Direct evidence of a glucagon-dependent regulation of the concentration of glucagon receptors in the liver.
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Biomedical subjects
Publications and source records attributed to A Santos.
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There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.
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Four new imide derivatives of 3-nitro-1,8-naphthalic acid have been synthesised. The compounds show strong cytostatic activity against both HeLa and KB cells and are moderately toxic towards both mice and rats (LD50 above 4 mg/kg IP). Two of the most active compounds, M-4212 and M-12210, prevented the development of mouse Ehrlich ascites and rat Yoshida carcinoma. All these drugs block cell growth by inhibiting the synthesis of both DNA and RNA. In particular, both M-4212 and M-12210 raise the melting point of double-stranded DNA.
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The effects of eighteen compounds obtained from bulbs of the Amaryllidaceae family were tested on (a) animal cell growth, (b) DNA, RNA and protein synthesis by intact cells and (c) protein synthesis in cell-free systems. Dihydrolycorine, haemanthamine, lycorine, narciclasine, pretazettine and pseudolycorine halted HeLa cell growth at 10(-1) mM or lower concentrations. These compounds at their growth inhibitory concentrations block protein synthesis in ascites cells and stabilize HeLa cell polysomes in vivo. Endomyocarditis virus RNA-directed cell-free polypeptide synthesis by an ascites S-30 extract and acetyl-[14C]leucyl-puromycin formation by ascites ribosomes are also inhibited by the six compounds indicated above. It is therefore concluded that they halt protein synthesis in eukaryotic cells by inhibiting the peptide bone formation step.
The suitability of the circumoval precipitin (COP) test in a field survey for schistosomiasis in the rural area using dried blood samples on filter paper was evaluated with reference to the stool examination by the merthiolate-iodine-formaldehyde concentration (MIFC) technique. Both blood and stool samples were collected simultaneously among over 600 inhabitants of two schistosomiasis endemic communities (barrios) of Palo, Leyte, Philippines. The method of collecting blood samples on filter paper, the procedure for COP test and its sensitivity in detecting schistosomiasis cases are described. Blood sampling from finger prick was acceptable to both adults and children so that blood samples were readily obtained while the collection of stool samples required repeated visits to the homes. A significantly higher percentage of schistosomiasis positives were obtained by COP test than by stool examination. The COP test results were comparable to the stool examination results on the following aspects: 1) highest infection rate in the 10-19 age group and lowest infection rate in the 60 years old and above; 2) positive rates for schistosomiasis did not differ significantly between the two barrios and 3) no family accumulation of the disease in the two communities was observed in this survey in 1972. The stability of the antibody in filter paper, the reliability of the test and the simple and rapid procedures involved make this filter paper method of COP test very practical and suitable for schistosomiasis survey in rural areas.
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The effectiveness of single oral doses of ivermectin (200 or 400 micrograms/kg) and diethylcarbamazine (DEC, 6 mg/kg), preceded 4 d earlier by either placebo or very small doses of these drugs, was compared, over a 2-year period, in a double-blind trial in 67 microfilaraemic Brazilian men with bancroftian filariasis. Regimens containing ivermectin alone decreased the number of microfilariae significantly faster and more effectively for the first month after treatment than regimens containing DEC alone, but the latter were significantly more effective throughout the second year after treatment (1.7-8.2% of pretreatment levels with DEC vs. 12.6-30.8% with ivermectin during that period); the higher ivermectin dose showed a tendency towards more effectiveness than the lower dose. Most effective was the combination of ivermectin (20 micrograms/kg) followed 4 d later by DEC (6 mg/kg), with reduction of microfilaraemia to 2.4% of pretreatment levels at 2 years. Adverse reactions were well tolerated with all regimens, the reactions being significantly more generalized (i.e., fever) following ivermectin and localized (i.e., scrotal inflammatory nodules around dying adult worms) following DEC. Further trials of single-dose combination therapy vs. single high doses of ivermectin or DEC should determine the ideal regimen for treatment and control of bancroftian filariasis.
Records on all patients with arterial gas embolism (AGE) presenting to UCSD from 1982-1989 and for whom chest radiographs were available were reviewed. Of the 31 patients, 13 roentgenograms (42%) showed evidence of pulmonary barotrauma demonstrated by pneumomediastinum (N = 8), subcutaneous emphysema (N = 3), pneumocardium (N = 2), pneumoperitoneum (N = 1), or pneumothorax (N = 1). Pneumopericardium was not seen. Sixteen (52%) of the 31 patients had pulmonary infiltrates. Radiographic evidence of barotrauma was on occasion subtle, and in four cases was overlooked. Evidence of barotrauma (i.e., extra-alveolar air) was often identified along the left cardiac border, aortic arch, descending aorta, and hilar vessels. Subtle findings of ectopic air can confirm the clinical diagnosis of AGE; however, radiographic evidence of concomitant near drowning occurs more frequently.
We retrospectively studied all 1149 transplants performed at our center between 1993 and 2003 to determine the incidence and clinical effect of pretransplant B-positive cross-match on kidney graft survival. The patients were divided in two groups: B-negative (n = 1102) and B-positive in current sera (n = 47; 4.1%). AB-positive test was more frequent among regrafted patients (14% vs 3%; P = .00). Demographic data were not different between the groups. The overall rate of graft loss was similar (26% vs 24%, respectively; P = .86). However, early nonsurgical graft losses were more frequent among B-positive patients (46% vs 20%, respectively; P = .04). IgM was the most frequent immunoglobulin in the B-positive group (76% IgM and 24% IgG). There was no significant difference between B-negative and B-positive groups in the 1-, 5-, and 10-year graft survival rates (87% vs 83%, 73% vs 78%, 64% vs 66%, respectively; P = .87). The graft survival was significantly reduced comparing an IgG anti-B cell to the B-negative group (P = .03) as well as IgG compared to IgM (P = .004). In conclusion, only B-positive cross-match due to IgG decreased graft survival. Even though it is an uncommon situation (0.9%), this study stressed the clinical value of the B-cell cross-match as a tool to identify patients with a higher immunological risk.
Cytomegalovirus (CMV) infection is a frequent complication in transplant recipients, causing a high level of morbidity and mortality. We studied 203 consecutive renal transplant recipients performed between January 2000 and December 2001. Patients underwent weekly measurements of CMV pp65 antigen to assess CMV activity from the 4th to the 12th week posttransplantation. The results were reported as number of cells positive for the pp65 antigen among 10(5) granulocytes. In order to define a best cutoff to diagnose CMV disease with desirable sensitivity and specificity, we used a receiver operator characteristics (ROC) curve. The cutoff of four positive cells corresponded to a sensitivity of 93% and specificity of 60% (AUC = 0.87) for the diagnosis of CMV disease. The chosen cutoff for starting antiviral treatment was 10 cells, since this was associated with a sensitivity of 92% and specificity of 70% (AUC = 0.90). In conclusion, the highly sensitive cutoff points for the diagnosis of antigenemia was four cells and 10 cells for initiation of antiviral therapy.
To determine the extent to which Wuchereria bancrofti infections can be detected in asymptomatic amicrofilaraemic men in Greater Recife, Brazil, we studied 100 asymptomatic men who were long-term residents (> or = 15 years) of this filariasis-endemic area and who were amicrofilaraemic in 60 microL of capillary blood collected at night. Increasing amounts (1, 5, and 10 mL) of venous blood were collected in consecutive weeks, filtered, and examined for microfilariae; 27 men were eventually found to be microfilariaemic and 10 remained amicrofilaraemic but were found to be carriers of living adult W. bancrofti by ultrasound examination of the scrotal area. Thus, 37% of 'amicrofilaraemic' men (in 60 microL of blood) were found to be infected by more thorough investigation. Ultrasound is a valuable tool to identify adult worm infections in amicrofilaraemic persons, particularly for evaluation of serological assays and immunological studies in which the distinction between 'amicrofilaraemic adult worm carriers' and 'endemic normal subjects' is critical.
To assess directly the effect of various doses of diethylcarbamazine (DEC) on adult Wuchereria bancrofti, 31 infected men were randomly assigned to receive an initial single DEC dose of 1 mg/kg (n = 7), 6 mg/kg (n = 10), or 12 mg/kg (n = 14). Beginning 7 d later, the dosage of DEC and duration of treatment were progressively increased for 7-10 weeks. Physical examinations were performed to detect scrotal nodules and the scrotal area was examined by ultrasound (7.5 MHz transducer) to monitor the 'filaria dance sign' (FDS), the characteristic pattern of adult worm movement. Of 53 adult worm 'nests' that were detected by ultrasound, 22 (41.5%) were DEC-sensitive (FDS became non-detectable and a nodule became palpable at the site); 20 (37.7%) were not sensitive (FDS remained unchanged and detectable and no nodule developed), and 11 (20.8%) showed mixed responses (FDS remained detectable but a palpable nodule developed). All but one sensitive or mixed response occurred within 1 week after the initial single dose. Of 39 'nests' in men who initially received a single 6 or 12 mg/kg dose of DEC, 20 (51.3%) had sensitive responses compared to 2 (14.3%) of 14 'nests' in men who received a single 1 mg/kg dose (P = 0.04). Above 6 mg/kg, the macrofilaricidal effect of DEC did not increase with dose; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period.
When ivermectin and diethylcarbamazine (DEC) are given simultaneously in a single dose to persons with Wuchereria bancrofti infection, the resulting suppression of microfilaraemia is more profound and sustained than when either drug is given alone. To assess whether this effect is a result of enhanced macrofilaricidal efficacy, we used ultrasound to monitor the adult worms in the scrotal area of men with W. bancrofti microfilaraemia. Twenty-one men were treated simultaneously with DEC (6 mg/kg) and either 200 micrograms/kg or 400 micrograms/kg of ivermectin (11 and 10 men, respectively). Ten other men received a single 200 micrograms/kg dose of ivermectin followed 5 d later by a 6 mg/kg dose of DEC (sequential treatment). All men became amicrofilaraemic after treatment and all except one remained so for one year. Cessation of adult worm movement, indicative of death of all the adult worms in a given 'nest', was observed in none of 30 nests in men who received simultaneous treatment and in 3 of the 19 nests (16%) in the men who received sequential treatment (P = 0.05). Scrotal nodules were detected in 5 of 21 men (24%) who received simultaneous treatment and in 8 men (80%) who received sequential treatment (P < 0.01). Thus, co-administration of ivermectin with DEC seems to interfere with the macrofilaricidal action of DEC. These findings have implications both for treatment of the individual patient and for community-based drug distribution programmes designed to interrupt transmission of W. bancrofti.