Brief report: melatonin-related hypogonadotropic hypogonadism.
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Biomedical subjects
Publications and source records attributed to J Serrano.
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The clinical utility of the Ga-67 scan has been studied in 9 patients with clinical suspicion of vascular graft infection. Eleven grafts were analyzed: 4 aortobifemoral, 2 iliofemoral, 3 femoropopliteal, 1 axillofemoral, and 1 axillobifemoral. The Ga-67 scan was positive in 8 grafts with bacteriological proof of infection and negative in 3 grafts in which infection was ruled out by clinical follow-up. A Ga-67 scan also demonstrated the spread of infection to the thigh in two patients and to the pelvis in another two patients. In 4 patients CT was performed. The CT findings included graft thrombosis, perigraft fluid collection and thickened graft wall. No discrepancies were found between the CT scan and Ga-67 scan. In three patients a control Ga-67 scan was carried out after specific antibiotic and surgical treatment. Two of these showed increased Ga-67 uptake and spreading of infection along the graft; in the other patient, a Ga-67 scan revealed normalization after resolution of an abdominal abscess. In conclusion, the Ga-67 scan proved useful in the diagnosis of vascular graft infection, the definition of location of the extent of the disease and in the evaluation of the efficiency of treatment.
PURPOSE: To propose a new aetiologic classification of the patients suffering from autoimmune haemolytic anaemia (AIHA). MATERIAL AND METHODS: Two-hundred cases of AIHA studied and followed-up between 1970 and 1989 are presented. From an aetiological and pathogenetic standpoint the disease was classified into 4 groups: (1) idiopathic, (2) secondary, (3) associated and (4) accompanying. RESULTS: The percentage of the different AIHA types, in accordance with the antibodies behaviour, was: (1) warm-reacting AIHA, 74.5%; (2) cold-reacting, 19%; (3) combined or mixed pattern, 6.5%. The immunoglobulins fixed on red cell surface and the specificity of the antibodies found corresponded to those reported in the literature. No treatment was needed in 27.5% of the cases. Corticosteroids were the therapy used in virtually all the cases. Corticosteroids were favourable effect could be appreciated in about 80% of the patients treated. Splenectomy had to be performed in 13.1% of the patients; 47.4% of them attained complete remission while 56.2 failed to respond. Nonsteroid immunosuppressive agents were used in 16.5% of the cases, with 50% of total or partial responses. There are striking prognostic-evolutive differences when this study is viewed from the patients or the AIHA standpoints. Thus, the mortality reached 57.5% of the cases, but in only 10% it was related with AIHA, and something similar could be said about remissions. CONCLUSIONS: The analysis of this series allows one to establish: (1) four aetiopathogenetic groups of AIHA; (2) a high percentage of cases related with severe underlying diseases; (3) over 50% incidence in people over 50 years of age, and (4) natural ageing of the series is appreciated after a long follow-up (1-20 years).
A forty-eight year old man with Hodgkin's disease in complete remission after 8 cycles of polychemotherapy (COPP) is presented. In an abdominal tomography, practiced 18 months after completion of treatment, two masses were found on the left kidney. Differential diagnosis between a Hodgkin's recidive and a second primary tumor and the implication of Hodgkin's treatment in the appearance of other neoplasms are discussed. Literature is reviewed.
Insulin and insulin-like growth factor I (IGF-I) initiate their metabolic, growth, and differentiation effects through binding to the insulin receptor and the IGF-I receptor, two members of the tyrosine kinase family of receptors. To study the role of these peptides and receptors in early development, we used the polymerase chain reaction and embryo-derived RNA to generate partial cDNA sequences of the insulin receptor and IGF-I receptor from the amphibian Xenopus laevis. Three unique tyrosine kinase-related sequences were obtained. Two of the nucleotide sequences, XTK 1a and XTK 1b, corresponded to peptide that share 92% amino acid identity, and each is 89% identical to the human insulin receptor. The third sequence, XTK 2, corresponds to a peptide that has 92% amino acid identity with the human IGF-I receptor but only 80% identity with XTK 1a and XTK 1b. On the basis of these similarities, the pattern of conserved amino acids, and the tetraploid nature of the Xenopus genome, we suggest that XTK 1a and XTK 1b most likely represent the product of two different nonallelic insulin receptor genes, while XTK 2 may be one of the probable two Xenopus IGF-I receptor genes. By reverse transcription-polymerase chain reaction and gene-specific hybridization, expression of the three XTK sequences was detected in the oocyte, unfertilized egg, and embryos through gastrulation, neurulation, and tailbud stages. Competition binding assays with Xenopus membrane preparations demonstrated insulin receptors and IGF-I receptors in older tadpoles. IGF-I receptors were also present in oocytes, eggs, and gastrula embryos. By contrast, insulin binding was present but atypical in oocytes and was barely detected in eggs and gastrula embryos. The expression of receptors for insulin and IGF-I in early Xenopus embryos and their apparent distinct developmental regulation suggest that these molecules and their ligands may be important in early Xenopus development.
Twenty-six symptomatic patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II Italian Lung Cancer Task Force (FONICAP) study to assess the activity and toxicity of doxorubicin and cisplatin combination chemotherapy. The drug schedule was as follows; 60 mg/m2 of doxorubicin and 60 mg/m2 of cisplatin both given intravenously (IV) on day 1 every 3 to 4 weeks. Of the 24 evaluable patients, 6 objective partial responses (25%; 95% confidence limits, 9.77% to 46.71%) were observed. Twelve of 24 patients (50%), including 6 with no radiologic evidence of response, had a clinical improvement as demonstrated by an objective reduction of symptom or performance status scores along treatment. The overall median survival time was 10 months. Toxicity was mild and dose reductions or suspensions were not required. The combination of doxorubicin and cisplatin is effective and well tolerated. It might be considered for palliation of symptomatic patients with DMPM.
The early expression of insulin and insulin-like growth factor I (IGF-I) in the chicken embryo suggests that these peptides play an important role in early development. The receptors for insulin and IGF-I, however, had not been studied at the molecular level in this model. We report two chicken sequences that, by comparison with known tyrosine kinases, appear to correspond to the tyrosine kinase domain of the insulin receptor homologue (CTK-1) and the IGF-I receptor homologue (CTK-2). Using reverse-transcription of RNA, amplification with the polymerase chain reaction (RT-PCR), and gene-specific hybridization, we demonstrate that the two genes, CTK-1 and CTK-2, are expressed in embryos at least as early as the blastoderm (Day 0), during neurulation (Day 1), and in early (Days 2-3) and late (Day 9) organogenesis.
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An experimental model of congenital intestinal obstruction (CIO) was created in rats by means of fetal intrauterine surgery between the 16th and 20th days of gestation. By the use of a microsurgical technique areas at the mid-jejunum or the jejuno-ileal junction were infarcted by coagulation of mesenteric vessels. Gestation was terminated by Cesarean section within 24 hours before expected term to avoid cannibalism. The structure of the intestinal mucosal cells proximal and distal to the CIO at the light microscopy as well as the ultrastructure level was not changed indicating that the surgical method was successful. The activities of the brush border enzymes, maltase and lactase were significantly reduced distal to the obstruction as compared to controls. Proximal to the obstruction lactase was the only enzyme showing reduced activity in comparison to controls. These findings were not dependent on the localization of the obstruction or when it was performed and suggest that CIO causes selective changes of the biochemical properties of the cell membrane. The results are in agreement with the findings of disaccharidase activities in biopsies taken from human infants with CIO and point to the importance of a normal intestinal passage for the development of brush border enzymes.
The avian embryo has been a useful model system for studies on the role of insulin and its close relative insulin-like growth factor-I (IGF-I) in development. The unfertilized chicken egg contains both peptides from maternal origin, and the embryo expresses insulin and IGF-I before the major organs are formed. Insulin receptors and IGF-I receptors are found in the blastoderm and in all tissues examined during organogenesis. When exogenous insulin or IGF-I are added to the embryo, growth and differentiation events are stimulated. By contrast, insulin antibodies and insulin receptor antibodies retard embryo development. In embryos cultured ex ovo, in which growth is impaired, the levels of serum IGF-I are decreased.
Since anti-Rho (D) was reputed as the major cause of significant haemolytic disease of the newborn (HDNB), the introduction of Rh-immunoglobulin (Rh-Ig) in the late 1960's made it possible to prevent the risk of sensitisation to Rho (D) in 85-90% of the cases. The use of Rh-Ig has no effect on ABO or non-ABO, non-D incompatibilities. These facts have induced a change in the frequency of HDNB. On the other hand, the use of Rh-Ig has provided evidence that treatment with exchange transfusion has strikingly decreased in HDNB. In order to assess the incidence of potential and actual ABO, Rho (D) and non-ABO, non-D foeto-maternal incompatibility, cord-blood samples from 12,830 newborns were studied. Although potential ABO incompatibility with their mothers was found in 2,470 babies (19.1%), only 183 of them (7.4%) developed actual sensitization. Such figure represents only 1.4% of the ABO incompatibility, as a whole, in all the newborns. Regarding Rho (D), foeto-maternal incompatibility was present in 1,168 babies (9.1%), of whom 39 (3.3%), i.e., 0.3% of all the newborns, developed actual sensitization. Assuming that before the introduction of Rh-Ig 17% of the pregnant women at risk developed anti-D, we had prevented 80.3% immunization. Most of the 39 sensitized women presented circumstances to explain this fact. Only 7 cases of non-ABO, non-D immunization have been found, which represent 0.05% of all the newborns studied. The prognosis of the different forms of foeto-maternal incompatibility is in our hands similar to that published elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)
Along 17 years (1973-1989), syphilis screening has been performed on 146,355 blood units in the author's blood bank. A total number of 143 positive results (confirmed by MHA-TP) was registered, which means an incidence of 0.097%. Of the total number of blood units, 31,529 came from professional donors, 51 of them (0.16%) being positive, while of the 114,826 blood units from voluntary donors 92 were positive (0.08%). With respect to voluntary donations, the highest incidence of positive reactions was found between 1980 and 1982, but this period registered also the highest number of blood units studied. Along this 17 year period 8 patients have received blood products with positive syphilis test. They were transfused on urgent request with fresh blood or platelet concentrates, the transfusion being performed before knowing the results of the screening for syphilis. No special measures were taken in 2 such cases, who died shortly after the transfusion on account of their disease. Two other were treated with penicillin at the time of transfusion. The remaining four patients received preventive penicillin. Even taking into account that positive screening tests are uncommon amongst blood donors, and that only under special circumstances the patients receiving contaminated blood may develop the illness, it seems advisable for every blood bank to perform the screening for syphilis on every blood donation.
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To assess the prognostic value of tumor proliferative activity, 89 patients with operable non-small cell lung cancer were studied. Tumor samples were obtained during surgery and cell kinetics were analyzed by the in vitro thymidine labelling index (TLI). The overall median TLI (2.9) was used to identify two subsets of patients with high and low proliferating tumors. In univariate analysis survival was significantly longer in patients with lower TLI (P = 0.047) and with stage I-II (P = 0.003) and T1-T2 tumors (P = 0.043). In multivariate analysis, stage was the most important prognostic parameter (P = 0.004). The risk of death for patients with TLI higher than 2.9 was increased (hazard ratio = 2.01, CI = 0.96-4.27).
A 66 year old patient with multiple myeloma and monoclonal cryoglobulinaemia who developed a severe haemolytic anaemia following a cytomegalovirus infection is reported. The presence of a high titre of anti-'i' cold antibody of IgM subclass is demonstrated. Anti-'i' antibody disappeared when complement-fixation antibody titres against cytomegalovirus decreased. Various pathogenetic mechanisms involved in the development of haemolytic anaemia associated with cytomegalovirus infection are discussed. To our knowledge, this is the first case described in the English language publications associating severe haemolytic anaemia with an anti-'i' antibody after a cytomegalovirus infection in an immunocompromised patient.
A definition of the role of IGF-I in differentiation and development requires a detailed understanding of its expression and tissue-specific regulation in embryogenesis. Standard techniques for analysis of IGF-I gene expression are not sufficiently sensitive for studies in early embryos. We have used the highly sensitive polymerase chain reaction (PCR) to study IGF-I gene expression in whole chick embryos from the late blastula stage (E0 = laying) through the end of organogenesis (day 8), and in liver, brain and pancreas during mid-late embryogenesis and perinatally (hatching = day 21). Although at low levels in the blastoderm and gastrula, IGF-I mRNA was detectable in the whole embryo in all stages studied, with a tendency of the signal to increase with age during the first week of embryogenesis. In mid- and late embryogenesis, we easily detected IGF-I mRNA transcripts in pancreas and brain while the levels in the liver were barely detectable. Liver IGF-I mRNA increased markedly at the peak of postnatal growth (day 50). These studies suggest that while the major source of postnatal IGF-I may be the liver, extrahepatic tissues may be the predominant source of IGF-I during prenatal chicken development.
The concentration of melatonin and LH were determined in plasma samples obtained at 10-min intervals during 4 h of darkness (00.00-04.00 h) from 4 normal women, age 23-27 years, in the early follicular phase of the menstrual cycle and in 6 normal men, age 23-31 years. Additionally, melatonin concentration was determined in samples obtained from the men at 10-min intervals for 4 h during the day (10.00-14.00 h). A pulsatile pattern of melatonin secretion was found for all the subjects during darkness. There was no significant difference between women and men as to the number of pulses (2.8 +/- 0.5 vs 5.2 +/- 1.0 per h), amplitude of pulses (51.3 +/- 28 vs 27.2 +/- 6 ng/l), concentration per 4 h (32.5 +/- 13 vs 31.0 +/- 5 ng/l), or apparent half-life of melatonin (19.3 +/- 2.3 vs 15.3 +/- 7.5 min). The mean amplitude of the melatonin pulse correlated (r = 0.863, p less than 0.001) with the mean melatonin concentration per 4 h. A pulsatile LH secretion pattern was found for the 10 subjects and did not correlate significantly with the melatonin secretion pattern. The results are consistent with an independent signal for the demonstrated nyctohemeral pulsatile melatonin and LH secretions.