Electrophysiological and morphological heterogeneity of slow firing neurons in medial septal/diagonal band complex as revealed by cluster analysis.

Slow firing septal neurons modulate hippocampal and neocortical functions. Electrophysiologically, it is unclear whether slow firing neurons belong to a homogeneous neuronal population. To address this issue, whole-cell patch recordings and neuronal reconstructions were performed on rat brain slices containing the medial septum/diagonal band complex (MS/DB). Slow firing neurons were identified by their low firing rate at threshold (<5 Hz) and lack of time-dependent inward rectification (Ih). Unsupervised cluster analysis was used to investigate whether slow firing neurons could be further classified into different subtypes. The parameters used for the cluster analysis included latency for first spike, slow after-hyperpolarizing potential, maximal frequency and action potential (AP) decay slope. Neurons were grouped into three major subtypes. The majority of neurons (55%) were grouped as cluster I. Cluster II (17% of neurons) exhibited longer latency for generation of the first action potential (246.5+/-20.1 ms). Cluster III (28% of neurons) exhibited higher maximal firing frequency (25.3+/-1.7 Hz) when compared with cluster I (12.3+/-0.9 Hz) and cluster II (11.8+/-1.1 Hz) neurons. Additionally, cluster III neurons exhibited faster action potentials at suprathreshold. Interestingly, cluster II neurons were frequently located in the medial septum whereas neurons in cluster I and III appeared scattered throughout all MS/DB regions. Sholl's analysis revealed a more complex dendritic arborization in cluster III neurons. Cluster I and II neurons exhibited characteristics of "true" slow firing neurons whereas cluster III neurons exhibited higher frequency firing patterns. Several neurons were labeled with a cholinergic marker, Cy3-conjugated 192 IgG (p75NTR), and cholinergic neurons were found to be distributed among the three clusters. Our findings indicate that slow firing medial septal neurons are heterogeneous and that soma location is an important determinant of their electrophysiological properties. Thus, slow firing neurons from different septal regions have distinct functional properties, most likely related to their diverse connectivity.

Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican mestizo population.

Major histocompatibility complex (MHC) alleles have been recognized as genetic factors for developing systemic lupus erythematosus (SLE). In the present study we analyzed whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to develop SLE in a Mexican Mestizo population. A HSP70-2 Pst I polymorphism was detected by a restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) in 107 SLE patients and 158 healthy controls. No statistically significant differences were observed in the HSP70-2 allele distribution between patients and healthy controls. HLA-DR analysis showed an increased frequency of HLA-DR3 allele in the patients group (P < 0.05, OR = 2.26, EF = 6.0%). On the other hand, when we analyzed HSP70-2 polymorphism in relation to HLA-DR3 allele, we could only detect an increased frequency of AB genotype in the DR3 negative patients (pC < 0.05, RR = 2.6, EF = 11.3%). Linkage disequilibrium was observed for three haplotypes: HLA-DR3-HSP70-2A (D = 0.03, D' = 0.67, P < 0.01); HLA-DR1-HSP70-2A (D = 0.03, D' = 0.86, P < 0.01) and HLA-DR8-HSP70-2B (D = 0.02, D' = 0.46, P = 0.02). Our data indicate that HSP70-2 gene polymorphism as opposed to the other ethnic groups does not appear to be relevant in SLE susceptibility in Mexican patients and that the distribution of the different alleles depend on the frequency of HLA alleles associated with them.

HLA-DRB and HLA-DQB loci in the genetic susceptibility to develop glaucoma in Mexicans.

PURPOSE: Glaucoma is a clinically heterogeneous disease with a pathophysiology that may include genetic susceptibility, possibly associated with an immunologic disorder. The aim of this study was to determine whether the DNA polymorphisms located in the HLA-DRB1 and HLA-DQB1 genes show a specific association pattern in Mexican mestizo patients with primary open-angle glaucoma. METHODS: This was a cross-sectional, case-control, multicenter study. We analyzed the HLA-DRB1 and DQB1 loci of 81 Mexican mestizo nonrelated patients with primary open-angle glaucoma and 98 healthy ethnic matched control subjects. Patients were diagnosed clinically and by visual fields examination. HLA typing was performed by PCR-SSO reverse dot blot. RESULTS: We documented increased frequencies of HLA-DRB1*0301, DRB1*1101, DRB1*0701, DRB1*1402, DQB1*0302, and DQB1*0301; however, none of them were significantly different from normal control subjects. Haplotype analysis showed that the HLA-DRB1*0407-DQB1*0302 haplotype is significantly increased in patients compared with control subjects (P = .0001). CONCLUSIONS: The haplotype HLA-DRB1*0407-DQB1*0302 is common among Mexican mestizo (haplotype frequency = 0.102), and it was increased in our patients (haplotype frequency = 0.259, P = .0001). This may reflect an independent association of this haplotype with the disease as the result of linkage disequilibrium or the influence of a neighboring gene. The pathophysiology of this illness is uncertain, and further studies are needed regarding the genetic susceptibility to develop primary open-angle glaucoma.

Genetic features of Mexican women predisposing to cancer of the uterine cervix.

Cervical carcinoma is the most common neoplasia in Mexican women. Previous studies report association of this neoplasia with the major histocompatibility complex (MHC) antigens in Caucasians. In the present study, we compared antigen frequencies of class I and class II MHC phenotypes in patients and ethnically matched healthy controls. Patients had significantly increased frequencies of HLA-A2 (PC = .000003) and HLA-DR5 (PC = .01) as compared with healthy controls. Conversely, we found a significant decrease of HLA-DR6 (PC = .01), HLA-DR2 (PC = .0005) and HLA-DR1 (PC = .0009) as compared with healthy controls. These results confirm some previous studies on HLA-associations with cervical carcinoma and reinforce the theory of independent mechanisms of MHC class I and class II genes in the etiopathogenesis of this disease.

Heat-shock protein (HSP70-2) allelic frequencies in three distinct Mexican populations.

The major histocompatibility complex (MHC) genes are highly polymorphic and therefore have been useful in population genetics and disease association studies. We analyzed restriction fragment length polymorphism of HSP70-2 alleles in healthy unrelated Mestizo, Mazatecan and Nahua populations. Both Indian groups, Mazatecans and Nahuas, were in Hardy-Weinberg equilibrium, while Mestizos were in disequilibrium (chi 2 = 0.399; P < 0.05). The Mazatecan Indians presented a high frequency of BB homozygosity (17.35%) compared to Mestizos (5%) (P = 0.01). Mexican ethnic groups present differences in distribution of BB genotype. The low frequency of BB genotype in Mestizos may be the result of a negative selection process.

Azygous lobe presenting as a posterior mediastinal mass in a 2-year-old boy.

Posterior mediastinal masses encompass a varied group of surgical lesions that include malignant diseases as well as the anatomic malformations of four organ systems. The authors report on a 2-year-old child with a posterior mediastinal mass who was found at thoracotomy to have a chronically infected "hepatized" azygous lobe of the right lung. The authors review current literature on this topic as well as the embryogenesis of azygous lobes.

Intron 2 and exon 3 sequences may be involved in the susceptibility to develop Takayasu arteritis.

We studied Major Histocompatibility Complex (MHC) Class I and Class II genes in seven Mexican Mestizo patients with Takayasu arteritis. Takayasu arteritis is an uncommon condition in Mexican Mestizo, however, previous studies report association of the disease in this population with Human Leukocyte Antigen (HLA)-B39 and HLA-DRB1*1301. The results in the present study show that the haplotypes of the Mexican Mestizo patients with Takayasu arteritis are very heterogeneous, even when the disease is much more rare in Mexico than in Japan. The sequence analysis of HLA-B39 shows that Mexican patients exhibit the HLA-B*39061 and HLA-B*39062 subtypes. These subtypes are more common in Mexico than in Japan, where the predominant subtype is HLA-B*3901. Interestingly, HLA-B*39061 and B-39062 share the 3' end of intron 2 and the 5' end of exon 3 with HLA-B*5101 and B*52012, alleles associated to Takayasu arteritis in Japanese. This fact suggests that Takayasu arteritis patients may share a specific sequence rather than a specific allele, even when the gene involved in the susceptibility to develop Takayasu arteritis may be a neighboring gene located between the genes related at present time with the disease, i.e. a gene located between MHC Class I and Class II regions.

Leptomeningeal metastasis from a paraspinal rhabdomyosarcoma with a der(13)t(1;13)(q23;q32) in a 14-month-old boy.

Cytogenetic analysis performed on a 14-month-old boy with a primary retroperitoneal/paraspinal alveolar rhabdomyosarcoma showed the presence of a der(13)t(1;13)(q23;q32) resulting in partial trisomy of the 1q23-->qter region and loss of the 13q32-->qter region. The present case is discussed with reference to a similar case reported in the literature.

Gastroduodenal disorders associated with emesis in infants.

Emesis is a common occurrence in newborns and infants. The causes are ubiquitous and unfortunately nonspecific. However, clues exist with respect to the timing of the onset of emesis as well as to its character. Emesis can be bilious or nonbilious, projectile or nonprojectile, and in some patients it is effortless. Newborns and infants with emesis of gastric origin may display a paucity of visible external signs. Ultrasound, contrast radiographic studies, and endoscopy coupled with physical examination are invaluable in the assessment of the emesis. Important in the management is prompt correction of fluid and electrolyte losses. Surgical correction, if warranted, can then be undertaken with significant lessening of morbidity.

Familial Hirschsprung's disease: study of a Texas cohort.

OBJECTIVE: To better define the types of transmission of Hirschsprung's disease (HD) in order to allow for earlier diagnosis and treatment and reduction of attendant morbidity. METHODS: A proband with HD was identified. A detailed family history was obtained and a 54-member, five-generation family pedigree constructed and analyzed. RESULTS: Six members of the kindred presented with classic biopsy-proven HD. Two of the six members were a pair of dizygotic twins. Three additional members had symptoms reminiscent of HD or HD variant (neuronal intestinal dysplasia) and were managed nonoperatively. There was one death related to HD. Hirschsprung's disease was manifested in offspring of both affected parent(s) and unaffected parents. Symptom manifestation was noted to skip generations. CONCLUSIONS: Analysis of this kindred lends strong evidence to the possibility of autosomal dominant inheritance. This inheritance has a variable penetrance (expression) that may be a factor of mutation or of a spectrum of the disease, ie a type of neural crestopathy. Kindreds of this sort need to be identified to allow for a complete data collection and understanding of the vagaries of HD transmission. This detailed documentation will allow for earlier diagnosis and effective treatment and possible gene localization of the specific defect.

A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10.

Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.

Observations of a pediatric surgeon in the Persian Gulf War.

In Third-World countries, infectious disease is the principal cause of childhood death and disability. During the Persian Gulf War trauma became the leading cause of death in children, prompting this review of experience with the delivery of pediatric trauma care to noncombatant children at a military hospital. Eight hundred seventy-seven patients were admitted to the 410th Evacuation Hospital from January to April 1991. Fifty of the patients (6%) were children, and 40 of the 50 were admitted for trauma. The mean age of the children was 9 years. Sixty-five percent of pediatric patients sustained penetrating injuries; mechanisms of injury included shrapnel wounds, gunshot wounds, burns, motor vehicle accidents, crush injuries, and falls. The overall mortality rate for children admitted to the hospital was 12%, but no injured child died as a result of trauma. Complications of dehydration or malnutrition in infants accounted for all the deaths.

Steroid therapy and duodenal ulcer in infants.

Two infants with acute life-threatening complications of duodenal ulcer following steroid administration are described. Although the possible association between steroid therapy and peptic ulcer disease is well known, the need for ulcer prophylaxis during such therapy in infants is not unanimously accepted. The case for ulcer prophylaxis in this setting is presented.

Arterial trauma of the upper extremity in children.

Thirty children with upper extremity arterial trauma were retrospectively reviewed. Trauma was penetrating in 87% of cases and in 53% injury was caused by broken plate glass. The injured artery was repaired in all but four cases. Nerves were injured in 53% and tendons in 23%. All severed nerves and tendons were repaired primarily. Postoperatively three children with proximal injuries had no palpable pulse in the affected extremity. One patient died of underlying disease and another required amputation during initial surgery due to extensive soft-tissue injury. Followup revealed no dysfunction directly related to vascular insufficiency. Neurologic deficit was found in 33% of the children followed, but only in one was the limb totally nonfunctional. We conclude that the long-term outcome is largely dependent upon neurologic injury. Glass doors and large glass windows should be avoided in the vicinity of children's play areas.

A technique for documenting central placement of long term catheters in neonates.

The aforementioned technique of confirmation of the central catheter has been used in the placement of 50 consecutive catheters placed through the greater saphenous venous approach. The drop test has proved to be positive in 49 of 50 insertions (98 per cent). The single false-positive result was obtained in a catheter with a hairpin bend at the tip. This technique has markedly decreased the amount of time required to place the catheter by avoiding multiple roentgenograms and the associated waiting time and reduces the increased cost of multiple roentgenograms.

Penetrating trauma to the buttock.

Penetrating trauma to the buttock is an injury with potential impact on multiple body systems. The purpose of this study was to review our experience with penetrating trauma to the buttock, to establish the frequency of system injury and related morbidity and mortality, and to make recommendations for the evaluation and management of these injuries. Among the 56 system injuries, soft tissue injuries predominated. Of the 25 operative procedures done, eight were for wound care and debridement and seven for rectal injuries; three were orthopedic, two vascular, three genitourinary, and one neurosurgical. One patient had examination under anesthesia, and one had laparotomy for missile trajectory. There were no deaths in this series. Morbidity consisted of nerve injury/defect in three patients, stroke in one patient, and impotence in one. An understanding of the systems at risk in penetrating buttock trauma is necessary for prompt multisystem work-up.