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.     

Clinical and histopathological findings of ''psoriatic neurodermatitis'' and of typical lichen simplex chronicus

BACKGROUND: We have seen several patients with itchy lichenified plaques located bilaterally on the elbows and/or knees and have named this condition 'psoriatic neurodermatitis' (PN). OBJECTIVE: The purpose of this study was to compare clinical and histopathological characteristics of these patients to those of patients with typical lichen simplex chronicus (LSC). METHODS: Nineteen patients with PN and 34 patients with typical LSC were included. Besides clinical dermatological evaluation, the prick test was carried out on 49 patients; the Phadiatop test on 40 patients; the patch test with European standard series on 47 patients; histopathological evaluation on 39 patients; and clinical psychiatric examination on 38 patients. RESULTS: Almost exclusively, PN was seen in females and was located on the extremities. It caused more plaques than typical LSC did. In PN, the plaques were smaller, sharper, more keratotic and less excoriated, and had fewer lichenoid papules around them. Itching was usually more severe in the evening, while resting and in a hot environment in typical LSC, but not in PN. In plaques of PN, microabscesses in the horny layer, hypogranulosis, regular acanthosis and thinning of the suprapapillary plates were more frequent, and hyperpigmentation in the basal layer was less. In patients with PN, depressive disorder was found more frequently; and generalized anxiety disorder or psychosomatic characteristics, less. There were no significant differences in the results of prick, Phadiatop and patch tests between patients with PN and those with typical LSC. CONCLUSION: In our opinion, it is most likely that the so-called PN is itchy psoriasis superimposed by LSC.     

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.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (α-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3–5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.     

Soy-based formulas and phyto-oestrogens: a safety profile

Phyto-oestrogens are non-steroidal plant-derived compounds that possess oestrogenic activity and act as selective oestrogen receptor modulators (SERMs). Among the dietary oestrogens, the isoflavone class enjoy a wide-spread distribution in most of the members of the Leguminosae family, including such prominent high-content representatives as soybean. Phyto-oestrogen research has grown rapidly in recent years owing to epidemiological studies suggesting that diets rich in soy may be associated with potential health benefits. There is a paucity of data on endocrine effects of soy phytochemicals during infancy, the most sensitive period of life for the induction of toxicity. The safety of isoflavones in infant formulas has been questioned recently owing to reports of possible hormonal effects. Infants fed soy formula receive high levels of phyto-oestrogens in the form of isoflavones (genistein, daidzein and their glycosides). To date, no adverse effects of short- or long-term use of soy proteins have been observed in humans and exposure to soy-based infant formulas does not appear to lead to different reproductive outcomes than exposure to cow milk formulas. Soy formula seems to be a safe feeding option for most infants. Nevertheless, much closer studies in experimental animals and human populations exposed to phyto-oestrogen-containing products, and particularly soy-based infant formulas, are necessary.     

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.     

Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP

Chronic idiopathic thrombocytopenic purpura (ITP) is caused by an antibody reactive with platelet-associated antigens. The present studies provide direct evidence that some patients with chronic ITP have autoantibodies against the platelet glycoprotein (GP) IIb/IIIa complex. Microtiter wells, coated with a monoclonal antibody (2G12) specific for GPIIb/GPIIIa were reacted with GPIIb/GPIIIa contained in a platelet extract. Control wells containing the same antibody were reacted with a cell extract containing no GPIIb/GPIIIa. After washing, the wells were reacted with patient or control plasma, and IgG binding was detected using 125I-Fab2-anti-human IgG. Assay values were expressed as binding ratios (cpm GPIIb/GPIIIa wells/cpm control wells). Plasma from 5 of 56 patients with chronic ITP had ratios (1.36-3.14) greater than 3 standard deviations above the mean (+/- SD) of control plasmas--0.93 +/- 0.12. Elevated values were also noted in two patients with anti-P1A1 antibody (ratios greater than 30) and in one patient with Hodgkin's disease and an ITP-like syndrome (ratio 1.53). Normal values were noted in 34 patients with a variety of immune and nonimmune diseases. Plasma from two of the positive ITP patients was reacted with 125I-surface-labeled platelets and, after solubilization, the IgG and bound antigen were precipitated with Staph-A. Autoradiographs from SDS- PAGE electrophoresis of the Staph-A-bound proteins shows two radioactive bands consistent in size with GPIIb and GPIIIa.