An unusual presentation of tuberculous lymphadenitis

A 43 years male presented with recurrent epistaxis and had generalised lymphadenopathy on examination. No haematological disorder could be established even after bone marrow aspiration and biopsy but the patient was found to have tuberculosis of the lymph node on histopathology, with severe thrombocytopenia in the peripheral blood and increased platelet precursor in the marrow suggesting peripheral platelet destruction. Anti-tuberculous therapy was started but the patient died due to subarachnoid haemorrhage.     

Novel vitamin E analogue and 9-nitro-camptothecin administered as liposome aerosols decrease syngeneic mouse mammary tumor burden and inhibit metastasis

Purpose To test the anticancer properties of a nonhydrolyzable ether-linked acetic acid analogue of vitamin E, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxyacetic acid (-TEA), and a derivative of camptothecin, 9-nitrocamptothecin (9-NC) singly and in combination against mouse mammary tumor cells (line 66 clone 4 stably transfected with green fluorescent protein; 66c1-4-GFP) cultured in vitro or transplanted subcutaneously into the inguinal region of female BALB/c mice to form established tumors.Methods Following in vitro treatment of 66cl-4-GFP cells with -TEA and suboptimal concentrations of 9-NC, singly or in combination, apoptosis was measured by morphological evaluation of nuclei stained with 4,6-diamidino-2-phenylindole (DAPI), and DNA synthesis arrest was measured by tritiated thymidine uptake. For in vivo analyses -TEA and 9-NC, both water-insoluble compounds, were formulated into liposomes using dilauroylphosphatidylcholine and administered by aerosol to deliver doses calculated to be 36 and 0.4 g/mouse per day, respectively, (singly or each separately for combined treatments) 7 days per week.Results Treatment of 66cl-4-GFP cells in culture for 3 days with a combination of -TEA (10 g/ml; singly produces 38% apoptosis), and suboptimal concentrations of 9-NC (15.6, 31.3, 62.5, or 125 ng/ml; singly produce 2–7% apoptosis), produced 47%, 58%, 64%, and 69% apoptosis. Likewise, combinations of -TEA + 9-NC inhibited DNA synthesis more than either agent administered singly. A significant reduction (P<0.001) in growth of subcutaneous transplanted tumors was observed with liposome-formulated and aerosolized delivery of -TEA + 9-NC to BALB/c mice. The incidence of macroscopic lung metastasis was 83% in control vs 8% in -TEA-, 9-NC-, or combination-treated mice. Fluorescence microscopic examination of lungs and axillary and brachial lymph nodes showed a statistically significant decrease in metastasis observed in -TEA-, 9-NC-, and combination- vs control-treated animals. Analyses of primary tumor tissue for proliferation and apoptosis showed treatment groups to have lower Ki-67 and higher terminal deoxynucleotidyl transferase-mediated nick end labeling, respectively. Treatments showed no measurable effects on two angiogenesis parameters, namely intratumoral blood volume as assessed by hemoglobin content and intratumoral blood vessel density as assessed with CD31 staining.Conclusions Combination treatments enhanced antiproliferative and proapoptotic activities in cell culture, and when formulated in liposomes and delivered via aerosolization to treat an aggressive and metastatic syngeneic murine mammary tumor, the combination treatment showed a significant reduction in tumor volume in comparison to either treatment alone. Mechanistically, it appears that neither enhanced apoptosis, reduced cell proliferation, nor reduced blood vessel density can fully account for the enhanced effects of the combination treatment.Abbreviations -TEA 2,5,7,8-Tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxyacetic acid - 9-NC 9-Nitro-camptothecin - 66cl-4-GFP BALB/c mouse mammary tumor line 66 clone 4 stably transfected with GFP - DAPI 4,6-Diamidino-2-phenylindole - DMSO Dimethylsulfoxide - GFP Green fluorescent protein - PECAM-1 Platelet-endothelial cell adhesion molecule - THF Tetrahydrofuran - TUNEL Terminal deoxynucleotidyl transferase-mediated nick end labeling     

Advancement of knowledge in the field of diabetes mellitus and related metabolic diseases

The European Association for the Study of Diabetes held its 40th annual meeting September 5-9, 2004, in Munich, Germany. This scientific program presented the results of extensive research on various issues of diabetes and the related disorders, which gave a broader insight into the pathophysiology of the metabolic process. It also focused on a broad range of new therapeutic possibilities and advances in the management of diabetes and its complications.     

Prevalence and distribution of peste des petits ruminants virus infection in small ruminants in India

Peste des petits ruminants (PPR) is an acute febrile viral disease of goats and sheep characterised by mucopurulent nasal and ocular discharges, necrotising and erosive stomatitis, enteritis and pneumonia. The disease is endemic in India and causes large economic losses each year due to the high rates of mortality and morbidity in infected sheep and goats. The present study reports observations from 58 laboratory confirmed outbreaks of PPR and provides details of the prevalence of antibodies to PPR virus (PPRV) in 4,407 serum samples of small ruminants. Most of the clinical specimens used for the study originated from the northern and central parts of India. Serum samples used for the detection of antibodies to PPRV were derived from a greater number of regions within the country, however, these samples may not be a true representation of the target population (unvaccinated sheep and goats over 3 months old). Indigenously developed monoclonal antibody-based diagnostic kits were used for the detection of PPRV antigen (sandwich enzyme-linked immunosorbent assay [ELISA]) and antibody (competitive ELISA). Findings suggested that the disease outbreaks were more severe in goats than sheep and that the frequency of disease outbreaks was greater between the months of March and June (51.7%) as compared to other periods of the year. Based on the screening of the 4,407 sera samples, the antibody prevalence of PPRV in small ruminants in India was 33% (95% confidence interval: 32.3% to 33.7%). The prevalence of antibodies to PPRV was noted to differ between species (i.e. sheep versus goats), age groups and geographical regions. A greater proportion of the sheep (36.3%) versus the goat (32.4%) population was infected with PPRV. The distribution and prevalence of antibodies to PPRV among various age groups of animals indicated that goats were exposed at an earlier age than the sheep, suggesting that goats may be more susceptible to infection with PPRV. A greater number of positive cases were observed in the southern and southwestern part of the country (30%-60%) as compared to northern India (10%-30%). These findings may be correlated with variations in the sheep and goat husbandry practices within different geographic regions, the topography of different states and the socio-economic status of individual Indian farmers.     

Beta-blockers in left ventricular systolic dysfunction--from evidence to practice

Five percent of all hospital medical admissions are patients with heart failure. The incidence is about one new case per 1000 of the general population per year, increasing to >10 per 1000 in those aged >or=85 years. Although the evidence that beta-blockers reduce mortality by about 36% when added to angiotensin-converting enzyme inhibitors is overwhelming, clinicians are still reluctant to use beta-blockers in heart failure, especially in older patients. Here, we examine the evidence for the use of beta-blockers in heart failure in older people and explore the practicalities of their use.     

PKC-zeta mediates insulin effects on glucose transport in cultured preadipocyte-derived human adipocytes

Insulin-stimulated glucose transport is impaired in the early phases of type 2 diabetes mellitus. Studies in rodent cells suggest that atypical PKC (aPKC) isoforms (zeta, lamda, and iota) and PKB, and their upstream activators, PI3K and 3-phosphoinositide-dependent protein kinase-1 (PDK-1), play important roles in insulin-stimulated glucose transport. However, there is no information on requirements for aPKCs, PKB, or PDK-1 during insulin action in human cell types. Presently, by using preadipocyte-derived adipocytes, we were able to employ adenoviral gene transfer methods to critically examine these requirements in a human cell type. These adipocytes were found to contain PKC-zeta, rather than PKC-lamda/iota, as their major aPKC. Expression of kinase-inactive forms of PDK-1, PKC-zeta, and PKC-lamda (which functions interchangeably with PKC-zeta) as well as chemical inhibitors of PI 3-kinase and PKC-zeta/lamda, wortmannin and the cell-permeable myristoylated PKC-zeta pseudosubstrate, respectively, effectively inhibited insulin-stimulated glucose transport. In contrast, expression of a kinase-inactive, activation-resistant, triple alanine mutant form of PKB-alpha had little or no effect, and expression of wild-type and constitutively active PKC-zeta or PKC-lamda increased glucose transport. Our findings provide convincing evidence that aPKCs and upstream activators, PI 3-kinase and PDK-1, play important roles in insulin-stimulated glucose transport in preadipocyte-derived human adipocytes.     

Laparoscopic reintervention for residual gallstone disease

Laparoscopic reintervention is being increasingly performed in patients who have previously undergone surgery for gallstone disease. A few patients with gallbladder remnants or a cystic duct stump with residual stones have recurrent symptoms of biliary disease. Patients with bile duct injuries were excluded from the study. We reviewed our experience in treating such patients over a 4-year period, January 1998 through December 2001. Five patients underwent laparoscopic reintervention after previous surgery for gallstone disease performed elsewhere during the period mentioned above. Of these 5 patients, 3 had impacted stones in gallbladder remnants (laparoscopic cholecystectomy, 2; open cholecystectomy, 1) and 2 had recurrent symptoms after cholecystolithotomy and tube cholecystostomy (conventional surgery) performed elsewhere. Laparoscopic excision of the gall bladder remnants was done in 3 patients and a formal laparoscopic cholecystectomy was done in 2 patients who had previously undergone cholecystolithotomy and tube cholecystostomy. The mean operating time was 42 minutes. No drainage was required postoperatively. All patients were symptom-free during a mean follow-up of 2.3 years (range, 7 months to 4 years). Reintervention may be required for patients with residual gallstones whose symptoms recur after gallbladder surgery such as cholecystectomy, subtotal cholecystectomy, and tube cholecystostomy. It is safe and feasible to remove the gallbladder or gallbladder remnants in such patients laparoscopically.     

A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells.

Transforming growth factor beta (TGF-beta) can promote late stage tumor progression in a number of model systems. In the present study, we have examined whether expression of a truncated soluble extracellular domain of TGF-beta type III receptor (sRIII) in human breast cancer MDA-MB-231 cells can antagonize the tumor-promoting activity of TGF-beta by sequestering active TGF-beta isoforms that are produced by the cancer cells. The secretion of sRIII reduced the amount of active TGF-beta1 and TGF-beta2 in the conditioned medium. This led to a significant reduction of the growth-inhibitory activity of the medium conditioned by sRIII-expressing cells on the growth of mink lung epithelial CCL64 cells in comparison with the medium conditioned by the control cells. The tumor incidence and growth rate of all of the three sRIII-expressing clones studied were significantly lower than those of the control cells in athymic nude mice. Four of five control cell-inoculated mice showed spontaneous metastasis in the lung, whereas none of the sRIII-expressing cell-inoculated mice had any lung metastasis. Thus, our results suggest that the sRIII may be used to antagonize the tumor-promoting activity of TGF-beta.     

An arrow in the nasal cavity,ethmoid and nasopharynx

A penetrating foreign body (Metallic arrow) involving the ethmoidal air cells nose and nasopharynx is being reported.