Biomedical subjects
Publications and source records attributed to M Dumić.
The structural element of alicyclic beta-amino acids shows some remarkable biological effects: For some 5- and 6-membered beta-amino acids a unique anti fungal activity has been observed, 7-membered beta-amino acid derivatives have been investigated for neurological disorders. The application of 5-, 6- and 7-membered alicyclic beta-amino acids in Medicinal Chemistry will be reported. [structure: see text]
We report on two brothers with mental deficiency, short stature of prenatal onset, microcephaly, alopecia/sparse hair, follicular ichthyosis, multiple skeletal anomalies, and recurrent respiratory infections. The younger brother has celiac disease, cryptorchidism, inguinal herniae, and hypohidrosis, while the older brother has hidrotic ectodermal dysplasia, juvenile autoimmune thyroiditis, hypolacrimation, photophobia, and optic atrophy. Striking resemblance exists between our patients and those previously reported by Schinzel ¿1980: Helv Paediatr Acta 35:243-251 and van Gelderen ¿1982: Am J Med Genet 13:383-387. The fact that boys are born to young and healthy nonconsanguineous parents and there are no other affected relatives suggests autosomal or X-linked recessive inheritance or parental germinal mosaicism for a dominant mutation.
Triple A syndrome is characterised by achalasia, alacrima, adrenal insufficiency and progressive neurological abnormalities including impaired autonomic nervous function. We present five patients with triple A syndrome in whom we describe xerostomia for the first time, a symptom which was presumed to be practically exclusive to Sjøgren syndrome and familial dysautonomia. Conclusion We recommend the investigation of salivation in all patients with triple A syndrome and treatment of xerostomia in order to ease swallowing. Further, our results corroborate earlier doubts that some patients with Sjøgren syndrome, especially those with the so-called "achalasia sicca" syndrome and adrenocortical insufficiency, actually had triple A syndrome. Therefore, adrenocortical function should be assessed in all patients with Sjøgren syndrome, particularly in those with difficulties in swallowing, because even latent adrenocortical insufficiency could be life-threatening for these patients in stressful situations.
We report on a female newborn, the youngest patient with Zimmermann-Laband syndrome hitherto reported. She had gingival hyperplasia, bulbous soft nose and ears, hypoplastic toenails, and hyperextensibility of the joints, as well as deep palmar and plantar creases, a sign not previously described in literature.
We report on a patient with Nevo syndrome manifesting intrauterine and postpartum overgrowth, accelerated osseous maturation, dolichocephaly, highly arched palate, large, low-set ears, cryptorchidism, delayed neuropsychological development, hypotonia, adema, contractures of the hands and feet, a single a transverse palmar crease, and tapering digits. After meningococcal sepsis at age 6 months, he remained decerebrate. Thereafter, overgrowth and especially weight gain were extremely accelerated until his death at age 18 months, at which time his height was 103 cm and his weight was 23 kg. In addition to low plasma concentrations of growth hormone and insulin-like growth factor, severe insulin resistance was observed. It is presumed that a selective defect in insulin-stimulated glucose uptake, with preservation of anabolic effect, was one of the causes of his "overgrowth without growth hormone," at least in the last 12 months of life after severe brain damage.
A 17 year and 10 month old boy with Johanson-Blizzard syndrome is presented as a case report for the first time. Diagnosis has been established on the basis of craniofacial abnormalities: microcephalia, parietal skin and bone defects, sparse hair with frontal up sweep, alae nasi hypoplasia, irregular dentition and nasolacrimal fistula, with mental insufficiency, partial exocrine pancreatic insufficiency and low birth-weight and length, hypotonia and failure to thrive in infancy. Congenital cataract and hiatus sacralis apertus are additional signs that have never been described in the literature concerning Johanson-Blizzard syndrome.
We studied the prevalence of limited joint mobility (LJM) in 100 diabetic children and 100 non-diabetic controls. Our objective was to find possible predictors for the expression and progression of LJM and to evaluate the relationship between LJM and other long-term complications of insulin-dependent diabetes mellitus. LJM was present in 36% of diabetic patients aged 2-20 years. It was significantly related to duration of disease and longitudinal glycated haemoglobin (HbA1c) concentrations, pubertal stage, number of ketoacidosis and skin changes. Fourteen patients had peripheral neuropathy, 16 had microalbuminuria, 8 had nephropathy, and 7 had retinopathy. After matching for duration of disease, HbA1c concentrations and pubertal stage, a comparison of the complication rates was made. All long-term complications were significantly associated with LJM. Longer duration of disease and higher mean longitudinal glycated haemoglobin level are independent predictors for expression of LJM. Thus, improvement of metabolic control in diabetic patients before puberty may diminish the expression and progression of LJM.
Congenital adrenal hyperplasia (CAH) is an inherited metabolic disease caused by the deficiency of one of the enzymes necessary for cortisol synthesis. Deficiency of 21-hydroxylase (21-OH) accounts for 95% of affected patients There are two forms of the disease. The first is classic, which may be incomplete (simple virilizing) or complete (salt wasting). The second is nonclassic, which may be symptomatic or asymptomatic. In classic 21-OH deficiency which occurs in 1:10000-15000 live births, prenatal exposure to excess androgens results in virilisation of female fetus. Newborn males have normal genitalia. Postnatally, untreated females as well as males present with signs of androgen excess. Three fourths of classic 21-OH deficiency cases do not effectively synthesize aldosterone and are salt wasting, a condition that is potentially fatal. Nonclassic 21-OH deficiency, allelic variant of classic 21-OH deficiency is associated with a milder enzymatic defect and no genital ambiguity at birth, but postnatal virilization may be seen. A subset of individuals with nonclassic 21-OH deficiency are asymptomatic, despite high levels of androgens (cryptic form of disease). The 21-OH enzyme, a cytochrome P450 hemoprotein (cytochrome P450 c21) is encoded by the gene CYP21, which has a closely neighboring homologous pseudogene, CYP21P. Mutations in the CYP21 gene, causing 21-OH deficiency, are common and occur owing to two mechanisms: gene deletion and apparent gene conversion. Prenatal diagnosis is important to identify a fetus affected with 21-OH deficiency. Genital ambiguity in affected females can be prevented by proper administration of dexamethasone to pregnant mother. Postnatally, the treatment of 21-OH deficiency is lifelong hormonal replacement. With carefully supervised medical treatment. CAH patients have the capacity for normal puberty and fertility.
A girl with Cohen syndrome is presented. The diagnosis has been established on the basis of the characteristic face appearance with hypoplastic maxilla and mandible, open mouth, prominent maxillary central incisors, as well as characteristic appearance of extremities (narrow hands and feet), childhood obesity, hypotonia, and mental insufficiency. The girls also has the so-called "mottled retina". The attempts of weight reduction have been unsuccessful so far.
A series of 1-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6-b]azirines, 4, has been synthesized and evaluated for its effects on blood glucose-decreasing activity. These derivatives were prepared from 4,7-dihydro-1,3-dioxepins 1 via vic(acylamino)halogenodioxepanes 2 and dioxepinoazirines 3. Quantitative structure--property relationship and quantitative structure--activity relationship models, based on X-ray and molecular mechanics analyses, to our knowledge the first in the field of antihyperglycemics, were developed. They allow the prediction of properties (RP-HPLC attention times) and activities (hypoglycemic activity ratio) by the Connolly's molecular surface areas. The lead compound in these models, sulfonyldioxepinoazirine 4i, expressed superior antihyperglycemic activity in comparison to metformin in alloxanized mice, irrespective of route of application. It significantly reduced blood glucose levels in glucose-primed mice, but it did not cause a dose dependent decrease of blood glucose level in healthy (nondiabetic, control) animals.
HLA (human leukocyte antigens) antigens A, B, and DR were determined in a series of 50 patients with gonadal dysgenesis (GD), separated into different groups according to karyotype. There were no significant differences in frequency of HLA antigen types between GD patients and the population control. When frequencies of the HLA antigens in the various GD patient groups by karyotype were compared, only one significant difference was found: HLA-A3 was more common among GD patients with isochromosome X than among GD patients with karyotype 45,X (p < 0.001, corr. p < 0.008). Although GD patients have a higher expectancy for development of autoimmune disorders, and in our 50 patients thyroglobulin and/or microsomal antibodies were detected in 20 (i.e., 40%), we failed to find any increased frequency of specific HLA antigen types known to be associated with juvenile autoimmune thyroiditis.
A survey of 5462 schoolchildren was conducted for signs of thyroid disease in the seaside region of Sibenik, Croatia. In this region, salt is regularly iodised with 0.01% potassium iodide. Thyromegaly was found in 152 children (2.8%). The most common disorder was simple goitre, which was established in 126 of these, 12 boys and 114 girls (combined prevalence of 2.3%, and of 0.45% in boys and 4.07% in girls). Juvenile autoimmune thyroiditis was found in 19 of the children (prevalence 0.35%), with a female:male sex ratio of 8:1. Diagnosis was confirmed in all cases by fine needle biopsy. Thyroglobulin antibodies were detected in all 19 of the patients with juvenile autoimmune thyroiditis, but microsomal antibodies in only eight. Three patients had decreased concentrations of thyroxine and raised concentrations of thyroid stimulating hormone (TSH), one of these also with clinical hypothyroidism. Raised concentrations of TSH but with normal triiodothyronine and thyroxine were seen in two patients. Graves' disease was diagnosed in four children, three girls and one boy (combined 0.07%). Thyroid nodules were identified in three children (0.055%; two benign adenomas and one cyst). Only seven of the 152 patients with thyromegaly (three with hyperthyroidism and four with simple goitre) had previously sought medical advice, which points to the need for careful thyroid examination of apparently healthy children even in regions where the regular iodide intake is assumed to be sufficient.
A 9-month-old infant with hypertrophic clitoris and separated urethral and vaginal opening was diagnosed as having 46,XY incomplete "pure gonadal dysgenesis". Examination of both gonads revealed gonadoblastoma and bilateral salpingo-gonadectomy and partial hysterectomy were performed. Patient is raised as a girl, and clitoroplasty will be done in next several months. The fact that gonadal neoplasia in our patient was found already at the age of 9 months, confirms the need for gonadectomy at the time of diagnosis in the patients with 46,XY gonadal dysgenesis.
A pair of twins, a brother and sister, with the complete form of Weaver syndrome (overgrowth, macrocephaly, facial, skeletal, nail and feet anomalies) and their mildly affected mother are reported, suggesting autosomal dominant inheritance. They all have plantar and palmar hyperhydrosis and twins also have nail dysplasia, symptoms which have not yet been described in this syndrome.
We assessed the effect of particular apolipoprotein (apo) E phenotypes, lipoprotein(a) [Lp(a)], and other lipoproteins on the development of dyslipoproteinemia in 450 patients with type I diabetes, ages 13-14 years. The control group consisted of 450 healthy school children of both sexes, ages 13-14 years. Both groups were found to be normolipidemic, but the concentration of Lp(a) was significantly (P < 0.05) higher in the diabetic children than in the control group. Apo E 3/2 and apo E 4/4 phenotypes were more frequent in the group of diabetics. Diabetics with the apo E 3/3 phenotype had higher concentrations of very-low-density lipoprotein (VLDL) and Lp(a), and lower concentrations of low-density lipoprotein (LDL) than the apo E 3/3 nondiabetics. For apo E 3/2 phenotypes, total cholesterol, LDL cholesterol, LDL, apo A-I, and Lp(a) concentrations were higher in the diabetic children than in the control group; for apo E 4/3 phenotypes, this was true for triglycerides and VLDL cholesterol. The distribution of Lp(a) lipoprotein concentrations between 0.01 and > 0.5 g/L indicated a more frequent occurrence of higher Lp(a) values in diabetic children than in the control group. Results of this study indicate that an increased concentration of Lp(a) lipoprotein and apo E 3/2 and apo E 4/3 phenotypes contribute to the expression of dyslipoproteinemia in type I diabetes in childhood.
This is a brief case report on a four-month-old girl who was admitted for failure to thrive and moderate dehydration. On admission she was mildly dehydrated and undernourished but with otherwise normal physical findings. Laboratory investigation disclosed mild but constant hyponatremia and hyperkalemia, very high plasma renin activity (greater than 900 ng/mL per hour) and low plasma aldosterone concentration (2.5 ng/dL). The plasma 18-hydroxycorticosterone (18-OH-B) was very high (1,682 ng/dL), producing thus an abnormally elevated 18-OH-B to aldosterone ratio of 542 (normally 6.3 +/- 3.6). The diagnosis of corticosterone methyloxydase deficiency type II was made, and the administration of fluorohydrocortisone resulted in rapid weight gain with normalization of blood electrolytes and gradual decrease in plasma renin activity. A very efficient catch-up growth resulted in normal body weight and length at the age of 2 years. This is the first well documented case of the disease in the population of Yugoslavia.
Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic nervous system disorders are described. At the time of diagnosis, four of them had osteoporosis. The fifth patient died and skeletal roentgenograms were not done. Osteoporosis was subsequently discovered in one of our previously reported patients with ACTH insensitivity. We assume that osteoporosis is, at least partly, the result of decreased adrenal androgen production. Human leucocyte antigen typing failed to establish any linkage.
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