Prenatal molecular genetic diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH), in its severe forms, produces virilization of the external genitalia of the affected female fetus. Early treatment with dexamethasone of the pregnant mother at risk of a fetus with 21-OH deficiency avoids the masculinization of the affected female fetus. We present a pregnant mother, where the prenatal diagnosis was established by DNA analysis of a chorionic villous sample obtained in the 9th week of gestation. Molecular analysis showed the female fetus to be affected of 21-OH deficiency. Maternal treatment with dexamethasone started on the 6th week of gestation has prevented the virilization of the affected baby. No significant side effects have been encountered. Prenatal diagnosis and treatment for 21-OH deficiency is effective and safe, as is described in the literature. This is the first case in Spain where both prenatal molecular diagnosis and treatment for 21-OH deficiency have been reported.     

Nutritional utilization of a low protein diet in alloxan diabetic rats

Dietary control is known to influence diabetic processes. Therefore, the purpose of this work was to determine possible effects brought about by two different dietary protein levels on the nutritional diet utilization in alloxan-diabetic rats. Rats were divided in two groups: 1) One fed on 12% and 2) one a 4% protein diet. Each group was then divided into two subgroups: A) non diabetic and B) diabetic. Weight parameters, food intake, food efficiency (FE), digestive efficiency (DE), metabolic utilization (MU), retained N/ingested N ratio as well as initial and final glycemia were evaluated at the beginning and at the end of the experiment. A decrease in body weight, FE, DE and MU was observed in the control rats of group 2A, in comparison with the group 1A. Experimental diabetes led to increased FE in 1B group in relation to those of group 1A. Also decreased body weight and FE as well as increased food intake and DE were found in the control animals of 2B group. Glycemia increased in diabetic rats as compared with non-diabetic rats, in both groups, 1 and 2. The data suggest that under the experimental conditions cited, both the nutritional utilization of the diet and the diabetogenic status might be modulated by the dietary protein ingested level.     

Hallux valgus due to cuneiform-metatarsal instability

We present a biomechanical rationale for the treatment of severe hallux valgus deformity by realignment and arthrodesis of the first cuneiform metatarsal (CM) joint. We think that this severe hallux valgus deformity represents instability at the CM-1 articulation, since normal motion at that joint is very small. A forefoot compression test was used to assess the foot preoperatively. This was found not only to realign the first metatarsal, but also to align the metatarsophalangeal joint. A surgical procedure has evolved to include a transverse screw between the first and second metatarsal bases, as well as a second screw from first cuneiform to first metatarsal base, along with a small-volume bone graft of the CM-1 articulation. This is a modern variant of the Lapidus procedure.     

SociaL aspects of pulmonology

A group of new-onset pulmonary tuberculosis patients has been studied and its social characterization is provided in the paper. Comparison of the 1991-1992 findings with those obtained in 1970-1980 has indicated that social aspects are topical as before and have some specific features in recent years. The most important issues are now living conditions, financial status of the patients, their social lifestyle, refugees and rational employment of tuberculosis patients and disabled persons.     

Comparative evaluation of the use of artificial neural networks for modelling the epidemiology of schistosomiasis mansoni

There has been a marked increase in the application of approaches based on artificial intelligence (AI) in the field of computer science and medical diagnosis, but AI is still relatively unused in epidemiological settings. In this study we report results of the application of neural networks (NN; a special category of AI) to schistosomiasis. It was possible to design an NN structure which can process and fit epidemiological data collected from 251 schoolchildren in Egypt using the first year's data to predict second and third years' infection rates. Data collected over 3 years included age, gender, exposure to canal water and agricultural activities, medical history and examination, and stool and urine parasitology. Schistosoma mansoni infection rates were 50%, 78% and 66% at the baseline and the 2 follow-up periods, respectively. NN modelling was based on the standard back-propagation algorithm, in which we built a suitable configuration of the network, using the first year's data, that optimized performance. It was implemented on an IBM compatible computer using commercially available software. The performance of the NN model in the first year compared favourably with logistic regression (NN sensitivity = 83% (95% confidence interval [CI] 78-88%) and positive predictive value (PPV) = 63% (95% CI 57-69%); logistic regression sensitivity = 66% (95% CI 60%-72%) and PPV = 59% (95% CI 53%-65%). The NN model generalized the criteria for predicting infection over time better than logistic regression and showed more stability over time, as it retained its sensitivity and specificity and had better false positive and negative profiles than logistic regression. The potential of NN-based models to analyse and predict wide-scale control programme data, which are inevitably based on unstable egg excretion rates and insensitive laboratory techniques, is promising but still untapped.     

A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34-kDa subunit of replication protein A

Uracil-DNA glycosylase releases free uracil from DNA and initiates base excision repair for removal of this potentially mutagenic DNA lesion. Using the yeast two-hybrid system, human uracil-DNA glycosylase encoded by the UNG gene (UNG) was found to interact with the C-terminal part of the 34-kDa subunit of replication protein A (RPA2). No interaction with RPA4 (a homolog of RPA2), RPA1, or RPA3 was observed. A sandwich enzyme-linked immunosorbent assay with trimeric RPA and the two-hybrid system both demonstrated that the interaction depends on a region in UNG localized between amino acids 28 and 79 in the open reading frame. In this part of UNG a 23-amino acid sequence has a significant homology to the RPA2-binding region of XPA, a protein involved in damage recognition in nucleotide excision repair. Trimeric RPA did not enhance the activity of UNG in vitro on single- or double-stranded DNA. A part of the N-terminal region of UNG corresponding in size to the complete presequence was efficiently removed by proteinase K, leaving the proteinase K-resistant compact catalytic domain intact and fully active. These results indicate that the N-terminal part constitutes a separate structural domain required for RPA binding and suggest a possible function for RPA in base excision repair.     

Selective changes in hippocampal neuropeptide Y neurons following removal of the cholinergic septal inputs

The number and distribution of subpopulations of hilar interneurons containing neuropeptide Y (NPY), somatostatin (SOM), or gamma-aminobutyric acid (GABA) immunoreactivities were examined in the hilus of the dentate gyrus following removal of the cholinergic septal inputs. One, 2, 4, 8, 12, and 24 weeks after intracerebroventricular injections of immunotoxin, consisting of antibody to the low-affinity nerve growth factor receptor conjugated to saporin (192 IgG-saporin), lesioned rats were processed simultaneously with controls for NPY, SOM, or GABA immunolabeling. Across all time points, the number of NPY-labeled neurons was reduced to a statistically significant level (paired t-test, P = 0.001) in the injected rats (73% of control values, on average). The decrease in the number of NPY-labeled neurons was not limited to any particular subregion rostrally but appeared greater in the central region caudally. The size of NPY-labeled neurons did not differ statistically between control and immunolesioned rats examined at 1, 2, and 24 week time points. In contrast, the number of both SOM- and GABA-immunoreactive neurons in injected rats did not appear to be affected in any consistent manner. Examination of the hilus in adjacent Nissl-stained sections with the optical dissector revealed that although the total number of small nonprincipal cells (5-15 microm in diameter) did not appear affected at the 4-week time point, there was a statistically significant (P = 0.03) reduction across the 8-24-week time points (to 80% of control values, on average). Dual-labeling studies on separate rats showed that a small subpopulation of the NPY- and SOM-labeled neurons, primarily in the infragranular hilus, were colocalized with neurons containing GABA immunoreactivity (18% and 5%, respectively). These studies demonstrate that removal of the cholinergic septal inputs (1) can cause relatively rapid, selective decreases in the number of NPY-immunoreactive hippocampal interneurons and (2) appears to lead to the death of hippocampal interneurons over a longer time course. The changes in NPY immunoreactivity seem to occur in the portion of interneurons that probably does not contain either SOM or GABA immunoreactivity.     

Antibiotic prophylaxis--Hobson's choice in burns management

Antibiotic prophylaxis is a routine procedure in management of burns. As such it is a safe practice, yet unusual complications can occur with the use of even safest antibiotics and their emergency management may be life saving. Here we present a case of 35% second and third degree burns who was taken for a second sitting of stamp grafting for remnant raw areas, who was administered intraoperative prophylactic antibiotic, developed a series of unusual complications sequentially, which were life threatening. Prompt recognition of signs and symptoms of adverse reactions of the drug used and timely management resulted in the successful outcome. A good team effort by surgeon, anaesthetist and the physician was mandatory.     

Skin testing after anaphylactoid reactions to dental local anesthetics. A comparison with controls

Reactions to scratch and intradermal challenge with a variety of local anesthetics were examined in 90 patients and compared with 45 controls. The frequency of a positive scratch test was 13 of 90 in the patient group and 12 of 45 in the control group. Thus scratch testing did not appear to discriminate between test and control groups. Significantly greater numbers of patients (22 of 90) gave a positive intradermal response than controls (4 of 45) (chi-squared test p < 0.05). Nine patients showed reactions to more than one agent. The majority of reactions in both patients and controls were in atopic subjects (chi-squared test p < 0.05). In 87 of the 90 patients with suspected anaphylactoid reactions to local anesthetic agents, negative skin reactions to at least one of the agents allowed intrabuccal challenge and subsequent recommendation of an agent for future use. Skin testing, though not providing formal proof of allergy, provides a useful test to indicate local anesthetics that may be used for future procedures.     

Clincal, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis

To examine the effect of elastic loading on variational activity of breathing, we studied 11 healthy subjects breathing at rest and with inspiratory elastic loads of 9 and 18 cm H2O/L, applied randomly for 1 h each. Compared with rest, a load of 18 cm H2O/L decreased gross variability, quantitated as standard deviation, of tidal volume (VT) and expiratory time (TE) (p < 0.01 in both instances) but increased that of inspiratory time (TI) (p < 0.03). The autocorrelation coefficients at a lag of 1 breath for each breath component were not altered by elastic loading, although the number of breath lags with significant serial correlations for TE tended to increase with a load of 18 cm H2O/L (p = 0.08). A load of 18 cm H2O/L decreased only the fraction of variational activity of VT and TE due to uncorrelated, random behavior (white noise), while it increased that fraction for TI (p < 0.05 in each instance); the correlated and oscillatory fractions did not change. Uncorrelated random behavior constituted > 87% of the variance of each breath component, correlated behavior represented 3 to 11%, and oscillatory behavior represented < 1.5% during both rest and loaded breathing. Elastic loading changed the gross variability of each primary breath component by altering the random fraction of variational activity; it had no significant effect on the structured, correlated fraction. We speculate that the observed changes in variational activity may reflect an attempt by the controller to compensate for the increased load while simultaneously minimizing load-induced dyspnea.