The diagnostic utility of a genetics evaluation in children with pervasive developmental disorders.

PURPOSE: A genetics evaluation of children with pervasive developmental disorders (PDDs) identifies a diagnosis in 6% to 15% of cases. However, previous studies have not measured the incidence of genetic disorders among children with autistic-like features who do not necessarily meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria for PDD. METHODS: We identified 101 patients at our institution referred for PDD, autism, Asperger syndrome, or autistic features. Seventy-eight were males and 23 were females, giving a male-to-female ratio of 3.4:1. No diagnosis was identified on examination alone, although Rett syndrome was suspected in six females. Seventeen patients did not undergo any type of testing because of noncompliance. RESULTS: Of the remaining 84 patients analyzed, seven (8.3%) were found to have abnormalities on testing. Three chromosomal anomalies were found: one with 5p duplication, one with low-level mosaicism for trisomy 21, and one with an unbalanced 10;22 translocation. Three females were diagnosed with Rett syndrome after MECP2 analysis identified a disease-causing mutation. The remaining patient was found to have an elevated urine orotic acid, with a normal ammonia level, of unknown significance. CONCLUSION: On the basis of our series, the yield of a genetics evaluation in patients with features of PDD who do not necessarily meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria is 8.3%. Approximately half of these were the result of a chromosomal abnormality. Three cases of Rett syndrome were identified for which autistic behaviors are a well-described feature. These findings suggest that a high-resolution karyotype provides the greatest diagnostic yield for patients with autistic-like features. MECP2 analysis should be considered for females who present with autistic behaviors.     

Presence and characterization of extraintestinal pathogenic Escherichia coli virulence genes in F165-positive E. coli strains isolated from diseased calves and pigs

The virulence genotype profile and presence of a pathogenicity island(s) (PAI) were studied in 18 strains of F165-positive Escherichia coli originally isolated from diseased calves or piglets. On the basis of their adhesion phenotypes and genotypes, these extraintestinal pathogenic strains were classified into three groups. The F165 fimbrial complex consists of at least two serologically and genetically distinct fimbriae: F165(1) and F165(2). F165(1) is encoded by the foo operon (pap-like), and F165(2) is encoded by fot (sfa related). Strains in group 1 were foo and fot positive, strains in group 2 were foo and afa positive, and strains in group 3 were foo positive only. The strains were tested for the presence of virulence genes found mainly in extraintestinal pathogenic E. coli (ExPEC) strains. Although all the strains were positive for the papA variant encoding F11 fimbriae incD, traT, and papC, the prevalence of virulence genes commonly found in PAIs associated with ExPEC strains was highly variable, with strains of group 2 harboring most of the virulence genes tested. papG allele III was detected in all strains in group 1 and in one strain in group 3. All other strains were negative for the known alleles encoding PapG adhesins. The association of virulence genes with tRNA genes was characterized in these strains by using pulsed-field gel electrophoresis and DNA hybridization. The insertion site of the foo operon was found at the pheU tRNA locus in 16 of the 18 strains and at the selC tRNA locus in the other 2 strains. Furthermore, 8 of the 18 strains harbored a high-pathogenicity island which was inserted in either the asnT or the asnV/U tRNA locus. These results suggest the presence of one or more PAIs in septicemic strains from animals and the association of the foo operon with at least one of these islands. F165-positive strains share certain virulence traits with ExPEC, and most of them are pathogenic in piglets, as tested in experimental infections.     

Local versus regional cerebral blood flow in the rat at high (hypoxia) and low (phenobarbital anesthesia) flow rates.

Local cerebral blood flow (CBF) was measured in rats, using an autoradiographic technique with 14C-iodoantipyrine as diffusible tracer, in situations with low, normal and high flow rates (phenobarbital anesthesia, analgesia with 75% N2O, and hypoxia, respectively). A comparison of the results with previous data obtained in conscious rats (Sakurada et al. 1978) demonstrates that 75% N2O moderately reduces local CBF in some, but not all, cortical and subcortical areas, that phenobarbital anesthesia reduces local CBF to between 30 and 65% of (conscious) control, and that pronounced hypoxia (arterial P02 about 25 mmHg) increases local CBF 3- to 4-fold. A comparison of the values obtained for cortical structures with those previously measured with a technique based on the Fick principle shows that the autoradiographic technique gives similar values at low and normal flow rates but that it moderately underestimates CBF at high flow rates, probably due to diffusion limitation.     

Selective isolation and rapid identification of Clostridium botulinum types A and B by toxin detection.

A simple procedure for rapid identification of Clostridium botulinum type A and B colonies from cultures and stool samples from infants with botulism was devised. The stool samples were directly streaked on C. botulinum isolation medium containing selective inhibitory agents. Typical lipase-positive colonies that appeared within 24 to 48 h were examined for the presence of botulinal toxin by the enzyme-linked immunosorbent assay and conventional mouse toxicity test. The amount of toxin associated with 48-h colonies of stock strains was comparable to that of 96-h broth culture. The quantity of toxin present in a single colony or combination of two was shown to be sufficient for toxin detection by the enzyme-linked immunosorbent assay. Of 42 additional stock strains tested in this manner, 41 (97.5%) were identified as toxigenic C. botulinum type A or B. The remaining one strain also proved to be toxigenic when it was tested as a concentrated cell suspension. This procedure should prove useful for large-scale serological screening of food and clinical specimens.     

Identification of an inducible bacteriophage in a virulent strain of Streptococcus suis serotype 2

Streptococcus suis infection is considered to be a major problem in the swine industry worldwide. Most virulent Canadian isolates of S. suis serotype 2 do not produce the known virulence markers for this pathogen. PCR-based subtraction hybridization was adapted to isolate unique DNA sequences which were specific to virulent strains of S. suis isolated in Canada. Analysis of some subtracted DNA clones revealed significant homology with bacteriophages of gram-positive bacteria. An inducible phage (named Ss1) was observed in S. suis following the incubation of the virulent strain 89-999 with mitomycin C. Phage Ss1 has a long noncontractile tail and a small isometric nucleocapsid and is a member of the Siphoviridae family. Ss1 phage DNA appears to be present in most Canadian S. suis strains tested in this study, which were isolated from diseased pigs or had proven virulence in mouse or pig models. To our knowledge, this is the first report of the isolation of a phage in S. suis.     

Cultural and physiological characteristics and antimicrobial susceptibility of Clostridium botulinum isolates from foodborne and infant botulism cases.

Isolates Clostridium botulinum from foodborne and infant botulism cases in the United States were compared on the basis of toxigenicity, cultural and biochemical characteristics, metabolic products, and susceptibility to antimicrobial agents. Seventy-eight strains, including 42 from foodborne and 36 from infant botulism sources, were examined. Cultures on anaerobic blood agar exhibited circular, spindle, and rhizoid (medusa head) colonies. Overall, the characteristics of isolates from foodborne and infant botulism cases were quite similar. We concluded that it was not possible to differentiate C. botulinum isolates associated with foodborne botulism from those recovered from infant botulism cases. All of the 78 strains produced an unidentified indole derivative(s), detected with paradimethylaminocinnamaldehyde reagent, and hydrocinnamic acid, detected by gas-liquid chromatography; all exhibited a high degree of resistance to cycloserine, sulfamethoxazole, and trimethoprim. These characteristics should prove to be useful in the isolation and identification of C. botulinum from mixed microbial populations.     

Long-term bowel disorders following radial cystectomy: an underestimated issue?

Purpose

Patients after radical cystectomy (RC) frequently complain about bowel disorders (BDs). Reports addressing related long-term complications are sparse. This cross-sectional study assessed changes in bowel habits (BH) after RC.

Methods

A total of 89 patients with a minimum follow-up ≥1 year after surgery were evaluated with a questionnaire. Patients with BD prior to surgery were excluded. Symptoms such as diarrhea, constipation, bloating/flatulence, incomplete defecation, uncontrolled stool loss, and impact on quality of life (QoL) were assessed.

Results

A total of 46.1 % of patients reported changes in BH; however, only 25.8 % reported experiencing related dissatisfaction. Primary causes of dissatisfaction were diarrhea and uncontrolled stool loss. The most common complaints were bloating/flatulence and the feeling of incomplete defecation, but these symptoms did not necessarily lead to dissatisfaction or impairment in quality of life. No difference was identified between an orthotopic neobladder and ileal conduit, and even patients without bowel surgery were affected. QoL, health status, and energy level were significantly decreased in unsatisfied patients.

Conclusions

About 25 % of patients complain about BDs after RC. More prospective studies assessing symptoms, comorbidities, and dietary habits are necessary to address this issue and to identify strategies for follow-up recommendations.

     

Prolonged administration of infusional cisplatin and oral etoposide in advanced non-small cell lung cancer

We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and the efficacy of prolonged infusion of cisplatin and oral etoposide in the treatment of advanced non-small cell lung cancer (NSCLC). Cisplatin was given via an infuser in escalating doses of 5, 6.5, 8, 9 and 10 mg/m(2)/day for 14 days along with etoposide at a fixed dose of 50 mg/m(2)/day orally followed by a 2-week rest period. All patients had stage IIIB or IV NSCLC. A cisplatin dose of 8 mg/m(2)/day was determined as the MTD. In the 13 patients treated at this dose level, grade III and IV toxicities were mainly hematologic including neutropenia (n = 5), febrile neutropenia (n = 4), thrombocytopenia (n = 3) and anemia (n = 6). Grade III/IV renal toxicity occurred in one patient. There were no treatment-related deaths. One patient had a partial response and three patients had stable disease. Thus, although the described regimen of cisplatin/etoposide is reasonably well tolerated, it does not appear to be better than the same combination administered over a shorter duration, in spite of a cumulative dose of 112 mg/ m(2) of cisplatin and 700 mg/ m(2) of etoposide per cycle.