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Biomedical subjects

A Gonzales

Publications and source records attributed to A Gonzales.

32 records · Page 2Linked to original sources

Pharmacokinetic studies in the rat on a o-raffinose polymerized human hemoglobin.

We have studied the plasma half-life (T 1/2), oxygen-binding affinity (P50), organ distribution, and excretion of the individual molecular weight (MW) components of human hemoglobin polymerized with periodate-oxidized, ring-opened raffinose (oR poly-Hb), following transfusion in the rat. The model was an isovolemic 50% exchange transfusion in the conscious, chronically catheterized rat. Total plasma Hb levels yielded a (T 1/2) of 10 to 11 hr for oR poly-Hb. The T 1/2 values of individual MW components of the poly-Hb as determined by size-exclusion HPLC were approximately: 4 hr for the monomeric fraction (Hb)1, 9 hr for the dimer (Hb)2, and 15 hr for the fraction representing trimers to nanomers (Hb)3-9. The P50 values of plasma samples containing oR poly-Hb (collected from 0-24 hr after exchange) remained unchanged at 28 +/- 3 mmHg. oR stabilized and polymerized Hb were not excreted via the kidneys. Hepatic and renal distribution as well as plasma and renal clearance were determined by liquid scintillation counting using individual tritium [3H] labelled MW components purified from [3H]-oR poly-Hb: (Hb)1/2, (Hb)1, (Hb)2, (Hb)3&4, and (Hb) greater than 9. In kidney, uptake (determined by the relative concentration of radioactivity) decreased with increasing MW of the labelled component. Conversely, in liver, uptake increased with increasing MW. Plasma and renal clearance results were consistent with those obtained by HPLC analysis. Hematocrit levels returned from a 20% post-transfusion level to normal pre-transfusion levels (44%) within 10 days after the exchange.

Animals↗

The role of the kidneys in the excretion of chemically modified hemoglobins.

Stroma-free hemoglobin (SFHb) can be chemically modified to prolong the intravascular retention (prevent renal filtration), and to improve oxygen delivering capability for use as a red cell substitute. Hb derivatives radioactively tagged with tritium [3H] or 14C were used to study their metabolic fate following clearance from the circulation. Fully conscious, chronically cannulated rats were treated by exchange transfusion (ET). Hb solutions tested were: PLPHb (Hb monovalently reacted with pyridoxal 5'-phosphate); HbXL (Hb crosslinked beta-beta with 2-nor-2-formylpyridoxal 5'-phosphate, or with bis-pyridoxal tetraphosphate); alpha alpha Hb (Hb cross-linked between the alpha-chains using bis-3,5-dibromosalicyl fumarate); and polyHb (polymerized with glutaraldehyde or o-raffinose). Plasma retention (T1/2) was significantly affected by dose and the degree of cross-linking. Urine flow rates all increased transiently above normal. In rats treated with any 64 kDa interdimerically cross-linked Hb, mild hemoglobinuria was evident and kidney tissue had the highest label concentration at all time points (1, 5, 10, 24, 48 hr, 7 d, and 14 days post-ET). For polymerized Hb derivatives, the amount of radioactivity in urine and kidneys was inversely related to the MW of the polyHb molecules. In all rats, regardless of the Hb derivative tested, the majority of radioactivity (dpm's) was excreted in urine. About 75% of all renal excretion of radioactivity occurred from 12-60 hours post-ET. This provided evidence that catabolism of cross-linked Hb's began early, and that the kidneys are primarily responsible for excreting smaller degradation fragments.

Animals↗

Pregnancy and relapse of peripheral T cell lymphoma. A case report.

A patient was admitted to our hospital, in the 34th week of her pregnancy, who presented a non-Hodgkin lymphoma. The delivery was induced in the 38th week and the newborn baby had no other anomalies than a single umbilical artery and a slight dilation of the cerebral ventricles which receded spontaneously. Peculiar characteristics, not previously described, were a peripheral T cell lymphoma with relapse after 5 years since its remission with chemotherapy.

Adult↗

Effects of hypertonic saline (7.5%)/dextran 70 on human red cell typing, lysis, and metabolism in vitro.

The introduction of a 7.5% hypertonic saline/6% dextran 70 (HSD) solution into clinical trials for the treatment of hypovolemic states, and the past concerns regarding the possible interference of dextran with blood serology, prompted us to investigate the effects of HSD on human red-cell typing and stability. HSD was evaluated with fresh and 35-day stored CPDA-1 red cells from 12 healthy donors. A 1:5 mixture of HSD to blood in vitro had no effect on ABO, Rh, and MN typing in both fresh and stored blood. HSD produced no significant lysis with fresh cells and a minimal level with stored blood. No evidence of metabolic or morphologic changes was seen after HSD treatment. The results of this study suggest that the clinical use of HSD for the treatment of hemorrhagic shock will not affect blood group determinations or red-cell stability from stored blood which may be infused after the HSD-treated patient is transported to a hospital.

Blood Grouping and Crossmatching↗

Response of blood pressure, cardiac output, peripheral resistance, and exercise performance to substitution of calcium blocker for beta-blocker plus thiazide diuretic therapy in patients with both systemic hypertension and mild stable angina.

We studied 14 patients to determine whether sustained-release diltiazem is a satisfactory long-term substitute for the combination of propranolol plus hydrochlorothiazide (HCTZ), control phase, in the treatment of systemic hypertension with coexisting chronic stable angina pectoris. All patients had either one- or two-vessel coronary disease and normal left ventricular systolic function. Measurements were made during the control phase and 4 and 8 weeks after substitution of sustained-release diltiazem. Only the sitting blood pressure was available before the control phase (pretreatment). Blood pressure and heart rate were measured with patients supine, sitting, and 5 minutes after standing. Cardiac output was measured in the supine position using a computerized Doppler system, and stroke volume, mean arterial pressure, and total systemic resistance were calculated. Symptom-limited modified Bruce protocol treadmill tests were performed to determine time to onset of 1 mm ST segment depression, time to termination of exercise, reason for cessation of exercise, and maximum rate-pressure product. The patients were initially receiving 160-240 mg/day of propranolol (40-60 mg q.i.d.) plus 25-50 mg/day of HCTZ and, subsequently, 12 of 14 had substitution with 240 mg/day (120 mg b.i.d.) of sustained-release diltiazem, and two received 360 mg/day with one of these patients also receiving 50 mg/day of HCTZ. These patients are a subset of a larger group of patients in whom the response of blood pressure alone has been previously reported. Diltiazem resulted in reduction of blood pressure equivalent to that with the propranolol plus HCTZ combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Effect of pharmacologic therapy on angina frequency, ST segment depression during ambulatory ECG monitoring, and treadmill performance in patients with chronic stable mild angina.

Fifteen patients aged 55 +/- 6 years (mean +/- SD) with mild, chronic stable angina were evaluated after 2 weeks of sublingual nitroglycerin therapy (control) and also after 12 weeks of treatment with either propranolol, up to 320 mg per day, or nifedipine, up to 120 mg per day, in order to measure signs of ischemia and the response of symptoms to therapy. Compared with the control period, there was a decrease in average daily episodes of angina from 1.0 +/- 0.8 to 0.5 +/- 0.4 with treatment (p = 0.10). There was a significant decrease of greater than or equal to 1.0 mm ST segment depression (both symptomatic and asymptomatic), from 6.1 +/- 6.5 to 1.5 +/- 2.4 episodes per 24 hours, p less than 0.001, and of asymptomatic episodes of ST segment depression, from 3.5 +/- 3.9 to 1.0 +/- 2.1 episodes per 24 hours, p = 0.03. The number of patients who had any episodes of greater than or equal to 1.0 mm ST segment depression on their 24-hour ECG decreased from 14 to 6 (93% to 40% of patients, p = 0.005) with treatment, and the number of patients with any episodes of ST segment depression without symptoms decreased from 11 to 5 (73% to 33% of patients, p = 0.07). There was an insignificant increase in treadmill time from 333 +/- 134 to 380 +/- 156 seconds, and an insignificant decrease in maximum double-product from 16,631 +/- 3,599 to 14,922 +/- 4,086; the number of patients with angina at maximum exercise decreased from 13 to 10 (87% to 67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients.

From May 1983 to January 1984, 517 patients with laboratory confirmed dengue were studied at a hospital in Manila. Secondary dengue infections were diagnosed in 78% of these cases. Peak admission (28%) occurred towards the end of the rainy season in November. Most patients (78%) were less than 15 years old but only 3 were infants. Although some type of hemorrhagic finding occurred in 460 cases (89%), only 110 were classified as dengue hemorrhagic fever and the remainder as dengue fever with hemorrhagic manifestations. The clinical course was usually mild. Gastrointestinal bleeding was present in 65 cases, but only 2 patients developed shock. No fatalities occurred. Dengue 2 was the predominant serotype with 53 isolates, followed by dengue 1 with 48 isolates, dengue 3 with 39 isolates, and dengue 4 with only 8 isolates. Dengue 2 was the only serotype with more isolates from sera with a homologous HI antibody titer greater than 1:20 (57%) than from sera with a homologous HI titer less than or equal to 1:20 (43%). In contrast, most of the dengue 1 isolates (63%) were from sera with a homologous HI antibody titer less than 1:10, and this serotype was strongly associated with primary infections. This study shows that dengue infections remain an important cause of pediatric hospitalization in the Philippines; however, the occurrence of life-threatening dengue hemorrhagic fever as has been described in several other large urban areas of Southeast Asia appears to be rare.

Adolescent↗

Hematologic changes after two exposures to 6.7 ATA air at three-day intervals.

Hematologic parameters were studied in human subjects exposed to various diving regimens. A series of exposures in a dry chamber to a simulated depth of 188 ft of seawater gauge (fswg), 6.7 ATA, utilizing compressed air, were carried out according to standard Navy diving tables. The subjects were serially followed for a control period prior to diving and subsequently for up to 1 wk. Little significant change occurred except for alterations in some platelet factors. In another series of experiments, the single excursion was followed by a second dive to 188 fswg 3 days later, again with appropriate hematologic monitoring. A pronounced eosinopenia and increased clotting times were observed soon after reaching the surface. Platelet depletion associated with increased clumping and elevated megathrombocyte levels persisted long after the second excursion. A latent hemodilution also developed 3--5 after the second dive. These findings clearly demonstrate that repeated hyperbaric exposures produce additive effects and further suggest that no diving procedure is completely innocuous.

Adult↗

Does human melanoma express carcinoembryonic antigen?

BACKGROUND: Several investigators have proposed that carcinoembryonic antigen (CEA), an immunogenic antigen expressed by colon carcinoma, may also be expressed by human melanoma. Because sialyl Lewisx (sLex), the carbohydrate moiety of CEA, has been identified in melanoma, we compared CEA and sLex levels in colon carcinoma cells and melanoma cells. METHODS: CEA levels were assessed for expression on the cell surface and in cell lysates of cutaneous melanoma cell lines by two different kinds of ELISA, and by Western blot analysis of immunoprecipitated CEA using monoclonal antibodies (Mabs) T84-66 and COL-1, which have defined specificities for CEA. Colon carcinoma cells and purified CEA were positive controls. RESULTS: Both Mabs reacted strongly with cell surface and cell lysates of colon cancer. Mab T84-66 reacted well with cell surface but not cell lysates of melanoma. COL-1 reacted poorly with cell surface but its binding increased with the density of melanoma cell lysates. Both Mabs intensely stained the blots of purified CEA and colon carcinoma lysates immunoprecipitated with the respective Mabs, but failed to stain the immunoprecipitates of melanoma cell lysates. Both Mabs bound to lysates immunoprecipitated with anti-sLex Mab in colon carcinoma, but not in melanoma. Cell-surface expression of CEA and sLex was significantly correlated (r2: 0.88) in colon cancer cells but not in melanoma. CONCLUSION: Our results confirm the presence of CEA in colon carcinoma but not in human cutaneous melanoma cell lines.

Animals↗