Pulmonary tumor thrombotic microangiopathy caused by a gastric carcinoma expressing vascular endothelial growth factor and tissue factor

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity causing severe pulmonary hypertension. Its histological features include widespread tumor emboli along with fibrocellular intimal proliferation and thrombus formation in the small arteries and arterioles of the lungs. The result is occlusion or stenosis of the pulmonary vasculature, but the detailed pathogenesis has yet to be clarified in spite of the serious clinical manifestations. Herein is described the case of a 62-year-old man with a gastric adenocarcinoma who died of sudden cardiopulmonary arrest. The autopsy revealed advanced cancer disease as well as findings of PTTM, which seemed to be the cause of his unexpected death. The carcinoma cells were immunohistochemically positive for vascular endothelial growth factor (VEGF) and also for tissue factor (TF). There is another report suggesting that TF might play an important role in the pathogenesis of PTTM. Also, VEGF has been reported to be involved in a variety of forms of pulmonary hypertension and to be upregulated by TF. These findings suggest that VEGF and TF may be involved in the pathogenesis of PTTM. The present PTTM case, in which the tumor cells demonstrate the coexpression of VEGF and TF, is important in facilitating understanding of the lethal disorder in the future.     

Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures

Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.     

Antimicrobial evaluation of nocathiacins, a thiazole peptide class of antibiotics

Nocathiacins are cyclic thiazolyl peptides with inhibitory activity against gram-positive bacteria. BMS-249524 (nocathiacin I), identified from screening a library of compounds against a multiply antibiotic-resistant Enterococcus faecium strain, was used as a lead chemotype to obtain additional structurally related compounds. The MIC assay results of BMS-249524 and two more water-soluble derivatives, BMS-411886 and BMS-461996, revealed potent in vitro activities against a variety of gram-positive pathogens including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin intermediate-resistant S. aureus, vancomycin-resistant enterococci, Mycobacterium tuberculosis and Mycobacterium avium. Analysis of killing kinetics revealed that these compounds are bactericidal for S. aureus with at least a 3-log(10) reduction of bacterial growth within 6 h of exposure to four times the MICs. Nocathiacin-resistant mutants were characterized by DNA sequence analyses. The mutations mapped to the rplK gene encoding the L11 ribosomal protein in the 50S subunit in a region previously shown to be involved in the binding of related thiazolyl peptide antibiotics. These compounds demonstrated potential for further development as a new class of antibacterial agents with activity against key antibiotic-resistant gram-positive bacterial pathogens.     

Randomized controlled study on the effectiveness of community pharmacists' advice for smoking cessation by Nicorette--evaluation at three months after initiation

We conducted a randomized, controlled study to evaluate whether pharmacists' advice on smoking cessation would result in a higher smoking cessation rate using Nicorette (nicotine gum preparation). Fourteen pharmacies in Tokyo, Kanagawa, and Nagano participated. Smokers who visited pharmacies to buy Nicorette from March 1, 2002, through August 31, 2002, were recruited and randomly assigned to two groups. For the intervention group (A), pharmacists provided both regular instructions on Nicorette use and smoking cessation advice at the first sale and then gave follow-up advice just before starting a cessation and 1, 3, and 8 weeks and 3 months thereafter. For the control group (B), pharmacists provided regular instructions alone. The primary outcome measure was the self-reported smoking cessation rate and the secondary outcome measure was the relationship between the smoker's egogram and effectiveness of intervention. Twenty-eight smokers were enrolled and randomized into group A (n=11) or group B (n=17). The absolute abstinence rate in groups A and B at 3 months was 45.5% and 31.2%, respectively. The odds ratio was 1.83, which was not statistically significant. There was no difference in egogram score between absolute abstinence subjects and nonabstinence subjects in group A. The egogram scores in Adapted Child of absolute abstinence subjects in group B were significantly higher than in nonabstinence subjects. In conclusion, instructions and advice given by pharmacists may improve the smoking cessation rate in smokers receiving nicotine replacement therapy.     

Trichosporon pullulans infection in 2 patients with chronic granulomatous disease: an emerging pathogen and review of the literature

BACKGROUND: Chronic granulomatous disease is a genetically determined primary immunodeficiency disease in which phagocytic cells are unable to kill certain bacteria and fungi after ingestion. Manifestations include recurrent pyogenic infections caused by catalase-positive microbes. Trichosporon species are emerging as opportunistic agents that cause systemic disease in immunocompromised patients. Typically disease has been described in association with T beigelii in patients with secondary immunodeficiency, such as underlying malignancy. OBJECTIVE: The objective was to report the first 2 cases of T pullulans infection in 2 male children with chronic granulomatous disease. METHODS: The records of the 2 patients were reviewed. In addition, all cases of T pullulans infection reported in the English language literature are presented. RESULTS: This report brings to 7 the total number of cases of T pullulans reported and the first in patients with chronic granulomatous disease, one with invasive pneumonia and the other with an infected paronychium and localized cellulitis. In the 5 additional cases malignancy was the principal risk factor. CONCLUSION: T pullulans has rarely been reported as a fungal pathogen. The most prominent risk factor for the development of trichosporonosis is immunocompromise, most notably with neutropenia. Abnormally functioning neutrophils, such as with chronic granulomatous disease, may also predispose individuals to this opportunistic pathogen.     

Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency

Fructose-1,6-bisphosphatase (FBPase) (EC 3.1.3.11) catalyzes the splitting of fructose-1,6-bisphosphate into fructose 6-phosphate and inorganic phosphate. FBPase deficiency is an autosomal recessive inherited disorder caused by distraction of the fructose-1,6-bisphosphatase 1 gene (FBP1) and features severely impaired gluconeogenesis. We studied a female patient with typical FBPase deficiency symptoms. The FBPase activity of her peripheral white blood cells was undetectable. Genetic analyses of FBP1 revealed her to be a compound-heterozygote of two new mutations F194S and P284R. Gene tracking in the family revealed the mother to be a heterozygote of F194S, and the father and a sister to be heterozygotes of P284R. As both Phe194 and Pro284 of FBPase are highly conserved in many species and close to crucial amino acid residues to FBPase functions, these mutations could be responsible for the loss of FBPase activities.