Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

A new de novo mutation in a non-hot spot region at the DMD gene in a Mexican family.

In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.

[Clinicopathologic characteristics of 127 cases of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) studied in an oncology hospital]. / Características clínico-patológicas de 127 casos de neoplasias neuroendocrinas del aparato gastrointestinal y páncreas (NNE-GEP) estudiadas en un hospital de oncología.

BACKGROUND: Neuroendocrine tumors (NETs) present all along the length of the gastrointestinal (GI) tract, from the esophagus to the anus, and they also present in the pancreas. AIMS: To classify NETs according to the WHO 2010 criteria and to evaluate their anatomic distribution and clinicopathologic characteristics. MATERIAL AND METHODS: A search was carried out in the hospital pathology archives of all the cases diagnosed with carcinoid tumor and neuroendocrine carcinoma of the GI tract and pancreas studied over a period of 11 years (1999-2010). The cases were reclassified according to the WHO 2010 criteria. The clinical case records of each patient were reviewed. RESULTS: The study group was made up of 127 cases (68 men; 59 women). Age ranged from 24 to 85 years with a median of 52 years. A total of 113 (89.00%) tumors occurred in the GI tract and 14 (11.00%) in the pancreas. Tumor size varied from 0.4cm to 9cm (median: 2.5cm). GI tumor histologic grades were: 54.00% grade 1; 31.00% grade 2; and 15.00% grade 3. Pancreatic tumor histologic grades were: 43.00% grade 1; 36.00% grade 2; and 21.00% grade 3. Ki-67 overexpression was correlated with tumor grade (22.00% grade 3 vs 2.50% grade 1). CONCLUSIONS: Histologic grade of the gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is one of the most important prognostic factors. The term carcinoid should be eliminated because it does not reflect the biological behavior of these tumors.

Distribution of CTG repeats at the DMPK gene in myotonic dystrophy patients and healthy individuals from the Mexican population.

Myotonic dystrophy type 1 (DM1), the most common form of adult muscular dystrophy, is caused by anormal expansion of CTG trinucleotide repeats located in the 3'-untranslated region of the DMPK gene. The clinical features of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations. In this study, we described to our knowledge for the first time the molecular diagnosis of myotonic dystrophy type 1 patients in the Mexican population, applying a fluorescent PCR method in combination with capillary electrophoresis analysis of the amplified products. We identified expanded alleles in 45 out of 50 patients (90%) with clinical features of myotonic disease. Furthermore, genotyping of 400 healthy subjects revealed the presence of 25 different alleles, ranging in size from 5 to 34 repeats. The most frequent allele was 13 CTG repeats (38.87%) and the frequency for alleles over 18 CTG repeats was 6.7%. Molecular test is essential for DM1 diagnosis and distribution of the CTG repeat alleles present in the Mexican population are significantly different from those of other populations.

Tomographic findings in traumatic globe evulsion caused by blunt head trauma.

Evulsion of the globe as a result of trauma is a rarity; to the best of our knowledge, only four "evulsions of the globe" have been described. We present the case of a 35-year-old Hispanic woman with traumatic evulsion of the right eye and subarachnoid haemorrhage. The management of brain injury was the priority over preservation of globe structures. We briefly describe the tomographic features of this uncommon situation and the proposed "evulsion" mechanism.

[Analysis of the interference pattern in patients with muscular dystrophy]. / Análisis del patrón de interferencia en pacientes con distrofia muscular.

INTRODUCTION: The conventional electromyography contribute to differentiation of myopatic and neuropatic patterns in neuromuscular disorders, however, the classical patterns related to myopatic changes can result in neurogenic components, this confusion could be due to denervation and reinervation changes involved at the different stages of those diseases. OBJECTIVE: Demonstrate the importance of quantitative electromyographic techniques, as the interference pattern analysis (IPA), for a better differentiation of muscular dystrophies. PATIENTS AND METHODS: IPA was done in 95 patients with 3 different muscular dystrophies: 52 Duchenne muscular dystrophy (DMD), 33 limb girdle muscular dystrophy (LGMD) and 10 myotonic muscular dystrophy (MD) individuals and in a control group of 25 individuals. The left braquial biceps and right anterior tibial muscles were evaluated; the variables analyzed were turns/seconds (t/s), amplitude/turns (a/t), ratio turns/amplitude mean and root squared mean (RSM). RESULTS: We found statistical significant differences in all variables in both braquial biceps and right anterior tibial muscles (p < 0.05) in DMD patients. In LGMD we only found differences in a/t in braquial biceps. In MD the differences were observed in a/t, ratio and RSM in braquial biceps, and in a/t (in anterior tibial). CONCLUSIONS: All the DMD patients show differences in IPA values in relation to control group, MD only in biceps, However there were not important changes in LGMD probably because the diversity and lack of homogeneity in affected muscles in this group.

Synthesis and hydrolytic stability studies of albendazole carrier prodrugs.

Three N-acyl (2, 3, and 4), two N-alkoxycarbonyl (5 and 6), and one N-acyloxymethyl (7) derivatives of albendazole (1) have been prepared and assessed as potential prodrugs. The determination of the aqueous solubility and partition coefficient, as well as the conversion of these derivatives to 1 in buffer solution, human plasma, and pig liver esterase were determined.

Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives.

2-(Trifluoromethyl)benzimidazole derivatives substituted at the 1-, 5-, and 6-positions have been synthesized and in vitro tested against the protozoa Giardia lamblia, Entamnoeha histolytica. and the helminth Trichinella spiralis. Results indicate that all the compounds tested are more active as antiprotozoal agents than Albendazole and Metronidazole. One compound (20) was as active as Albendazole against T. spiralis. These compounds were also tested for their effect on tubulin polymerization and none inhibited tubulin polymerization.

HLA characterization in adult asymptomatic cyst passers of Entamoeba histolytica/E. dispar.

The present work aimed at studying the possible association of HLA antigens with Entamoeba histolytica/E. dispar asymptomatic infection in a Mexican mestizo population. A case-control design was selected for evaluation of the role of genetic markers in parasite infection. For this purpose the HLA-A, HLA-B, and HLA-DR profiles of a population of asymptomatic E. histolytica/E. dispar adult cyst passers (cases) and a corresponding nonparasitized adult group (controls) followed for 12 months were identified. Entamoeba species were identified through zymodeme patterns and/or amplification of species-specific DNA sequences. A healthy, nonparasitized group of individuals was included as a control. Our results show that apparently, no specific HLA marker is associated with the asymptomatic cyst passers' condition. These findings have to be added to previous results in which, in contrast to a demonstrated association between HLA-DR3 and amebic liver abscess in Mexican mestizo adults and infants, no significant association with amebic rectocolitis was found.

Antigenic and genomic diversity of human rotavirus VP4 in two consecutive epidemic seasons in Mexico.

In the present investigation we characterized the antigenic diversity of the VP4 and VP7 proteins in 309 and 261 human rotavirus strains isolated during two consecutive epidemic seasons, respectively, in three different regions of Mexico. G3 was found to be the prevalent VP7 serotype during the first year, being superseded by serotype G1 strains during the second season. To antigenically characterize the VP4 protein of the strains isolated, we used five neutralizing monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B, and P2 in earlier studies. Eight different patterns of reactivity with these MAbs were found, and the prevalence of three of these patterns varied from one season to the next. The P genotype of a subset of 52 samples was determined by PCR. Among the strains characterized as genotype P[4] and P[8] there were three and five different VP4 MAb reactivity patterns, respectively, indicating that the diversity of neutralization epitopes in VP4 is greater than that previously appreciated by the genomic typing methods.

Serotype specificity of the neutralizing-antibody response induced by the individual surface proteins of rotavirus in natural infections of young children.

The relative contribution of the rotavirus surface proteins, VP4 and VP7, to the induction of homotypic as well as heterotypic neutralizing antibodies (NtAbs) in natural infections was studied. The NtAb titers of paired sera from 70 infants with serologically defined primary rotavirus infections were determined with a panel of rotavirus reassortants having one surface protein from a human rotavirus (serotypes G1 to G4 for VP7 and P1A and P1B for VP4) and the other surface protein from a heterologous animal rotavirus strain. A subset of 37 children were evaluated for epitope-specific antibodies to the two proteins by an epitope-blocking assay. The infants were found to seroconvert more frequently to VP4 than to VP7 by both methods, although the titers of the seroconverters were higher to VP7 than to VP4. Both proteins induced homotypic as well as heterotypic NtAbs. G1 VP7 frequently induced a response to both G1 and G3 VP7s, while G3 VP7 and P1A VP4 induced mostly homotypic responses.

Isolation of Mycoplasma pneumoniae from asthmatic patients.

Asthmatic patients frequently develop wheezing after respiratory tract infection. Mycoplasma pneumoniae causes respiratory tract infections in children and in adults. The purpose of this study was to determine the frequency of recovery of M. pneumoniae from patients with asthma. Seventy-seven patients with asthma and 88 persons without asthma or any other respiratory tract disease (controls) were included in the study. Ages ranged from 8 months to 31 years. Throat swabs were taken and deposited in egg yolk broth with methylene blue in order to isolate M. pneumoniae. The bacterium was identified using inhibition of growth with homologous antiserum. The isolation rate in patients with asthma was 24.7% while that in controls was 5.7% (P < .01). The results suggest that M. pneumoniae colonizes a higher percentage of patients with asthma than controls and could possibly have induced the wheezing.

[The perinatal aspects of surviving low-birth weight neonates]. / Aspectos perinatales de neonatos sobrevivientes de bajo peso.

We analyzed prenatal history of 277 live low birth weight infants (less than 2,500 g). We tried to determine some perinatal factors that may be associated with good prognosis in this group of babies. The variables analyzed were: maternal age, number of prenatal visits, complication of pregnancy, mode of delivery, birth weight, sex, gestational age. Apgar score at 1 minute and the neonatal morbidity. The population was divided in 3 groups: 1. Less than 1,000 g, (3).2. 1,000-1,499 g, (37) and 3. 1,500-2,499 g (237). Each group was also divided in appropriate for gestational age (AGA) and small for gestational age (SGA). We found that morbidity and the risk of death, is less in the SGA compared with AGA, associated with better prenatal care, higher birth weight and gestational age.

[Indomethacin in the prevention of subependymal-intraventricular hemorrhage in preterm newborns with conventional mechanical ventilation]. / Indometacina en la prevención de la hemorragia subependimaria-intraventricular del recién nacido pretérmino con ventilación mecánica convencional.

The results of a double blind study to evaluate the efficiency of prophylactic endovenous indomethacin versus placebo for prevention of intraventricular hemorrhage (IVH) in newborn infants between 28 to 36 weeks of age who were intubated at the delivery room and required mechanical ventilation in NICU are presented. Fourty six patients required mechanical ventilation, but 14 neonates had IVH evaluated by ultrasound when were admitted to the Unit. At least 32 infants were studied, 16 for each group. There were no differences between the groups in weight, gestational age, sex and delivery way. The mobility was the same in relation to hialine membrane disease, sepsis, pneumonie and pneumotorax. The placebo group had more frequency of PDA and mortality (P < 0.5). There were no differences in mean airway pressure and arterial gases, also in glucose, platelets and urinary volume. The indomethacin group had mayor urinary density and FeNa but the results were always in normal ranges. The IVH was the same in both groups. We concluded that the indomethacin at the levels used did not produced alterations, and if the IVH is not prevented, were observed lesser severity of the same and the frequency of PDA and mortality are lesser. But still is necessary more number of cases for best conclusions.

[Usefulness of C-reactive protein for the diagnosis of neonatal sepsis]. / Utilidad de la proteína C reactiva para el diagnóstico de sepsis neonatal.

With the object to determine the utility of C-reactive protein (CRP) in the diagnosis of neonatal sepsis. We proceeded to create the prospective study of cases and controls of newborn included in the study of neonatal sepsis in the Instituto Nacional de Perinatologia. We measured the seric CRP in samples obtained by capillary punction simultaneously with blood culture and/or CSF culture, for bacterial infection criteria. We included 64 newborn divided in two groups: 42 patients were not infected and 22 cases had positive cultures. The results in the uninfected newborn group of CRP were negative to positive dilutions 1:32; with the newborn infected the CRP had values of 1:32 to 1:2048. The probability to find values equal or major to 1:32 in the infected newborn with positive cultures the CRP have values of sensitivity of 91% and specificity of 93% to get this values. We accept that the CRP could be used systematically for the diagnosis of neonatal sepsis, being a simple procedure and accessible for use in the newborn with sepsis suspicion.

Prevalence of Clostridium difficile and its cytotoxin in infants in Mexico.

The incidence of Clostridium difficile and its cytotoxic activity were determined in the feces of 122 children under 1 year of age. Samples were obtained from children receiving antibiotics and with (52 cases) or without (26 cases) diarrhea, from children with diarrhea who did not receive antibiotics (22 cases), and from healthy children (22 cases). Isolation of C. difficile in feces from children in all groups was similar (mean 23.4%) except for the group with non-antibiotic-associated diarrhea (4.5%). In both groups of children receiving antibiotics, with or without diarrhea, the cytotoxin was detected in 7.6% of the cases. In the group with non-antibiotic-associated diarrhea, none of the samples was positive for cytotoxicity. In healthy children, cytotoxin was positive in 4.5% of the cases.