New radiological typing system for rhinosinusitis and comparison with existing system: Initial finding

The objective of this study was to determine whether the proposed Malan radiological sinusitis typing (RST) system facilitated a level of agreement and ease of use comparable with the Lund–Mackay (LM) system for chronic rhinosinusitis. Ten observers (one otolaryngologist and nine radiologists), in two separate centres (regional and tertiary), blinded to all clinical data, used these two systems to independently and randomly score and type 15 sets of scans, recording the time to score each film. Using unweighted kappa scores, both methods facilitated a moderate level of agreement, slightly better with the LM system. The Malan system is more time efficient. Preliminarily, this study shows that the Malan RST system is easy to apply with a comparable level of agreement. The Malan RST system is a focused attempt at classifying disease extent radiologically and correlating it to a surgical approach. It emphasizes that scoring systems are vulnerable and proves to be superior to the LM system as a surgical planning tool. To score sinus disease, a Quality‐of‐Life questionnaire in association with this typing method is more appropriate.     

亚临床甲状腺疾病

亚临床甲状腺功能亢进和甲状腺功能减退属于试验诊断。2002年美国甲状腺协会、美国临床内分泌医师协会和内分泌腺协会的委员组成的一个专家小组，明确了亚临床甲状腺疾病的概念，回顾了涉及风险和治疗益处的文献，并且建议进行评估和人口筛查。     

Pulmonary Hypertension in Congenital Heart Disease: Irreversible Vascular Changes in Young Infants

Among 280 infants under 1 year of age with congenital heart disease autopsied at the University of Colorado Health Sciences Center between 1959 and 1978, there were six instances of grade IV¹ pulmonary artery hypertension. Five were patients with ventricular septal defect (four associated with other cardiovascular malformations). The sixth was a patient with atrioventricular canal. The youngest was 2¹/₂ months of age. Advanced degrees of pulmonary hypertensive arteriopathy (grade IV or more) have been said to be rare in infants, especially under the age of 1 year. The fact that all of these cases occurred within the last few years of the study suggests the possibility of improved supportive care leading to the prolonged survival of infants who might otherwise have died prior to developing severe disease. In addition, the role of altitude in accelerating the arteriopathy must be considered in the present series. In any case, this unexpected increase in the frequency of severe pulmonary hypertensive arteriopathy should stimulate consideration of early surgical correction of the underlying cardiovascular malformation, especially in areas of relatively high altitude.     

Bcl-6 p53 mutations in lymphomas carrying the bcl-2/Jh rearrangement

BACKGROUND AND OBJECTIVES: The t(14;18)(q32;q21) chromosomal translocation is the hallmark of follicular lymphomas (FL). The translocation induces the overexpression of the Bcl-2 protein and prolongs the survival of clonogenic cells. Tumor cells may acquire additional molecular alterations that may be associated with histologic progression or with chemo-resistance. DESIGN AND METHODS: We analyzed the distribution and association of bcl-6 and p53 mutations in 55 consecutive bcl-2/Jh+ lymphoma samples derived from 43 patients obtained at the time of diagnosis and, in 5 of these patients, during follow-up. A total of 29 bcl-6 point mutations were detected in seventeen patients (40%) associated with major or minor breakpoints of the bcl-2/Jh fusion gene. In seven cases a p53 mutation was detected. Three cases corresponded to FL with the minor breakpoint in the bcl-2 gene and these patients had a favorable clinical evolution, whereas the 4 patients with p53 mutations and the major breakpoint had a bad clinical outcome with morphologic transformation to high-grade lymphoma in three cases. The sequential analysis of 5 patients showed a different timing in the acquisition of mutations: one patient showed bcl-6 and p53 mutations at diagnosis, another patient showed bcl-6 mutations at diagnosis and acquired a p53 mutation later whereas the third patient had a p53 mutation before the appearance of the bcl-6 mutation. RESULTS: We did not find significant differences in survival between patients with FL who showed exclusively bcl-6 mutations and those without bcl-6 mutations, but those patients with a high International Progostic Index score and p53 mutations showed the lowest overall survival (p = 0.002). INTERPRETATION AND CONCLUSIONS: These findings suggest that bcl-2/Jh lymphomas show molecular heterogeneity and that bcl-6 and p53 mutations may be acquired during the evolution of such lymphomas. Bcl-6 mutations, by themselves, do not seem to be associated with a bad prognosis. Rearrangements at the minor bcl-2 locus may have a different molecular evolution.     

Glomerulonephritis in Behçet’s Disease: Report of Seven Cases and Review of the Literature

Despite being recognised much more frequently than in the past, renal involvement has not previously been regarded as a feature of Behcet's disease (BD). In this study we aimed to assess the frequency of renal involvement in BD by performing urinalyses of 674 consecutive BD patients; we also retrospectively evaluated the charts of 4212 BD patients for the incidence of glomerulonephritis (GN). Urinary abnormalities (proteinuria and/or haematuria) were present in 10.8%; and during a period of 23 years GN was detected by renal biopsy in seven (0.16%) BD patients. Two patients with GN were lost to follow-up; end-stage renal failure developed in only one patient, and she underwent renal transplantation. We were unable to determine any pathognomonic feature that was predictive of renal involvement. Although males tend to have a more serious clinical course of BD the incidences of urinary abnormalities and GN were similar in both sexes in our series. According to our results, we can conclude that urinary abnormalities are more frequent in BD; however, serious renal lesions develop in only very few of these patients.     

A new model for prenatal brain damage. I. GABAA receptor activation induces cell death in developing rat hippocampus

Premature infants are at exceptionally high risk for hypoxic-ischemic insults and other traumatic events that result in permanent brain damage. However, no current models adequately mimic these events. An emerging concept is that the major excitatory drive in immature neurons is derived from depolarizing responses following activation of the gamma-aminobutyric acid (GABA)(A) receptor, resulting in the opening of voltage-sensitive calcium channels. While calcium-mediated signal transduction is trophic in developing neurons, excessive calcium entry is a major mediator of excitotoxicity. We report that exogenous activation of GABA(A) receptors by muscimol in newborn rats increases cell death in the hippocampus. The effects are region specific, persistent, and greater in males. Muscimol-induced damage is prevented by pretreatment with diltiazem, an L-type voltage-sensitive calcium channel blocker. Results using hippocampal cultures parallel those observed in vivo, indicating that the effects are mediated directly in the hippocampus. Existing models of pediatric hypoxic-ischemic brain damage focus on the effects of glutamate in the postnatal day 7 rat, because it is considered analogous to the newborn human. This makes the newborn rat analogous to the late gestational human. Ischemia in newborn rats induces GABA release and we propose that treatment with muscimol mimics the cell death cascade induced by hypoxia-ischemia in premature human infants.     

A novel model for prenatal brain damage. II. Long-term deficits in hippocampal cell number and hippocampal-dependent behavior following neonatal GABAA receptor activation

Premature infants are at especially high risk for asphyxia, seizures, and other conditions that cause hypoxia-ischemia. These events result in abnormal brain pathology and behavioral deficits that persist throughout adolescence and into adulthood. Current rodent models of human infant hypoxic-ischemic brain damage have focused on exogenous glutamate receptor agonist exposure in the postnatal day 7 rat. While this model is considered analogous to the newborn human, no adequate models for preterm infant brain damage have been developed. Recent work from our lab has proposed a potential model for preterm infant brain damage in which neonatal rats are treated with exogenous muscimol, the selective gamma-aminobutyric acid(A) (GABA(A)) receptor agonist, on postnatal days 0 and 1. In the companion paper to this one (Exp. Neurol., in press), we report fewer neurons in the hippocampal formation on postnatal day 7 (6 days after treatment), but the persistence of these anatomical deficits, and potential resultant behavioral dysfunctions, were not investigated. In the current experiment, we documented that muscimol exposure on postnatal days 0 and 1 leads to fewer neurons in the male and female rat hippocampus (CA1, CA2/3, and dentate gyrus) on postnatal day 21. Also, neonatal muscimol exposed males and females displayed deficits on hippocampal-dependent learning tasks such as a preweanling version of the Morris water maze task and the open field task. We conclude that exposure to exogenous GABA(A) receptor activation over the first 2 days of postnatal life, a model for preterm infant hypoxic injury, produces anatomical and behavioral deficits observed into adolescence.     

Efficacy and tolerability of lower-dose topotecan in recurrent ovarian cancer: a retrospective case review

Topotecan (1.5 mg/m(2)/day for 5 consecutive days of a 21-day cycle) is an established recurrent ovarian cancer treatment, but myelosuppression can be dose limiting. This study evaluates the activity and tolerability of low-dose topotecan in our clinical experience. Case records were reviewed for patients with recurrent ovarian cancer in first through third relapse. Eligible patients had received > or =2 cycles of < or =1.25 mg/m(2) topotecan. Adverse events were evaluated using laboratory and clinical evaluation data. Twenty-seven eligible patients, most with advanced disease, received a total of 209 cycles (median, six cycles). Grade 3 or 4 hematologic toxicities during 184 cycles in 24 assessed patients were neutropenia, leukopenia, thrombocytopenia, and anemia in 35%, 28%, 36%, and 11% of cycles, and 21, 19, 16, and 10 patients, respectively. Only four grade 4 toxicities occurred: anemia (one) and thrombocytopenia (three). Myelosuppression was reversible, noncumulative, and manageable. Moreover, nonhematologic toxicity was generally mild to moderate, and the only two grade 3 events were constipation and deep vein thrombosis. Low-dose topotecan was active in this setting. Lower-dose topotecan is generally well tolerated and active in patients with pretreated ovarian cancer. Prospective clinical trials of low-dose topotecan in recurrent ovarian cancer are warranted.     

A changing paradigm of glioma biology

The past 30 years have witnessed a major paradigm shift in brain tumor research with the development of a wide variety of molecular