The nuclear/mitotic apparatus protein NuMA is a component of the somatodendritic microtubule arrays of the neuron

Neurons are terminally post-mitotic cells that utilize their microrubule arrays for the growth and maintenance of axons and dendrites rather than for the formation of mitotic spindles. Recent studies from our laboratory suggest that the mechanisms that organize the axonal and dendritic microtubule arrays may be variations on the same mechanisms that organize the mitotic spindle in dividing cells. In particular, we have identified molecular motor proteins that serve analogous functions in the establishment of these seemingly very different microtubule arrays. In the present study, we have sought to determine whether a non-motor protein termed NuMA is also a component of both systems. NuMA is a ~230 kDa structural protein that is present exclusively in the nucleus during interphase. During mitosis, NuMA forms aggregates that interact with microtubules and certain motor proteins. As a result of these interactions, NuMA is thought to draw together the minus-ends of microtubules, thereby helping to organize them into a bipolar spindle. In contrast to mitotic cells, post-mitotic neurons display NuMA both in the nucleus and in the cytoplasm. NuMA appears as multiple small particles within the somatodendritic compartment of the neuron, where its levels increase during early dendritic differentation. A partial but not complete colocalization with minus-ends of microtubules is suggested by the distribution of the particles during development and during drug treatments that alter the microtubule array. These observations provide an initial set of clues regarding a potentially important function of NuMA in the organization of microtubules within the somatodendritic compartment of the neuron.     

Pelvic inflammatory disease and intrauterine devices: Prophylactic antibiotics to reduce febrile complications

In the present study, we tried to determine whether IUD insertion related PID and febrile complications could, be prevented by prophylactic use of antibiotics. We studied 300 patients who were admitted to our family planning clinic for IUD contraception. Of these, 150 patients received prophylactic Doxycycline (group 1) and the second 150 received no therapy (group 2). Five cases experienced fever with or without leucocytosis and none required hospitalization. PID was observed in one woman in each group.Positive culture (gonorrhea) was obtained in one woman who was then treated by relevant, antibiotics; the other woman required hospitalization for two days. The overall infection rates for group 1 and 2 were 2.1% and 2.9%, respectively and this difference was not significant. The incidence of PID infection and febrile complications was found to be very low for both groups when compared to other studies, suggesting that aseptic conditions with proper insertion reduce the risk of infection.

---

Resumen En el presente estudio, intentamos determinar si la inflamación pélvica y las complicationes febriles relacionadas con la inserción, de DIU podían evitarse mediante la administración profiláctica de antibióticos. Estudiamos a 300 pacientes de nuestra clínica de planificación familiar que recibieron DIU. Se administró un tratamiento profiláctico de doxicilina a 150 pacientes (Grupo 1) mientras que las restantes no recibieron ningún tratamiento (Grupo 2). Hubo cinco casos de fiebre con o sin leucocitosis pero ninguno requirió hospitalización. La inflamación pélvica se observó en dos casos, uno de cada grupo. Se obtuvo un cultivo positivo (gonorrea) en uno de los casos, que fue tratado con antibióticos apropiados, y el segundo caso debió ser hospitalizado durante dos días. Las tasas generales de infección fueron para el Grupo 1 y el Grupo 2, respectivamente, del 2,1% y del 2,9%, diferencia que no es significativa. Una comparación con otros estudios permitió verificar que la incidencia de infección pélvica inflamatoria y complicaciones febriles era muy baja en los dos grupos, lo cual hace pensar que las condiciones de asepsia y la inserción correcta reducen el riesgo de infección.

---

Resumé Dans la présente étude, nous avons tenté de déterminer si l'inflammation pelvienne et les complications fébriles liées à l'insertion de DIU pouvaient être évitées par une administration prophylactique d'antibiotiques. Nous avons suivi 300 patientes de notre clinique de planning familial, admises pour l'insertion, de DIU. Un traitement prophylactique de doxycycline a été administré à 150 de ces patientes (Groupe 1) et les autres n'ont reçu aucune, thérapie (Groupe 2). Nous avons eu cinq cas de fièvre avec ou sans leucocytose mais aucune de ces femmes n'a d être hospitalisée. L'inflammation pelvienne s'est manifestée dans deux cas, un dans chaque groupe. Une culture positive (gonorrhée) a été obtenue chez une de ces patientes, à laquelle un traitement aux antibiotiques appropriés a été administré, et la seconde a d être hospitalisée pendant deux jours. Les taux globaux d'infection ont été, respectivement pour le groupe 1 et le groupe 2, de 2,1% et 2,9%, ce qui ne représente pas une différence significative. Une comparaison avec d'autres études a permis, de constater que l'incidence d'infection pelvienne inflammatoire et de complications fébriles était très faible dans les deux groupes, ce qui laisse penser que les conditions d'asepsie et une insertion correcte réduisent le risque d'infection.

     

Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey

Effects of tobacco smoking and alcohol use on risks of cancers of thelarynx and lung have been evaluated extensively in industrialized countries.Few studies on the effect of these risk factors have been reported fromdeveloping countries. We conducted a case-control study to evaluate risks oflaryngeal and lung cancers in men by subsite and cell type in relation tosmoking and alcohol drinking in Turkey, a country where smoking and alcoholconsumption patterns are different from those in industrialized countries. Weidentified 832 laryngeal and 1,210 lung cancer cases and 829 controls withinformation on smoking and alcohol use (amount and duration) and histologiccell type from an oncology treatment center of a Social Security Agencyhospital in Istanbul, Turkey, admitted between 1979 and 1984. Both laryngealand lung cancer showed significant associations with smoking and alcoholdrinking, but no monotonic dose-response was obtained for alcohol drinking.Among smokers, the highest risks were observed in the supraglottis region ofthe larynx (odds ratio [OR] = 4.1) after adjustment for age and alcohol use.Among alcohol drinkers, the highest risks were observed in the glottis regionof the larynx (OR = 1.7) after adjustment for age and smoking. In theanalysis by the cell type of lung cancer among ever-smokers, small cell typeshowed the highest risk (OR = 5.4), while it showed no association withalcohol drinking. Cumulative cigarette use (pack-years) and number ofcigarettes per day showed stronger associations than years smoked for bothcancer sites. The relative risks of joint exposure to smoking and alcoholwere 12.2 for laryngeal cancer and 14.1 for lung cancer among heavy smokersand heavy alcohol drinkers. This study provides epidemiologic evidence fromTurkey that smoking and alcohol use are associated with risks of cancers ofthe larynx and lung.     

Does post dural puncture headache exist in idiopathic intracranial hypertension? A pilot study

Background/ObjectiveOccurrence of post-dural puncture headache (PDPH) after diagnostic lumbar puncture (LP) for idiopathic intracranial hypertension (IIH) may seem very unlikely in clinical practice. Nevertheless, it has been suggested by several studies, mainly in sub-group analyses. We aimed to evaluate the prevalence of PDPH in an IIH population and determine any eventual predictive factors of PDPH occurrence.MethodsWe conducted a retrospective multiple-center observational study. All newly diagnosed IIH patients who met the International Classification of Headache Disorders (ICHD-3) or the Dandy modified criteria were included from three different French hospitals. They all underwent LP following the same process with the same type of needle. We recorded PDPH occurring within five days after LP, as defined by ICHD-3 criteria.ResultsSeventy-four IIH patients were recruited, of whom 23 (31%) presented with PDPH. Neither classical risk factors for PDPH such as body mass index, age or gender, nor cerebrospinal fluid opening pressure, or specific IIH features were associated with occurrence of PDPH.ConclusionPDPH can occur after LP in IIH patients. Clinicians should be aware of this possible event during the IIH diagnosis assessment and should not automatically reconsider IIH diagnosis. PDPH prevention using an atraumatic needle and dedicated PDPH treatment seem relevant in IIH patients.     

DoesHelicobacter pylori-induced gastritis enhance food-stimulated insulin release?

The fact thatH. pylori gastritis results in an increased secretion of basal and meal-stimulated gastrin, which is also a physiologic amplifier of insulin release directed us to investigate whetherH. pylori gastritis may lead to an enhancement of nutrient-stimulated insulin secretion. For this purpose, we have investigated the insulin responses to both oral glucose and a mixed meal in 15 patients withH. pylori gastritis before and one month after the eradication therapy and also in 15H. pylori-negative control subjects. The areas under the curve (AUC) for serum insulin following both oral glucose and a mixed meal in the patients withH. pylori gastritis before the eradication were significantly (P<0.05) higher than those in theH. pylori-negative controls. After the eradication ofH. pylori, the AUC for serum insulin following oral glucose and mixed meal decreased by 9.4% and 13.1%, respectively (P<0.001 in both), and serum basal and meal-stimulated gastrin levels decreased significantly (P<0.001). These results suggest thatH. pylori gastritis enhances glucose and meal-stimulated insulin release probably by increasing gastrin secretion.Presented in part as an abstract at the 8th Balkan Congress of Endocrinology, Bursa, Turkey, May 3–5, 1995.     

Reliability and Validity of the Turkish Version of the Abiloco-Kids

ABILOCO-Kids is a scale that assesses the walking ability of children with Cerebral Palsy (CP) from the viewpoint of parental perception. The aim of this study was to translate the ABILOCO-Kids scale into Turkish and to establish its reliability and validity in children with CP. Turkish children were recruited in this study. ABILOCO-Kids is a scale developed by Caty and et al. This scale assess the walking ability of children with CP focusing on the activity domain of the International Classification of Functioning, Disability and Health (ICF). The ABILOCO-Kids scale was translated from English into Turkish using the forward-backward-forward method. The motor functions of the 63 children participating in the study were evaluated by the Gross Motor Function Classification System (GMFCS) and the Gross Motor Function Measurement-88 (GMFM-88). The ABILOCO-Kids scale was repeated in 30 children after one week to establish test-retest reliability. While internal and external construct validity were investigated using Rasch analysis and Spearman correlation coefficient, respectively; reliability was evaluated in terms of internal consistency by Cronbach’s alpha and Person Separation Index (PSI). All items of the ABILOCO-Kids were found to fit the Rasch Model (chi-square 14.35 (df?=?20), p?=?0.813). The internal construct validity was good, overall mean item fit residual was ?0.109 (SD: 0.719) and mean person fit residual was ?0.215 (SD: 0.817). The reliability was good with Cronbach’s Alpha of 0.98 and PSI of 0.99. When the test-retest was examined via Differential Item Functioning (DIF) by time, none of the items showed DIF. Spearman correlation coefficients of the ABILOCO-Kids scale in relation to the GMFM and GMFCS were r?=?0.824, p?<?0.001; r?=??0.788, p?<?0.001 respectively. The Turkish version of the ABILOCO-Kids scale is a valid, reliable and unidimensional scale for children with CP. This scale will allow the differences in the locomotion of children with CP to be evaluated from the perspective of the family.     

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock

Purpose

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.

Methods

We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.

Results

Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).

Conclusions

Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

     

Safety and tolerability of a single administration of AR-301, a human monoclonal antibody,in ICU patients with severe pneumonia caused by <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>: first-in-human trial

Purpose

Hospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics.

Methods

Eligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤?30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start <?36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement.

Results

Thirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days.

Conclusions

Adjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.