The clinical radiological and histological correlation of orbital assessment in malignant lesions of the maxillo-ethmoid complex

Twelve patients undergoing surgery between May 1995 and March 1999 for malignant tumours of the paranasal sinuses abutting or invading the orbital walls were studied for the need to remove orbital contents. Alt patients were evaluated clinically, radiologically (CT Scan) and per-operatively to delineate the extent of orbital invasion. Combined regimen (Surgery + Radiotherapy) were used in all patients. A biopsy from periorbita was taken when eye was spared. It was found that per-operative evaluation of the orbit is equally specific in comparision to clinical and CT Scan combined and eye may be preserved in selected patients with involvement of orbital periosteum provided there is no frank soft tissue mass in the orbit.     

Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.

PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.     

Frequency of proteinuria in type 2 diabetes mellitus seen at a diabetes centre in southern India

The frequency of proteinuria was assessed in a cohort of 1848 diabetic patients attending a diabetes centre in south India. A total of 127 (6.9%) patients had evidence of macroproteinuria and 49 (2.5%) patients had microproteinuria. Thus overall 9.4% of patients had diabetes related proteinuria. In addition, 70 patients (3.8%) had evidence of proteinuria with no evidence of retinopathy. The frequency of both microproteinuria and macroproteinuria increased linearly with duration of diabetes. Multiple logistic regression analysis showed that duration of diabetes, serum creatinine, and glycated haemoglobin were risk factors for macroproteinuria.     

Udp-glucuronosyltransferase 2b7 is the major enzyme responsible for gemcabene glucuronidation in human liver microsomes.

The predominant metabolic pathway of gemcabene in humans is glucuronidation. The principal human UDP-glucuronosyltransferases (UGTs) involved in the glucuronidation of gemcabene were determined in this study. Glucuronidation of gemcabene was catalyzed by recombinant UGT1A3, recombinant UGT2B7, and recombinant UGT2B17, as well as by human liver microsomes (HLM). Gemcabene glucuronidation in recombinant UGTs and HLM followed non-Michaelis-Menten kinetics consistent with homotropic activation, but pharmacokinetics in humans were linear over the dose range tested (total plasma C(max), 0.06-0.88 mM). Gemcabene showed similar affinity (S(50)) for recombinant UGTs (0.92-1.45 mM) and HLM (1.37 mM). S-Flurbiprofen was identified as a more selective inhibitor of recombinant UGT2B7-catalyzed gemcabene glucuronidation (>23-fold lower IC(50)) when compared with recombinant UGT1A3- or recombinant UGT2B17-catalyzed gemcabene glucuronidation. The IC(50) for S-flurbiprofen inhibition of gemcabene glucuronidation was similar in HLM (60.6 microM) compared with recombinant UGT2B7 (27.4 microM), consistent with a major role for UGT2B7 in gemcabene glucuronidation in HLM. In addition, 5,6,7,3',4',5'-hexamethoxyflavone inhibited recombinant UGT1A3 and recombinant UGT2B17-catalyzed gemcabene glucuronidation (with 4-fold greater potency for recombinant UGT1A3) but did not inhibit gemcabene glucuronidation in HLM, suggesting that UGT1A3 and UGT2B17 do not contribute significantly to gemcabene glucuronidation. Reaction rates for gemcabene glucuronidation from a human liver bank correlated well (r(2)=0.722, P<0.0001; n=24) with rates of glucuronidation of the UGT2B7 probe substrate 3'-azido-3'-deoxythymidine. In conclusion, using the three independent experimental approaches typically used for cytochrome P450 reaction phenotyping, UGT2B7 is the major enzyme contributing to gemcabene glucuronidation in human liver microsomes.     

Anaesthetic management of a patient with pemphigus vulgaris for emergency laparotomy

A 45-year-old man with a long-standing history of duodenal ulcer presented with symptoms and signs of perforation peritonitis. He also had lesions of pemphigus vulgaris throughout the body, involving both skin and mucous membranes. Care was taken to avoid pressure and friction during placement of monitoring devices, intravenous and arterial lines. Since the patient had to undergo exploratory laparotomy, intubation was performed in an atraumatic manner after rapid sequence induction. However, there was minor bleeding from the mucous lesions of the oral cavity, which was controlled by a saline adrenaline throat pack. The patient was extubated at the end of the surgery and steroids were continued in the peri-operative period.     

Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster

Primary simian varicella virus (SVV) infection and reactivation in nonhuman primates is a valuable animal model in the study of varicella zoster virus disease [varicella (chickenpox) and herpes zoster (shingles)]. To understand SVV pathogenesis in skin, we inoculated 10 rhesus macaques with SVV, resulting in varicella rash. After the establishment of latency, eight of the monkeys were immunosuppressed using tacrolimus with or without irradiation and prednisone and two monkeys were not immunosuppressed. Zoster rash developed in all immunosuppressed monkeys and in one non-immunosuppressed monkey. Five monkeys had recurrent zoster. During varicella and zoster, SVV DNA in skin scrapings ranged from 50 to 10⁷ copies/100 ng of total DNA and 2–127 copies/100 ng of total DNA, respectively. Detection of SVV DNA in blood during varicella was more frequent and abundant compared to that of zoster. During varicella and zoster, SVV antigens colocalized with neurons expressing β-III tubulin in epidermis, hair follicles, and sweat glands, suggesting axonal transport of the virus. Together, we have demonstrated that both SVV DNA and antigens can be detected in skin lesions during varicella and zoster, providing the basis for further studies on SVV skin pathogenesis, including immune responses and mechanisms of peripheral spread.     

Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

Background To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.Methods Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression.Results Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus.Conclusions These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.Subject terms: Prognostic markers, Colorectal cancer     

The Usefulness of the DBC‐ASA as a Screening Instrument for Autism in Children with Intellectual Disabilities: A Pilot Study

Aims To explore the validity of Developmental Behaviour Checklist‐Autism Screening Algorithm (DBC‐ASA) as a screening instrument for autism among children with intellectual disabilities. Method Data were collected from the case notes of 109 children with intellectual disabilities attending a specialist clinic in the UK. Results The mean score of the DBC‐ASA was significantly higher (t = 6.1; P < 0.001) among children with autism compared with those without. The DBC‐ASA score of 20 yielded a sensitivity of 0.9 and specificity of 0.6, and a score of 18 yielded a sensitivity of 0.92 and specificity of 0.5. The receiver–operating characteristic for the DBC‐ASA score of 20 yielded a large area under the curve (AUC) (0.864) for children with intellectual disabilities when compared against the International Classification of Diseases 10th Revision, Research Diagnostic Criteria (ICD10 DRC) diagnosis of autism. Conclusions The DBC‐ASA score may be able to discriminate between children with intellectual disabilities with and without autism.