Biomedical subjects
Publications and source records attributed to J M Graham.
A unique interstitial deletion of the long arm of chromosome 6 involving bands q22.2 and q23.1 was observed in a patient referred for craniostenosis and developmental delay. The associated phenotypic anomalies are compared with other reported cases of deletion 6q involving adjacent regions.
The clinical findings of seven girls and one woman, 2 to 25 years of age, with Rett syndrome are presented. Previous diagnoses included Prader-Willi syndrome, Angleman syndrome, toxic reaction to pertussis vaccine, CNS dysgenesis, and encephalitis. Rett syndrome has a recognizable neurodevelopmental phenotype without a specific biologic marker, which makes the diagnosis difficult at times. Treatment is largely supportive, and an active parents' association has been helpful to many families.
Two groups of 4-year-old children were examined by a dysmorphologist without knowledge of previous examination results or prenatal exposure and categorized as to whether or not they showed fetal alcohol effects. A priori classification of children into the two groups was on the basis of their mothers' self-report of drinking when interviewed during pregnancy. Children born to 108 mothers in a "heavier" drinking group (absolute alcohol concentration greater than or equal to 30 mL/d [1.0 oz/d]) were compared with a matched group of children born to 97 mothers whose average absolute alcohol concentration was less than 0.3 mL/d (0.01 oz/d). The percentage of children with fetal alcohol effects in the heavier drinking v the comparison group was 20.4% v 9.3%. When fetal alcohol effects were studied in relation to only the absolute alcohol concentration scores, there was a significantly greater chance of a child being classified as having fetal alcohol effects with increasing levels of alcohol exposure prior to recognition of pregnancy (P = .013). A logistic regression, run on the absolute alcohol concentration scores and other primary exposures, indicated that fetal alcohol effects classification was not significantly related to nicotine, caffeine, or marijuana but was significantly related to absolute alcohol concentration scores even after statistically adjusting for these other exposures (P = .002). Classification of fetal alcohol effects at 4 years of age was compared to a fetal alcohol effects classification obtained at birth by an independent dysmorphologist in a sample of 75 subjects examined at both ages, and 80% of the infants classified as having fetal alcohol effects at birth were classified as having fetal alcohol effects at 4 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous studies of XXY boys suggest that they are at risk for certain communication disorders involving oral and written language. In this study, the language, reading, and spelling skills of a group of 14 XXY boys identified during neonatal cytogenetic screening were compared with those of a group of 15 control children. The two groups were matched for age, grade, race, parity, birth weight, parental age and education, and socioeconomic status. The mean age of the XXY group was 9 years 7 months and that of the control group was 9 years 3 months. The mean academic grade level for both groups was at the transition between third and fourth grade. There was selective reduction in verbal IQ scores for the XXY group and no significant differences apparent between groups for performance IQ scores. The decrease in verbal IQ was associated with a reduced full-scale IQ and also with significant problems in expressive language, auditory processing abilities, and auditory memory. Word-finding difficulties and problems in the production of syntax were major components of the specific expressive language deficit. Except for difficulties in the understanding of complex sentence structures, the receptive language skills of XXY boys did not differ significantly from those of the control group. These reductions in speech and language abilities correlated with decreased achievement by the XXY group on a variety of reading and spelling tasks. These results suggest that difficulty learning how to read and spell may be due to a preexistent language disability. Early attention to such expressive language problems may be essential to ameliorate secondary maladaptive behaviors due to chronic language-related learning disabilities.
We have demonstrated in vitro the efficacy of the taurine-conjugated dihydroxy bile salts deoxycholate and chenodeoxycholate in solubilizing both cholesterol and phospholipid from hamster liver bile-canalicular and contiguous membranes and from human erythrocyte membrane. On the other hand, the dihydroxy bile salt ursodeoxycholate and the trihydroxy bile salt cholate solubilize much less lipid. The lipid solubilization by the four bile salts correlated well with their hydrophobicity: glycochenodeoxycolate, which is more hydrophobic than the tauro derivative, also solubilized more lipid. All the dihydroxy bile salts have a threshold concentration above which lipid solubilization increases rapidly; this correlates approximately with the critical micellar concentration. The non-micelle-forming bile salt dehydrocholate solubilized no lipid at all up to 32 mM. All the dihydroxy bile acids are much more efficient at solubilizing phospholipid than cholesterol. Cholate does not show such a pronounced discrimination. Lipid solubilization by chenodeoxycholate was essentially complete within 1 min, whereas that by cholate was linear up to 5 min. Maximal lipid solubilization with chenodeoxycholate occurred at 8-12 mM; solubilization by cholate was linear up to 32 mM. Ursodeoxycholate was the only dihydroxy bile salt which was able to solubilize phospholipid (although not cholesterol) below the critical micellar concentration. This similarity between cholate and ursodeoxycholate may reflect their ability to form a more extensive liquid-crystal system. Membrane specificity was demonstrated only inasmuch as the lower the cholesterol/phospholipid ratio in the membrane, the greater the fractional solubilization of cholesterol by bile salts, i.e. the total amount of cholesterol solubilized depended only on the bile-salt concentration. On the other hand, the total amount of phospholipid solubilized decreased with increasing cholesterol/phospholipid ratio in the membrane.
We report on a developmental malformation of the lung and kidney which has not been previously described and which we have chosen to call "cystic hamartomata of the lung and kidney" to emphasize the non-malignant nature of these lesions. We also confirm a previous case report by Weinberg and Zumwalt [1977] as a different distinct disorder that results in a multifocal cystic hamartomata of the lung with associated marked parenchymal overgrowth of the kidney (the Weinberg-Zumwalt syndrome). These cases represent a spectrum of abnormal morphogenesis affecting both kidney and lung. Patients 1 and 2 presented during infancy with abdominal masses and hypertension due to bilateral multilocular cysts of the kidney with associated hamartomatous pulmonary cysts; patient 2 also had one area of cellular mesoblastic nephroma. Patient 3 demonstrated markedly hyperplastic renomegaly with medullary dysplasia in association with bilateral cystic hamartomata of the lungs. During the fifth week of gestation, the ureteric bud invades the unsegmented mesoderm that becomes the metanephric system, and the lung bud invades the splanchic mesoderm, which provides the stimulus for its growth. We suggest that the predominant pattern of a congenital kidney or lung hamartoma might reflect the timing of a prenatal neoplastic event affecting these developmental processes.
We report here an unusual recurrence of bilateral renal agenesis (BRA) in three consecutive siblings. Chromosome analysis was normal, as were renal ultrasound studies on both parents and their surviving child. Ultrasound was employed prenatally to diagnose Potter's syndrome in both of the recurrences, and autopsy confirmed BRA in otherwise normal fetuses. Recurrence of BRA points to the usefulness of ultrasound in monitoring subsequent pregnancies in couples who have had one such occurrence. Ultrasound studies should also be performed in non-affected family members to detect the presence of asymptomatic anomalies of the genitourinary system, but a negative family study does not preclude recurrence of BRA.
Markedly decreased fetal activity (akinesia/hypokinesia) is usually readily apparent to experienced mothers, and frequently this concern leads to attempts at prenatal diagnosis. We report prenatal diagnosis of two fetuses with congenital contractures, markedly decreased fetal movement, and microcephaly due to severe holoprosencephaly. Such familial recurrence to phenotypically normal parents suggests a newly recognized autosomal recessive or X-linked syndrome that is readily detectable by prenatal ultrasonography.
Thoracoabdominal and suprarenal aortic aneurysms may occur more frequently than originally thought. A review of our operative experience with aortic aneurysm during a 4 1/2 year period disclosed 17 (8 percent) aneurysms of the thoracoabdominal and suprarenal aorta. Acute rupture in five patients (29 percent) emphasizes the possible need for urgent treatment precluding transfer to a major university referral center. Nine patients (53 percent) had previously been operated on for aortic aneurysm, illustrating the systemic nature of aortic aneurysm disease and the need for lifelong follow-up. All patients survived, but paraplegia resulted in 2 patients (12 percent) with ruptured aneurysms. Pulmonary insufficiency was the major cause of postoperative morbidity. The high incidence of paraplegia reported for extensive chronic dissecting aneurysms has influenced our decision to postpone resection and carefully follow three additional patients with such lesions.
Six consecutive patients with acute aortic dissection involving the transverse aortic arch underwent surgical repair using profound hypothermia and circulatory arrest. All patients survived without neurological deficit. Postoperative angiographic evaluation has revealed complete resection or obliteration of patent false lumen within the aortic arch and ascending aorta in all patients. Use of this adjunct in the operative management of aortic arch dissection has allowed bloodless inspection and repair of extensive intimal tears, complete intimal adventitial reapproximation or resection, avoidance of clamp injury to fragile dissected aortic tissue, and assurance of patent arch-cerebral revascularization.
From 1969 to 1985, 129 patients with combined pancreatoduodenal injuries were treated at one urban trauma center. A total of 104 patients (80.6%) had penetrating wounds, and multiple visceral and vascular injuries were usually associated with the pancreatoduodenal injury. Primary repair or resection of one or both organs coupled with pyloric exclusion and gastrojejunostomy (68 patients) and drainage was used in 79 patients (61.2%) in the entire study and in 59% (36 of 61) of all patients treated since 1976. Simple primary repair of one or both organs and drainage was performed in 31 patients (24%), whereas the remaining 19 patients (14.8%) had pancreatoduodenectomies (13 patients) or no repair before exsanguination (six patients). Major pancreatoduodenal complications occurring in the 108 patients surviving more than 48 hours included pancreatic fistulas (25.9%), intra-abdominal abscess formation (16.6%), and duodenal fistulas (6.5%). The overall mortality rate for the study was 29.5% (38 of 129). The acute mortality rate with these injuries will remain high secondary to injuries to associated organs and vascular structures. The morbidity and late mortality rates related to the moderate to severe pancreatoduodenal injury itself can be decreased by the addition of pyloric exclusion and gastrojejunostomy to the primary repairs.
Fifteen patients with unstable pelvic fractures were treated with immediate anterior external fixation followed by delayed posterior fixation, including five sacroiliac lag screws, six transiliac rods, and four iliac plates. Initial anterior external fixation aided in resuscitation of hemodynamically unstable patients and allowed early mobilization. Delayed posterior internal fixation avoided infection and hemorrhage but failed to achieve anatomic reduction of disrupted sacroiliac joints and sacral fractures. Followup examination confirmed maintenance of fixation and fracture healing but pain and persistent neurologic deficits were common findings. Lumbosacral nerve plexus injuries occurred in patients with fractures through the sacral foramina. Fixation of these fractures with sacroiliac screws and transiliac rods caused overcompression and the resulting foraminal encroachment may be a factor in the lack of neurologic recovery. In this study, delayed posterior internal fixation was not associated with perioperative morbidity and achieved better reductions than those obtained with external fixation alone. Delaying the fixation, however, increased the difficulty of obtaining anatomic reduction of certain posterior arch disruptions.
Analysis of partial duplication of chromosome 21 suggests that band 21q22 contains determinants for the Down syndrome. We report two cases of free proximal trisomy 21 without manifestations of the Down syndrome. Phenotypic anomalies included marked microcephaly, short stature, hypoplastic nails, and mental retardation/developmental delay. Our cases are consistent with the assignment of band 21q22 as the causal duplicated segment in the Down syndrome.
Attempts to study the genetics of human thumb polydactyly have been hampered by lack of awareness of the extremely varied expression of upper limb preaxial anomalies. It has been appreciated that thumb polydactyly could range from a broadened distal phalanx to complete duplication of the entire thumb. Most cases are sporadic and unilateral, but rare familial cases with wide variability and occasional nonpenetrance have been described. Four unrelated families are described who have thumb polydactyly as part of the range of expression for a dominant gene that is frequently associated with absence of thenar intrinsic muscles and flexor pollicis longus with inability to flex the thumb across the palm (the Fromont anomaly). These families and previous literature reports suggest that expression of the gene can range from thumb hypoplasia (most commonly the Fromont anomaly) to triphalangeal thumb or thumb polydactyly. As a consequence of this experience, we urge that parents, siblings, and other close relatives of patients born with thumb polydactyly be carefully examined for mild degrees of thumb hypoplasia or any other thumb anomaly, and that these findings be considered when providing recurrence risk counseling.
A family is reported in which the mother and both of her children developed insulin-dependent diabetes mellitus between 9 and 19 months of age, reflecting the importance of heredity in the natural history of this disease. That overt complications of diabetes were not present in any of the individuals, and that blood sugars were maintained close to normal on relatively small amounts of exogenous insulin, suggests a protective function in these patients related to residual secretion of insulin by beta cells. Human lymphocyte antigen (HLA) typing in this family showed that, although the diabetic children had identical HLA types, neither the mother nor her children possessed the diabetes-associated antigen HLA-DR3 or HLA-DR4. This raises the possibility that selective loss of diabetes-susceptible fetuses (suggested to be responsible for the low risk of diabetic mothers producing diabetic offspring) may be influenced by the HLA type of the mother.
A case is reported of bilateral congenital popliteal aneurysms in a 10-year-old girl. Spontaneous thrombosis of the left aneurysm resulted in acute ischemia of the left leg below the knee, and the aneurysm was bypassed with an autogenous saphenous vein graft. Elective resection of the right aneurysm revealed fibromuscular dysplasia, of the medial hyperplasia type, as the cause of the aneurysm. One year after operation, the grafts remained patent, and the patient was asymptomatic.
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Mosaic trisomy 22, ascertained in three unrelated patients, was found to be associated with body asymmetry and signs of the Ullrich-Turner syndrome including short stature, ptosis, webbed neck, nevi, cubitus valgus, dysplastic nails, malformed great vessels, and abnormal ovaries. These anomalies in trisomy 22 mosaicism have not been emphasized heretofore. In each of our patients, trisomy 22 mosaicism was found only in fibroblasts. In one patient, the trisomy resulted from a paternal first meiotic nondisjunction, and in the 46,XX cells, both chromosomes 22 were of paternal origin.