Clinical and genetic complexity of Mitchell-Riley/Martinez-Frias syndrome.

Mitchell-Riley syndrome/Martinez-Frias syndrome (MRS/MFS) is a rare, autosomal recessive disorder with multisystem involvement and poor prognosis. Most reported cases have been associated with homozygous or compound heterozygous mutations in the RFX6 gene, a transcriptional regulatory factor for pancreatic morphogenesis. Given the limited number of reported cases, the syndrome may be under-recognized. When the particular phenotype of MFS includes a mutation on the RFX6 gene and neonatal diabetes, it has been called Mitchell-Riley syndrome. Because of this, we propose that MFS/MRS is a symptom continuum or an RFX6 malformation complex. We report an infant with all of the key clinical features of MRS/MFS without a definable mutation in RFX6 gene, supporting the consideration of these features as a symptom complex, and raising the question of genetic heterogeneity.

Retrospective study of 24 cases of septic calcaneal bursitis in the horse.

REASONS FOR PERFORMING STUDY: Wounds to the plantar aspect of the tarsus present a diagnostic and treatment challenge. This study was undertaken to describe specific features of traumatic wounds involving the calcaneal bursa, with a view to determining which clinical examination findings and diagnostic tests results could provide reliable indicators of prognosis. OBJECTIVES: To report clinical presentation, diagnostic findings, treatment and outcome of 24 cases of septic calcaneal bursitis; and to determine the importance of the involvement of specific anatomical structures in relation to the prognosis for survival and return to athletic function. METHODS: Records of 24 horses that had suffered traumatic wounds involving the calcaneal bursae were reviewed and divided into 3 groups, based on the bursa involved and presence or absence of involvement of the tuber calcanei. Clinical, diagnostic imaging and surgical findings were recorded for each case. Differences between groups and outcome were examined for significance with Chi-squared, Fisher's Exact or Kruskal-Wallis tests, as appropriate. RESULTS: Wounds involving only the subcutaneous bursa had an excellent prognosis for survival. Seventy-five percent of horses with wounds involving the intertendinous calcaneal bursa survived. Involvement of the tuber calcanei presented a fair to guarded prognosis, with only 44% of horses with involvement of this structure surviving. CONCLUSIONS: In contrast to other studies of septic synovial structures, the time between initial injury and referral did not affect the outcome. Correct identification of invasion of the calcaneal bursa(e) and/or tuber calcanei in wounds to the plantar aspect of the tarsus allows for more accurate pronostication. Damage to the tuber calcanei presents a poorer prognosis than for cases that involve only the soft tissue structures in the region. POTENTIAL RELEVANCE: This study demonstrates the importance of correct anatomical identification of structures involved in wounds in the region of the calcaneal bursa. The use of radiography, ultrasonography and synoviocentesis are essential in these cases to provide the most appropriate treatment for the horse and accurate prognosis for the owner.

Fructosamine levels demonstrate improved glycemic control for some children attending a diabetes summer camp.

Residential summer camps for youths with diabetes may have a positive effect on glycemic control. Hemoglobin A1c (HbA1c) is considered the best measure of control, but it reflects too long a period to evaluate a camp session. The fructosamine test reflects control over a period of 2-3 wk and may be ideal for this purpose. A portable device was used to examine the relationship between 2 wk of glycemic control and the change in fructosamine in order to determine whether control improved at camp. Thirty children, 8-12 yr old, were studied during a 2-wk session of a diabetes summer camp. Pre-camp HbA1c levels were obtained from the childrens' physicians. Each camper measured his/her blood glucose four times daily. Insulin doses were readjusted frequently by camp physicians. Each child's fructosamine was measured at the beginning and end of camp. The baseline fructosamine correlated with HbA1c. The final fructosamine correlated with the 2-wk mean glucose. The subgroup who started camp in below average glycemic control improved their fructosamine levels by the end of camp. Those who started camp in better control did not change. Without continuous glucose monitoring, it is impossible to accurately determine how well fructosamine reflects glucose levels. In this study, fructosamine correlated with the mean glucoses and with an HbA1c obtained prior to camp. Fructosamine appears to be a valid measure of glycemic control and being at camp was at least transiently beneficial to the children who needed it most.

Thyroxine screening values in premature infants.

OBJECTIVES: Premature infants often have low thyroxine levels when compared to fullterm infants. We sought to determine gestational age specific normal ranges for thyroxine screening results for premature infants in neonatal intensive care units. METHODS: Thyroid screening results for infants less than 38 weeks gestation admitted to two NICUs were examined. For each sample the thyroxine Z-score was computed using parameters from fullterm infants. The mean thyroxine Z-score was calculated for each gestational age for days of life 1, 2, 3-7, 8-14, 15-21, 22-28, and 29-60. RESULTS: There were 1144 specimens obtained from 543 premature infants. The mean thyroxine Z-score was below 0 for almost every gestational age and days-of-life category. The mean thyroxine Z-score increased with gestational age, but did not rise with increasing postpartum age. CONCLUSION: The data show that normal thyroxine Z-scores for premature infants are lower than for fullterm infants and remain low at least as long as the infants remain ill.

Thyroid screening for early discharged infants.

OBJECTIVE: As neonatal discharge before 24 hours of life becomes commonplace, the rejection of congenital hypothyroidism (CH) screening specimens obtained too early has created the need for numerous additional tests. We sought to determine whether the specimens obtained before 24 hours could be used safely. METHODS: During a 31-day period we measured thyrotropin in all thyroid-screening specimens that had been obtained before 24 hours. We also examined the early specimens from every infant diagnosed in New Jersey with CH during 1993 or 1994. RESULTS: Among the 663 specimens, those obtained at or before 12 hours and those from infants with birth weights less than 2500 g had too many low thyroxine results to be useful. Among the 515 specimens obtained at more than 12 to 24 hours from newborns weighing 2500 g or more, 37 (7%) had low thyroxine levels and 12 (2.3%) had thyrotropin levels of 20 microIU/mL (mU/L) or higher. Four hundred seventy-one of the 515 infants had subsequent specimens obtained at more than 24 hours, and none of the results were abnormal. There was no child weighing more than or equal to 2500 g who was diagnosed with CH in 1993 and 1994 whose specimen obtained at 24 hours or less was normal. CONCLUSIONS: Accepting specimens obtained at more than 12 to 24 hours from infants weighing 2500 g or more would have resulted in more than the usual number of false-positive results but no false-negative results. This would have decreased the requests for additional specimens by more than 90%.

Olfactory performance during childhood. I. Development of an odorant identification test for children.

Because there has been no suitable diagnostic instrument for evaluation of olfaction in children, we designed an odorant identification test for that purpose. We screened 40 microencapsulated odorants ("scratch 'n' sniff" cards) by randomly grouping them into 40 overlapping sets of five odorants each. Forty-one children, 4 and 5 years of age, tried to identify each test odorant, selecting their responses from among five photographs depicting the substances in the set of odorants. We used the results to select a subset of five odorants (baby powder, bubble gum, candy cane, fish, and orange). To determine how well these odorants could be identified by normal children, we tested another 134 subjects, 3 1/2 to 13 years of age. For children 3 1/2 years to 5 years 4 months of age, the mean (+/- SEM) percentage of correct responses increased from 66% +/- 8% to 92% +/- 2%. Thereafter the mean percentage of correct responses remained at a plateau of about 90%. The 10th percentile for the percentage of correct responses tended to be higher for girls than for boys throughout childhood. We concluded that this set of five odorants can be correctly identified by most normal children 5 years of age or older. The performances of three older subjects with Kallmann syndrome were all subnormal, but the overall efficacy of the test for evaluating children with olfactory deficits needs to be determined.

Olfactory deficits in boys with cleft palate.

An odor identification task was used to determine whether individuals with cleft palate (with or without cleft lip) also have an increased prevalence of olfactory deficits. Olfactory responses of 35 affected subjects (7 to 22 years of age) were compared with those of 68 subjects of comparable age without cleft palates. Subjects were requested to identify the smell of ten common household odors. They selected their responses from an alphabetized list of the test odorants. After a practice trial, the set of odorants was presented five times in randomized sequences. The percentage of correct responses increased with age for prepubertal and pubertal subjects without cleft palates. Although the olfactory scores of girls without cleft palates continued to increase after puberty, this trend was absent in boys. On the average, the girls with cleft palates, compared with only three of 34 boys without cleft palates, had olfactory scores less than 60% correct. There was no evidence of heterogeneity in the magnitude or direction of the relationship between any of the subtypes of cleft palate and olfactory dysfunction. In this study, cleft palate is more strongly associated with olfactory deficits in boys than in girls, suggesting the possibility that the deficit may be a sex-influenced trait.

An analysis of 248 initial mobilization tests performed on an ambulatory basis.

Data are presented on 248 initial mobilization tests performed in an ambulatory setting over an 11-year period. Results demonstrate that there is no single, consistent predictor of body burden of lead, although the higher the blood lead level, the greater the amount of excretable (mobilizable) lead. It is recommended that an appropriate ratio of lead excreted in response to chelant is equal to or greater than 0.5 based on this series of tests. A recommendation is also made to realign the Centers for Disease Control (Atlanta) guidelines for classification of risk. This realignment would coincide with a recommendation that mobilization tests be reserved for children whose blood lead levels ranged from 1.93 to 2.57 mumol/L (40 to 60 micrograms/dL). Those with higher levels would undergo chelation without prior mobilization studies.

Association of arterial hypertension with poor outcome in children with acute brain injury.

We studied intensive care unit (ICU) records of 42 comatose children with acute brain injuries to define the relationship between high arterial blood pressure and poor neurologic recovery. Diagnoses included head trauma, anoxia, Reye's syndrome, and central nervous system infection. The highest systolic blood pressure in all 42 patients exceeded the 95th percentile. In those whose highest systolic pressure exceeded 95th percentile by more than 20 torr, severe neurologic deficit or death occurred in 19 of 34 (56%), while in those with milder hypertension, poor outcome occurred in only one of eight (13%, p = 0.0316). Of those with high blood pressure persisting until ICU discharge, 14 of 19 (74%) had poor outcome, while those with blood pressure normalizing prior to ICU discharge had poor outcome in only six of 23 (26%, p = 0.0026). High blood pressure was not usually a reflex effect of elevated intracranial pressure. This finding suggests that measures to control high blood pressure are indicated in the management of the acutely brain-damaged child.

Currently available shunt systems: a review.

Many different types of shunt equipment have become available as shunting procedures have become commonplace. Variations among different systems can be subtle, and the choice between them is somewhat arbitrary. The author reviews some of the devices currently in use for the purposes of clarification and comparison.

Abnormalities of thyroid function in infants with Down syndrome.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

Desmopressin response of enuretic children. Effects of age and frequency of enuresis.

To characterize the children with enuresis likely to respond to desmopressin acetate, we performed a double-blind crossover study that included the use of a placebo. During the two weeks of desmopressin administration, six children (12%) had 13 or 14 dry nights, and 15 children (29%) had eight to 12 dry nights. Among the 17 children aged 9 years or older, with four to seven dry nights during the two-week baseline period, 12 children (71%) responded to desmopressin (eight to 14 dry nights). In contrast, none of the 15 children younger than 9 years of age with fewer than three dry nights before therapy responded. During the posttreatment period, only four of the 21 drug responders reported a persistent effect. Desmopressin may be effective in reducing the frequency of enuresis, especially in children older than 9 years of age without nightly enuresis.

Psychosocial aspects of constitutional short stature: social competence, behavior problems, self-esteem, and family functioning.

To determine the psychosocial effects of short stature, we administered a battery of psychologic tests to 24 children (ages 6 to 12 years) with constitutional short stature. Their results were compared to those of a group of 23 healthy children with normal stature matched for age, IQ, sex, and socioeconomic status. The short children had significantly higher scores on parental ratings of behavioral difficulties, especially somatic complaints, social withdrawal, and schizoidal tendencies. There were also indications of impaired self-concept as expressed by feelings of unpopularity and dissatisfaction. Parental responses suggested a tendency to set less clear limits on behavior, but not necessarily toward overprotectiveness. Parents of short children also gave responses indicating poorer communication and cooperation among family members. In contrast to recent studies of growth hormone-deficient children, in which no maladjustment surfaced, these results indicate that children with constitutional delay have characteristic behavioral difficulties.

"Subacute" postoperative subdural empyema.

Although subdural empyema (SDE) has long been a recognized postoperative complication, little has been written to suggest that SDE's following operative procedures are different from those occurring in patients who have not had previous surgery. Four cases of postoperative SDE are reported which seem to have several distinguishing features and are grouped under the title of "subacute" subdural empyemas. These include: occurrence in a previous craniotomy site, a prolonged course, the insidious onset of symptoms, and the absence of signs of constitutional illness. The presence of an inner subdural membrane which limits the size of the empyema and separates it from the underlying brain is thought to be the reason for the relatively benign nature of the presenting symptoms and the extremely good prognosis. Computerized tomography scanning was not able to provide a preoperative diagnosis of empyema in any case.

Simplifying the diagnosis of diabetes insipidus in children.

We simplified the procedures for identifying children with diabetes insipidus by using the relationship between urine and plasma osmolality (Uosm and Posm). We defined the normal Uosm-Posm relationship as the area within the 95% confidence regions for pairs of osmolality measurements obtained from normal children during periods of free access to fluids and after oral hydration. In 13 patients with diabetes insipidus, Uosm-Posm coordinates were outside these regions in 50 of 64 pairs (one to ten per patient) during periods of free access to fluids. After three hours of fluid deprivation, the Uosm-Posm relationship was abnormal in 12 patients; the 13th was unable to void. For those with a normal Posm, and Uosm less than Posm, another pair of osmolality measurements after three hours of fluid restriction should determine the diagnosis.