxford, and assessed whether the time of onset fitted more with the European or North American pattern. RESULTS: There were 1383 renal transplants in the study period and 27 patients developed lymphoma: 26 NHLs and one Hodgkin's disease (1.95%). Four of the patients never received cyclosporin. The mean time of diagnosis after transplant was 46 months. Most tumours (21/27) presented extranodally. Management included reduction of immunosuppression, surgical excision, antiviral treatment, radiotherapy, and chemotherapy. Three patients presented in the first post-transplant year-0.34% of cyclosporin managed patients-similar to the North American incidence, although the incidence of extranodal late PTLDs was also high (mean onset, 36 months v 15 months international mean). Post-transplant lymphomas were the most common malignancy associated with death in transplant patients. CONCLUSIONS: PTLDs occurred in 2% of renal transplant patients, presenting both in the first year in association with cyclosporin use, as in North America, but also in subsequent years, giving an overall presentation time later than the international mean. The disease usually presented extranodally, accounting for the wide range of symptoms and signs. Despite awareness and active management, the disease contributed to death in more that 50% of patients with PTLDs.

Adolescent↗

Leiomyoma of the bladder in a patient with von Recklinghausen's neurofibromatosis.

Leiomyomas are an uncommon manifestation of neurofibromatosis type 1 (NF-1) and occur most often in the gastrointestinal tract. Here, they have a proclivity for the proximal small bowel and tend to be multiple. Urinary tract involvement by NF-1 is usually in the form of neurofibromas, and leiomyomas are exceptionally rare. This report describes a case of solitary leiomyoma occurring in a 49 year old woman with NF-1. The patient had symptoms related to a lower urinary tract infection and on examination was found to have a distended bladder. Imaging of the bladder showed a mass involving the posterior wall, neck, and trigone causing bilateral hydronephrosis. The mass was excised with part of the bladder. Microscopic examination revealed typical features of a leiomyoma and there was strong immunoreactivity for desmin and smooth muscle actin. Leiomyoma must be considered in the differential diagnosis of spindle cell neoplasms in patients with NF-1.

Female↗

Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E.

Apolipoprotein E (APOE) is thought to be responsible for the transportation of lipids within the brain, maintaining structural integrity of the microtubule within the neurone, and assisting with neural transmission. Possession of the APOE epsilon4 allele has also been shown to influence neuropathological findings in patients who die from traumatic brain injury, including the accumulation of amyloid beta protein. Previous clinical studies reporting varying outcome severities of traumatic brain injury, including cognitive and functional recovery, all support the notion that APOE epsilon4 allele possession is associated with an unfavourable outcome. Evidence from experimental and clinical brain injury studies confirms that APOE plays an important role in the response of the brain to injury.

Alleles↗

Upper gastrointestinal bacillary angiomatosis causing hematemesis: a case report.

A 38-year-old HIV-positive woman presented with massive hematemesis on initial admission to hospital. Endoscopy revealed ulcerated nodular lesions in the esophagus, stomach, and duodenum. The clinical impression was of Kaposi's sarcoma. The stomach was biopsied when the patient re-presented, and another endoscopy was performed. The biopsy showed mucosal ulceration with a proliferation of vascular channels associated with neutrophils and clumps of purplish, granular bacterial colonies, which were highlighted by a Warthin-Starry stain. The histopathological features were typical of bacillary angiomatosis. This case highlights bacillary angiomatosis involving the gastrointestinal tract at multiple sites, the cause of massive upper gastrointestinal hemorrhage that was the initial presentation of an HIV-positive patient, and the occurrence of visceral bacillary angiomatosis in the absence of cutaneous lesions.

AIDS-Related Opportunistic Infections↗

Severe hypokalaemia and weakness due to Nurofen misuse.

Nephrotoxicity from non-steroidal anti-inflammatory drugs (NSAID) is well recognized. We report a case of severe hypokalaemia and weakness due to renal tubular acidosis in a young woman who was taking 40-60 tablets per day of Nurofen Plus (ibuprofen 200 mg and codeine phosphate 12.8 mg). Proprietary brands of ibuprofen are freely available to the public and those containing codeine may be potentially subject to abuse. This case highlights the need to be aware of this potential and of the life-threatening electrolyte and acid-base disturbances that might be encountered with the widespread availability of these types of NSAID.

Acidosis, Renal Tubular↗

ALK protein expression in rhabdomyosarcomas.

AIMS: The ALK p80 chimeric protein is thought to be up-regulated as a result of the t(2;5) as classically seen in anaplastic large cell lymphoma. However, rhabdomyosarcomas (in particular, the alveolar subtype) have also been noted to show expression of this protein. This study set out to examine ALK expression in a large number of rhabdomyosarcomas. METHODS AND RESULTS: Eighty-three cases of rhabdomyosarcomas and 16 cases of malignant mixed müllerian tumours with a rhabdomyosarcomatous component were retrieved from the archives of the Department of Anatomical Pathology for the period 1983-2001. The sections were stained with polyclonal ALK antibody. There were 52 male and 30 female patients. In one case, the gender of the patient was not indicated. The ages ranged from 1 week to 77 years. The most common site was the head and neck region, followed by the pelvis and extremities. Thirty-one cases were of the alveolar subtype while 40 cases were embryonal. There were four mixed embryonal/alveolar, six pleomorphic and two unclassifiable rhabdomyosarcomas. Fourteen of the 31 (45%) alveolar rhabdomyosarcomas stained positively for the ALK protein, while only six of the 40 embryonal (15%) cases showed positivity. One case each of the mixed embryonal/alveolar, pleomorphic and unclassified cases was also immunopositive. The rhabdomyosarcomatous component in the malignant mixed müllerian tumours was positive in four of the 16 cases. CONCLUSION: We conclude that a proportion of alveolar rhabdomyosarcomas (in particular) exhibit ALK protein expression. However, ALK expression is not restricted to this subtype. An extension of this study is to determine if this over-expression is as a result of the t(2;5) translocation.

Adolescent↗

Malakoplakia in association with colorectal carcinoma: a series of four cases.

AIMS: Malakoplakia is a characteristic inflammatory condition which is usually seen in the urogenital tract. Gastrointestinal malakoplakia is seen in association with a variety of conditions such as ulcerative colitis, diverticular disease, adenomatous polyps and carcinoma. The purpose of this paper is to report four additional cases of colorectal cancer associated with malakoplakia and review the literature on this association. METHODS: All specimens were colectomies for cancer. Routine handling of the specimen with lymph node harvesting was performed. In addition to H&E stains, PAS, Perls' Prussian Blue and von Kossa stains were performed. RESULTS: Three of the cases were encountered in males and the patients ranged in age from 55 to 64 years. One case each occurred in the caecum/ascending colon and descending colon, while the remaining two were located in the rectum. All four cases were Dukes' stage B tumours. Furthermore, all four cases had spread to pericolic fat and two had perforated. Microscopic examination showed the malakoplakia to be present at the infiltrating edge of the tumours. The draining lymph nodes were involved by malakoplakia to varying degrees in all cases. CONCLUSIONS: From this series and the literature review, malakoplakia associated with colorectal cancer tends to occur in elderly males in the rectum. The malakoplakia is found at the infiltrating front of the tumour and is not admixed with the neoplastic glands. Although lymph node involvement by malakoplakia has been reported only once previously, all four cases in this series showed evidence of involvement. The association does not appear to have any prognostic significance.

Carcinoma, Ductal, Breast↗

Postmodern cancer: the role of human immunodeficiency virus in uterine cervical cancer.

The association between cervical cancer and human papillomavirus (HPV) is well known, but its association with human immunodeficiency virus (HIV) is controversial. Coinfection with HPV and HIV is to be expected and recent epidemiological data from Africa show that cervical cancer is the most common AIDS defining neoplasm in women. Unlike other AIDS defining neoplasms, the occurrence of cervical cancer is not dependent on immune compromise. HIV alters the natural history of HPV infection, with decreased regression rates and more rapid progression to high grade and invasive lesions, which are refractory to treatment, requiring more stringent intervention and monitoring. The more aggressive behaviour is mirrored by a different molecular pathway. HIV associated cervical cancers are thought to progress through the microsatellite instability pathway, whereas HIV negative ones progress through loss of heterozygosity. Interaction is probably via viral proteins, with HIV proteins enhancing effectiveness of HPV proteins, and perhaps contributing to cell cycle disruption. Dysregulation of the cellular and humoral arms of the local and systemic immune systems may ensure disease progression. Furthermore, HPV infection may predispose to HIV infection and facilitate its progression.

Female↗

Plexiform spitz nevus.

In 1999, Spatz et al. reported the first 2 cases of a plexiform variant Spitz nevus. We describe another case of this variant on the upper thigh of a 10-year-old boy and discuss the differential diagnosis. Histologically, it comprised nodules of epithelioid cells with a plexiform arrangement distributed throughout the superficial and deep dermis. The cells had moderate eosinophilic cytoplasm with vesicular nuclei and prominent nucleoli. Intranuclear inclusions were present focally. The tumor nodules were embedded in a myxoid stroma with intratumoral and peritumoral inflammatory cells including both lymphocytes and eosinophils. There were occasional melanin-containing spindle-shaped cells. An intraepidermal component could not be assessed, since the lesion was ulcerated. The differential diagnosis includes both melanocytic and nonmelanocytic lesions exhibiting a plexiform pattern of growth as well as myxoid lesions.

Child↗

An unusual pleural cyst in a child presenting as a pseudo-pneumothorax. Case report.

This case highlights an unusual pleural cyst in a 3-year-old child that simulated a pneumothorax on chest radiograph. The child presented with mild respiratory distress and the 'pneumothorax' failed to respond to pleural intubation. At thoracotomy, a 10 cm air-filled cyst was found attached to the visceral pleura by a narrow pedicle. This was transfixed and divided, with removal of the cyst. Postoperatively, the lung expanded and the child recovered without any sequelae. Histological examination of the cyst showed it to be lined with mesothelial cells. It is suggested that this cyst arose from a mesothelial inclusion cyst or sub-mesothelial pleural tissue, which communicated with the peripheral lung tissue.

Child, Preschool↗

Cell cycle aberrations in the pathogenesis of squamous cell carcinoma of the uterine cervix.

Cancer cells are characterized by limitless proliferative autonomy and immunity to inhibitory and apoptotic signals, thus ensuring growth and metastasis [1]. Epidemiological studies have long implicated human papillomavirus (HPV) as a pathogenic agent in cervical cancer. Progress in cancer research now provides an understanding of how these characteristics are achieved by the interaction of HPV proteins with the cell cycle machinery. Expression of oncoproteins E7 and E6 induces immortalization of cells through their inhibitory effects on tumor suppressor proteins pRb and p53, respectively. Undermining of pRb's growth-inhibitory role with release of E2F transcription factors renders the cells independent of mitogenic stimuli. The abundance of growth transcription factors grants limitless proliferative potential by allowing expression of products such as cyclins A, E, and B, dihydrofolate reductase, and DNA polymerase which fuel the various stages of the cell cycle. There is subsequent disruption of both the G1-S and G2-M cell cycle checkpoints. Overexpression of cyclin E results in chromosomal instability and possible unmasking of genetic mutations, allowing disease progression. Cyclin A grants anchorage-independent growth, facilitating tissue invasion and tumor spread. Apoptotic and growth-inhibitory mechanisms are also evaded. p53 is degraded by E6 and its own downstream protein mdm2. Its other downstream protein, p21 is rendered ineffective against cyclin-cyclin-dependent kinase units by E7, as is p27. The understanding of the molecular pathology of disease will provide us with the ability to prognosticate and treat patients more effectively.

Animals↗

Cyclin E immunoexpression in breast ductal carcinoma: pathologic correlations and prognostic implications.

Abnormalities of the cell cycle are present in all neoplasms. Cyclin E, which regulates the G1/S phase transition of the cell cycle, plays an important role in many different cancers. To further investigate the role of cyclin E in invasive breast ductal carcinomas in South African women, representative sections from 157 mastectomy and axillary clearance specimens were stained with the cyclin E antibody. The results were compared with known clinicopathologic prognostic factors, namely lymph node metastases, size, estrogen receptor status, and histologic grade. Positive (nuclear) cyclin E immunostaining strongly correlates with negative estrogen receptor status and high grade. These correlations may account for the observation that although cyclin E staining is associated with poor prognosis in univariate analysis, no prognostic significance remains after multivariate analysis.

Aged↗

Spontaneous arteriovenous fistula resulting from HIV arteritis.

Arteriovenous fistulas (AVFs) are uncommon and usually follow trauma or preceding arterial catheterization or puncture. Spontaneous AVFs are rare. A case of spontaneous AVF of the superficial femoral artery and vein in an HIV-infected patient is presented. Histologic examination of the artery showed features similar to those seen in HIV-related large-vessel aneurysms. It would appear that spontaneous AVF are part of the spectrum of macrovascular arteritis related to HIV infection.

Adult↗