Norman Wolfish

Role of respiratory viruses in exacerbations of primary nephrotic syndrome

To determine whether respiratory virus infections (URI) are associated with exacerbation of nephrotic syndrome (NS) in childhood, a prospective two-winter study of 32 children with NS was done. We obtained pre- and post-season viral serologic studies, biweekly nose and throat viral cultures, daily urinalysis, biweekly telephone follow-up for URI and renal complaints, and clinical assessments as indicated. When a URI occurred, viral cultures were done weekly if the child was at home and twice weekly if hospitalized. Sixty-one URIs occurred; the agent was identified in 33 (51.6%) (respiratory syncytial virus 14, influenza virus five, parainfluenza virus five, varicella zoster virus four, adenovirus three, Mycoplasma pneumoniae one, and Chlamydia trachomatis one). Forty-one exacerbations occurred, 71% with URI; 29% had no URI during the preceding 10 days (P less than 0.01). Total relapse occurred in 29 of 41 exacerbations, 69% with URI and 31% without URI (P less than 0.01). Patients with unstable NS had more exacerbations than those with stable NS (15 of 19 (79%) vs four of 13 (31%), P less than 0.001) and more URI (2.32 vs 1.46 per child, P less than 0.05). Exacerbations in patients with minimal change, mesangioproliferative, and focal glomerulosclerosis occurred in 40%, 60%, and 64%, respectively. We conclude that exacerbations and relapses of childhood NS are temporally related to URI. Inasmuch as multiple viral agents were associated with exacerbations, nonspecific host response to infection, not viral antigen or antibody response, may be the link to NS.

Reliability and validity of the objective structured clinical examination in paediatrics

Summary. The assessment of clinical competence has traditionally been carried out through standard evaluations such as multiple choice question and bedside oral examinations. The attributes which constitute clinical competence are multidimensional, and we have modified the objective structured clinical examination (OSCE) to measure these various competencies. We have evaluated the validity and reliability of the OSCE in a paediatric clinical clerkship. We divided the examination into the four components of competence (clinical skills, problem‐solving, knowledge, and patient management) and evaluated the performance of 77 fourth‐year medical students. The skill and content domains of the OSCE were carefully defined, agreed upon, sampled and reproduced. This qualitative evaluation of the examination was both adequate and appropriate. We achieved both acceptable interstation and intertask reliability. When correlated with concurrent methods of evaluation we found the OSCE to be an accurate measure of paediatric knowledge and patient management skills. The OSCE did not correlate, however, with traditional measures of clinical skills including history‐taking and physical examination. Our OSCE, as outlined, offers an objective means of identifying weaknesses and strengths in specific areas of clinical competence and is therefore an important addition to the traditional tools of evaluation.

Evaluation of renal scars by technetium-labeled dimercaptosuccinic acid scan, intravenous urography, and ultrasonography: A comparative study

The objective of our prospective study was to compare the sensitivity and specificity of ultrasonography, intravenous pyelography, and dimercaptosuccinic acid scan in detecting scarred kidneys. Twenty-seven consecutive subjects with recurrent urinary tract infections, vesicoureteral reflux, scarred kidneys, or a combination of these problems had all three imaging procedures performed. With the total number of scars serving as the gold standard, the sensitivity (94%) and specificity (100%) in identifying renal scars in children were highest for the DMSA scan. Intraobserver (95%) and interobserver (90%) reliability were also high for the DMSA scan. However, the clinical interpretation of the increased sensitivity of the DMSA scan is unknown. Changes on the scan not identified by intravenous urography may not represent true scars. Research into the long-term significance of these scars is indicated.

SLEEP/AROUSAL AND ENURESIS SUBTYPES

PURPOSE The mechanisms responsible for enuresis are maturational delays and the extent of the maturational lag equates with the severity of the clinical picture. MATERIALS AND METHODS A literature review was conducted comparing the similar mechanisms of bladder physiology in normal and children with enuresis. RESULTS Several mechanisms are associated with enuresis including nocturnal urine volume, nocturnal functional bladder capacity, spontaneous bladder contractions and the inability to arouse to the stimulus of a large and/or contracting bladder. There is adequate evidence for children with enuresis who demonstrate nocturnal spontaneous bladder contractions (detrusor dependent enuresis) and nocturnal polyuria (volume dependent enuresis). A recent study has shown that children with enuresis are difficult to arouse in the first two-thirds of the night, which is also associated with the period of greatest wetting frequency. Night dry children may demonstrate daytime frequency and urgency, others may have nocturia and others are difficult to arouse. Subtyping into volume dependent and detrusor dependent types may only describe specific entities of a larger array of clinical presentations. CONCLUSIONS It is proposed that the mechanisms responsible for enuresis are maturational delays and the extent of the maturational lag equates with the severity of the clinical picture. Included in this clinical spectrum are children who demonstrate diurnal incontinence and those with secondary enuresis. The former is a condition of maturational severity and the latter is a maturational change. The ability to arouse is fundamental to those who are continent.

Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its pathogenesis and mutations in inverted formin 2 (INF2) cause autosomal dominant FSGS. In order to delineate the role of INF2 mutations in familial and sporadic FSGS, we sought to identify variants in a large cohort of patients with FSGS. A secondary objective was to define an approach for genetic screening in families with autosomal dominant disease. A total of 248 individuals were identified with FSGS, of whom 31 had idiopathic disease. The remaining patients clustered into 64 families encompassing 15 from autosomal recessive and 49 from autosomal dominant kindreds. There were missense mutations in 8 of the 49 families with autosomal dominant disease. Three of the detected variants were novel and all mutations were confined to exon 4 of INF2, a regulatory region responsible for 90% of all changes reported in FSGS due to INF2 mutations. Thus, in our series, INF2 mutations were responsible for 16% of all cases of autosomal dominant FSGS, with these mutations clustered in exon 4. Hence, screening for these mutations may represent a rapid, non-invasive and cost-effective method for the diagnosis of autosomal dominant FSGS.

Sleep Arousal Function in Enuretic Males

Enuretic children are described as difficult to arouse from sleep. This paper reports on the clinical implications of auditory sleep arousal thresholds in 15 enuretic and 18 control subjects (7-12-year-old males). All children were studied in a sleep laboratory for four consecutive nights using standard polysomnographic recording techniques. Sleep was undisturbed for the first two nights and waking thresholds were measured on the following two nights. Enuretic children were found to wet most frequently in the first two-thirds of the night. Arousal attempts were successful in 39.7% of controls and 9.3% attempts were successful in enuretics. The results of this study suggest that enuretic males were more difficult to arouse than age-matched controls. The elevated arousal thresholds may have been the result of delayed maturation. Therefore, treatment programs that rely on awakening should be cognizant of these features.

The Canadian Enuresis Study and Evaluation--short- and long-term safety and efficacy of an oral desmopressin preparation.

Objective: To evaluate the long-term (12 months) efficacy and safety of oral desmopressin (DDAVP). Material and Methods: A total of 256 healthy children (6-18 years old) with nocturnal enuresis with a frequency of S 10 wet nights during a 4-week observation period were eligible for inclusion in the study. Initially 0.2 r mg of DDAVP was given for 14 nights. Those achieving a >90% reduction in the number of wet nights over the observation period (full responders) began a 12-week continuous treatment period at this dose. The remaining children received 0.4 r mg for an additional 14 nights. Those achieving a S 50% reduction in the number of wet nights (responders) commenced a 12-week continuous treatment period at this dose. Children with a <50% reduction in the number of wet nights at this point were withdrawn from the study. Each 12-week treatment period was followed by a treatment-free period of 7-28 days. Children who remained dry during that period were assigned a full response and terminated the trial. Children with S 2 wet nights during that period immediately began a new 12-week treatment period at the previous dose. This was repeated for 12 months and thereafter the medication dose was tapered by halving over a 4-week period. Results: A total of 117/236 children who completed the titration period (49.6%; 95% confidence interval 40-57%) responded (>50% reduction over baseline). Throughout the study their response rate remained constant at , 74%. Continuous treatment reduced the median number of wet nights during the observation period from 5.75 to 1.00 per week. A total of 12.4% of children received the 0.2 r mg dose and 87.6% the 0.4 r mg dose. The proportion of full responses increased over the course of the study from 5.8% to 37.5%. DDAVP was well tolerated: the majority of reported adverse events were mild, although two adverse events leading to withdrawal were reported. Conclusions: Oral DDAVP provides an effective and well-tolerated means of providing long-term control in children with nocturnal enuresis. Long-term treatment increases the response rate.

Familial urinary tract anomalies: association with the major histocompatibility complex in man.

Histocompatibility typing of a family with 15 members and a history of ureteropelvic junction stenosis and 4 families with 23 members and a history of vesicoureteral reflux revealed that these anomalies of the urinary tract may be hereditary and segregate with histocompatibility haplotype within a family. Thus, a close linkage of childhood reflux and ureteral stenosis with that of the major histocompatibility complex of man is suggested. If confirmed by further family studies it will place the gene(s) for vesicoureteral reflux and ureteral stenosis on the 6th pair of human chromosome and open the possibility of using histocompatibility typing as a marker for these anomalies within a family.

A study of a multi-source feedback system for international medical graduates holding defined licences

Objective  To develop and assess the feasibility and psychometric properties of multi‐source feedback questionnaires to monitor international medical graduates practising in Canada under ‘defined’ licences.

Idiopathic unilateral gross hematuria in the pediatric patient.

Microscopic hematuria is not an uncommon finding in the pediatric population. Since gross hematuria elicits parental and physician concern, its presence may result in extensive investigation. Unilateral hematuria is an unusual feature of gross hematuria, particularly in the pediatric patient. Although a number of structural and pathologic entities have been described to account for the laterality, in the majority of instances no overt underlying process has been uncovered. Unilateral hematuria appears to be benign, idiopathic, and has a prognosis no different than other idiopathic hematurias in the pediatric age group.