Contribution of molecular analyses to the estimation of the risk of congenital myotonic dystrophy.

A molecular analysis of the maternal and child CTG repeat size and intergenerational amplification was performed in order to estimate the risk of having a child with congenital myotonic dystrophy (CMD). In a study of 124 affected mother-child pairs (42 mother-CMD and 82 mother-non-CMD) the mean maternal CTG allele in CMD cases was three times higher (700 repeats) than in non-CMD cases (236 repeats). When the maternal allele was in the 50-300 repeats range, 90% of children were non-CMD. In contrast, when the maternal allele was greater than 300 repeats, 59% inherited the congenital form. Furthermore, the risk of having a CMD child is also related to the intergenerational amplification, which was significantly greater in the mother-CMD pairs than in the mother-non-CMD pairs. Although the risk of giving birth to a CMD child always exists for affected mothers, our data show that such a risk is considerably higher if the maternal allele is greater than 300 repeats.     

Rotavirus diarrhea severity is related to the VP4 type in Mexican children

This report is of a community-based case control study to assess whether the severity of acute diarrhea by rotavirus (RV) in young children is associated with a particular VP7 (G) or VP4 (P) RV serotype. Five hundred twenty children younger than 2 years of age with diarrhea lasting less than 3 days were age and gender matched with 520 children with no diarrhea. The G and P serotypes were determined with specific monoclonal antibodies, and the VP4 serotype specificity in a subgroup was confirmed by genotyping. Infection with a G3 serotype led to a higher risk of diarrhea than infection with a G1 serotype. Infection with a G3-nontypeable-P serotype was associated with more severe gastroenteritis than infection with a G3 (or G1) P1A[8] serotype. A child with diarrhea-associated dehydration was almost five times more likely to be infected with a G3-nontypeable-P serotype than a child without dehydration (P < 0.001). Moreover, the two predominant monotypes within serotype P1A[8] had significantly different clinical manifestations. In this study, the severity of RV-associated diarrhea was related to different P serotypes rather than to G serotypes. The relationship between serotype and clinical outcomes seems to be complex and to vary among different geographic areas.     

Precipitating antibodies to DNA induced by heat-denatured DNA-albumin conjugates in the rabbit

(1) Antibodies reactive with purified DNA in the complement fixation system and induced by active immunization of rabbits with methylated bovine serum albumin—DNA aggregate (MBSA—DNA) have been previously described. The present study demonstrates their reactivity in the quantitative and double diffusion preciptin systems. In these systems they have shown preferential reactivity with heat denatured DNA and great cross-reactivity with denatured DNA from various sources.

(2) Methylated rabbit serum albumin—DNA aggregate (MRSA—DNA) is an effective immunizing antigen resulting in the production of antibodies similar to those produced by MBSA—DNA.

(3) The precipitating antibodies in this system are 19S immunoglobulins and appear to be identical to the complement fixing antibodies.

(4) The precipitin reaction is not significantly inhibited by mono-nucleotides.

     

Utilization of carbohydrates and free fatty acids by the gastrocnemius of the dog during long lasting rhythmical exercise

Summary Utilization of carbohydrates and free fatty acids (FFA) has been investigated in gastrocnemii of dogs during long lasting isotonic rhythmical exercise induced by supramaximal stimulation of the sciatic nerve. Uptake or output of gases and substrates was determined according to the Fick principle. The first measurements were done at about 2 min after the beginning of work when blood flow has reached a steady state, and the latest at about 100 min after the beginning of exercise.During the first 7 min when the work performed exceeded 5 kg/100g×min and O₂ consumption exceeded 11 ml/100g×min, uptake of arterial glucose and FFA was low, accounting for less than 40% of the total O₂ consumption. Since the RQ values at the same time were about 1.0, glycogen must have been oxidized as the major aerobic energy source.About 13 min after the beginning of exercise, the work the muscles could perform declined to about half of the initial value and remained so for the following 90 min. During this time the oxygen extraction ratio of FFA was about 50% and of arterial glucose was 40–50%, while the RQ value was about 0.8.During initial strong exercise an output of lactic acid (LA) of about 10 mg/100 g×min was measured. With the decrease of work as a consequence of fatigue, LA output became negligible, and in many experiments small amounts of LA were taken up by the working gastrocnemii.It is concluded that glycogen is the major aerobic energy source for strong muscular exercise which cannot be substituted for by the oxidation of arterial glucose or FFA.Supported by the Deutsche Forschungsgemeinschaft.     

The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching

To determine the effects of creatine supplementation during short-term resistance training overreaching on performance, body composition, and resting hormone concentrations, 17 men were randomly assigned to supplement with 0.3 g/kg per day of creatine monohydrate (CrM: n=9) or placebo (P: n=8) while performing resistance exercise (5 days/week for 4 weeks) followed by a 2-week taper phase. Maximal squat and bench press and explosive power in the bench press were reduced during the initial weeks of training in P but not CrM. Explosive power in the bench press, body mass, and lean body mass (LBM) in the legs were augmented to a greater extent in CrM (P0.05) by the end of the 6-week period. A tendency for greater 1-RM squat improvement (P=0.09) was also observed in CrM. Total testosterone (TT) and the free androgen index (TT/SHBG) decreased in CrM and P, reaching a nadir at week 3, whereas sex hormone binding globulin (SHBG) responded in an opposite direction. Cortisol significantly increased after week 1 in CrM (+29%), and returned to baseline at week 2. Insulin was significantly depressed at week 1 (–24%) and drifted back toward baseline during weeks 2–4. Growth hormone and IGF-I levels were not affected. Therefore, some measures of muscular performance and body composition are enhanced to a greater extent following the rebound phase of short-term resistance training overreaching with creatine supplementation and these changes are not related to changes in circulating hormone concentrations obtained in the resting, postabsorptive state. In addition, creatine supplementation appears to be effective for maintaining muscular performance during the initial phase of high-volume resistance training overreaching that otherwise results in small performance decrements.     

Comparison of two urinary antigen tests for establishment of pneumococcal etiology of adult community-acquired pneumonia

The Binax NOW immunochromatographic test (ICT) detecting the pneumococcal C polysaccharide and a serotype-specific latex agglutination (LA) test detecting 23 pneumococcal capsular antigens were evaluated for establishing pneumococcal etiology in community-acquired pneumonia (CAP) by use of nonconcentrated urine. ICT was considered to be strongly positive for result lines at least as intense as the control line and weakly positive for less intense result lines. When 215 adult CAP patients were tested, strong ICT, weak ICT, and LA positivity were found in 28, 24, and 16 patients, respectively; of these patients, 13 (46%), 6 (25%), and 13 (81%), respectively, had pneumococcal bacteremia and 27 (96%), 17 (71%), and 15 (94%), respectively, had Streptococcus pneumoniae isolated from blood, sputum, and/or nasopharynx. Among 108 controls tested, 2 (1.9%) were weakly ICT positive. When weak positivity was considered negative, the sensitivity of ICT decreased from 79% (19 of 24) to 54% (13 of 24), while the specificity increased from 83% (158 of 191) to 92% (176 of 191); no controls were false positive. The sensitivity and specificity of LA were 54% (13 of 24) and 98% (188 of 191), respectively. Eight of nine LA serotypes corresponded to culture serotypes. In conclusion, using nonconcentrated urine and dividing ICT-positive results into strongly and weakly positive results is a suitable way of performing ICT. While weak ICT positivity should be interpreted with caution, strong ICT positivity and LA positivity should be considered supportive of pneumococcal etiology in adult CAP. As such, these assays might have implications for antibiotic use in CAP. LA has promising potential for pneumococcal serotyping, although further evaluation is required.     

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).