Care in a midwife managed delivery unit. Conclusions are not supported by results.
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Consultants↗
Biomedical subjects
J Garcia
Publications and source records attributed to J Garcia.
Myocardial high-energy phosphate and substrate metabolism in swine with moderate left ventricular hypertrophy.
BACKGROUND: Although left ventricular hypertrophy (LVH) is frequently associated with impaired coronary vasodilator reserve, it is uncertain whether this leads to myocardial ischemia under physiological conditions. The goal of the present study was to determine whether swine with moderate LVH exhibit metabolic evidence of ischemia when myocardial oxygen requirements are increased. METHODS AND RESULTS: Myocardial metabolism was evaluated in an open-chest anesthetized preparation at baseline and during dobutamine infusion in 13 adolescent pigs with moderate LVH induced by supravalvular aortic banding and 12 age-matched control pigs. Transmural myocardial blood flow was quantified with radioactive microspheres; the ratio of phosphocreatine to ATP (PCr/ATP) in the anterior LV free wall was measured by 31P-nuclear magnetic resonance; and anterior wall lactate release was quantified from the arterial-coronary venous difference in 14C- or 13C-labeled lactate. In a subset of 5 animals from each group, the metabolic fate of exogenous glucose was determined from the transmyocardial difference in 6-14C-glucose and its metabolites 14C-lactate and 14CO2. Coronary reserve, as assessed by the ratio of blood flow during adenosine infusion to baseline blood flow, was significantly lower in the LVH pigs compared with controls (3.5 +/- 0.4 versus 5.5 +/- 0.4 mL/g.min, P < .05); however, transmural myocardial blood flow was similar in both groups of pigs, both at baseline and with dobutamine stimulation, probably reflecting the higher coronary perfusion pressure in the LVH pigs. At baseline, PCr/ATP tended to be lower in the LVH pigs (P = .09) but decreased similarly with dobutamine infusion in both groups. Isotopically measured anterior wall lactate release did not differ between the groups at baseline, nor did the increase in lactate release differ during dobutamine stimulation. The uptake of glucose, lactate, and free fatty acids did not differ between the groups in the basal state. However, during dobutamine stimulation, glucose uptake was greater in the LVH group (0.84 +/- 0.09 mumol/g.min versus 0.59 +/- 0.08 mumol/g.min, P < .05). In a subset of animals, 14C-glucose was used to assess glucose oxidation. These data showed that the LVH animals had a greater rate of glucose oxidation (0.6 +/- 0.10 versus 0.28 +/- 0.08 mumol/g.min, P < .05) and a greater rate of glucose conversion to lactate (0.20 +/- 0.04 versus 0.09 +/- 0.02 mumol/g.min, P < .05) compared with the control pigs. CONCLUSIONS: These results suggest that despite their reduced coronary vasodilator reserve and the absence of a greater rise in myocardial blood flow to compensate for a substantially higher LV double product, pigs with this model of moderate LVH do not exhibit a greater susceptibility to myocardial ischemia during dobutamine stress. However, LVH pigs exhibit significantly greater use of exogenous glucose during dobutamine stress, as evidenced by increases in both glucose oxidation and anaerobic glycolysis.
Adenosine Triphosphate↗
Primary bronchogenic squamous cell carcinoma in children: report of a case and review of the literature.
The authors report a case of primary bronchogenic squamous cell carcinoma (SCC) revealed by recurrent pneumonia in an 11-year-old boy. Four years after complete surgical resection followed by external radiotherapy, the patient is currently relapse- and metastasis-free. To our knowledge, this is only the sixth pediatric case of primary bronchogenic SCC reported to date.
Carcinoma, Squamous Cell↗
Mind is back in control of pavlovian and skinnerian responses: was it ever away?
Introspections, anecdotes, mnemonics, and observations of large animals like us can only be adequately described in the mapping language of the mind/brain delineated by renaissance philosophers--time, space, sensations and reflections. But modern behaviorists, confused by this richness, sought clarification by adhering strictly to narrow paradigms, excluding the mind/brain, and inventing recondite neologisms. The cognitive map underground survived the behavioral storms. And psychology, the study of the mind/brain in all its wonders, is flourishing once again in respectability.
Animals↗
Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Chilean National Committee for Meningococcal Disease.
A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile. A total of 40 811 volunteers, ages 1-21 years, enrolled in the study. Volunteers received two doses of vaccine six weeks apart by jet injector. Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects. Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique. Eighteen cases of group B meningococcal disease were confirmed during the 20 months. Efficacy was estimated to be 51% (p = 0.11) for all ages combined. In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045). The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months. The youngest children had the highest responses. The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children.
Adolescent↗
Bilateral ocular toxocariasis demonstrated by aqueous humor enzyme-linked immunosorbent assay.
PURPOSE/METHODS: A 14-year-old girl with a history of contact with puppies and chronic bilateral panuveitis was examined. The fundus of the right eye showed an inferotemporal pars plana exudate. The fundus of the left eye showed an elevated posterior mass. RESULTS/CONCLUSION: Toxocara antibodies in the aqueous humor detected by enzyme-linked immunosorbent assay had a Goldmann-Witmer coefficient of 8.63 in the right eye and 8.94 in the left eye. Toxocariasis may be a cause of bilateral panuveitis.
Adolescent↗
Appendicitis as a complication of colonoscopy.
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Acute Disease↗
The effects of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transmyocardial impedance. Implications for implantable cardioverter-defibrillator implantation.
The influence of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transcardiac impedance is not well characterized. However, this relationship is of clinical importance during automatic defibrillator implantation done with concomitant cardiac surgery, and there is anecdotal information that criteria for successful implantation are harder to achieve after such operations. We studied the effect of controlled hypothermia on defibrillation energy requirements and transcardiac impedance in a canine model of cardiopulmonary bypass in which 26 animals underwent right atrial and femoral arterial cannulation, as well as continuous hemodynamic and intramyocardial temperature monitoring. The defibrillation energy requirements were evaluated at 60-minute intervals with an epicardial patch system, and transcardiac impedance was measured before and after the multiple inductions and terminations of ventricular fibrillation. In group 1 (n = 10) defibrillation energy requirements were evaluated immediately after initiation of cardiopulmonary bypass at 37 degrees C (T0), after gradual cooling to 28 degrees C (T1), and after rewarming to 37 degrees C (T2). Group 2 (n = 16) comprised time controls that were identically instrumented and studied, but maintained at 37 degrees C throughout. Percent successful defibrillation was plotted against delivered energy, and the raw data fit by logistic regression. The energy at which 50% of shocks were successful (E50) was 3.23 +/- 0.89 joules at T0, 5.12 +/- 1.85 joules at T1, and 4.42 +/- 1.22 joules at T2 in group 1; this was not significantly different from the corresponding group 2 E50 values, which were 3.11 +/- 1.39 joules, 4.95 +/- 2.47 joules, and 5.59 +/- 3.18 joules, respectively. Both groups demonstrated a significant increase in E50 during the first hour of cardiopulmonary bypass (mean increase from T0 to T1 was 1.89 joules in group 1 and 1.84 joules in group 2, p < 0.05). Transmyocardial impedance fell progressively during the group 2 experiments from 73.6 +/- 12.9 omega at the beginning of the T0 shock series to 61.4 +/- 8.9 omega at the end of the T2 shock series. A similar reduction in transmyocardial impedance was observed during the course of all the group 1 experiments; however, at the beginning of the T1 shock series impedance was significantly elevated to 77.4 +/- 12.3 omega (p < 0.05 compared with group 2 and with end T0 in group 1). There was no relationship between defibrillation energy requirements and transcardiac impedance; there was also no correlation between either of these parameters and intramyocardial extracellular pH or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle.
BACKGROUND: Age-related differences in responses to verapamil have been noted in both intact humans and isolated denervated perfused rat hearts. The study was designed to determine the effects of aging on intracardiac conduction and pharmacodynamic responses to verapamil, and also to determine the potential role of autonomic responses in previously reported age-related differences in responses to verapamil. METHODS: After stability of measures was demonstrated in senescent animals, nine young (aged 3-4 years: 12.3 +/- 2.4 kg; 5 female, four male) and nine senescent (aged 8-11 years: 12.0 +/- 2.2 kg; 5 female, four male) beagles were randomized to undergo 60-minute verapamil infusions during pentobarbital anesthesia alone or after 1 mg/kg propranolol and 0.5 mg/kg atropine. RESULTS: In the nonblocked state, verapamil increased A-A intervals (p < .001), P-R (p < .001), A-H intervals (p < .001), and AV Wenckebach block cycle length (p < .0001) and decreased blood pressure (p < .001) without age-related differences in responses. After autonomic blockade, heart rate and blood pressure decreased (p < .0001) and AV conduction intervals (p < .05) and AV Wenckebach block cycle length increased (p < .006). A-A intervals, A-H intervals, and AV Wenckebach block cycle length were significantly longer in senescent vs young beagles (559 +/- 87 vs 471 +/- 42 msec, p < .002; 103 +/- 6 vs 89 +/- 14, p < .05), 273 +/- 21 vs 238 +/- 26, p < .006, respectively). Verapamil effects on heart rate (p < .001) and AV conduction intervals (p < .007) and diastolic blood pressure (p < .003) were enhanced in younger, but not senescent, beagles after propranolol and atropine. DISCUSSION: Verapamil produced similar effects on heart rate, blood pressure, and AV conduction in young and senescent beagles during barbiturate anesthesia. After double pharmacologic autonomic blockade, heart rate and AV conduction intervals and AV Wenckebach cycle length were significantly longer in senescent beagles when compared to younger beagles. Responses to verapamil after pharmacologic double autonomic blockade were enhanced only in younger beagles, suggesting greater contribution of reflex responses to results during verapamil infusions in the nonblocked state in younger animals.
Aging↗
Micronutrient levels in HIV-1-infected children.
OBJECTIVE: Micronutrients (zinc, copper, selenium, vitamin A, E, and carotenoids) are essential for the integrity of host defences. This study was designed to determine the prevalence of abnormalities of the micronutrient levels in HIV-1-seropositive children. DESIGN: Prospective study. SETTING: The study was performed on HIV-1-infected children at the Paediatric Haematology and Oncology Unit of Toulouse Hospital, France. PATIENTS: Twenty-one children, suffering from HIV-1 infection and 21 control subjects of similar age (2-9 years) were included in the study. In the HIV-1-infected children, two subgroups were considered according to stage (non-AIDS or AIDS), based on the Centers for Disease Control and Prevention 1987 criteria. RESULTS: The first statistically significant deficiencies occurred at non-AIDS stage and were confirmed at AIDS stage: P < 0.05 for lycopene, retinol, tocopherol and P < 0.001 for transthyretin and serum albumin. Levels of copper (40%) and long-chain polyunsaturated fatty acids (21%) were higher in the non-AIDS group than the controls. CONCLUSION: Biological impairing of the micronutrient levels was observed in the non-AIDS stage without clinical sign. This information is useful in delineating eventual and well considered nutritional intervention strategies that may improve the clinical status of HIV-1-infected children and perhaps alter the course of their disease.
Carotenoids↗
Nonimmediate reactions to betalactams: prevalence and role of the different penicillins.
In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6% of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93% of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens.
E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the isolates were inhibited (MIC90s) were 0.06 to 0.5 microgram/ml for gram-positive cocci, including species of the genera Staphylococcus, Streptococcus, and Enterococcus, and the MIC90s against gram-negative pathogens such as members of the family Enterobacteriaceae (with the exception of Providencia spp. [MIC90, 8 micrograms/ml]) and Pseudomonas aeruginosa were 0.015 to 0.5 microgram/ml. E-4695 inhibited 90% of the Clostridium perfringens and Bacteroides fragilis isolates at 0.25 and 4 micrograms/ml, respectively. Against gram-positive cocci the potency of E-4695 was 2- to 8-fold higher than that of ciprofloxacin, 4- to 8-fold higher than that of ofloxacin, and 8- to 16-fold higher than that of fleroxacin. Against enteric bacteria and P. aeruginosa the potency of E-4695 was, in general, similar to that of ciprofloxacin and eightfold higher than those of ofloxacin and fleroxacin. E-4695 was four- and eightfold more potent than ciprofloxacin against C. perfringens and B. fragilis isolates, respectively. E-4695 and ciprofloxacin showed similar properties when the effects of pH or magnesium concentration were tested on them. E-4695 and ciprofloxacin had substantial reductions of activity only when pH decreased below 4.8. E-4695 and ciprofloxacin activities were not markedly affected by the presence of 5 or 10 mM Mg2+. The presence of serum and human urine at pH 7.2 decreased the activity of E-4695 between two- and fourfold. After an oral dose of 50 mg/kg of body weight, the maximum level in serum, the biological half-life, and the area under the concentration-time curve from 0 to 10 h for E-4695 were 13.2 microgram/ml, 3.3 h, and 45.6 microgram . h/ml, respectively. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was 2.3 microgram . h/ml at the same dose. Fifty-percent effective doses (ED50S) against Staphylococcus aureus HS-93 infections in mice were 4.5 mg/kg with E-4695 and 37.6 mg/kg with ciprofloxacin. Infection with Streptococcus pneumoniae 29206 was more effectively treated with E-4695 (ED50, 41,2 mg/kg) than with ciprofloxacin (ED50, 200 mg/kg). The ED50 of E-4695 for infections with Streptococcus pneumoniae 1625 was 132.2 mg/kg; ciprofloxacin was ineffective at 400 mg/kg against this strain. E-4695 was also more potent than ciprofloxacin in treatment of infections caused by gram-negative organisms such as Escherichia coli HM-42 (ED50S, 1.0 and 3.9 mg/kg, respectively). The ED50S of E-4695 and ciprofloxacin were 33.0 and 145.5 mg/kg against P. aeruginosa HS-116 and 9.6 and 18.9 mg/kg against P. aeruginosa B-120, respectively. The therapeutic efficacy of E-4695 may depend not only on its in vitro activity but also on its improved pharmacokinetic properties.
Animals↗
Thiosulfate reduction, an important physiological feature shared by members of the order thermotogales.
Several members of the order Thermotogales in the domain Bacteria, viz., Thermotoga neapolitana, Thermotoga maritima, Thermosipho africanus, Fervidobacterium islandicum, and Thermotoga strain SEBR 2665, an isolate from an oil well, reduced thiosulfate to sulfide. This reductive process enhanced cellular yields and growth rates of all the members but was more significant with the two hyperthermophiles T. neapolitana and T. maritima. This is the first report of such an occurrence in this group of thermophilic and hyperthermophilic anaerobic bacteria. The results suggest that thiosulfate reduction is important in the geochemical cycling of sulfur in anaerobic thermal environments such as the slightly acidic and neutral-pH volcanic hot springs and oil reservoirs.
Journal Article↗
Clinical trials and neonatal intensive care.
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Humans↗
Effects of inotropic stimulation on energy metabolism and systolic function of ischemic right ventricle.
This study determined whether dobutamine enhances regional systolic function in the ischemic right ventricle (RV) at the cost of adverse effects on regional energy metabolism. Seventeen alpha-chloralose-anesthetized, open-chest pigs were studied under four conditions: 1) control; 2) dobutamine infusion (mean dose 9 micrograms.kg-1.min-1); 3) RV ischemia (45 +/- 5% reduction in RV free wall blood flow for 100 min); and 4) continued ischemia with dobutamine. Regional RV free wall high-energy phosphate metabolites were measured by 31P nuclear magnetic resonance (NMR) spectroscopy or by high-speed drill biopsies of the RV free wall. Regional RV free wall substrate and O2 consumption were measured using coronary venous blood sampling. Global RV systolic function was assessed by the maximal first derivative of RV pressure (dP/dtmax), and regional RV free wall systolic function was assessed by systolic segment shortening in the ischemic zone. Right coronary artery constriction caused markedly depressed regional RV systolic function, net lactate production, and coronary venous acidosis. Surprisingly, high-energy phosphates were unchanged compared with control. Addition of dobutamine caused a further decline in coronary venous pH and continued lactate production but did not reduce high-energy phosphates. While dobutamine markedly enhanced global RV systolic function (RV dP/dtmax 201 +/- 19% of control), systolic shortening in the ischemic RV free wall remained severely depressed (47 +/- 18% of control) despite dobutamine. The mechanism of high-energy phosphate preservation is likely due to diminished consumption of ATP in the hypocontractile ischemic region.
Animals↗
Methylene blue as a cause of chemical peritonitis in a patient on peritoneal dialysis.
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Diabetic Nephropathies↗
Suppression of the skin reaction to histamine by ebastine.
BACKGROUND: Ebastine is a nonsedating histamine H-1 antagonist undergoing evaluation for treatment of allergic rhinitis and urticaria. OBJECTIVE: To compare the suppression of prick and intradermal skin reactions to histamine over a period of 24 hours produced by a single dose of ebastine. Also to record side effects and assess changes in the electrocardiogram, particularly the QTc interval. METHOD: Single doses of 1, 3, 10, and 30 mg of ebastine or placebo were administered double-blind at approximately 8 AM after baseline measurement of the reaction to intradermal testing with 5 micrograms histamine base and prick skin testing with three concentrations of histamine. Intradermal testing with histamine was repeated hourly for four hours, every two hours for eight hours, and after 24 hours. Titrated prick skin testing with histamine was performed at 6, 12, and 24 hours. Potential side effects were recorded each time skin testing was performed. Electrocardiograms were repeated at 4 and 24 hours. RESULTS: Intradermal skin test reactions were suppressed between 4 and 24 hours and prick skin tests to 10 mg/mL histamine base were suppressed between 6 and 24 hours with all doses of ebastine. Prick skin test reactions were significantly smaller at 12 and 24 hours in the group receiving the 30 mg dose of ebastine than in all other groups. CONCLUSION: Ebastine is a potent antihistamine that suppresses skin reactions to histamine for 24 hours following single doses in the doses tested (1 to 30 mg). No differences from placebo were noted in either the incidence of side effects or in the QTc intervals of serial electrocardiograms.
Adult↗
Four days' continuous infusion of cisplatin-5-fluorouracil and short daily infusion of high-dose leucovorin as induction chemotherapy for locally advanced head and neck cancer.
Cisplatin-fluorouracil (PF) is the most frequently used combination as induction chemotherapy (CT) for the treatment of locally advanced squamous cell head and neck cancer. This study was designed to evaluate the role of leucovorin (L) in the modulation of the therapeutic activity of PF continuously infused for 4 days. Between June 1990 and June 1992, stage III and IV previously untreated patients received PFL induction chemotherapy followed by surgery, radiotherapy, or both. The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF. PFL was administered every 3 weeks for 4 cycles. The overall response rate at the completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus radiotherapy, and 37 (54%) radiotherapy. Complete response status after both induction and locoregional therapy was 71%. Biopsies of the primary tumor or definitive resection specimens immediately after PFL therapy were available in 25 patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up of 44 months, the overall survival rate is 51% and the median survival has not been reached. PFL is highly active as induction chemotherapy. A randomized comparison between PF and PFL is necessary to define the place of leucovorin modulation in the treatment of head and neck cancer.
Antineoplastic Combined Chemotherapy Protocols↗