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Biomedical subjects

D Garcia

Publications and source records attributed to D Garcia.

At least 55 records · Page 3Linked to original sources

Initial screening for antituberculous drug resistance at an inpatient facility in Leon, Nicaragua.

Antituberculous (anti-TB) drug resistance has become a major tuberculosis control issue in the United States, where this situation has closely paralleled the current acquired immunodeficiency syndrome epidemic associated with human immunodeficiency virus type-1 (HIV-1) infections. In less developed countries, especially those like Nicaragua with an apparently low prevalence of known HIV-1 infections, less is known about the epidemiology of antituberculous drug resistance. To understand the potential extent of this problem in Nicaragua, we conducted a cross-sectional prevalence study at Nicaragua's only inpatient tuberculosis treatment facility, located in Leon, Nicaragua. A radiometric method was used during recovery, purification, and drug susceptibility testing of clinical Mycobacterium tuberculosis isolates. Resistance to at least one of the major anti-TB medications was found in 15 (40.5%) of 37 sputum isolates, of which seven (19%) were resistant to either isoniazid alone, or to isoniazid plus another agent other than rifampin. Five were resistant to at least isoniazid and rifampin (i.e., 13.5% demonstrated multidrug resistance). Two isolates were resistant to pyrazinamide alone, and one was resistant to streptomycin alone. These initial results suggest that anti-TB drug resistance is a defined problem for tuberculosis control programs in Nicaragua, a problem that is largely related to individual noncompliance, lack of extensive drug susceptibility testing facilities, and a general unavailability of expensive anti-TB medications for re-treatment. Ongoing surveillance for drug resistance, using the methodology presented here, might assist Nicaraguan public health officials in their tuberculosis control programs.

Adult↗

Brachytherapy or electron beam boost in conservation therapy of carcinoma of the breast: a nonrandomized comparison.

PURPOSE: The results of breast-conservation therapy using breast irradiation and a boost to the tumor excision site with either electron beam or interstitial 192Ir implant are reviewed. METHODS AND MATERIALS: A total of 701 patients with histologically confirmed Stage T1 and T2 carcinoma of the breast were treated with wide local tumor excision or quadrantectomy and breast irradiation. The breast was treated with tangential fields using 4 or 6 MV photons to deliver 48 to 50 Gy in 1.8 to 2 Gy daily dose, in five weekly fractions. In 80 patients the regional lymphatics were irradiated. In 342 patients with Stage T1 and 107 with Stage T2 tumors, boost to the primary tumor excision site was delivered with 9 MeV and, more frequently, with 12 MeV electrons. In 91 patients with Stage T1 and 38 patients with Stage T2 tumors an interstitial 192Ir implant was performed. Tumor control, disease-free survival, cosmesis, and morbidity of therapy are reviewed. Minimum follow-up is 4 years (median 5.6 years; maximum, 24 years). RESULTS: The overall local tumor recurrence rates were 5% in the T1 and 11% in the T2 tumor groups. There was no significant difference in the breast relapse rate in patients treated with either electron beam or interstitial 192Ir boost. Regional lymph node recurrences were 1% in patients with T1 and 5% with T2 tumors. Distant metastases were recorded in 5% of the T1 and 23% of the T2 groups. The 10-year actuarial disease-free survival rates were 87% for patients with T1 and 75% with T2 tumors. Disease-free survival was exactly the same in patients receiving either electron beam or interstitial 192Ir boost. Cosmesis was rated as excellent/good in 84% of patients with T1 tumors treated with electron beam and 81% of patients treated with interstitial implant, and 74 and 79% respectively, in patients with T2 tumors. CONCLUSIONS: Breast-conservation therapy is an effective treatment for patients with T1 and T2 carcinoma of the breast. There is no difference in local tumor control, disease-free survival, cosmesis, or morbidity in patients treated with either electron beam or interstitial 192Ir implant boost. Clinical trials in progress will further elucidate this controversial subject.

Brachytherapy↗

Morning report: a forum for reporting adverse drug reactions.

BACKGROUND: Most hospitals that monitor adverse drug reactions (ADRs) through reporting by nurses, pharmacists, medical record technicians, and quality improvement staff experience low rates of reporting. In teaching hospitals, inadequate orientation about the hospital activities, frequent changes in rotations between hospitals, and time commitments to educational pursuits may all undermine house staff's ability to perform ADR monitoring. The authors describe their experience since 1989 at the Department of Veterans Affairs Medical Center in Amarillo, Texas, in the use of verbal ADR reporting by physicians (mostly house staff) during the morning report in the medical service. ADR MONITORING PROGRAM: The morning report begins with a discussion of adverse outcomes of medications, usually from the previous 24 hours. The staff physicians use the opportunity to address the nature of the ADRs and the clinical circumstances leading up to them. Some ADR episodes require further peer review by a physician before being forwarded to the Pharmacy and Therapeutics Committee. EFFECT OF THE PROGRAM: Since the start of the ADR monitoring program in 1989, the number of self-reported ADRs in the medical service has increased over historical controls, even though no special training was given to house staff to detect ADRs. The surgical and psychiatric services, which did not hold morning reports, did not experience the same increase in ADR reports. CONCLUSIONS: The ADR monitoring program is notable for the simplicity of the reporting mechanism, the integration of the reporting into the regular work flow activities, the concurrent nature of the reporting, the educational opportunities, and the potential benefit for quality improvement of patient care.

Adverse Drug Reaction Reporting Systems↗

Mapping 638 STSs to regions of human chromosome 3.

The initial step of mapping STSs to chromosome 3 has been by mapping to a reference panel of 21 somatic cell hybrids containing fragments of chromosome 3. In this study we map 638 STSs to 23 bins on chromosome 3. The bin information greatly facilitates further mapping by radiation hybrids and YAC clones.

Chromosome Mapping↗

Effect of hypoxia on glucose-modulated cerebral lactic acidosis, agonal glycolytic rates, and energy utilization.

Newborn and 1-mo-old swine were exposed to identical durations (18 min) and degrees of hypoxia (O2 content = 4 mL/dL), to examine the effects of hypoxia on cerebral energy metabolism and intracellular pH (pHi) in vivo, using 31P and 1H nuclear magnetic resonance spectroscopy. Hypoxia produced the same extent of reductions in phosphocreatine (PCr) (63 +/- 28% and 65 +/- 10%, newborns and 1-mo-olds, respectively) and pHi (6.93 +/- 0.06 and 6.89 +/- 0.06, respectively) for either age group. The magnitude of changes in PCr, lactate, and pHi was larger for subgroups of data collected when cardiovascular instability was present, suggesting that hypotension and possibly reduced cerebral perfusion contributed to cerebral energy failure and lactic-acidosis for either age group. There were no correlations between the blood plasma glucose concentration at 18 min of hypoxia and the extent of change in PCr, lactate, or pHi for either age group. During a subsequent period of complete ischemia induced via cardiac arrest after 20 min hypoxia, the decline in PCr and nucleoside triphosphate (NTP), and increase in lactate followed similar rates compared with previously studied age-matched animals that were normoxic before ischemia. The rate constants for the change in PCr, NTP, and lactate followed similar rates compared with previously studied age-matched animals that were normoxic before ischemia. The rate constants for the change in PCr, NTP, and lactate during ischemia showed no correlation with the blood plasma glucose concentration measured immediately before cardiac arrest. These results suggest that cerebral glycolytic rates and energy utilization during ischemia are unaffected by a preceding interval of hypoxia and that hyperglycemia does not delay cerebral energy failure during hypoxia or combined hypoxic-ischemia.

Acidosis, Lactic↗

Calcium-independent regulation of pigment granule aggregation and dispersion in teleost retinal pigment epithelial cells.

In the eyes of teleosts and amphibians, melanin pigment granules of the retinal pigment epithelium (RPE) migrate in response to changes in light conditions. In the light, pigment granules disperse into the cells' long apical projections, thereby shielding the rod photoreceptor outer segments and reducing their extent of bleach. In darkness, pigment granules aggregate towards the base of the RPE cells. In vitro, RPE pigment granule aggregation can be induced by application of nonderivatized cAMP, and pigment granule dispersion can be induced by cAMP washout. In previous studies based on RPE-retina co-cultures, extracellular calcium was found to influence pigment granule migration. To examine the role of calcium in regulation of RPE pigment granule migration in the absence of retinal influences, we have used isolated RPE sheets and dissociated, cultured RPE cells. Under these conditions depletion of extracellular or intracellular calcium ([Ca2+]o, [Ca2+]i) had no effect on RPE pigment granule aggregation or dispersion. Using the intracellular calcium dye fura-2 and a new dye, fura-pe3, to monitor calcium dynamics in isolated RPE cells, we found that [Ca2+]i did not change from basal levels when pigment granule aggregation was triggered by cAMP, or dispersion was triggered by cAMP washout. Also, no change in [Ca2+]i was detected when dispersion was triggered by cAMP washout in the presence of 10 microM dopamine, a treatment previously shown to enhance dispersion. In addition, elevation of [Ca2+]i by addition of ionomycin neither triggered pigment movements, nor interfered with pigment granule motility elicited by cAMP addition or washout. Since other studies have indicated that actin plays a role in both pigment granule dispersion and aggregation in RPE, our findings suggest that RPE pigment granule migration depends on an actin-based motility system that is not directly regulated by calcium.

Animals↗

Modulation of interleukin-6-induced plasma protein secretion in hepatoma cells by p53 species.

The ability of p53 species (wild-type and mutant) to modulate the "differentiated" response of human hepatoma cell lines Hep3B and HepG2 to interleukin-6 (IL-6) was investigated. Transient transfection experiments were carried out in Hep3B and HepG2 cell cultures in which IL-6 was used to activate a beta-fibrinogen (beta Fib) enhancer/reporter construct containing two copies of the 36-base pair IL-6-response element (IL-6RE) (p beta FibCAT). Cotransfection with constitutive expression vectors for wild-type (wt) human or murine p53 inhibited the activation of the p beta FibCAT reporter by IL-6 in both Hep3B and HepG2 cells. Several mutant p53 species either did not inhibit the activation of p beta FibCAT or up-regulated the response. Hepatoma cell lines stably expressing the Val-135 temperature-sensitive mutant of murine p53 (wt-like at 32.5 degrees C and mutant-like at 37 degrees C) were derived from Hep3B cells and tested for the temperature-sensitive phenotype of their ability to synthesize and secrete fibrinogen and alpha 1-antichymotrypsin in response to IL-6. In an experimental protocol in which the parental Hep3B cells did not show a significant difference in plasma protein secretion at the two temperatures, hepatoma line 3 (p53Val-135+) had a greater response to IL-6 at 37 degrees C than parental Hep3B cells, while line 3 cells had a reduced response to IL-6 at 32.5 degrees C. Similarly, hepatoma lines 1 and 2 (both p53Val-135+) had reduced IL-6 responsiveness at 32.5 degrees C, whereas line 22 (transfected with pSVneo alone) and the parental Hep3B cells did not. These data indicate that mutations in p53 contained in tumor cells can modulate the "differentiated" response of these cells to cytokines.

Animals↗

A comparison of hospital policies for measles, mumps, and rubella infection control in Los Angeles County, 1989 and 1992.

BACKGROUND: A survey was conducted in 1992 in Los Angeles County, California, to assess changes since an earlier survey in 1989 in the numbers of acute care hospitals that had established policies on measles, mumps, and rubella infection control and the extent to which these policies were implemented. METHODS: A questionnaire inquiring about measles, mumps, and rubella infection control was sent to ICPs of 133 acute care hospitals in Los Angeles County. The results were compared with those of a similar survey conducted in 1989. The increase in the number of hospitals with such policies between 1989 and 1992 was analyzed. RESULTS: In 1989, 29 (28%), 9 (9%), and 65 (64%) of the 102 respondent hospitals had measles, mumps, and rubella infection control policies, respectively. Larger proportions of the 95 respondent hospitals in 1992 had measles (56, 59%), mumps (15, 16%), and rubella (69, 73%) infection control policies. CONCLUSIONS: The number of hospitals with infection control policies for measles, mumps, and rubella increased from 1989 to 1992. Efficiency and scope of such policies varied, however, and could be improved by making the policies mandatory, requiring written documentation of employee immunity, and extending policies to cover all employees. The most dramatic increase was in the number of hospitals with infection control policies for measles; this increase may have been caused by the 1987 to 1989 measles epidemic in Los Angeles County, by increased awareness of the Immunization Practices Advisory Committee recommendations, or by increased sensitivity to the issue of infection control triggered by the 1989 survey.

California↗

Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice.

Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate were studied in male F344 rats and B6C3F1 mice. Benzyl acetate was rapidly hydrolysed to benzyl alcohol and then oxidized to benzoic acid. After gavage administration of benzyl acetate in corn oil at 500 mg/kg (rats) and 1000 mg/kg (mice), high benzoic acid plasma concentrations were observed. In contrast, much lower benzoic acid plasma concentrations were found after dosed feed administration at about 615 mg/kg/day for rats and about 850 mg/kg/day for mice. Results show that although the daily doses of benzyl acetate are comparable, bolus gavage administration effectively saturated the benzoic acid elimination pathway whereas dosed feed administration did not. In contrast, hippuric acid plasma concentrations were similar after both gavage and dosed feed administration due to the depletion of the glycine supply pool. Study results could explain the different toxicity and carcinogenicity responses of benzyl acetate observed in 2-yr chronic gavage and dosed feed studies.

Administration, Oral↗

Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects.

To investigate the metabolic and renal effects of the nonsulfhydryl, tissue-active ACE inhibitor quinapril in diabetes and in hypertension, we studied 30 essential hypertensives and 24 non-insulin-dependent (type II) diabetic (NIDDM) subjects with hypertension. Systolic and diastolic blood pressures, plasma glucose, and insulin responses to an oral glucose load (75 g), lipid profile, and urinary albumin excretion were evaluated before and after 8 weeks' administration of quinapril (10 to 40 mg/day). Quinapril produced a significant and comparable reduction of arterial blood pressure in both groups. Mean arterial pressure decreased from 114.8 +/- 0.9 to 94.2 +/- 1.1 (-17.9 +/- 1.5%) in the essential hypertensive group and from 118.4 +/- 1.6 to 96.2 +/- 1.4 (-18.4 +/- 1.6%) in the diabetic hypertensive group. In both essential hypertensives and diabetic-hypertensive subjects with microalbuminuria, quinapril significantly and comparably reduced the urinary albumin excretion rate (UAE); UAE decreased from 32.5 +/- 5.5 micrograms/min to 14.7 +/- 3.7 micrograms/min (P < .05 v baseline) in the diabetic-hypertensive group and from 27.5 +/- 3.0 micrograms/min to 11.6 +/- 2.7 micrograms/min (P < .05 v baseline) in the essential hypertensives. Altogether, a direct correlation was found between the initial level of UAE and the UAE reduction after quinapril (delta UAE) (r = 0.706, p < .05). Insulin and glucose responses to an oral glucose tolerance test and the lipid profiles were not modified by quinapril treatment. The results confirm that quinapril is an effective antihypertensive agent that additionally reduces microalbuminuria in both hypertensive diabetics and in patients with essential hypertension, without altering insulin sensitivity and lipid profiles.

Albuminuria↗

A visual inspection protocol for measuring characteristics of used syringes.

This article reports on the use of a Visual Inspection Protocol (VIP) to measure observable characteristics of syringes deposited at the San Francisco needle exchange program. Syringes received by the program were evaluated by several inspectors using the VIP, and interrater reliability was assessed for each item. In Study I, syringes bearing individual markings made by the user (n = 568) were more likely to be capped at the point end and plunger end, and more often were new in appearance when compared with unmarked syringes (n = 2,820). In Study II, syringes with a short street life (n = 250) were more often new in appearance and were less likely to contain blood than syringes with a long street life (n = 246). Syringes having individual markings also show signs of more careful use, and marking syringes may represent an ad hoc HIV prevention strategy for some injection drug users.

HIV Infections↗

Evolution of speech and voice following supracricoid partial laryngectomy.

The evolution of voice and speech parameters following supracricoid partial laryngectomy (SCPL) has been evaluated in a prospective fashion over an 18-month period of time in three patients using the Computerized Speech Lab (from Kay Elemetrics). Preliminary results demonstrate the post-operative instability of voice parameters. Speech parameters remain stable with time. Our data stresses that voice is attained post-operatively even if one arytenoid cartilage is disarticulated at time of resection.

Aged↗

Quantitative relationship between brain temperature and energy utilization rate measured in vivo using 31P and 1H magnetic resonance spectroscopy.

In neonatal and adult animals, modest reduction in brain temperature (2-3 degrees C) during ischemia and hypoxia-ischemia provides partial or complete neuroprotection. One potential mechanism for this effect is a decrease in brain energy utilization rate with consequent preservation of brain ATP, as occurs with profound hypothermia. To determine the extent to which modest hypothermia is associated with a decrease in brain energy utilization rate, in vivo 31P and 1H magnetic resonance spectroscopy (MRS) was used to measure the rate of change in brain concentration of phosphocreatine, nucleoside triphosphate, and lactate after complete ischemia induced by cardiac arrest in 11 piglets (8-16 d). Pre-ischemia metabolite concentrations and MRS-determined rate constants were used to calculate the initial flux of high energy phosphate equivalents (d[approximately P]/dt, brain energy utilization rate). Baseline physiologic and MRS measurements were obtained at 38.2 degrees C and repeated after brain temperature was adjusted between 28 and 41 degrees C. This was followed by measurement of d[approximately P]/dt during complete ischemia at 1-2 degrees C increments within this temperature range. Adjusting brain temperature did not alter any systemic variable except for heart rate which directly correlated with brain temperature (r = 0.95, p < 0.001). Before ischemia brain temperature inversely correlated with phosphocreatine (r = -0.89, p < 0.001), and reflected changes in the phosphocreatine-ATP equilibrium, because brain temperature inversely correlated with intracellular pH (r = -0.77, p = 0.005). Brain temperature and d[approximately P]/dt were directly correlated and described by a linear relationship (slope = 0.61, intercept = -12, r = 0.92, p < 0.001). A reduction in brain temperature from normothermic values of 38.2 degrees C was associated with a decline in d[approximately P]/dt of 5.3% per 1 degree C, and therefore decreases in d[approximately P]/dt during modest hypothermia represent a potential mechanism contributing to neuroprotection.

Adenosine Triphosphate↗

A clinical trial of continuous cisplatin-fluorouracil induction chemotherapy and supracricoid partial laryngectomy for glottic carcinoma classified as T2.

BACKGROUND: Vertical partial laryngectomy (VPL) and radiation therapy (RT) are the recommended conventional conservative options for glottic carcinoma classified as T2. In series presenting more than 100 patients with a minimum 3-year follow-up, however, local recurrence rates were reported as 22-43.5%. The authors' experience with a new strategy based on continuous cisplatin-fluorouracil induction chemotherapy (IC) and supracricoid partial laryngectomy with cricohyoepiglottopexy (CHEP) is presented. METHODS: A retrospective analysis of 67 patients who presented with untreated moderately to well differentiated invasive glottic carcinoma classified as T2, managed from 1983 to 1991 with IC and CHEP, was conducted. Statistical analysis of survival, local control, nodal control, distant metastasis, and metachronous second primary tumor incidence was based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors and survival, local recurrence, and nodal recurrence. Clinical response, histologic response, IC toxicity and postoperative course were reported. RESULTS: The Kaplan-Meier 5-year survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate were 92.3%, 5.6%, 1.5%, 1.8%, and 5.6%, respectively. Overall laryngeal preservation was achieved in 65 patients (97%). Ultimate local control was achieved in all patients but one. Nodal recurrence was statistically more likely in patients presenting with a local recurrence. Analysis of the specimens demonstrated complete histologic response to IC in 25 (37.3%) patients. A strong statistical relation (P < 0.0001) was noted between complete clinical response after IC and complete histologic response. CONCLUSIONS: The change from the prevailing treatment modalities of RT and VPL to a new multimodal strategy (IC+CHEP) did not decrease survival and allowed for an increase in laryngeal preservation rate. The high rate (37.3%) of complete histologic response suggests that IC deserves further consideration in the management of patients with glottic carcinoma classified as T2. The favorable results achieved in this series, when compared with historic controls, should stimulate prospective clinical trials comparing the two surgical procedures (CHEP vs. VPL with or without IC) for resection of Stage II glottic carcinoma.

Adult↗

The effects of systemic glucose concentration on brain metabolism following repeated brain ischemia.

Since systemic glucose concentration is an important determinant of ischemic brain metabolism in neonates, we sought to determine if the systemic glucose concentration influences brain metabolic alterations following repeated partial ischemia. A group of hyperglycemic piglets (n = 12) were compared to a group of modestly hypoglycemic piglets (n = 12) using in vivo 2H and 31P magnetic resonance spectroscopy to simultaneously measure cerebral blood flow and phosphorylated metabolites before, during and 30 min after two 10-min episodes of ischemia (i.e. Recovery 1 and 2). For both groups, beta-ATP levels at Recovery 1 and 2 were lower than Control (91 +/- 11 and 83 +/- 15% of Control, respectively for both groups combined, P = 0.002 vs Control). Inorganic phosphorus was elevated in hyperglycemic piglets at Recovery 1 and 2 (117 +/- 15 and 118 +/- 10% of Control). In contrast, in modestly hypoglycemic piglets inorganic phosphorus progressively rose from Recovery 1 (131 +/- 24% of Control) to Recovery 2 (149 +/- 37% of Control), and differed from the hyperglycemic group (P = 0.02). These changes did not correlate with post-ischemic cerebral blood flow, cerebral O2 delivery or cerebral glucose delivery. In both groups phosphocreatine and intracellular pH returned to Control values during Recovery 1 and 2. The progressive increase in inorganic phosphorus post-ischemia in hypoglycemic piglets suggests that modest hypoglycemia during and following repeated partial ischemia adversely affects immediate brain metabolic recovery.

Adenosine Triphosphate↗