Fetal Alcohol Effects: Mechanisms and Treatment

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the third trimester equivalent, by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.     

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

Introduction

Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.

Methods

We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.

Results

Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.

Conclusions

Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.     

A case representing coexistence of acute myeloblastic leukemia and dedifferentiated liposarcoma: the possible role of chemotherapy in triggering dedifferentiation

Acute myelogenous leukemia (AML) is a hematological disorder that is characterized by an abnormal proliferation of immature myeloid cells. Dedifferentiated and well-differentiated liposarcomas are the two pathological subtypes of liposarcoma, based on the WHO classification. Transition from well-differentiated to dedifferentiated liposarcoma is a well-recognized phenomenon. Well-differentiated tumors are known to have low malignancy grade. However, when dedifferentiation occurs, the tumor acquires the aggressive features of a fully malignant lesion. This process largely is believed to progress in a time-dependant manner; however, time is not the only factor of importance. The potential roles of other factors in this transition are still unclear. To date, the coexistence of AML and liposarcoma has not been reported in the literature. In this paper, we report on a case of coexistence of AML and liposarcoma, and on the unusual behavior of a well-differentiated tumor after dedifferentiation occurs.     

Familial clustering of beta-cell autoimmunity in initially non-diabetic children

BACKGROUND: Type 1 diabetes is characterised by familial aggregation. We set out to explore whether beta-cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering. METHODS: Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families. When a child tested positive for ICA, all his/her previous or subsequent samples that were available were also tested for insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to the IA-2 protein (IA-2A). RESULTS: Forty-four families were observed to have two or more children positive for at least ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p < 0.001). The frequency of multiple (>/=2) autoantibodies also showed familial aggregation, the observed proportion (0.39%) being three times that expected (0.13%; p < 0.001). In 72.7% of the families with at least two ICA-positive siblings, the children with autoantibodies had the same HLA DQB1 genotype. The median age difference between the ICA-positive children within the same family was 3.3 years (range 0.0-10.5 years), and the median time interval in the appearance of ICA within the family was 1.6 years (range 0.0-3.2). CONCLUSIONS: beta-cell autoimmunity, as defined by the appearance of ICA, demonstrates familial aggregation, although the antibodies do not appear in close temporal proximity or at an identical age within the same family. The HLA-DQB1 genotypes are more often identical in siblings with autoantibodies than in other siblings.     

Gluten-free diet improves iron-deficiency anaemia in patients with coeliac disease

Two cases of newly-diagnosed asymptomatic coeliac disease with 3 years of unexplained severe iron-deficiency anaemia are presented. Oral iron supplementation had no effect on their serum iron levels and, therefore, had no influence on their anaemia. Upper gastrointestinal endoscopy confirmed normal macroscopic findings. Duodenal biopsies revealed subtotal villous atrophy of the mucosa of the small intestine. A strict gluten-free diet led to an increase in serum iron, resolution of anaemia, and restitution of normal mucosal morphology. Thus, severe iron-deficiency anaemia associated with asymptomatic coeliac disease is responsible to gluten-free diet.     

Surgical treatment of hereditary lens subluxations

BACKGROUND AND OBJECTIVE: To evaluate the effectiveness and results of pars plana vitreolensectomy approach with transscleral fixation of intraocular lens in hereditary lens subluxations. METHODS: Fifteen eyes of 9 consecutive patients with a mean age of 12.8+/-6.2 years (6-26 years) with hereditary lens subluxation were operated on and the results were evaluated in a prospective study. Surgery was considered if best spectacle corrected visual acuity (BSCVA) was less than 20/70. All eyes underwent a 2-port pars plana vitreolensectomy and transscleral fixation of an intraocular lens (IOL). RESULTS: The mean follow-up period was 12.6+/-7.5 months (6-22 months). There was no major intraoperative complication. Preoperatively, 8 eyes (53.3%) had a BSCVA of counting fingers (CF) and 7 eyes (46.6%) had a BSCVA of 20/200 to 20/70. Postoperatively, 14 eyes (93.3%) had a BSCVA of 20/50 or better. None of the patients had IOL decentration or intraocular pressure (IOP) increase during the follow-up period. There was a macular hole formation in 1 eye postoperatively. CONCLUSIONS: The early results of pars plana vitreolensectomy with IOL implantation using scleral fixation technique had shown that it not only promises a rapid visual rehabilitation but it is also a relatively safe method. More serious complications, however, may occur in the long term.     

Genetic risk determines the emergence of diabetes-associated autoantibodies in young children

Timing of onset of autoimmunity is a prerequisite for unmasking triggers and pathogenesis of type 1 diabetes. We followed 4,590 consecutive newborns with 8 or 3% HLA-DQB1 conferred risk for type 1 diabetes at 3-, 6-, or 12-month intervals up to 5.5 years of age. Islet cell autoantibodies (ICAs) and, in the 137 children with ICAs, insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and IA-2 protein autoantibodies (IA-2As) were measured. Children with high genetic risk developed ICAs more often than those with moderate risk (log-rank P = 0.0015); 85 and 91% remained ICA negative by 5 years of age, respectively. The time of appearance of biochemical autoantibodies was then compared with the appearance of ICAs. IAAs and GADAs emerged usually before ICAs (means -1.8 and -1.5 months, respectively) and IA-2As after ICAs (mean 2.0 months). Ninety-five percent of all IAAs, GADAs, and IA-2As seroconversions occurred in a cluster (-12 to 8 months) around the ICA seroconversion. We conclude that diabetes-associated autoantibodies emerged in children with predisposing HLA-DQB1 alleles after 3 months of age at a constant tempo, determined by the genetic risk level, usually in the order of IAA, GADA, ICA, and IA-2A. Seroconversion to multiple autoantibody positivity usually occurred tightly clustered in time.