Flow cytometric analysis of DNA synthetic phase fraction of the normal appearing colonic mucosa in patients with colorectal neoplasms.

DNA synthetic (S) phase fractions of normal appearing colonic mucosa in Japanese and British patients with colorectal neoplasms were compared with those in patients without colonic neoplasms. Normal crypts were isolated from fresh surgical specimens of the large intestine by the use of EDTA. After fixation with 70% ethanol, isolated crypts were digested with pepsin into single nuclei suspensions. These were stained with propidium iodide and examined by flow cytometry. S phase fraction was calculated from the flow cytometry DNA histogram using Baisch's method. S phase fractions of normal appearing crypts in Japanese and British patients with colorectal tumours were not significantly different and analysed together. S phase fraction of normal appearing colonic crypts in 14 patients with familial adenomatous polyposis (FAP) was 10.23 (2.59%) (mean SD)) ranging from 5.8 to 18.8. S phase fraction of background normal mucosal in patients with large adenomas (over 2 cm) and adenocarcinomas were 9.74 (3.76%) (range, 2.7-16.1) and 8.93 (3.54%) (range, 2.9-18.9) respectively. In normal mucosa of patients without any colorectal neoplasms, S phase fraction was 8.99 (3.94)% (range, 3.9-17.7). There was no statistically significant difference in S phase fractions of normal mucosa in the four groups. Our results show that an increase in proliferative activity of background colonic crypts is not necessary for tumour development.     

Coronavirus infection and hospitalizations for acute respiratory illness in young children

There is only limited knowledge on the burden of disease due to both new (HCoV‐NL63 and HKU‐1) and previously discovered coronaviruses (OC43 and 229E) in children. Respiratory specimens and clinical data were prospectively collected in an active, population‐based surveillance study over a 2‐year period from children aged <5 years hospitalized with acute respiratory symptoms or fever. These samples were retrospectively tested by real‐time RT‐PCR for HCoV‐NL63, HKU1, OC43, and 229E. Human coronaviruses (HCoVs) were identified in 2.2% of study children <2 years of age. Rates of HCoV‐associated hospitalization per 10,000 were 10.2 (95% CI 4.3, 17.6), 4.2 (95% CI 1.9, 6.9), and 0 (95% CI 0, 3.7) in children aged <6 months, 6–23 months, and 24–59 months, respectively. Coronaviruses were identified in a modest number of hospitalized children. J. Med. Virol. 81:853–856, 2009. © 2009 Wiley‐Liss, Inc.     

Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin

Variations in the gene encoding the novel protein dysbindin-1 (DTNBP1) are among the most commonly reported genetic variations associated with schizophrenia. Recent studies show that those variations are also associated with cognitive functioning in carriers with and without psychiatric diagnoses, suggesting a general role for dysbindin-1 in cognition. Such a role could stem from the protein's known ability to affect neuronal glutamate release. How dysbindin-1 might affect glutamate release nevertheless remains unknown without the discovery of the protein's neuronal binding partners and its subcellular locus of action. We demonstrate here that snapin is a binding partner of dysbindin-1 in vitro and in the brain. Tissue fractionation of whole mouse brains and human hippocampal formations revealed that both dysbindin-1 and snapin are concentrated in tissue enriched in synaptic vesicle membranes and less commonly in postsynaptic densities. It is not detected in presynaptic tissue fractions lacking synaptic vesicles. Consistent with that finding, immunoelectron microscopy showed that dysbindin-1 is located in (i) synaptic vesicles of axospinous terminals in the dentate gyrus inner molecular layer and CA1 stratum radiatum and in (ii) postsynaptic densities and microtubules of dentate hilus neurons and CA1 pyramidal cells. The labeled synapses are often asymmetric with thick postsynaptic densities suggestive of glutamatergic synapses, which are likely to be derived from dentate mossy cells and CA3 pyramidal cells. The function of dysbindin-1 in presynaptic, postsynaptic and microtubule locations may all be related to known functions of snapin.     

Strain variation among Bordetella pertussis isolates from Québec and Alberta provinces of Canada from 1985 to 1994

Pulsed-field gel electrophoresis and gene typing were able to differentiate among 3,597 Bordetella pertussis isolates circulating in Alberta and Québec Provinces, Canada, from 1985 to 1994 and distinguish them from the strains used in vaccine production. This study provides a baseline for continued surveillance of prevalent and emerging strains of B. pertussis in Canada.     

Management of apparent life-threatening events

Apparent life-threatening events in infancy (ALTE) present a common yet complex management problem for the clinician. While an ALTE generally represents a benign event, in rarer instances it may indicate a serious underlying disorder. In most circumstances patients will require admission for a short period, thus providing the opportunity to perform a systematic, thorough examination, followed by the selective use of investigations. In all situations, however, even those with an unambiguous diagnosis, follow-up must be provided to detect recurrent episodes and to monitor long-term sequelae.     

A randomized phase II pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer.

PURPOSE: The primary aim of this study was to measure the objective tumor response rate following treatment with indisulam [E7070; N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide] as second-line therapy in patients with advanced non-small cell lung cancer. The secondary aims were to determine progression-free survival, to assess the safety and tolerability of indisulam, and to study its pharmacokinetic and pharmacodynamic profile. EXPERIMENTAL DESIGN: Patients were randomized to receive indisulam every 3 weeks either as a single i.v. dose of 700 mg/m(2) on day one (dx1) or 130 mg/m(2) given on days 1 to 5 inclusive as a daily infusion (dx5). All patients had previously received platinum-based chemotherapy. RESULTS: Forty-four patients were randomized. Only minor responses were seen. Myelosuppression, gastrointestinal symptoms, and lethargy were the most common toxicities and were more frequent in the dx1 arm. The pharmacokinetics of indisulam in each treatment schedule were adequately described using a previously developed population pharmacokinetic model and were mostly consistent with the results of the phase I program. Flow cytometric analysis of endobronchial and metastatic disease revealed a reduction in the fraction of cycling cells and an increase in apoptosis following indisulam compared with pretreatment levels. CONCLUSIONS: We conclude that, despite evidence of tumor-specific indisulam-induced apoptosis, neither of these treatment schedules has single-agent activity as second-line treatment of non-small cell lung cancer.     

Choroidal neurofibromatosis with congenital iris ectropion and buphthalmos: relationship and significance

We report a case of unilateral buphthalmos in neurofibromatosis-1 without the other classical characteristics of the Fran?ois syndrome (triad of unilateral buphthalmos, homolateral eyelid plexiform neuroma, and homolateral facial hemihypertrophy) and emphasize the difficulties in early diagnosis. The painful buphthalmic right eye was enucleated at the age of 13 months. Histopathology demonstrated diffuse choroidal neurofibromatosis in association with congenital iris ectropion syndrome. Cutaneous manifestations of neurofibromatosis subsequently developed in the patient and stigmata of the disease were later identified in other asymptomatic family members.