[MEDICAL AND SOCIAL STATE OF HEALTH IN FAMILIES WITH THE FOCUS OF RESPIRATORY CHLAMYDIA].

Medical and social state of health in family persons was assessed on the basis of a questionnaire. Developed by the author's questionnaire included two sections, reflecting the state of health, health risk factors and social characteristics of the family members of ENT patients. In the article there is presented an analysis of the medical and social state of 44 families of patients with diseases of the upper respiratory tract associated with chlamydial infection. The comparison was performed with 43 families of ENT patients with unconfirmed respiratory chlamydia. Diagnosis of Chlamydia infection complex was carried out with the use of laboratory methods (direct immunofluorescence and enzyme-linked immunosorbent assays, polymerase chain reaction). The health and social status of families with hearth respiratory chlamydia were shown to be significantly worse compared with families with the lack of the latter

Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999-2010.

The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 recipients of allogeneic clinical islet transplantation in 1999-2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p<0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007-2010 when compared to 1999-2002 (445.4±156.8 vs. 421.3±155.4×0(3) IEQ; p<0.05). Islet purity and total number of ß cells significantly improved over the study period (p<0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999-2010, and these parallel improvements in clinical outcomes over the same period.

Distinct and opposing roles for the phosphatidylinositol 3-OH kinase catalytic subunits p110α and p110ß in the regulation of insulin secretion from rodent and human beta cells.

AIMS/HYPOTHESIS: Phosphatidylinositol 3-OH kinases (PI3Ks) regulate beta cell mass, gene transcription, and function, although the contribution of the specific isoforms is unknown. As reduced type 1A PI3K signalling is thought to contribute to impaired insulin secretion, we investigated the role of the type 1A PI3K catalytic subunits α and ß (p110α and -ß) in insulin granule recruitment and exocytosis in rodent and human islets. METHODS: The p110α and p110ß subunits were inhibited pharmacologically or by small hairpin (sh)RNA-mediated knockdown, and were directly infused or overexpressed in mouse and human islets, beta cells and INS-1 832/13 cells. Glucose-stimulated insulin secretion (GSIS), single-cell exocytosis, Ca(2+) signalling, plasma membrane granule localisation, and actin density were monitored. RESULTS: Inhibition or knockdown of p110α increased GSIS. This was not due to altered Ca(2+) responses, depolymerisation of cortical actin or increased cortical granule density, but to enhanced Ca(2+)-dependent exocytosis. Intracellular infusion of recombinant PI3Kα (p110α/p85ß) blocked exocytosis. Conversely, knockdown (but not pharmacological inhibition) of p110ß blunted GSIS, reduced cortical granule density and impaired exocytosis. Exocytosis was rescued by direct intracellular infusion of recombinant PI3Kß (p110ß/p85ß) even when p110ß catalytic activity was inhibited. Conversely, both the wild-type p110ß and a catalytically inactive mutant directly facilitated exocytosis. CONCLUSIONS/INTERPRETATION: Type 1A PI3K isoforms have distinct and opposing roles in the acute regulation of insulin secretion. While p110α acts as a negative regulator of beta cell exocytosis and insulin secretion, p110ß is a positive regulator of insulin secretion through a mechanism separate from its catalytic activity.

The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer.

Despite recent advances in therapy, breast cancer remains the second most common cause of death from malignancy in women. Chemotherapy plays a major role in breast cancer management, and combining chemotherapeutic agents with nonchemotherapeutic agents is of considerable clinical interest. Cucurbitacins are triterpenes compounds found in plants of the Cucurbitaceae family, reported to have anticancer and anti-inflammatory activities. Previously, we have shown antiproliferative activity of cucurbitacin B (CuB) in breast cancer, and we hypothesized that combining CuB with chemotherapeutic agents can augment their antitumor effect. Here, we show that a combination of CuB with either docetaxel (DOC) or gemcitabine (GEM) synergistically inhibited the proliferation of MDA-MB-231 breast cancer cells in vitro. This antiproliferative effect was accompanied by an increase in apoptosis rates. Furthermore, in vivo treatment of human breast cancer orthotopic xenografts in immunodeficient mice with CuB at either low (0.5 mg/kg) or high (1 mg/kg) doses in combination with either DOC (20 mg/kg) or GEM (12.5mg/kg) significantly reduced tumor volume as compared with monotherapy of each drug. Importantly, no significant toxicity was noted with low-dose CuB in combination with either DOC or GEM. In conclusion, combination of CuB at a relatively low concentration with either of the chemotherapeutic agents, DOC or GEM, shows prominent antiproliferative activity against breast cancer cells without increased toxicity. This promising combination should be examined in therapeutic trials of breast cancer.

Autologous islet transplantation after total pancreatectomy for renal cell carcinoma metastases.

Pancreatic metastases from renal cell carcinoma (RCC) may have a chronic and highly indolent course, and may be resected for cure after considerable delay following treatment of the primary tumor, in contrast to other more common pancreatic tumors. Surgical resection is the treatment of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive resection. We present a 70-year-old patient with multifocal pancreatic metastases from RCC causing obstructive jaundice. A total pancreatectomy was required to excise two distant tumors in the head and tail of the pancreas, together with a segment VI liver resection. An autologous islet transplant (AIT) prepared from the central, uninvolved pancreas was carried out to prevent postpancreatectomy diabetes. The patient was rendered insulin-free and remains so with excellent glycemic control for 1 year of follow-up, and there is no evidence of tumor recurrence. The patient has been treated with adjuvant sunitinib to minimize risk of further recurrence. In conclusion, AIT after pancreatectomy may represent a useful option to treat patients with metastatic RCC. A critical component of this approach was dependent upon elaborate additional testing to exclude contamination of the islet preparation by cancerous cells.

[Optimization of medical care provided to the patients suffering respiratory chlamydiosis].

The objective of the present study was to elaborate the complex of measures intended to optimize medical care for the patients suffering respiratory chlamydiosis. The adequate organizational measures concerning the prophylactic and therapeutic treatment of inflammatory pathology of the upper respiratory tract associated with Chlamydia infection have not been proposed up to the present time and need to be urgently developed. The importance of this issue has been confirmed in a study involving 245 subjects that demonstrated the imperfection of the structure of the currently operating system of outpatient and hospital-based service provided to the patients with respiratory chlamydiosis. The authors propose the program that defines priority activities in the field under discussion and outline possible ways to reduce morbidity and the number of cases.

The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function.

AIMS/HYPOTHESIS: It is thought that the voltage-dependent potassium channel subunit Kv2.1 (Kv2.1) regulates insulin secretion by controlling beta cell electrical excitability. However, this role of Kv2.1 in human insulin secretion has been questioned. Interestingly, Kv2.1 can also regulate exocytosis through direct interaction of its C-terminus with the soluble NSF attachment receptor (SNARE) protein, syntaxin 1A. We hypothesised that this interaction mediates insulin secretion independently of Kv2.1 electrical function. METHODS: Wild-type Kv2.1 or mutants lacking electrical function and syntaxin 1A binding were studied in rodent and human beta cells, and in INS-1 cells. Small intracellular fragments of the channel were used to disrupt native Kv2.1-syntaxin 1A complexes. Single-cell exocytosis and ion channel currents were monitored by patch-clamp electrophysiology. Interaction between Kv2.1, syntaxin 1A and other SNARE proteins was probed by immunoprecipitation. Whole-islet Ca(2+)-responses were monitored by ratiometric Fura red fluorescence and insulin secretion was measured. RESULTS: Upregulation of Kv2.1 directly augmented beta cell exocytosis. This happened independently of channel electrical function, but was dependent on the Kv2.1 C-terminal syntaxin 1A-binding domain. Intracellular fragments of the Kv2.1 C-terminus disrupted native Kv2.1-syntaxin 1A interaction and impaired glucose-stimulated insulin secretion. This was not due to altered ion channel activity or impaired Ca(2+)-responses to glucose, but to reduced SNARE complex formation and Ca(2+)-dependent exocytosis. CONCLUSIONS/INTERPRETATION: Direct interaction between syntaxin 1A and the Kv2.1 C-terminus is required for efficient insulin exocytosis and glucose-stimulated insulin secretion. This demonstrates that native Kv2.1-syntaxin 1A interaction plays a key role in human insulin secretion, which is separate from the channel's electrical function.

Anakinra potentiates the protective effects of etanercept in transplantation of marginal mass human islets in immunodeficient mice.

Anti-inflammatory agents are used routinely in clinical islet transplantation in an attempt to promote islet engraftment. Infliximab, and more recently etanercept, is being used to neutralize tumor necrosis factor alpha, but this tenet is based on limited preclinical data. One group has promoted the potential of combined etanercept with an IL-1 receptor antagonist, anakinra in a small clinical study, but without strong preclinical data to justify this approach. We therefore sought to evaluate the impact of combined anakinra and etanercept in a marginal islet mass transplant model using human islets in immunodeficient mice. The combination of anakinra and etanercept led to remarkable improvement in islet engraftment (control 36.4%; anakinra 53.9%; etanercept 45.45%; anakinra and etanercept 87.5% euglycemia, p < 0.05 by log-rank) compared to single-drug treated mice or controls. This translated into enhanced metabolic function (area under curve glucose tolerance), improved graft insulin content and marked reduction in beta-cell specific apoptotis (0.67% anakinra + etanercept vs. 23.5% control, p < 0.001). These results therefore strongly justify the combined short-term use of anakinra and etanercept in human islet transplantation.

[Peculiar manifestations of familial chlamydiasis of the upper respiratory tract].

The aim of the present study was to elucidate the frequency of chlamydial infection in the members of the families having the confirmed disease and concomitant ENT pathologies. Another objective was the comparative analysis of otorhinolaryngological morbidity in the families with and without the carriers of respiratory chlamydiasis. A total of 87 families were involved in the study. Chlamydial infection was diagnosed by a set of laboratory methods including direct immunofluoresent and immunoenzyme analysis as well as polymerase chain reaction (PVR). It was shown that the presence of a patient suffering from respiratory chlamydiasis in the family creates the risk of infection for its remaining members. Moreover the frequency of ENT morbidity increases in the families that serve as a hotbed of chlamydiasis of the upper respiratory tract.

Late cytomegalovirus transmission and impact of T-depletion in clinical islet transplantation.

The epidemiology of cytomegalovirus infection (CMV) in islet transplantation (IT) is not well defined. This study defines incidence, transmission and clinical sequelae of CMV reactivation or disease in 121 patients receiving 266 islet infusions at a single institution. The donor (D)/recipient (R) serostatus was D+/R- 31.2%, D+/R+ 26.3%, D-/R+ 13.2% and D-/R- 29.3%. CMV prophylaxis with oral ganciclovir/valganciclovir was given in 68%. CMV infection occurred in 14/121 patients (11.6%); six had asymptomatic seroconversion and eight others had positive viremia (six asymptomatic and two with CMV febrile symptoms). Median peak viral loads were 1755 copies/mL (range 625-9 100 000). Risk factors for viremia included lymphocyte depletion (thymoglobulin or alemtuzumab, p < 0.001). Viremia was more common in D+/R+ versus D+/R- (p = 0.12), occurring mostly late after transplant (median 306 days). Presumed transmission from IT occurred in 8/83 of D+/R- procedures (9.6%). Of the two cases of CMV disease, one resulted from islet transmission from a CMV positive donor (D+/R-); the other was due to de novo exogenous infection (D-/R-). Therefore, CMV transmission presents rarely after IT and with low incidence compared to solid organ transplantation, but occurs late posttransplant. The use of lymphocyte depleting therapies is a primary risk factor.

Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation.

Percutaneous transhepatic portal access avoids surgery but is rarely associated with bleeding or portal venous thrombosis (PVT). We herein report our large, single-center experience of percutaneous islet implantation and evaluate risk factors of PVT and graft function. Prospective data were collected on 268 intraportal islet transplants (122 subjects). A portal venous Doppler ultrasound was obtained on Days 1 and 7 posttransplant. Therapeutic heparinization, complete ablation of the portal catheter tract with Avitene paste and limiting packed cell volume (PCV) to <5 mL completely prevented any portal thrombosis in the most recent 101 islet transplant procedures over the past 5 years. In the previous cumulative experience, partial thrombosis did not affect islet function. Standard liver volume correlated negatively (r =-0.257, p < 0.001) and PCV correlated positively with portal pressure rise (r = 0.463, p < 0.001). Overall, partial portal thrombosis occurred after 10 procedures (overall incidence 3.7%, most recent 101 patient incidence 0%). There were no cases of complete thrombosis and no patient developed sequelae of portal hypertension. In conclusion, portal thrombosis is a preventable complication in clinical islet transplantation, provided therapeutic anticoagulation is maintained and PCV is limited to <5 mL.

Hemodynamic Analysis of Cerebral AVMs with 3D Phase-Contrast MR Imaging.

BACKGROUND AND PURPOSE: The hemodynamics associated with cerebral AVMs have a significant impact on their clinical presentation. This study aimed to evaluate the hemodynamic features of AVMs using 3D phase-contrast MR imaging with dual velocity-encodings. MATERIALS AND METHODS: Thirty-two patients with supratentorial AVMs who had not received any previous treatment and had undergone 3D phase-contrast MR imaging were included in this study. The nidus diameter and volume were measured for classification of AVMs (small, medium, or large). Flow parameters measured included apparent AVM inflow, AVM inflow index, apparent AVM outflow, AVM outflow index, and the apparent AVM inflow-to-outflow ratio. Correlation coefficients between the nidus volume and each flow were calculated. The flow parameters between small and other AVMs as well as between nonhemorrhagic and hemorrhagic AVMs were compared. RESULTS: Patients were divided into hemorrhagic (n = 8) and nonhemorrhagic (n = 24) groups. The correlation coefficient between the nidus volume and the apparent AVM inflow and outflow was .83. The apparent AVM inflow and outflow in small AVMs were significantly smaller than in medium AVMs (P < .001 for both groups). The apparent AVM inflow-to-outflow ratio was significantly larger in the hemorrhagic AVMs than in the nonhemorrhagic AVMs (P = .02). CONCLUSIONS: The apparent AVM inflow-to-outflow ratio was the only significant parameter that differed between nonhemorrhagic and hemorrhagic AVMs, suggesting that a poor drainage system may increase AVM pressure, potentially causing cerebral hemorrhage.

[Comparative characteristics of the staphylococcus landscape of nasal mucosa in patients with sinusitis and rhinitis].

This paper reports results of the study of nasal mucosal microflora in patients with chronic sinusitis (CS) and rhinitis (CR). The study revealed dysbacteriosis of nasal mucosa in the patients of both groups. At the same time, the structure of mucosal microbiocenoses was not significantly different in patients with CS and CR. Moreover, the study has demonstrated enhanced pathogenic activity of Staphylococcus bacteria in both CS and CR.

[Properties of nasal mucosal microflora in patients with allergic rhinosinusitis].

Analysis of microbial composition of nasal mucosa in patients with allergic rhinitis revealed marked changes in microflora compared with healthy subjects. Specifically, the overall diversity of staphylococci decreased while the abundance of S. aureus increased. The number of strains with pathogenic and persisting properties in patients with allergic rhinitis was greater than in controls.

Integrating 3D Rotational Angiography into Gamma Knife Planning.

3D rotational angiography provides remarkable spatial resolution for cerebrovascular disorders; however, it cannot be integrated directly into gamma knife planning due to the discrepancy of DICOM "tag" information, and most physicians still cannot benefit from 3D rotational angiography. Here, we describe a simple and easy technique to enable the integration of 3D rotational angiography.

[Microbiocenosis of nasal mucous membrane during allergic rhinosinusitis].

Overall quantity of microorganisms and their relative prevalence on nasal mucous membrane in patients with allergic rhinosinusitis are determined. Microbial flora in studied group was characterized qualitatively and quantitatively. Obtained results showed that there were changes of microbiocenosis of nasal mucous membrane during allergic rhinosinusitis and in characteristics of species in Staphylococcus genus.

Global and region-specific analyses of apparent diffusion coefficient in dentatorubral-pallidoluysian atrophy.

BACKGROUND AND PURPOSE: Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar ataxia. Techniques for the quantitative assessment of neurodegenerative lesions remain to be established in this disease. We attempted to quantify global and region-specific neurodegeneration in DRPLA using analysis of apparent diffusion coefficient (ADC) maps. METHODS: Diffusion-weighted images (b = 1000 s/mm(2)) by echo-planar sequences were obtained with the use of a 1.5T clinical scanner. Whole-brain histogram and region of interest (ROI) analyses of ADC values as well as conventional MR imaging studies were performed in 6 patients with genetically confirmed DRPLA. RESULTS: Histograms demonstrated significantly higher mean ADC values in the patients than in age- and sex-matched control subjects (P < .01). ROI analysis revealed that the patients had significantly higher ADC values in the cerebellum and globus pallidus, preferentially affected regions (P < .05), but not in the thalamus, the region relatively spared in this disease. ADC values in the white matter were higher only in patients with adult-onset disease. Histogram analyses could more sensitively identify abnormalities than ROI analyses, because the former avoided errors associated with setting ROIs and thus had smaller P values on statistical analysis than the latter. CONCLUSIONS: Histogram ADC analyses were more sensitive for the detection of neurodegeneration in DRPLA than ROI analyses, whereas ROI analyses revealed regional alterations reflecting the distribution of pathologic changes. Thus, histogram and ROI analyses complement each other and may permit the sensitive, quantitative evaluation of neurodegeneration in DRPLA, especially that involving the globus pallidus showing normal T2 signals.