Biomedical subjects
Publications and source records attributed to K Kozlowski.
We report on a 5(1/2) year-old Italian girl with a distinctive form of metaphyseal chondrodysplasia simulating cartilage hair hypoplasia. The pattern of metaphyseal changes and the associated bony abnormalities differentiate this patient from all the recognized forms of metaphyseal chondrodysplasia.
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A case of crippling osteoporosis with muscular weakness, hypophosphatemia, hyperparathyroidism, defective skeletal calcification and cartilage destruction is reported. The patient, a male was observed from the age of 2 1/2 until his death at the age of 33 years. This bone/cartilage disease failed to respond to phosphate supplementation, parathyroidectomy and calcitriol. We believe this may represent a hitherto undescribed entity.
We describe a sporadic case of lethal prenatal onset infantile cortical hyperostosis (Caffey disease), which resulted in early postnatal death at 30 weeks gestation. The mother presented with antepartum haemorrhage and preterm labour. She was found to have polyhydramnios. The infant showed extensive symmetrical diaphyseal subperiosteal cortical thickening throughout the skeleton with short extremities. Hepatomegaly and lung hypoplasia were present. Currently, in the absence of a specific marker, diagnostic ultrasound offers the only prospect of prenatal diagnosis. This diagnosis should be considered in infants with short angulated long bones, where the diaphyses are irregular and echodense, and where there is no sign of fractures.
Spondyloepipmetaphyseal dysplasias (SEMDS) are characterized by flattening of the vertebral bodies and epi-metaphyseal involvement of all the tubular bones. We report a 13 year-old boy with a novel variant of SEMD that presents with rhizomelic/mesomelic shortening of the extremities and normal head, hands and feet. Variable metaphyseal involvement and relatively large proximal humeral and knee epiphyses are further distinctive radiographic features in this patient.
The autosomal dominant disorders iris hypolasia (IH), iridogoniodysgenesis syndrome (IGDS) and Axenfeld-Rieger syndrome (ARS) are characterized by maldevelopment of the anterior segment of the eye associated with an increased risk of early-onset glaucoma. IH, IGDS and ARS are allelic disorders, as all three can result from mutations of the transcription factor PITX2. IH is the mildest of the three, whereas ARS exhibits the most severe ocular malformations. We hypothesize that varying amounts of residual PITX2 activity could underlie the severity of these phenotypes. Missense mutations of the PITX2 homeodomain identified in IH (Arg46Trp), IGDS (Arg31His) and ARS patients (Leu16Gln; Thr30Pro; Arg53Pro) were introduced into recombinant PITX2 cDNA by site-directed mutagenesis. PITX2 mutant proteins expressed in COS-7 cells were determined to be stable and localized to the nucleus; however, the Arg53Pro ARS mutant also displayed cytoplasmic staining. Our findings are consistent with the possibility of a novel nuclear localization signal (NLS) within helix 3 of the PITX2 homeodomain, homologous to the NLS of the related transcription factor PDX-1. Analysis of the five mutant PITX2 proteins by DNA-binding shifts and transactivation studies demonstrated reduced activity of the IH and IGDS mutant PITX2 proteins, with the IH mutant retaining the most activity in both studies, whereas the ARS mutant PITX2 proteins proved to be non-functional. In addition to providing insight into the etiological mechanism of IH, IGDS and ARS, these results are consistent with the hypothesis that mutant PITX2 proteins that retain partial function result in milder anterior segment aberrations.
Acampomelic campomelic dysplasia is a rare clinical variant of the more commonly encountered campomelic dysplasia (CMD1), characterized by absence of long bone curvature (acampomelia). We present a patient with acampomelic CMD1 with a de novo SOX9 missense mutation and report his clinical course to age one year, thereby contributing to genotype-phenotype correlation in CMD1. 2000.
OBJECTIVE: To investigate the hypothesis that children with juvenile rheumatoid arthritis (JRA) would have more social and emotional problems than case-control classmates. METHODS: Using a case-control design, children with JRA (n = 74), ages 8-14, were compared with case-control classmates (n = 74). Peer relationships, emotional well-being, and behavior, based on peer-, teacher-, parent-, and self-report scores on common measures, were compared using analysis of variance. RESULTS: Relative to case-control classmates, children with JRA were similar on all measures of social functioning and behavior. Mothers reported more internalizing symptoms in the child with JRA, but child self reports and father reports showed no differences. Scores on all standardized measures were in the normal range for both the JRA and the case-control groups. CONCLUSION: Children with JRA were remarkably similar to case-control children on measures of social functioning, emotional well-being, and behavior. These findings are not supportive of disability/stress models of chronic illness in childhood and suggest considerable psychological hardiness among children with JRA.
OBJECTIVE: Partial gastric resection alters the anatomy and secretory activity of the gastrointestinal tract. It might be expected that the consequences of such changes should affect the pharmacokinetics, especially concerning the absorption of orally administered drugs. Propranolol and atenolol, as representatives of lipophilic and hydrophilic beta-adrenoreceptor antagonists, have been studied in order to define their pharmacokinetic characteristics in patients after partial gastrectomy. METHODS: The study was carried out in 29 patients after gastric resection with Billroth I (B1) anastomosis and in 18 healthy volunteers as controls. Pharmacokinetics of propranolol and atenolol was investigated after a single oral dose of 80 mg and 100 mg, respectively, following a cross-over schedule. Blood samples were collected ten times during the 24 h after the drug administration. Pharmacokinetic parameters of propranolol and atenolol were calculated using a one-compartment open model with first-order absorption. RESULTS: The average blood plasma concentrations of propranolol in gastrectomised patients were lower than those in controls, reaching significance between 1.5 h and 6.0 h of the observation period. Pharmacokinetic parameters of propranolol were different in subjects submitted to surgery compared with healthy persons. We observed a significant decrease in the area under the concentration-time curve (32%) and the peak plasma concentration (20%), and an increase in half-life (25%). Mean plasma concentrations and pharmacokinetic parameters of atenolol in patients following partial gastric resection were not significantly different from those in the controls. No relationship between time interval following partial gastrectomy and pharmacokinetic parameters of the investigated drugs was noted. CONCLUSION: Partial gastrectomy with B1 anastomosis affects the pharmacokinetics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).
Metaphyseal dysplasia, type Jansen (JMD), is a rare skeletal dysplasia with characteristic radiographic abnormalities. Of the various types of metaphyseal dysplasia, JMD shows the most severe alteration in metaphyseal architecture. All of the long tubular bones, including those of the hands and feet, show metaphyseal irregularity with a fragmented appearance and slight widening. The adjacent physes are abnormally widened, while the epiphyses tend to be slightly enlarged, rounded but otherwise normal. The spine in infancy and childhood usually appears normal. This report describes a young girl with metaphyseal changes typical of JMD except for the hands and feet, which appeared normal. She also showed very unusual abnormalities of the spine. This appears, therefore, to represent a unique osteochondrodysplasia for which we propose the term spondylometaphyseal dysplasia, type Jansen.
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The cases of two sisters with severe diastrophic dysplasia who showed some unusual radiographic features (kyphosis secondary to hypoplasia/dysplasia of the lumbar spine and a 'monkey wrench' appearance of the proximal femur) are reported here. Absent patellae were another feature that has not previously been reported in diastrophic dysplasia.
We report a third patient, a female, with thoraco-pelvic dysostosis. This rare disorder is similar in phenotypic and radiographic appearances to thoraco-laryngo-pelvic dysplasia (Barnes syndrome). The only major difference between these two diseases is absence of laryngeal involvement in thoraco-pelvic dysplasia. They may represent two different entities or a contiguous gene syndrome.
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Two patients with a unique generalised bone dysplasia demonstrating severe distinctive platyspondyly are reported. This group of crippling disorders defies metabolic and histological classification. The radiographic examination is, at present, the only practical method of documentation of these rare disorders.
Dominantly inherited isolated hyperparathyroidism (DIIH) is rare in childhood. It may be the first biochemical abnormality in the multiple endocrine neoplasia type I (MEN I) and type II (MEN II) syndromes. Its clinical course is usually asymptomatic or of low morbidity. Radiographic examination is most often normal. We describe six members of a family with distinctive phenotype and DIIH. Limited systemic symptoms and severe radiographic osteitis fibrosa cystica were further unusual features in this family. The diagnosis of DIIH was made only after a 9-year-old girl developed hypercalcaemic crisis after a pathological femoral fracture. Distinctive phenotype, unusual clinical course and unparalleled radiographic changes suggest a not yet described syndromic association.
Four infants with kyphomelic dysplasia ascertained from three families demonstrate variability within the syndrome. In the first family, sibling recurrence in female sibs was noted with atypical kyphomelic dysplasias, suggesting autosomal recessive inheritance. In the second family, with a male affected with the 'typical findings' of lethal kyphomelic dysplasia, diagnosis of a skeletal dysplasia was suspected at 29-30 weeks' gestation following US detection of short, bent femurs. In the third family, with a female affected, severe radiographic changes were documented at birth. The clinical course of the disease was mild with almost complete regression of the radiographic findings at the age of 7 years.