High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma

Immunohistochemical expression of neuronal (n), endothelial (e), and inducible (i) NOS and their association with the type, grade, apoptotic index, proliferation of tumors and the survival of patients were investigated in 89 biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS staining was seen significantly more often in adenocarcinomas than in squamous cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors (p=0.024). There was no significant difference between the low and high apoptotic indexes or between the low and high proliferation rates of tumors in any instance of NOS staining. The patients with tumors showing high nNOS expression tended to have better survival than the others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the patients with tumors showing high expression of iNOS, eNOS and nNOS, as determined by a combined sum index, had a better survival than those with a low sum index for these enzymes (p<0.05). The results show intense expression of eNOS and nNOS, and moderate expression of iNOS in tumor cells of non-small cell carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non-small cell lung carcinoma.     

Antifungal Activity of Nonantifungal Drugs

The antifungal activity of synthetic, nonchemotherapeutic compounds, antineoplastic agents and antibacterial drugs, such as sulphonamides, has been known since the early 20^th century (1932). In this context, the term "nonantifungal" is taken to include a variety of compounds that are employed in the management of pathological conditions of nonfungal infectious etiology but have been shown to exhibit broad-spectrum antifungal activity. In this review, the antifungal properties of compounds such as chlorpromazine, proton pump inhibitors, antiarrhythmic agents, cholesterol-lowering agents, antineoplastic and immunosuppressive agents, antiparasitic drugs and antibiotics are described. Since fungi are eukaryotic cells, they share many pathways with human cells, thus increasing the probability of antifungal activity of "nonfungal drugs". The potential of these drugs for treatment of fungal infections has been investigated sporadically using the drugs alone or in combination with "classic" antifungal agents. A review of the literature, supplemented with a number of more recent investigations, suggests that some of these compounds enhance the activity of conventional antifungal agents, eliminate natural resistance to specific antifungal drugs (reversal of resistance) or exhibit strong activity against certain fungal strains in vitro and in animal models. The role of these agents in the epidemiology and in the clinical manifestations of fungal infections and the potential of certain drugs for treatment of invasive fungal infections require further investigation.     

Four and one-half-year follow-up of the effectiveness of diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b and diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus/H. influenzae type b combination vaccines in Germany

BACKGROUND: Recently an increase in the number of invasive Haemophilus influenzae type b (Hib) cases was observed in the United Kingdom, which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis (DTaP) Hib vaccines. A study in Germany based on approximately 2 years of follow-up, estimated vaccine effectiveness (VE) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high. OBJECTIVES: To assess VE of DTaP-containing Hib vaccines against Hib in Germany with the use of extended follow-up of case surveillance and vaccine uptake. SUBJECTS AND METHODS: Cases with confirmed systemic Hib infections in children born between June 1, 1996 and December 31, 1998 were ascertained by a nationwide active surveillance system from January 1998 through June 2002. A representative subcohort of 667 children born in the same time frame was randomly sampled in a nationwide vaccine coverage survey. VE was determined with a case-cohort approach of Cox regression with time-dependent covariates. RESULTS: Thirty-six cases of Hib disease were reported. Of these, 10 were vaccinated with DTaP-containing Hib vaccines only and 20 were not vaccinated. Of the 10 vaccinated cases, 4 had received an incomplete primary series (1-2 doses), and 6 had received the full primary series (3 doses), 3 of whom also received the booster dose. VE of combination vaccines against invasive Hib infection was 89.6% [95% confidence interval (CI), 67.0-96.7] for an incomplete primary series, 96.7% (95% CI 87.7-99.1) for a full primary series and 98.5% (95% CI 94.5-99.6) for a booster dose (irrespective of priming). CONCLUSION: Hib combination vaccines containing acellular pertussis antigens continue to be highly effective in Germany.     

Evaluation of 2407 fetuses in a Turkish population

OBJECTIVES: Congenital anomalies and intrauterine fetal death (IUFD) are frequent problems in pregnancies. Detection of the etiology is important for genetic counseling, and presenting the geographic distribution of the causes of disorders is necessary for a national policy on precautions. Here, we report the findings of terminated fetuses due to IUFD and congenital anomalies in Turkish population. METHODS: Physical examinations of fetuses and genetic evaluations of families were done. X-ray studies and autopsy were done in the event of necessity. Findings of these studies were combined with prenatal ultrasound results. All cases were classified according to ICD-10. RESULTS: The number of fetuses examined was 2407. Out of these, 1268 fetuses had congenital anomalies. Neurologic anomalies and musculoskeletal system malformations were the most frequent disorders. Specific diagnoses were possible in 64% of all multiple malformation syndromes.Abnormal findings were detected in 18.8% of IUFD fetuses. Nine percent had congenital anomalies and 5.2% had cord complications. The percentage of twins and triplets was 7.5% and 13% of them had anomalies. CONCLUSION: Postmortem evaluation is useful to detect findings necessary for genetic counseling. Our protocol is effective especially in fetuses with congenital anomalies but it can detect only some of the fetal reasons in IUFD cases. A more detailed protocol is needed to investigate IUFD cases.     

Internal models underlying grasp can be additively combined

Our ability to additively combine two learned internal models was investigated by studying the forces people generate when lifting objects with a precision grip. Subjects were required to alternately lift two objects of identical physical appearance but differing weight. Grip force scaling prior to lift-off was used to estimate the output of the internal model associated with each object. Appropriate internal models were formed when alternately lifting two objects of different weight. The objects were then combined by stacking them one upon the other, and the combined object was lifted. Results show that subjects can additively combine internal models of object dynamics but the sum is biased by a default estimate of the objects weight.     

Implication of the Pro12Ala polymorphism of the <Emphasis Type="Italic">PPAR-gamma 2</Emphasis>gene in type 2 diabetes and obesity in the French population

Background  

The Pro12Ala Single Nucleotide Polymorphism (SNP) of the Peroxisome Proliferator-Activated Receptor gamma 2 (PPAR-gamma 2) has been associated with insulin resistance and type 2 diabetes (T2D) and also inconsistently with obesity. The aim of this study was to evaluate the impact of this SNP with regards to T2D and childhood and adult obesity in the French Caucasian population.     

Effect of gaze direction on neck muscle activity during cervical rotation

Control of the neck muscles is coordinated with the sensory organs of vision, hearing and balance. For instance, activity of splenius capitis (SC) is modified with gaze shift. This interaction between eye movement and neck muscle activity is likely to influence the control of neck movement. The aim of this study was to investigate the effect of eye position on neck muscle activity during cervical rotation. In eleven subjects we recorded electromyographic activity (EMG) of muscles that rotate the neck to the right [right obliquus capitis inferior (OI), multifides (MF), and SC, and left sternocleidomastoid (SCM)] with intramuscular or surface electrodes. In sitting, subjects rotated the neck in each direction to specific points in range that were held statically with gaze either fixed to a guide (at three different positions) that moved with the head to maintain a constant intra-orbit eye position or to a panel in front of the subject. Although right SC and left SCM EMG increased with rotation to the right, contrary to anatomical texts, OI EMG increased with both directions and MF EMG did not change from the activity recorded at rest. During neck rotation SCM and MF EMG was less when the eyes were maintained with a constant intra-orbit position that was opposite to the direction of rotation compared to trials in which the eyes were maintained in the same direction as the head movement. The inter-relationship between eye position and neck muscle activity may affect the control of neck posture and movement.     

Pneumocystis pneumonia during medicamentous treatment of Cushing's syndrome--a description of two cases

Only a few cases of pneumocystis pneumonia (PCP) in Cushing's syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushing's syndrome. A 60-year-old woman and 20-year-old man with Cushing's syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.     

Histopathological and immunohistochemical features of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have become a model of targeted therapy in oncology. The diagnosis of GISTs relies on histological arguments - proliferation of spindle cells, seldom of epithelioid cells or both spindle and epithelioid cells - and on immunohistochemical arguments - expression of CD117 usually associated with CD34 expression. The evaluation of the prognosis is essential and based on a simple algorithm using two prognostic parameters, tumor size and mitotic index. The aim of this paper is a complex histopathological assessment, using both classic and modern (immunohistochemistry) techniques, of the GISTs comprised in the study. GISTs occur mainly in older adults (median age 60-69 years), anywhere along the gastrointestinal tract but also retroperitoneal. Most of them were nodular (75%), tumor necrosis and mucosal ulceration being the most frequent encountered secondary alterations; these modifications proved to be significantly correlated with large tumor size and high malignancy. Immunohistochemical evaluation revealed that 77 (97%) cases of GISTs presented a positive reaction for CD117, 50 (63%) cases were positive for CD34, 19 (24%) were positive for SMA and only 10 (13%) were positive for S100. Immunohistochemical evaluation remains an important tool of pathology in the diagnosis of GISTs, in the differential diagnosis from other gastrointestinal mesenchymal tumors and represents the gold standard for diagnosis of these tumors and an eligibility criterion for imatinib therapy.