Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

Patterns and prognosis ofClostridium difficile colitis

The incidence of Clostridium difficile colitis has increased during recent years, presumably because of liberal use of broad-spectrum antibiotic regimens. METHODS: A retrospective review to determine patterns of C. difficile colitis development, morbidity, and treatment results was undertaken. During an 18-month period, 90 patients were diagnosed with C. difficile colitis by fecal toxin assays. Patient demographics, symptoms, previously administered antibiotic regimens, diagnostic evaluations, treatment modalities, morbidity, and mortality were identified, entered into a computer data base, and analyzed. RESULTS: The mean age was 58 years; males outnumbered females 1.21. Among 90 patients, 41 (46 percent) developed C. difficile colitis after surgical procedures. Eighty (89 percent) patients received antibiotic therapy before developing C. difficile colitis: 35 (44 percent) for documented infections and 45 (56 percent) as empiric or prophylactic therapy. Cephalosporins, penicillins, quinolones, vancomycin, and aminoglycosides were the most frequently administered antibiotic classes prior to C. difficile colitis diagnosis. Ten (11 percent) patients developed C. difficile colitis without previous antibiotic therapy. Eighty-two (91 percent) patients presented with diarrhea, while eight (9 percent) had fever only. Primary C. difficile colitis treatment for both groups included vancomycin (66 percent), metronidazole (24 percent), or both drugs (10 percent). Ten (11 percent) patients received no treatment. No patient developed toxic colitis or megacolon. Colonoscopy was performed in four (4 percent) patients; pseudomembranes were identified in one (25 percent) patient. There was one C. difficile colitis recurrence after treatment, but no C. difficile colitis-associated morbidity. Mortality (14 patients, 16 percent) was not related to C. difficile colitis, but to underlying illness. No difference in patient age, sex, previous antibiotic administration, serum albumin, total days hospitalized, duration of C. difficile colitis antibiotic therapy,C. difficile colitis treatment regimens, or mortality was identified between nonsurgical and surgical patients. The white blood cell count was significantly lower in the nonsurgical group however.Clostridium difficile colitis developed most commonly after antibiotic administration with symptoms of diarrhea, but did occur without previous antibiotic administration or diarrhea. CONCLUSION: Despite the clinical setting,C. difficile colitis had no associated morbidity and treatment was highly effective. Mortality was related to underlying medical illness, not C. difficile colitis.Read at the meeting of The American Society of Colon and Rectal Surgery, Chicago, Illinois, May 2 to 7, 1993.     

Levels of messenger-RNA coding for DNA topoisomerase-ii isoforms do not correlate with in-vitro drug-sensitivity

The relationship between cellular levels of mRNA coding for DNA topoisomerase II, both the alpha and beta isoforms, and in vitro sensitivity to anticancer drugs were evaluated. Using a sensitive RNA-polymerase chain reaction technique, the levels of mRNA coding for the alpha and beta isoforms of topoisomerase II were estimated relative to beta-actin mRNA. A relatively narrow range of expression was observed across a broad range of approximately 60 human tumor cell lines representing eight major histological types which have been characterized in detail with respect to their in vitro sensitivity to standard anticancer drugs. No significant correlations were observed between mRNA level and cellular response to drugs thought to inhibit topoisomerase II or any of the other drugs studied. These results suggest that predictive tests for response to topoisomerase II-related drugs can not be based on estimation of levels of mRNA.     

Selective epileptic gait disorder.

Two children with an unusual gait disorder, one combined with acquired aphasia, in association with focal epilepsy are reported. Both children also showed paroxysmal "dystonic" phenomena, and a clear therapeutic response to corticosteroids. This newly described condition widens the range of discrete, recoverable defects of cerebral function that are associated with epilepsy in the developing nervous system and suggests that the site of action is at a functionally combined bilateral motor/sensory level of the cerebral cortex.     

Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy

BACKGROUND: Haemophilus aphrophilus is a rare cause of ocular infection. It has been reported once as a cause of late-onset endophthalmitis in a patient with an inadvertent bleb after cataract surgery. We present a case of Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy. METHODS: A 56-year-old woman presented with a bleb infection 10 weeks after a mitomycin C augmented trabeculectomy at a University tertiary referral practice of one of the authors (GET). The causative organism was Haemophilus aphrophilus, identified by the Toronto Public Health Laboratory, Ontario, Canada. RESULTS: The bleb infection resolved following topical, subconjunctival and intravenous antibiotic therapy. A formal bleb revision was required to repair a persistent bleb leak. CONCLUSION: Patients who have had trabeculectomies augmented with mitomycin C may be predisposed to bleb infection with unusual organisms. Prompt diagnosis and treatment is necessary to control the infection. Increased awareness and communication with laboratory personnel may increase the isolation of this fastidious organism.     

Dissecting Obesogenic Environments: The Development and Application of a Framework for Identifying and Prioritizing Environmental Interventions for Obesity

Background. The “obesogenicity” of modern environments is fueling the obesity pandemic. We describe a framework, known as ANGELO (analysis grid for environments linked to obesity), which is a conceptual model for understanding the obesogenicity of environments and a practical tool for prioritizing environmental elements for research and intervention.Methods: Development of the ANGELO framework. The basic framework is a 2 × 4 grid which dissects the environment into environmental size (micro and macro) by type: physical (what is available), economic (what are the costs), political (what are the “rules”), and sociocultural (what are the attitudes and beliefs). Within this grid, the elements which influence food intake and physical activity are characterized as obe sogenic or “leptogenic” (promoting leanness).Results: Application of the ANGELO framework. The ANGELO framework has been piloted at the population level (island communities) to prioritize the settings/sectors for intervention and at the setting level (fast food outlets) to prioritize research needs and interventions. Environmental elements were prioritized by rating their validity (evidence of impact), relevance (to the local context), and potential changeability.Conclusions. The ANGELO framework appears to be a flexible and robust instrument for the needs analysis and problem identification stages of reducing the obe sogenicity of modern environments.     

Recreational bicycling and injury to the external iliac artery

Because the bony girdle of the pelvis protects the external iliac artery except where it enters the femoral canal, reports of blunt injury to this artery are rare. Emphasizing the importance of a thorough physical examination and judicious use of angiography, this case study discusses the diagnosis and treatment of an isolated external iliac artery injury rendered by a bicycle handlebar, a previously unreported cause of this type of injury.     

Altered bladder function in transgenic mice expressing rat elastin

The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.     

Trends in prenatal diagnosis of Down syndrome and other autosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemiological findings

The present report summarizes findings on 670 cases of autosomal trisomy diagnosed in Scotland, with actual or expected dates of delivery in 1990 to 1994 inclusive. Cases were notified by cytogenetic service laboratories. There were 277 prenatal and 369 postnatal diagnoses and 24 spontaneous losses. Excluding the latter, numbers diagnosed with trisomy 21, trisomy 18, trisomy 13, and other trisomies were, respectively, 470 (72.8%), 108 (16.7%), 36 (5.6%), and 32 (5.0%). Estimated maternal age-specific birth rates for trisomy 21 were close to published values from other jurisdictions. However, comparisons with a clinically based national register of congenital anomalies suggested that 3-4% of Down syndrome births were never karyotyped, most being early neonatal deaths. There was a striking increase over the period in the proportion of cases detected prenatally, associated with increased maternal serum screening in mothers <35 years old. Over the 3 final years (1992-1994), prenatal screening followed by elective termination was estimated to reduce the birth rate in trisomy 21 by 24% in mothers aged <35 years, by 57% in older mothers, and by 35% in all mothers. The crude incidence per 1,000 births fell from 1.08 in 1990-1991 to 0.77 in 1992-1994, in spite of an upward shift in the overall maternal age distribution. For trisomies 18 and 13, the estimated overall reductions in the birth rate over the whole 5-year period were respectively, 26 and 17%. In free trisomy 18, there was a significant reduction in the sex ratio (male/female) to 0.65, in line with earlier studies.