Gestational diabetes mellitus

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and offspring. GDM is diagnosed by an oral glucose tolerance test (OGTT) or fasting glucose concentrations in the diabetic range. In case of a high risk for GDM/type 2 diabetes (history of GDM or prediabetes [impaired fasting glucose or impaired glucose tolerance]; malformation, stillbirth, successive abortions or birth-weight > 4500 g in previous pregnancies) performance of the OGTT (120 min; 75 g glucose) is recommended already in the first trimester and--if normal--the OGTT should be repeated in the second/third trimester. In case of clinical symptoms of diabetes (glucosuria, macrosomia) the test has to be performed immediately. All other women should undergo a diagnostic test between 24 and 28 gestational weeks. If fasting plasma glucose exceeds 95 mg/dl, 1 h 180 mg/dl and 2 hrs 155 mg/dl after glucose loading (OGTT) the woman is classified as GDM (one pathological value is sufficient). In this case a strict metabolic control is mandatory. All women should receive nutritional counseling and be instructed in blood glucose self-monitoring. If blood glucose levels cannot be maintained in the normal range (fasting < 95 mg/dl and 1 h after meals < 130 mg/dl) insulin therapy should be initiated. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g OGTT (WHO criteria).     

Liver response to indomethacin-induced intestinal injury

The aim of our study was to evaluate the impact of impaired barrier function of the small intestine induced by indomethacin on biochemical markers of liver damage (serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin), and liver functional parameters (serum concentration of albumin, liver DNA synthesis). Indomethacin (Sigma) was administered in 2 injections in a dose of 7.5 mg/kg subcutaneously spaced 24 hours apart, rats were sacrificed 24, 48 or 72 hours after the second dose of indomethacin. Control rats received indomethacin vehicle (5% NaHCO3, pH 7.4, 1.0 ml/kg) in the same manner. Small intestine injury was approved by increased permeability (measured as a lactulose-mannitol index). Significant increase of small intestine DNA synthesis (estimated by incorporation of 3H thymidine) in indomethacin-treated rats 48 (p < 0.01) and 72 (p < 0.05) hours after the second dose of indomethacin documents induction of reparative process. All biochemical markers of liver injury were significantly decreased in indomethacin treated rats in all recorded intervals (p < 0.05). By contraries, serum concentration of albumin, which predicates about liver function, was in indomethacin-treated rats significantly decreased in all intervals (p < 0.01). To explain these contrarious results of indomethacin-induced impaired barrier function of the small intestine on the liver deserves further studies.     

Antibiotics produced by Streptomyces olivaceus 142. III. Influence of antibiotic Wr 142 FPG on development of transplantable tumors in mice

The action of two preparations (I and II) of antibiotic Wr 142 FPG on development of Ehrlich carcinoma, Nemeth-Kellner lymphoma and leukemias L 1210 and P 388 was studied. Preparation I injected s.c. daily during 14 days in doses of 10 mg/kg (1/25 LD50) inhibited growth of Ehrlich carcinoma and Nemeth-Kellner lymphoma subcutaneous tumors in R 3 mice by about 70%. The same preparation in a single i.p. injection (10 mg/kg) in FDF1 mice distinctly prolonged survival of mice inoculated with L 1210 leukemia, but was without effect on P 388 leukemia. Preparation II inhibited growth of solid tumors in doses as low as 0.1-0.2 mg/kg (about 65% inhibition), but in the same doses was ineffective against leukemias L 1210 and P 388 in CDF1 mice.     

Monoclonal antibody Leu-22 (L60) permits the demonstration of some neoplastic T cells in routinely fixed and paraffin-embedded tissue sections

Monoclonal antibody Leu-22 (L60) detects a T cell-associated antigen which is stably expressed in routinely fixed and paraffin-embedded tissue sections. We investigated the utility of monoclonal antibody Leu-22 to immunophenotype routinely processed lymphoid neoplasms by determining its reactivity in 105 archival pathologic specimens of lymphoid neoplasia that had been previously immunophenotyped by standard cell suspension and frozen tissue section techniques. Monoclonal antibody Leu-22 reacted with 69% of T cell non-Hodgkin's lymphomas (NHLs), including cases belonging to each of the major clinicopathologic categories, and with 22% of B cell NHLs, but did not react with the Reed-Sternberg (RS) cells of Hodgkin's disease (HD). We concluded that monoclonal antibody Leu-22 reacts preferentially but not exclusively with T cell NHLs. Therefore, we performed parallel analyses of the same 105 cases with monoclonal antibodies leukocyte common antigen (LCA), Leu-M1, LN1, and LN2, which detect various paraffin-resistant antigens, and of 80 of these cases with monoclonal antibody UCHL1, which detects a paraffin-resistant T cell-associated antigen. UCHL1 reacted with 61% of the T cell NHLs studied. Sixty-nine percent of T cell NHLs expressed the LCA+, Leu-22+ or Leu-M1+, LN1- phenotype and 47% of B cell NHLs expressed the LCA+, Leu-22-, Leu-M1-, LN1+ phenotype. These phenotypes had a false-positive rate of only 7%. The substitution of UCHL1 for Leu-22 or the combined use of UCHL1 and Leu-22 in this panel did not improve our ability to correctly predict the T cell phenotype of these lymphoid neoplasms. LN1 and LN2 reacted with 13% and 56% of T cell NHLs, respectively, and LN2 reacted with RS cells in 85% of cases of HD. In summary, our results demonstrate that the judicious use of monoclonal antibody Leu-22 in combination with other selected commercially available monoclonal antibodies permits the determination of the B cell or T cell origin of a high proportion of NHLs, and is helpful in the differential diagnosis between HD and NHL among cases that have been routinely fixed and paraffin-embedded.     

The interleukin-13 production by peripheral blood T cells from atopic dermatitis patients does not require CD2 costimulation

BACKGROUND: Although allergic mechanisms appear to be important, the pathogenesis of both extrinsic and intrinsic forms of atopic dermatitis (AD) is unknown. METHODS: We compared the cytokine production of peripheral blood mononuclear cells of extrinsic AD (EAD) and intrinsic AD (IAD) patients and normal control individuals after stimulation with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAbs) in the presence or absence of anti-CD2-blocking mAb. The cytokine production was measured by immunoassays in supernatants of 24-hour cultures. RESULTS: EAD patients showed a decreased capacity to synthesize interferon gamma and granulocyte-macrophage colony-stimulating factor upon anti-CD3 mAb stimulation as compared with IAD patients. Both EAD and IAD patients demonstrated an increased production of interleukin (IL)-5 and IL-13. As expected, interferon gamma, granulocyte-macrophage colony-stimulating factor, and IL-5 levels were reduced in the presence of anti-CD2-blocking mAbs. CD28 costimulation restored the release in cultures with anti-CD2 mAbs added, suggesting that CD2 and CD28 have redundant functions in T cell activation and subsequent cytokine production. Strikingly, the IL-13 production was not blocked by anti-CD2 mAbs and also not increased by agonistic anti-CD28 mAb, in particular within the EAD patient group. CONCLUSION: The signalling pathway initiated by the T cell receptor complex leading to increased IL-13 production in AD patients appears to be highly sensitive and is largely independent on CD2 costimulatory signals.     

Mortality prognostication scores do not predict long-term,health-related quality of life after burn: A burn model system national database study

ObjectiveDespite improved mortality rates after burn injury, many patients face significant long-term physical and psychosocial disabilities. We aimed to determine whether commonly used mortality prognostication scores predict long-term, health-related quality of life after burn injury. By doing so, we might add evidence to support goals of care discussions and facilitate shared decision-making efforts in the hours and days after a life-changing injury.MethodsWe used the multicenter National Institute of Disability, Independent Living and Rehabilitation Research Burn Model System database (1994–2019) to analyze SF-12 physical (PCS) and mental component (MCS) scores among survivors one year after major burn injury. Ninety percent of the observations were randomly assigned to a model development dataset. Multilevel, mixed-effects, linear regression models determined the relationship between revised Baux and Ryan Scores and SF-12 measures. Additionally, we tested a model with disaggregated independent and other covariates easily obtained around the time of index admission: age, sex, race, burn size, inhalation injury. Residuals from the remaining 10% of observations in the validation dataset were examined.ResultsThe analysis included 1606 respondents (median age 42 years, IQR 28–53 years; 70% male). Median burn size was 16% TBSA (IQR 6–30) and 13% of respondents sustained inhalation injury. Higher revised Baux and Ryan Scores and age, burn size, and inhalation injury were significantly correlated with lower PCS, but were not correlated with MCS. Female sex, black race, burn size, and inhalation injury correlated with lower MCS. All models poorly explained the variance in SF-12 scores (adjusted r² 0.01–0.12).ConclusionHigher revised Baux and Ryan Scores negatively correlated with long-term physical health, but not mental health, after burn injury. Regardless, the models poorly explained the variance in SF-12 scores one year after injury. More accurate models are needed to predict long-term, health-related quality of life and support shared decision-making during acute burn care.     

Agreement between proxy- and self-report scores on PROMIS health-related quality of life domains in pediatric burn survivors: a National Institute on Disability,Independent Living,and Rehabilitation Research Burn Model System Study

Quality of Life Research - To examine agreement between pediatric burn survivor self- and caregiver proxy-report on multiple PROMIS domains and examine factors associated with differences between...     

Immunoregulatory properties of the proteins present in human milk

The immunoregulatory properties of several proteins, isolated from human milk, were investigated. Secretory component and galactothermin exhibited immunoregulatory activities in the in vivo and in vitro assays, generating helper cells, changing the ARFC levels and the resistance of thymocytes to hydrocortisone (HC). In addition, the immunoregulatory action of the P protein and its four fractions was studied. The bulk of the activity was found in the fraction II and III. The results suggest that the postneonatal development of the mammalian immune system is under the surveillance of various immunoregulatory proteins contained in maternal secretory fluids.     

Surgical pitfalls in a patient with type IV Ehlers-Danlos syndrome and spontaneous colonic rupture

PURPOSE: This paper intends to stress the importance of early diagnosis and discuss surgical treatment of Type IV Ehlers-Danlos syndrome (EDS-4), an autosomal dominant connective tissue disease characterized by typical features of the face and extremities, inappropriate and easy bruising, and extreme tissue fragility, which may lead to dramatic and often fatal complications, mostly spontaneous arterial or intestinal rupture. METHODS: We report the case of a 41-year-old female who presented with spontaneous perforation of the sigmoid colon. RESULTS: The patient was seen over a nine-year period, during which time she required six operations and presented with a great number of surgical complications including stenosis of an end-colostomy, repeated subocclusive episodes caused by intraperitoneal adhesions, and enterocutaneous fistulas, finally ending with an ileostomy and short bowel syndrome. It is only after a difficult laparotomy for ovarian cyst excision, marked by numerous adhesions and friable bowel, that the diagnosis of EDS-4 was considered and established. CONCLUSIONS: In case of “idiopathic” spontaneous perforation of the colon in a young adult, features of EDS-4 should be thoroughly looked into and, if found, skin fibroblast culture with collagen Type III analysis performed. The surgical treatment of choice consists of subtotal colectomy and permanent endileostomy. In case of patient refusal, a second-stage ileorectal anastomosis can be performed but carries the high risk of anastomotic leakage.