Biomedical subjects
K Cooper
Publications and source records attributed to K Cooper.
Adenoid cystic and adenoid basal carcinoma of the uterine cervix: comparative morphologic, mucin, and immunohistochemical profile of two rare neoplasms of putative 'reserve cell' origin.
Adenoid cystic carcinomas (ACCs) and adenoid basal carcinomas (ABCs) are rare neoplasms of the uterine cervix that are currently regarded as distinct clinicopathologic entities. Accurate distinction between ABCs and ACCs is of clinical importance because of differences in their biological behavior. This study compares the morphologic, mucin, and immunohistochemical profiles of 18 cervical ACCs, 8 ABCs, and 1 combined ABC-ACC. Serial sections from the 27 cases were stained with hematoxylin and eosin, periodic acid-Schiff-diastase, mucicarmine, and alcian blue and subjected to a panel of immunoperoxidase markers, namely, MNF116, CAM 5.2, CK7, CK20, epithelial membrane antigen, carcinoembryonic antigen (CEA), S-100, HHF 35, laminin, and type IV collagen. One ACC was also examined ultrastructurally. Almost all patients were postmenopausal black women. The distinction between ABC and ACC was best made morphologically. Divergent epithelial differentiation was seen in 18 cases (11 ACCs, 6 ABCs, and 1 ABC-ACC). Six cases with intact surface epithelium showed a high grade squamous intraepithelial lesion. There was no significant difference in mucin staining. Both tumor types had a similar immunohistochemical profile, apart from type IV collagen and laminin staining, which occurred exclusively in relation to the extracellular basement membranelike material in the ACC. Eleven ACCs and three ABCs were S-100-positive, including the respective ACC and ABC components of the combined ABC-ACC. Eight of the S-100-positive neoplasms with ACC morphology also stained with HHF 35, suggesting myoepithelial differentiation. The latter was confirmed in one ACC examined ultrastructurally. The similar clinical profiles, apart from the different biological behavior, capacity for divergent differentiation, and the occurrence of ABC areas in some ACCs and vice versa suggest that these tumors may share a common histogenesis, forming part of a morphologic and biologic spectrum of basaloid cervical neoplasms of putative "reserve cell" origin. Circumstantial evidence suggests that ABC may be a precursor of cervical ACC.
A randomised controlled trial of specialist health visitor intervention for failure to thrive.
AIMS: To determine whether home intervention by a specialist health visitor affects the outcome of children with failure to thrive. METHODS: Children referred for failure to thrive were randomised to receive conventional care, or conventional care and additional specialist home visiting for 12 months. Outcomes measured were growth, diet, use of health care resources, and Bayley, HAD (hospital anxiety and depression), and behavioural scales. RESULTS: Eighty three children, aged 4-30 months, were enrolled, 42 received specialist health visitor intervention. Children in both groups showed good weight gain (mean (SD) increase in weight SD score for the specialist health visitor intervention group 0.59 (0.63) v 0.42 (0.62) for the control group). Children < 12 months in the intervention group showed a higher mean (SD) increase in weight SD score than the control group (0.82 (0.86) v 0.42 (0.79)). Both groups improved in developmental score and energy intake. No significant differences were found for the primary outcome measures, but controls had significantly more dietary referrals, social service involvement, and hospital admissions, and were less compliant with appointments. CONCLUSIONS: The study failed to show that specialist health visitor intervention conferred additional benefits for the child. However, the specialist health visitor did provide a more coordinated approach, with significant savings in terms of health service use. Problems inherent to health service research are discussed.
HHV-8 (KSHV) is not associated with bacillary angiomatosis.
AIMS: Bacillary angiomatosis is a rare pseudoneoplastic angioproliferative lesion occurring in patients with AIDS. This condition has been associated with Bartonella henselae and Bartonella quintana infections. Human herpesvirus 8 (HHV-8) is thought to be the causative agent of Kaposi's sarcoma, a vasoproliferative neoplasm, also commonly found in patients with AIDS. The presence of HHV-8 in a cohort of patients with bacillary angiomatosis was investigated. METHODS: Eight cutaneous cases of biopsy confirmed bacillary angiomatosis were assessed for HHV-8 using standard solution phase polymerase chain reaction (PCR). RESULTS: No case of bacillary angiomatosis harboured HHV-8 DNA. CONCLUSIONS: HHV-8 was not demonstrated in the lesions of bacillary angiomatosis and therefore does not appear to play a role in the pathogenesis of this pseudoneoplastic angioproliferative disorder. This finding might be useful in the distinction of bacillary angiomatosis from Kaposi's sarcoma, because lesions from patients with Kaposi's sarcoma almost always contains HHV-8 DNA.
A new device for the treatment of perineal wounds.
Explore the source record for details and available documents.
bcl-2 immunoreactivity, human papillomavirus DNA, and cervical intraepithelial neoplasia.
The aim of this study was to identify the role of bcl-2 protein expression in precancerous lesions of the cervix in patients from Johannesburg, South Africa and to correlate this expression with human papillomavirus (HPV) status. Archival cervical biopsy specimens (n = 107) of normal squamous epithelia (n = 18), pure HPV squamous epithelial lesions (n = 15), cervical intraepithelial neoplasia (CIN) I lesions (n = 17), CIN II lesions (n = 26), and CIN III lesions (n = 31) underwent bcl-2 immunohistochemical analysis with use of the streptavidin-biotin complex/horseradish peroxidase system and nonisotopic in situ hybridization for the detection of HPV DNA. Although 45 (61%) of the 74 CIN lesions demonstrated bcl-2 protein expression in the epithelia, most seemed to be in a patchy basal cell distribution, with a 1+ to 2+ intensity. Furthermore, comparison of bcl-2 immunoreaction between the low and high grades of the CIN lesions did not reveal significant differences. In addition, there was no apparent link between the presence of HPV DNA and bcl-2 expression in the CIN lesions. In contrast to previous studies that showed an increase in bcl-2 immunostaining intensity with increasing severity of CIN, only 4 (5.4%) of our 74 CIN specimens satisfied this pattern. Hence, we suggest that bcl-2 protein expression might not play a significant role in the majority of CIN lesions in this population group and that it might not correlate with HPV status.
Effects of N-acetylcysteine and 2,3-dimercaptosuccinic acid on lead induced oxidative stress in rat lenses.
Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.
trans-3-Benzyl-4-hydroxy-7-chromanylbenzoic acid derivatives as antagonists of the leukotriene B4 (LTB4) receptor.
The SAR of a series of 2-(7-chromanyl)benzoic acids has been investigated with the aim of identifying potent and selective LTB4 receptor antagonists that maintain potency in complex biological fluids. We found optimal activity in derivatives with electron-withdrawing groups in the benzoic acid ring and with an unsubstituted C-3 benzyl group on the chromanol nucleus. While compounds containing a 3-(4-phenyl)benzyl chromanol substituent were potent LTB4 receptor antagonists, the increased lipophilicity imparted by the additional phenyl substituent led to decreased potency in the presence of plasma proteins. From among the potent compounds identified, CP-195543, the 5'-trifluoromethyl 3-benzyl chromanol, was selected for development.
Natural killer cell lymphoma in cytology: breaking all the rules--a case report.
A testicular mass aspirate was received from a 22-yr-old patient with known non-Hodgkin's lymphoma. The cells were large and pleomorphic, occurring in syncytial fragments and demonstrating abundant cytoplasm. No lymphoglandular bodies were seen. As characteristic lymphoma criteria were not present, a cytodiagnosis of germ-cell tumor was suggested, and testicular biopsy advised. The final histopathology report, however, was of a CD 56-positive (large-cell) T-natural killer cell lymphoma, of which this appears to be the first example described and illustrated cytologically.
Spindle epithelial tumour with thymus-like element (SETTLE): the predominantly monophasic variant.
AIMS: To describe two cases of spindle epithelial tumour with thymus-like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics. METHODS AND RESULTS: The thyroid masses were in a 4-year-old boy and a 25-year-old male. Both patients were euthyroid and were well except for thyromegaly. The specimens were formalin fixed, and immunohistochemistry was performed on this material using a panel of antibodies following microwave antigen retrieval. Morphologically, the dominant pattern was of sheets of spindle cells arranged in several patterns. There was mild pleomorphism and occasional mitoses. There were very small foci of squamous epithelium and occasional ductular structures. The stroma was composed of fibrous tissue and isolated areas of calcification were noted. The spindle cells showed strong and diffuse immunoreactivity with AE1/3, CAM5.2 and vimentin. CONCLUSION: We describe two cases of SETTLE that are composed mainly of spindle cells and only a very focal ductular component. In addition, calcification was noted within the stroma in one of the cases. These predominantly spindle examples of SETTLE must be separated from synovial sarcoma, which is a more mitotically active, aggressive tumour displaying only patchy immunopositivity with epithelial markers.
Biotin inclusions: a potential pitfall in immunohistochemistry.
Explore the source record for details and available documents.
bcl-2, p53 immunophenotypes and apoptosis in squamous cell carcinoma of the oesophagus.
Explore the source record for details and available documents.
The role of the human papilloma virus in esophageal cancer.
Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV-positive and -negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.
Primary extrarenal Wilms' tumor of the uterus presenting as a cervical polyp.
Extrarenal Wilms' tumor is rare in any site, and only three cases arising within the uterus have been reported. Two of the previous cases were in adolescent girls, appearing as polypoid vaginal masses, and the third was in a 22-year-old woman who had menometrorrhagia. An extrarenal Wilms' tumor in an 11-year-old girl that initially appeared as a 10-cm polyp protruding through the cervix is described. Triphasic differentiation with mesenchymal stroma showing rhabdomyoblastic differentiation both morphologically and immunohistochemically was demonstrated. Epithelial differentiation with focal glomerular differentiation also was present. Most of the primary tumor and almost the entire recurrent tumor were composed of blastemal cells. The diagnosis of an extrarenal Wilms' tumor should be entertained when examining a polypoid tumor of the cervix or a polypoid mass within the vagina in an adolescent patient.
An approach to papillary urothelial lesions, including a discussion of newly described papillary lesions of the urinary bladder.
Explore the source record for details and available documents.
Identification of HHV8 in early Kaposi's sarcoma: implications for Kaposi's sarcoma pathogenesis.
AIMS: Kaposi's sarcoma is a vascular tumour of uncertain pathogenesis possibly caused by an infectious agent, identified in high risk groups. Accumulating solution phase polymerase chain reaction (PCR) and seroepidemiological data suggest that a previously undescribed herpes DNA virus (human herpesvirus 8 (HHV8)) is the causative agent. Using a unique cohort of early Kaposi's sarcoma, the precise cell type infected with HHV8 in such lesions was identified to elucidate further the role of HHV8 in the pathobiology of Kaposi's sarcoma. METHODS: Sixteen cases of early Kaposi's sarcoma (derived from skin and lymph node) were assessed for the presence of HHV8 using both standard solution phase PCR and TaqMan PCR to the KS330 Bam region of HHV8. In situ amplification was also performed on a selected group in an attempt to identify the candidate infected cells. RESULTS: Using both conventional solution phase and TaqMan PCR, 87% of cases were positive. In addition, HHV8 amplicons were localised in situ to endothelial and spindle cell proliferations in early Kaposi's sarcoma. The HHV8 viral load varied from lesion to lesion. CONCLUSIONS: The presence of HHV8 in early lesions supports a role for HHV8 in the pathogenesis of Kaposi's sarcoma. Coupled with recent seroepidemiological studies, these results suggest that HHV8 is the aetiological agent of Kaposi's sarcoma. Its precise interaction with other factors known to be involved in the development of Kaposi's sarcoma, including cytokines and anti-apoptosis genes, requires elucidation.
HHV-8 is not associated with follicular dendritic cell tumours.
Follicular dendritic cell tumours are rare malignancies derived from the follicular dendritic cells of lymphoid follicles. These tumours have been associated with Epstein-Barr virus infections and with the hyaline vascular subtype of Castleman's disease. Because many examples of Castleman's disease have been associated with Kaposi's sarcoma associated herpes virus (HHV-8), this study uses polymerase chain reaction technology to examine five cases of follicular dendritic cell tumours for HHV-8. One of these cases had previously been documented to arise from pre-existing Castleman's disease. HHV-8 DNA was not detected in any of the follicular dendritic cell tumours examined, or in the original case of Castleman's disease. These findings suggest that HHV-8 plays no role in the aetiology of follicular dendritic cell tumours and the cause of this tumour remains obscure.
Hyperparathyroidism: a seven-year follow-up.
Hyperparathyroidism (HPT) is a common finding in patients with end-stage renal disease (ESRD). Most chronic peritoneal dialysis (CPD) patients with HTP can be successfully managed with phosphate binders, calcium supplements, and calcitriol therapy. Noncompliance with diet, prescribed binder, or calcitriol therapy may also lead to HPT. We reviewed New Haven CAPD unit patients who failed medical therapy and required parathyroidectomy (PTX) for control of severe HPT [sustained immunoreactive parathyroid hormone (iPTH) level > 600 pg/mL]. From 1990 to 1997, 18 out of 620 patients (3.0%) required PTX. Time on dialysis prior to PTX was 44.8 +/- 17.5 (mean +/- SD) months with a range of 13 to 71 months. The mean age was 43.6 +/- 11.8 years with a range of 30 to 66 years. There were 10 females and 8 males. Of the 18 patients, 14 had total parathyroidectomy with arm implants, and 4 had subtotal PTX. Seven of 18 patients had iPTH levels of < 100 pg/mL at 1 year post-PTX (5 patients with arm implants, 2 with subtotal PTX). Three patients required partial arm implant PTX to correct recurrent HPT. Pulse oral calcitriol (POC) was prescribed in 10 patients post PTX to maintain iPTH at target levels. Parathyroidectomy was necessary to correct HPT in 18 of 620 CPD patients from 1990 to 1997. The majority of these patients had excellent results after their PTX. Intact PTH levels of < 100 pg/mL for 1 year or more were noted in 5 of 14 patients with arm implants, and 2 of 4 patients with subtotal PTX. The significance of a persistent iPTH of < 100 pg/mL has yet to be determined in CPD patients.