Clinical and biochemical studies in mucopolysaccharidosis type II carriers.

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers' and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

A locus for spondylocarpotarsal synostosis syndrome at chromosome 3p14.

Spondylocarpotarsal synostosis syndrome is a rare autosomal recessive disorder characterised by vertebral fusions, frequently manifesting as an unsegmented vertebral bar, as well as fusions of the carpal and tarsal bones. In a study of three consanguineous families and one non-consanguineous family, linkage analysis was used to establish the chromosomal location of the disease gene. Linkage analysis localised the disease gene to chromosome 3p14. A maximum lod score of 6.49 (q = 0) was obtained for the marker at locus D3S3532 on chromosome 3p. Recombination mapping narrowed the linked region to the 5.7 cM genetic interval between the markers at loci D3S3724 and D3S1300. A common region of homozygosity was found between the markers at loci D3S3724 and D3S1300, defining a physical interval of approximately 4 million base pairs likely to contain the disease gene. Identification of the gene responsible for this disorder will provide insight into the genes that play a role in the formation of the vertebral column and joints.

Glycogen storage disease type Ia: molecular study in Brazilian patients.

Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen storage disease type Ia (GSDIa). This disease is characterized by growth retardation, hepatomegaly, hypoglycemia, hyperlipidemia, and lactic acidosis. In this study, we report mutations in the G6Pase gene in 8 of 25 Brazilian patients with clinical symptoms of GSDIa. Five previously described mutations (R83C, Q347X, V338F, D38V, and G68R) were detected. The two most common mutations identified were R83C and Q347X, accounting for 8 of 14 (57.14%) mutant alleles. A 1,176 single-nucleotide polymorphism and two intronic mutations (IVS3-58T>A and IVS4+10G>A) were also analyzed. We used the minigene strategy in order to verify the effect of these intronic mutations on the splicing mechanism. This study emphasizes that molecular genetic analysis is a reliable and convenient alternative to the assay of enzyme activity in a fresh liver biopsy specimen for diagnosing GSDIa.

Spondylocarpotarsal synostosis with ocular findings.

We report on three sibs presenting with spondylocarpotarsal synostosis, short-trunk dwarfism of postnatal onset, scoliosis, unsegmented thoracic vertebrae with unilateral bar, and carpal bone fusion. Tarsal bone fusion and dental abnormalities were noted in some of them, indicating pleiotropy and intrafamilial variability. Lens opacities, rarefaction of retinal pigmentation, and narrowing of retinal vessels, detected in two patients, are findings that have not been described to date in this condition.

The feasibility of introducing a visual screening test for children during vaccination campaigns.

PURPOSE: A visual screening test for children was prepared for the use of paramedics during vaccination campaigns. This test was used in a vaccination campaign in Taquaritinga, São Paulo, Brazil. METHODS: The campaign was carried out by two paramedics trained by ophthalmologists. The first 130 children vaccinated whose families showed interest in participating in the visual screening program were chosen. The program consisted of demographic information and eight questions, a visual screening test for children >4 years, and an external eye examination. After studying the data collected, the paramedic decided if the child needed a more thorough ophthalmologic examination. RESULTS: Of the 4505 children vaccinated, 130 children participated in the screening test. One (76.9%) hundred of the 130 children were reexamined by ophthalmologists. Of these, 38 (29.2%) were initially considered to have visual disorders. Ophthalmologic disorders were confirmed in 22 (57.9%) children; of these, 3 were already under ophthalmologic care. The paramedics correctly screened a total of 77 (77%) children. CONCLUSION: Visual screening during vaccination campaigns is simple and rapid, and provides the opportunity to identify children with visual disorders during the critical stage of visual development without the need of ophthalmologists.

Multimedia system based on programmed instruction in medical genetics: construction and evaluation.

A multimedia system used as an auxiliary didactic tool for teaching medical genetics, HGEN, is based on non-linear programmed instruction and multimedia. HGEN was implemented in layers for PC compatible using MULTIMEDIA TOOLBOOK and DELPHI. It includes basic medical genetics concepts (inheritance patterns and cytogenetics) and it is based on multiple choice questions with images, diagrams and animations. The student-program interaction occurs by choosing an alternative in a question and receiving a specific answer as feedback and additional information. Links send the students to a glossary, to short descriptions of diseases used as examples, or to references for further studies. In order to evaluate the performance of the HGEN the authors used two questionnaires: (a) about the students' background in using computers; and (b) the system efficiency as a didactic tool, the software quality and user satisfaction. HGEN was used by 63 students from three medical schools and it was considered efficient as a learning tool (100%). Furthermore the implementation of a navigation map for frequencies analysis of followed path enable the study to detect structure and content inadequacies that could be correct for version 1.1 and proved to be an efficient tool to optimize a didactic software.

A study on hemostasis parameters in the neurosurgery of cerebral aneurysms.

BACKGROUND: This prospective study was accomplished with 14 patients, 10 women and 4 men, where some pre-, intra- and immediate postoperative parameters of hemostasis were analyzed and compared to a control group of normal individuals. METHODS: The patients included in this study were admitted to the Hospital das Clinicas at Unicamp in the 1990-1993 period. All the accepted patients have had their latest bleeding at least 30 days before surgery, therefore, after the acute bleeding phase, because in this phase there are alterations in hemostasis. In this period only dipyrone was used in all patients as analgesics and antipyretics. Opiates were used in all the anesthetic proceedings. The following parameters were determined: coagulation; prothrombin time, (PT), thrombin time, (TT), activated partial thromboplastin time, (APTT), platelets (PQ), fibrinogen, (FG) factor V, (F V), protein C, (P C), protein S (PS), antithrombin III (AT III); fibrinolysis, plasminogen (PLG), C 1 inhibitor (C 1), alfa 2 macroglobulin (A2M), prekallikrein (PK), euglobulin lysis time (ELT), lysis area in fibrin plates (LAFP), in 5 of these 14 patients. Activity of both plasminogen tissue activator (t-PA) and plasminogen activator inhibitor (PAI-1) were also determined. For analyze the hepatic function pre-albumin (PRE ALB) was determined. RESULTS AND CONCLUSIONS: In this study, the analysis of LAFP and ELT in the different surgical times suggests that the patients submitted to cerebral aneurysm surgery are head to hypofibrinolysis from the intraoperative to the immediate postoperative period and this evidence do not related whit PAI-1.

Metacarpophalangeal pattern profile in Marfan syndrome and Marfan-like patients.

Marfan syndrome (MFS) is an autosomal dominant trait due to mutations in the fibrillin gene (FBN1). The MFS expressivity is variable, and its diagnosis relies completely on clinical criteria. Atypical cases and Marfan-like (marfanoid) clinical presentations are commonly found. The metacarpophalangeal pattern profile (MCPP), a radiological method in which the 19 tubular hand bones are assessed, has been used in the diagnosis of various syndromes. To investigate whether the MCPP was adequate to discriminate between MFS and Marfan-like subjects, we studied 38 patients who were referred to our service because they had an MFS diagnosis, diagnostic hypothesis, or differential diagnosis or had arachnodactyly with dolichostenomelia. Two groups were formed: 1) MFS: 21 patients with a mean age of 18.3 (10.8 S.D.) years and 2) Marfan-like syndromes: 16 patients who did not meet the current criteria, with a mean age of 14.6 (4.6 S.D.) years. The MCPP was performed in each case following the classical technique, and a characteristic mean profile was obtained for group I (MFS), with Z scores ranging from 0.69 to 2.73 (1.80+/-0.50; mean+/-S.D.). In group I, three cases had no correlation with the typical MFS pattern. In group II, three cases had an MFS pattern. The correlation with the mean MCPP of MFS permitted the differential diagnosis of MFS and marfanoid syndromes with 86% sensitivity, 81% specificity, and 86% positive and 81% negative predictive values. The results suggest that MCPP can be used effectively as an auxiliary tool in the nosology of these conditions and, because there is no change in MCPP with age, can be helpful in early diagnosis.

Total body zinc depletion and its relationship to the development of hyperprolactinemia in chronic renal insufficiency.

Modulation of free plasma zinc levels has been implicated in the increase in plasma prolactin levels seen in patients with chronic renal insufficiency (CRI). The relative importance of this mechanism in comparison to others, however, has not been elucidated. Zinc equilibrium between plasma and red blood cells is partly dependent upon red blood cell carbonic anhydrase (CA). In the present paper, we have investigated the interrelationships among total plasma zinc, leukocyte zinc, prolactin, and erythrocyte CA in patients with CRI. Uremic patients were shown to have significantly increased levels of plasma prolactin and erythrocyte CA activity when compared to normal controls. Moreover, red blood cell CA total concentration and isoenzyme-I and-II levels, as well as plasma zinc were found to be significantly decreased in uremic patients in comparison to normal controls. In patients with CRI, a negative correlation was demonstrated between erythrocyte CA catalytic activity and plasma zinc, as well as between plasma zinc and plasma prolactin levels. Moreover, leukocyte zinc content, which is a reliable indicator of total body zinc stores, was found to be significantly decreased in uremic patients when compared to normal controls. A strong negative correlation between leukocyte zinc content and plasma prolactin levels was documented in CRI patients. Our results suggest that alterations in erythrocyte CA levels, enzymatic activity or isoenzyme profile are most probably mechanistically and etiologically unrelated to the high plasma prolactin levels in CRI patients. Contrariwise, depletion of total body zinc stores, rather than redistribution of this trace metal among extracellular compartments, may represent one of the major contributing mechanisms leading to uremic hyperprolactinemia.

Nucleolar organizer region (NORs) in pseudocarcinomatous hyperplasia and squamous cell carcinoma of the oral mucosa.

Counts of nucleolar regions (NORs) demonstrated by a silver staining technique in paraffin sections, have been used to distinguish benign from malignant lesions. AgNORs were studied in 24 biopsies from oral cavity (5 cases of normal oral mucosa, 5 of pseudocarcinomatous hyperplasia and 14 of squamous cell carcinoma, subdivided according to degree of differentiation: 5 grade 1, 5 grade 2 and 4 grade 3) to find whether they were helpful in distinguishing pseudocarcinomatous hyperplasia due to chronic parasitic infections from squamous cell carcinoma. Two methods of counting AgNORs were used: (A) a simpler one which counts nucleolar clusters (AgNU) and satellite AgNORs and the other (B) counting all individual AgNORs, including those within AgNUs. In both methods the lowest mean values were observed for grade 3 carcinoma, while the highest belonged to grade 2 carcinoma. The simpler method (A) was the most useful because AgNU counts showed significant difference when pseudocarcinomatous hyperplasia was compared with grade 1 and 2 carcinomas, which are the most difficult to discriminate from it. However the overlapping of values render the technique of limited use in individual cases.

Immunological studies in placentas with villitis of unknown etiology: complement components and immunoglobulins in chorionic villi.

Villitis of unknown etiology (VUE) is a common placental lesion and complement-fixing immune complexes is one of the mechanisms proposed for its development. We examined 16 placentas with VUE and 16 without VUE by immunofluorescence in order to compare the distribution and amount of C1q, C3d, IgG and IgM in the chorionic villi between the two groups. We found both in cases with and without VUE a distribution of the complement components and immunoglobulins similar to that described in normal placentas. The amount of deposit was also not significantly different in the two groups. Only the inflamed villi showed an abnormal distribution of C1q which was present diffusely in the stroma of these villi.