Increased glucose excursion in cystic fibrosis and its association with a worse clinical status

BACKGROUND: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. METHODS: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. RESULTS: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV(1)). CONCLUSION: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.     

Alveolar capillary dysplasia with misalignment of the pulmonary veins and hypoplastic left heart sequence caused by an in frame deletion within FOXF1

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare, autosomal dominant disorder of interstitial lung development, leading to pulmonary hypertension, and death in infancy. Associated features include malformations of the heart, gastrointestinal tract, and genitourinary system. ACDMPV is caused by heterozygous variants in the FOXF1 gene or microdeletions involving FOXF1. We present a male infant with ACDMPV, hypoplastic left heart sequence (HLHS), duodenal atresia, and imperforate anus due to a de novo, in frame deletion in FOXF1: c.209_214del (p.Thr70_Leu71del). Previous reports have suggested that microdeletions involving FOXF1 are associated with ACDMPV with congenital heart defects, including HLHS, gastrointestinal atresias, and other anomalies; whereas likely pathogenic variants within FOXF1 have not been reported with ACDMPV and HLHS. This is the first patient reported with ACDMPV, HLHS, imperforate anus, and duodenal atresia associated with a likely pathogenic variant in the FOXF1 gene.     

Age-dependent increase of peritoneal B-1b B cells in SCID mice

The impact of increasing age upon immunoglobulin production and B-lymphocyte generation in "leaky" severe combined immune-defective (SCID) mice was examined by enzyme-linked immunosorbent assay and flow cytometry. By 1 year of age, the mice had normal numbers of B cells in their peritoneal cavity, while their spleen had very few immunoglobulin M-positive (IgM+) cells. The majority of B cells expressed the CD11b marker characteristic of the B-1b subset. B-1a (CD5+) cells were present at a lower frequency and B-2 cells were absent. The frequency of mice producing detectable immunoglobulin increased with age, and isotype diversity within individual mice was variable. IgM production was most frequently observed followed by IgG3 and IgG2a, then IgG1, and finally IgA. The selective persistence of the B-1 B-cell subset in the peritoneal cavity of aging SCID mice is a natural model for the study of those genetic and environmental influences that determine lymphocyte longevity.     

Leiomyosarcoma of the inferior vena cava

A 61-year-old woman with symptoms of inferior vena caval obstruction was investigated with computed tomography and ultrasound imaging and found to have a tumor of the inferior vena cava. Transvenous biopsy revealed a leiomyosarcoma, which at surgical exploration was considered to be unresectable. Autopsy showed that the tumor extended form its origin in the inferior vena cava just above the left renal vein to the right atrium. Hepatic metastases were documented. This rare tumor has seldom been diagnosed prior to exploratory surgery or necropsy and should be included in the differential diagnosis of inferior vena caval obstruction. The case illustrates the relative ease and efficacy of transvenous biopsy in establishing this diagnosis antemortem.     

Incidence of cervical squamous intraepithelial lesions in HIV-infected women

CONTEXT: Women infected with human immunodeficiency virus (HIV) are at increased risk for cervical squamous intraepithelial lesions (SILs), the precursors to invasive cervical cancer. However, little is known about the causes of this association. OBJECTIVES: To compare the incidence of SILs in HIV-infected vs uninfected women and to determine the role of risk factors in the pathogenesis of such lesions. DESIGN: Prospective cohort study conducted from October 1,1991, to June 30, 1996. SETTING: Urban clinics for sexually transmitted diseases, HIV infection, and methadone maintenance. PARTICIPANTS: A total of 328 HIV-infected and 325 uninfected women with no evidence of SILs by Papanicolaou test or colposcopy at study entry. MAIN OUTCOME MEASURE: Incident SILs confirmed by biopsy, compared by HIV status and risk factors. RESULTS: During about 30 months of follow-up, 67 (20%) HIV-infected and 16 (5%) uninfected women developed a SIL (incidence of 8.3 and 1.8 cases per 100 person-years in sociodemographically similar infected and uninfected women, respectively [P<.001]). Of incident SILs, 91% were low grade in HIV-infected women vs 75% in uninfected women. No invasive cervical cancers were identified. By multivariate analysis, significant risk factors for incident SILs were HIV infection (relative risk [RR], 3.2; 95% confidence interval [CI], 1.7-6.1), transient human papillomavirus (HPV) DNA detection (RR, 5.5; 95% CI, 1.4-21.9), persistent HPV DNA types other than 16 or 18 (RR, 7.6; 95% CI, 1.9-30.3), persistent HPV DNA types 16 and 18 (RR, 11.6; 95% CI, 2.7-50.7), and younger age (<37.5 years; RR, 2.1; 95% CI, 1.3-3.4). CONCLUSIONS: In our study, 1 in 5 HIV-infected women with no evidence of cervical disease developed biopsy-confirmed SILs within 3 years, highlighting the importance of cervical cancer screening programs in this population.     

Correction to: Working Overtime: Altered Functional Connectivity in Working Memory Following Regular Cannabis Use in Young Adults

International Journal of Mental Health and Addiction - The caption for Fig.&nbsp;1 was incorrect in this article as originally published.     

The intriguing normal acute inflammatory response in mice lacking vimentin

Neutrophils express only two intermediate filament proteins, vimentin and, to a lesser extent, lamin B. Lamin B mutant mice die shortly after birth; however, mice lacking vimentin (vim(-/-)) develop and reproduce normally. Herein, we investigate for the first time the role of vimentin in general inflammation in vivo and in neutrophil functions ex vivo. Using the murine air pouch model, we show that the inflammatory response induced by lipopolysaccharide, interleukin-21 or carageenan is, intriguingly, uncompromised in vim(-/-) mice and that neutrophil functions are not altered ex vivo. Our results suggest that vimentin is dispensable for the establishment of an acute inflammatory response in vivo. In addition, based on several criteria presented in this study, one has to accept the existence of a very complex compensatory mechanism to explain the intriguing normal inflammatory response in absence of vimentin.     

The use of information technology for the management of intensive insulin therapy in type 1 diabetes mellitus

OBJECTIVE: The purpose of the study was to evaluate the safety of a computer program used by the patient for the adjustment of insulin doses to achieve tight glycemic control in type 1 diabetic subjects on intensive insulin therapy. METHODS: Ten type 1 diabetic patients participated in the study. Using the basal-bolus (UL-Humalog) insulin regimen, they were randomized in a crossover design to 2 intensive treatment periods of 8 weeks each, one with and the other without the assistance of a computer program via the Internet. They measured their capillary blood glucose regularly, and the results were entered on a daily basis into their log-book or in the computer. During intensive treatment with the computer, the software would provide recommendation for insulin dose adjustment according to specific algorithms. When on intensive treatment without computer assistance, they would adjust their own insulin dose according to the same algorithms. RESULTS: The study subjects followed 89% of the recommendations made by the computer. With the computer, subjects made more insulin dose adjustments (98 versus 50) than without. Intensive treatments with and without computer assistance resulted in a similar improvement of pre-meal/post-prandial capillary blood glucose from 7.6 +/- 2.7/9.5 +/- 2.5 to 6.7 +/- 2.3/8.8 +/- 2.5 and 6.7 +/- 2.6/9.0 +/- 2.6 mmol/L, respectively. Glygated hemoglobin also improved from 7.7 +/- 0.9% to 7.2 +/- 0.7 and 7.3 +/- 0.8%, respectively. The incidence of minor hypoglycemia was similar under both intensive treatments (7.9 +/- 4.0 and 7.1 +/- 5.0/patient/28 days, respectively). Both treatments increased patient behavior while patient knowledge of their disease was improved only during computer assistance. There was no effect on quality of life. The study subjects greatly appreciated the software and wanted to continue using it. CONCLUSIONS: The study demonstrated that the use of computer software by the patient to adjust insulin doses for intensive insulin therapy is feasible and is not associated with increased adverse events.     

Douching practices among women at high risk of HIV infection in the United States: implications for microbicide testing and use

BACKGROUND: Douching may interfere with determination of microbicide safety and effectiveness. This practice has not been adequately studied among women at risk of HIV infection. GOAL: This study assessed douching practices among women at risk of HIV infection in the United States. STUDY DESIGN: Data were collected on douching practices, sexually transmitted diseases, birth control, use of spermicidal products, and sexual risk behaviors among HIV antibody-negative women. RESULTS: Of 623 women, 70.2% had recently douched. Most women had been told that douching was not healthy. No associations were found between recent douching and measures of risk behaviors, except number of male partners. Recent douching was associated with being aged 26 to 30 years, compared with being 18 to 25 years of age (odds ratio [OR] = 2.2), black (OR = 3.0), or sterilized (OR = 2.0); having 5 or more male partners (OR = 4.4); and being told that douching is unhealthy (OR = 0.4). CONCLUSIONS: Recent douching was very common. The high prevalence of douching has implications for the design of microbicide trials and prevention interventions.     

Polymorphism of the thymidylate synthase gene and outcome of acute lymphoblastic leukaemia

Interindividual variability in response to methotrexate could be caused by variable concentrations of thymidylate synthase. We investigated the possible association between a tandem-repeat polymorphism in the thymidylate synthase promoter, of which a triple repeat is associated with increased expression of thymidylate synthase, and outcome of acute lymphoblastic leukaemia in 205 children treated with methotrexate. We obtained DNA samples from buccal epithelial cells, peripheral blood, or bone marrow in remission, and analysed them for the polymorphism by PCR amplification. Individuals who were homozygous for the triple repeat had a poorer outlook than those with other genotypes (odds ratio 4.1, 95% CI 1.9-9.0, p=0.001). Genotyping of thymidylate synthase might make it possible to individualize treatment for patients with acute lymphoblastic leukaemia.