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Biomedical subjects

A Kastelan

Publications and source records attributed to A Kastelan.

At least 37 records · Page 2Linked to original sources

Application of HLA class II polymorphism analysis to the study of the population structure of the Island of Krk, Croatia.

The population structure of the northern Adriatic island of Krk, Croatia, was studied using PCR methodology and nonradioactive oligonucleotide hybridization for the analysis of HLA-DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 polymorphisms. Allele frequencies, genetic kinship (R), and genetic distances (E2) were computed, and correlations between distance (genetic, linguistic, geographic) and kinship (migration) matrices were examined. The results, reflecting past (micro-) evolutionary processes, indicate that ethnohistorical and sociocultural events rather than geographic distances are the primary determinants of today's population structure of the island.

Adult↗

Molecular analysis of HLA class II polymorphism in Croatians.

HLA-class II polymorphisms have been studied in a population of 141 unrelated healthy Croatians using PCR amplification, followed by non-radioactive oligonucleotide hybridization. Thirty one DRB1, 8 DQA1, 13 DQB1 and 16 DPB1 alleles were found in the tested population. DRB1*1601, 0701, 1501, 0101 and 1104 are the most frequent alleles at the DRB1 locus. At the DQA1 locus two alleles predominate: DQA1*0501 and 0102, while the most frequent DQB1 allele is *0301. Analysis of HLA-DPB1 polymorphism showed that, as in other Europeans, DPB1*0401 is the most frequent allele. Four different two locus haplotypic associations (DRB1-DRB3, DRB1-DRB5, DRB1-DQB1 and DQA1-DQB1) as well as three locus DRB1-DQA1-DQB1 haplotypic associations were assigned on the basis of known linkage disequilibria. Several unusual two-locus associations have been observed: DRB1*0301-DRB3*0202, DRB1*1501-DRB5*02, DRB1*1601-DRB5*0101, DRB1*1502-DRB5*0101, DQA1*0103-DQB1*0503 and DQA1*0501-DQB1*0302. Among 236 examined DRB1-DQA1-DQB1 haplotypic combinations, the most frequent was DRB1*1601-DQA1*0102-DQB1*0502 that was found with statistically significant higher frequency than in other Europeans. Twenty-eight distinct probable haplotypes were observed just once, suggesting that the main characteristic of Croatian population is great heterogeneity of haplotypes. This study will serve as a reference for further anthropology studies, HLA and disease associations studies and for donor/recipient matching in organ and bone marrow transplantation.

Alleles↗

The preexcitation syndrome: epidemiological and genetic study.

A sample of 4210 subjects of both sexes aged 35-54 years was examined, chosen at random from six regions of Croatia. An electrocardiogram at rest was performed in all subjects and changes analyzed by the Minnesota code. A short P-R interval together with a widening QRS complex and a delta wave was found in 0.05%, while 42 (1.0%) of the examinees had a short P-R interval, but only 0.21% were symptomatic. Three years after the first examination 0.06% of the subjects had preexcitation with a delta wave, and in one subject it appeared after three years. 0.35% of the subjects had a short P-R interval after three years but only 0.18% were symptomatic and in 22 (0.65%) it had disappeared in three years. After 13 years these subjects did not appear for an examination, and the short P-R interval did not appear in any of other subjects during this period. There were more short P-R intervals: 3.22% in females and 1.96% in males, but 0.33% only were symptomatic. Antigens of the human leukocyte group A (HLA) system were analyzed in 46 patients: the Wolff-Parkinson-White syndrome was found in 35, while 11 had the Lown-Ganong-Levine syndrome. Antigens of the HLA-A, HLA-B and HLA-DR locuses were determined by the microlymphocytotoxicity method. The results of the frequency of HLA system antigens were compared to the results of the control group of a Croatian population consisting of 175 people. There was an increased frequency of HLA-A9 and HLA-B5 (P = 0.026 and 0.0092) in the investigated population as a whole. The participation of HLA-A3 antigen was significantly less among patients (P = 0.03), while HLA-B14 antigen was not found in patients with preexcitation. Within 10 HLA-DR locuses, HLA-DR7 antigen was rather more frequently present, although this was not statistically significant (P = 0.173).

Adult↗

An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population.

Nonclassic steroid 21-hydroxylase deficiency is an attentuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035-0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21-hydroxylase deficiency occurring among Yugoslavs and HLA-B14; DR1.

17-alpha-Hydroxyprogesterone↗

A prospective study on the etiology of uveitis.

We prospectively studied and classified 152 cases of endogenous uveitis treated at the Ophthalmological Clinic in Split, Yugoslavia, according to clinical presentation, several immunologic parameters including HLA subtyping, and the presence of an associated systemic disease. Using our diagnostic criteria we successfully classified 91.4% of patients. Anterior uveitis was the most common form of clinical presentation (94 patients, 61.8%), whereas an intermediate uveitis was present in only 5.3% of patients (8 patients). By HLA typing we found that 115 patients (75.7%), were positive for HLA-B27 (57 patients, 50%), B5 (30 patients, 26%) and B35 (28 patients, 24%) risk antigens. Of these patients 96 (83%) had an associated systemic illness. In the 8.6% of cases (13 cases) in which the etiology of an endogenous uveitis was not determined, none were associated with an HLA-B risk antigen. Our study emphasizes the association of HLA-B risk antigens and concurrent systemic disease in patients with endogenous uveitis.

Adolescent↗

Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation for leukemia.

From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups. The incidence of moderate to severe acute GVHD was significantly higher in the CSP group compared with the CSP + MTX group (20 (51%) versus 9 (25%), chi 2 = 4.76, p less than 0.02). There was no significant difference in the incidence of chronic GVHD. Survival was significantly better for the CSP + MTX group (63 +/- 16%) compared to CSP alone (42 +/- 18%). Leukemia-free survival tended to be better for the CSP + MTX group (55 +/- 17% versus 32 +/- 16%).

Adolescent↗

[Changes in the skin in transplantation versus host reaction. 2. Our clinical findings from observations using light microscopy and electron microscopy].

A clinical, light microscope and electron microscope study of skin changes was undertaken in 19 patients after bone marrow transplantation. Thirteen of the total number of 19 patients were clinically suspect of the acute and 6 of the chronic form of GvHD. Skin biopsy between the seventh and thirtieth day following transplantation confirmed the diagnosis of the acute form of GvHD in 7 of the 19 patients. In 4 of the 6 patients in whom skin biopsy did not verify the diagnosis of the acute form of GvHD, completely atypical rash in addition to signs of GvHD of the liver and intestines developed between the 30th and 50th day following transplantation. In all 6 patients who were clinically suspect of the chronic form of GvHD, skin biopsy performed some 4-10 months after transplantation confirmed the diagnosis of chronic, sclerodermoid or lichenoid GvHD. Furthermore in 71% of the patients with histologically verified chronic form of skin GvHD, symptoms of liver and intestine GvHD were present too at the time of the skin biopsy. With regard to the fact that histologically the least reliable seems to be the diagnosis of Grade 1 cutaneous GvHD, the authors recommend that regular dermatological follow-up examinations be made in the period of 7 to 50 days following transplantation in addition to skin biopsy in the case of appearance of any rash. Electron microscopy revealed in both forms of GvHD, the acute and the chronic, the most significant epidermal changes, i.e. degeneration of the cellular organelles and the appearance of numerous intracytoplasmic vacuoles.

Adolescent↗

HLA and red blood group antigens in pregnancy disorders.

Total of 356 women with various types of pregnancy disorders as well as their husbands were classified in four groups regarding the type of the disorder as follows: 1. Recurrent spontaneous abortions (RSA) of unknown etiology (N = 105) and RSA - primary aborters only (N = 84); 2. Blighted ovum (N = 80); 3. Rh immunization in pregnancy (N = 90); 4. ABO immunization in pregnancy (N = 47). Two groups of couples were used as controls: 1. Couples randomly taken from forensic medicine cases of paternity evaluation (N = 104); 2. Couples having two or more children with HLA immunization in pregnancy (N = 78). The couples from all groups were typed for red blood group antigens of ABO, Rhesus, MNSs, Kell, Duffy, Lewis, Kidd and P systems and also for HLA antigens. Significantly higher frequency of antigen HLA-A9 was found in women with RSA (corr. p = 0.0003) and in women with pregnancy disorders caused by Rh immunization (corr. p = 0.0136). In couples with RSA the degree of HLA compatibility was significant (p = 0.0048) and the reactivity of spouses in MLR was significantly decreased (p = 0.0001). Significantly, more low responders in MLR were also found among the women with RSA as compared to the controls (p = 0.0217). Two possible pathologic mechanisms may explain the association between HLA antigens and RSA: 1. immunological defects which are linked to HLA-D/DR region causing malfunction of immunosuppressive mechanisms during pregnancy; 2. endocrinological defect which is linked to HLA region as 21-OH hydroxylase deficiency gene.

Female↗

Anthropometry and the biological structure of the Hvar population.

Biological structure of the population of the island of Hvar was investigated by using the data on anthropometric variation among nine village populations; 24 body and 14 head dimensions were analysed from 487 male and 437 female adult subjects. Univariate and multivariate analyses revealed heterogeneity among the populations, which says much for the strength of the isolating factors on the island. Using correlations of anthropometric and geographic distance, the observed patterns of variation among villages were closely related to geography, suggesting migration to be an important factor in the formation of the island's population structure. Populations of the examined villages were further grouped to form the population of the eastern part and the population of the western part of the island, which have an ethnodemographic and sociocultural basis. The analyses revealed heterogeneity between the populations and thus provided evidence to support the hypothesis about the existence of the genetically different groups living in the same biotope.

Adult↗

Cyclosporin neurotoxicity in patients treated with allogeneic bone marrow transplantation.

Toxicity to the central nervous system was observed in 3 out of 15 patients receiving cyclosporin prophylaxis for graft-versus-host-disease after allogeneic bone marrow transplantation. Neurological clinical features included grand mal seizures, dysarthria and vestibular and cochlear toxicity. In all three patients, cyclosporin plasma levels were increased at the time of overt clinical neurological signs. The symptoms resolved quickly with the reduction of the cyclosporin dose.

Adult↗

Experience with bone marrow transplantation for severe aplastic anemia and leukemia. Two years experience with 31 patients in Zagreb (Yugoslavia).

Since 1983, twelve patients with severe aplastic anemia and nineteen patients with leukemia were treated with bone marrow transplantation. Six patients with severe aplastic anemia are still alive at 300 to 1,210 days after transplantation, and twelve patients with leukemia are alive at 199 to 671 days. The incidence of GvHD was relatively high (60%). Bacterial infections were the main causes of death.

Adolescent↗

'Cryptic' form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the Yugoslav population.

Five individuals with the asymptomatic, 'non-classical', 'cryptic' form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency from 5 unrelated families were discovered during hormonal studies and HLA-typing performed in a series of 24 families with CAH due to 21-OH deficiency. Four of the 5 individuals with the 'cryptic' form of CAH belong to families where the index case was a patient with the classical form of CAH due to 21-OH deficiency. The fifth one originated from a family where the index case was a girl with the 'non-classical', 'late-onset' form of the disease. All the 5 individuals had no clinical symptoms in spite of clearcut biochemical signs of 21-OH deficiency: increased 17-OH-progesterone (17-OHP), dehydroepiandrosterone and androstenedione levels, particularly after ACTH-stimulation. The 17-OHP response upon ACTH stimulation of heterozygotes for this 'non-classical' form of 21-OH deficiency did not differ from the response of heterozygous individuals for the classical form of the disease. The results of this study confirm the hypothesis that individuals with the 'cryptic' form of CAH due to 21-OH deficiency are genetic compounds bearing one allele for the severe, classical form, and on the homologous locus, another one for the mild 'non-classical' form of CAH due to 21-OH deficiency. Their genotype was 21-OH severe/21-OH mild.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗