The homozygous state for the band 3 protein mutation in Southeast Asian Ovalocytosis may be lethal.
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Biomedical subjects
Publications and source records attributed to D Amato.
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The sleep inducing effect of a 15 min treatment with either an active or an inactive Low Energy Emission Therapy (LEET) device emitting amplitude-modulated electromagnetic (EM) fields was investigated in a double-blind cross-over study performed on 52 healthy subjects. All subjects were exposed to both active and inactive LEET treatment sessions, with an interval of at least 1 week between the two sessions. LEET consists of 27.12 MHz amplitude-modulated (sine wave) EM fields emitted intrabuccally by means of an electrically conducting mouthpiece in direct contact with the oral mucosa. The estimated local peak SAR is less than 10 W/kg in the oral mucosa and 0.1 to 100 mW/kg in brain tissue. No appreciable sensation is experienced during treatment, and subjects are therefore unable to tell whether they are receiving an active or an inactive treatment. In this study the active treatment consisted of EM fields intermittently amplitude-modulated (sine wave) at 42.7 Hz for 3 s followed by a pause of 1 s during which no EM fields were emitted. During the inactive treatment no EM fields were emitted. Baseline EEGs were obtained and 15 min post-treatment EEGs were recorded and analyzed according to the Loomis classification. A significant decrease (paired t test) in sleep latency to stage B2 (-1.78 +/- 5.57 min, P = 0.013), and an increase in the total duration of stage B2 (1.15 +/- 2.47 min, P = 0.0008) were observed on active treatment as compared with inactive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
The Radiation Therapy Oncology Group conducted a prospective comparison of a compensated split course radiotherapy technique (300 cGy x 10, 3 weeks rest, 300 cGy x 10), versus continuous radiotherapy (200-220 cGy up to 6000-6600 cGy), in 137 evaluable patients. The complete response (CR) was 57% in 63 patients, treated with the split-technique vs 61% in 74 patients submitted to continuous course radiotherapy. The completion of therapy as planned was better in the split-technique, but acute and late tissue reactions were the same. Locoregional control of tumor at 5 years was 25% for split and 28% for continuous therapy. At 7 years this was 25% and 24%, respectively. Absolute survival in the split-course patients tended to be lower than in the continuous group, but when the sample of patients was enlarged by the addition of cases from similar trials of nasopharynx and base of tongue lesions, the survival difference was eliminated. On the basis of the results of this study we conclude that the stated compensated split-course technique gives equal clinical results as conventional continuous therapy, with the advantage of requiring fewer radiation fractions, and less burden on the patient and therapy facilities.
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In previous works our group has demonstrated that intracellular concentration of calcium ionized is greater in patients with pre-eclampsia than in normotense pregnant patients, and that these figures correlate with arterial pressure. Both indicators become normal six weeks after delivery. With the idea of searching the possible participation of soluble factors in the plasma, in increasing free, intracellular calcium, eight pre-eclamptic patients, were studied; the patients were diagnosed by the criteria of the American College of Gynecologists and Obstetricians. As a control group, eight normotense pregnant patients, were included; they were paired by age, chronological and gestational. To measure transmembrane calcium flow, platelets from healthy males, were used. The platelets were incubated during 0, 15, 30 and 60 minutes in sera of pre-eclamptic patients, or of normotensive pregnant patients, marked with Ca. The differences in calcium transportation, were evaluated with variance analysis of Kruskall Wallis. Calcium transportation was greater when the platelets were incubated in pre-eclamptic patients sera, Md = 1.475 +/- 0.311 nanomoles than when were incubated in normotensive women sera, Md = 0.9725 +/- 0.58 nanomoles, p < 0.02. This finding suggests that in pre-eclamptic patients serum, exists some factor that facilitates the entrance of calcium to the cell, that provokes an increase in free calcium concentration, and it participates in the gestational hypertension.
To evaluate the contribution of systemic hypertension in the progression of nephropathies to glomerular sclerosis, a mild form of puromycin aminonucleoside (PAN) nephrosis was associated with Goldblatt hypertension and studied after 18 weeks. We studied four groups: Group I, controls; Group II, Goldblatt hypertension; Group III, PAN nephrosis; and Group IV, both conditions. Systolic blood pressure, 24-h proteinuria, serum cholesterol, triglycerides, glomerular hemodynamics, and histological studies were compared among the groups. Rats in groups II and IV developed systemic hypertension, but only group IV rats showed persistent proteinuria. No alterations in lipid metabolism were present in any of the groups. The most striking findings in the micropuncture studies were a significant increase of glomerular capillary pressure in group IV rats (63.15 +/- 1.34 mm Hg) as compared to controls (48.74 +/- 0.97 mm Hg) and to groups II and III (55.31 +/- 2.11 and 48.17 +/- 1.23 mm Hg, respectively), and a marked fall in Kf in groups III and IV. Only group IV showed significant histological alterations such as glomerular sclerosis, interstitial damage, and increased glomerular area. These results suggest that, in the presence of an underlying nephropathy, a greater fraction of systemic pressure is transmitted to the glomerular capillaries when systemic hypertension is present; the resulting elevation in glomerular pressure and proteinuria seems to be responsible for the progression to glomerular sclerosis.
A 29-year-old man presented with a four-week history of pneumonic symptoms and progressive roentenographic infiltrates which were unresponsive to orally administered antibiotics. Bronchoscopy failed to identify an infectious etiology, but abundant atypical lymphocytes in the bronchial washings were present. A diagnosis of adult T-cell leukemia/lymphoma was subsequently made. After administration of cancer chemotherapy, the pneumonic symptoms and chest roentgenogram infiltrates resolved. This report suggests that ATL can present as an acute noninfectious pneumonitis.
To assess if neonatal circumcision may decrease the incidence of urinary tract infection (UTI), published papers on these topics were reviewed, to address their methodological shortcomings, and to analyze them in individual and grouped form. A systematic search of the papers on circumcision and UTI was conducted in Index Medicus (1975-1991) and MEDLINE (1988-1991). Six papers were included in the meta-analysis because all of them presented original data obtained from groups of patients. All of the elected articles were considered in individual and grouped form to calculate odds ratio (OR) and confidence interval at 95% (CI 95%). The number of patients included in each paper ranged from 112 to 219,775. Clustering of the articles enabled us to obtain a global sample number of 221,799 patients. In each individual article there was a higher risk of UTI in uncircumcised patients (OR from 10.82 to 156.42). Global risk obtained from the six clustered papers was of 13.05 with a CI 95% from 10.86 to 15.70. Uncircumcised males have low risk of UTI during their first year of life, but the risk may decrease even more with circumcision. This conclusion may not be considered as definitive because of the methodological shortcomings of the papers reviewed. Recommendation of routinely circumcision to all newborns in not justified with these data.
Subcutaneous emphysema is an uncommonly reported complication of routine dentistry. Two cases are presented, one occurring during root canal therapy and the second during routine restorative dentistry. The etiology and consequences of this phenomenon are reviewed, and the prompt recognition and management of this condition are discussed.
Southeast Asian ovalocytosis (SAO) is a hereditary condition that is widespread in parts of Southeast Asia. The ovalocytic erythrocytes are rigid and resistant to invasion by various malarial parasites. We have previously found that the underlying defect in SAO involves band 3 protein, the major transmembrane protein, which has abnormal structure and function. We now report two linked mutations in the erythrocyte band 3 gene in SAO: (i) a deletion of codons 400-408 and (ii) a substitution, A----G, in the first base of codon 56 leading to substitution of Lys-56 by Glu-56. The first defect leads to a deletion of nine amino acids in the boundary of cytoplasmic and membrane domains of band 3. This defect has been detected in all 30 ovalocytic subjects from Malaysia, the Philippines, and two unrelated coastal regions of Papua New Guinea, whereas it was absent in all 30 controls from Southeast Asia and 20 subjects of different ethnic origin from the United States. The Lys-56----Glu substitution has likewise been found in all SAO subjects. However, it has also been detected in 5 of the 50 control subjects, suggesting that it represents a linked polymorphism. We conclude that the deletion of codons 400-408 in the band 3 gene constitutes the underlying molecular defect in SAO.
Two patients with acquired deletions of the long arm of chromosome 5 (5q-) are presented and discussed. For both, clinical and other laboratory tests are highly atypical of patients with haematological malignancy characterized by 5q-. These unusual presentations of the 5q- anomaly further emphasize the heterogeneity of clinical presentations associated with this acquired chromosomal abnormality.
Due to the participation of intracellular free calcium in the mechanisms of vascular smooth muscle contraction, and its importance in the physiopathology of essential arterial hypertension, its possible role in pre-eclampsia physiopathology, was investigated as a cellular model, platelets, were use, as they are similar to vascular smooth muscle cells. The study purpose was to investigate if intracellular concentration of ionized calcium is greater in the patients with pre-eclampsia than in normotensive pregnant women, and also, if there exists a correlation between intracellular calcium concentrations and arterial tension, Seven pre-eclamptic patients, diagnosed by the following criteria: arterial tension greater than or equal to 130/90 mmHg, edema and proteinuria, between 20 to 35 years of age, during the third trimester of gestation, without personal nor family antecedents of hypertension; none of them received treatment at the time, were studied. As control group seven normotensive pregnant women, equal by chronologic and gestational age, were included. Intracellular calcium in platelets was measured by Fluo-3-Am, and arterial blood pressure with conventional sphygmomanometer. Intracellular calcium and arterial blood pressure values, were compared, in both groups by Student's t, and analysis of lineal regression between intracellular calcium and mean arterial blood pressure, was done. Intracellular calcium was significantly greater in patients with pre-eclampsia, than the ones in the control group (142 +/- 5.6 vs 110 +/- 14 p less than 0.0001). Mean arterial blood pressure was also significantly greater in patients with pre-eclampsia (114 +/- 5 vs 83 +/- 3 p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
In order to evaluate the usefulness of certain clinical and paraclinical characteristics to be able to discriminate the minimal change disease (MCD) from other histopathological lesions associated with the nephrotic syndrome (NS), the clinical charts of 31 patients were reviewed and relevant data were analyzed. Those patients with no history of biopsy and those with documented MCD through biopsy, were placed in one group (MCD = 25) and the rest as others (others = 6). None of the clinical or paraclinical indicators analyzed showed significant differences between either group. In the MCD group, 76% of the patients entered remission after receiving steroid treatment, while none of the others entered remission. The magnitude of the proteinuria, hypoalbuminemia, hypercholesterolemia, and the presence of hematuria, hypertension or hyperazoemia, were not useful to discriminate those with MCD from other lesions. The response to treatment with prednisone was the most useful data to differentiate the groups.
BACKGROUND: Southeast Asian ovalocytosis is a form of hereditary elliptocytosis in which the red cells are rigid and resistant to malaria invasion. The underlying molecular defect is unknown. METHODS AND RESULTS: We studied the red cells of 54 patients with ovalocytosis and 122 normal controls. We found that ovalocytes contain a structurally and functionally abnormal band 3 protein, the principal transmembrane protein of red cells. The structural lesion of ovalocyte band 3 was revealed by limited proteolytic cleavage of the protein, which produced fragments of abnormal size that were derived from the cytoplasmic domain of the protein. The structural lesion was present in all the subjects with ovalocytosis but none of the controls. This region of band 3 serves as the principal binding site for the membrane skeleton, a submembrane protein network composed of ankyrin, spectrin, actin, and protein 4.1. The structural defect is dominantly inherited, being tightly linked with the inheritance of ovalocytosis (the probability of linkage is in excess of 10 million to 1). Ovalocyte band 3 bound considerably more tightly than normal band 3 to ankyrin, which connects the membrane skeleton to the band 3 protein. This tight binding of ovalocyte band 3 to the underlying skeleton containing ankyrin was directly confirmed in intact cells by the finding that ovalocyte band 3 had markedly reduced lateral mobility in the membrane. CONCLUSIONS: The red cells in Southeast Asian ovalocytosis carry a structurally and functionally abnormal band 3 protein. This molecular defect may underlie the increased rigidity of the red cells and their resistance to invasion by malaria parasites.
We report the development of chronic lymphocytic leukemia in a 48-year-old woman with systemic lupus erythematosus of 5 years' duration. Although the association of autoimmunity and lymphoreticular malignancy is well known, this particular association has only rarely been reported. Possible mechanisms of pathogenesis are discussed.
Part of the teaching of clinical haematology to our third year medical students involves lectures given to the entire class. For the past several years, we have provided, at the beginning of each lecture, handouts on which are reproduced all or most of the 35-mm slides that will be projected during that lecture. The frames are positioned vertically on the left side of each page, thus allowing the students to add notes on the right side. There are advantages and disadvantages to this pedagogical method, but we believe that the former outweigh the latter.
A case is presented of a mother with unanticipated profound thrombocytopenia who received a continuous epidural anaesthetic for labour. No neurological sequelae or excessive bleeding occurred. It is clear, after a review of the literature, that more information is needed to define the lower limits of platelet count at which it is safe to proceed with epidural anaesthesia.
This article reports the rare occurrence and investigation of a specific anti-factor XI inhibitor that arose after fresh-frozen plasma infusion into a patient with previously unrecognized Factor XI deficiency. The IgG fraction of the patient's plasma that contained anti-Factor XI antibody was isolated by chromatography on DEAE-Affigel and concentrated. It was shown to exert inhibitory effect on purified Factor XI and XIa both in the activated and nonactivated partial thromboplastin time assay.