Efalizumab-induced aseptic meningitis.
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Adult↗
Biomedical subjects
V Gonzalez
Publications and source records attributed to V Gonzalez.
Long-term improvement of slow-channel congenital myasthenic syndrome with fluoxetine.
We report on a 15-year-old patient who was diagnosed with congenital myasthenic syndrome (CMS) at the age of 7 months. At initial diagnosis, the CMS was not further characterized. The patient was treated for several years with the anticholinesterase drug (Mestinon), without clinical benefit. The patient deteriorated progressively and became dependent on home nocturnal ventilatory support, being unable to take part in daily life activities at age of 12 years. At age 14, the slow-channel syndrome mutation CHRNE L269F (805C>T) was detected and acetylcholinesterase inhibitor therapy was immediately stopped. Fluoxetine therapy was started and gradually increased over 2 months. The boy improved dramatically in strength and endurance and was taken off ventilatory support 1 month after the fluoxetine therapy was initiated. The clinical improvement was confirmed by functional respiratory and electrophysiological tests.
Adolescent↗
Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice.
Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of A beta deposits. In the present study, we asked whether elevating the levels of Apo E can, in a dominant fashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via the mouse prion protein promoter, resulting in high expression in both astrocytes and neurons; only astrocytes efficiently secreted Hu Apo E4 (at least 5-fold more than endogenous). Mice hyper-expressing Hu Apo E4 developed normally and lived normal lifespans. The co-expression of Hu Apo E4 with a mutant amyloid precursor protein (APP) (Mo/Hu APPswe) or mutant APP and mutant presenilin (PS1dE9) did not lead to proportional changes in the age of appearance, relative burden, character or distribution of A beta deposits. We suggest that these data are best explained by proposing that the mechanisms by which Apo E influences A beta deposition involves an aspect of its normal function that is not augmented by hyper-expression.
Amyloid beta-Peptides↗
Control of nosocomial Clostridium difficile transmission in bone marrow transplant patients.
This is a report of six cases of Clostridium difficile-associated diarrhea (CDAD) that occurred among cancer patients undergoing bone marrow transplantation in a tertiary-care cancer hospital. Specific infection control measures that were taken to minimize the nosocomial spread of CDAD also are discussed.
Bone Marrow Transplantation↗
Differential efficacy of olanzapine for deficit and nondeficit negative symptoms in schizophrenia.
OBJECTIVE: Atypical antipsychotic medications have generally been found to be more effective than conventional antipsychotics in the treatment of negative symptoms. Whether the benefits derived from the atypical agents are the result of improvements in primary versus secondary negative symptoms is unclear. The authors examined the effects of olanzapine on primary and secondary negative symptoms for patients with severe negative symptoms who did or did not have the deficit syndrome. METHOD: Thirty-nine outpatients with schizophrenia and severe negative symptoms were assessed for the presence of the deficit syndrome and entered into a 12-week, open-label study of olanzapine. Positive and negative symptoms, extrapyramidal side effects, quality of life, and level of functioning of the patients were assessed at baseline and endpoint. RESULTS: All 39 patients completed the 12-week protocol; 13 of the patients had deficit negative symptoms, and 26 had nondeficit negative symptoms. Patients who had nondeficit negative symptoms demonstrated improvements in positive and negative symptoms, level of functioning, and extrapyramidal side effects over baseline. In contrast, patients meeting criteria for the deficit syndrome improved significantly over baseline only in extrapyramidal side effects. CONCLUSIONS: The results of this study suggest that olanzapine is efficacious for secondary negative symptoms in schizophrenia but fail to support the contention that olanzapine has a direct beneficial effect on primary negative symptoms.
Adult↗
Central administration of zinc increases renal sodium and potassium excretion in rats.
The aim of the present study was to investigate the effect of acute third ventricle injections of zinc on the brain control of renal sodium and potassium excretion. Adult Wistar male rats received third ventricle injections of zinc acetate in three different doses (0.03, 0.3 and 3.0 nmol/rat). Third ventricle administration of zinc acetate provoked a significant intensification of natriuresis and kaliuresis as compared to sodium acetate-treated controls. When rats were pretreated with losartan, a selective angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central zinc injection) the increase in both natriuresis and kaliuresis was abolished. Furthermore, pretreatment with gadolinium, a calcium channel blocker (0.3 nmol/rat into the third ventricle 20 min before central zinc injection), also blunted the increase in renal sodium and potassium excretion seen in animals receiving zinc alone. In a group of rats receiving the same water load used in the previous experiments, the injection of zinc acetate into the third ventricle (3.0 nmol/rat) did not modify arterial blood pressure. It is suggested that zinc in the central nervous system may be involved in the control of renal sodium and potassium excretion by a mechanism unrelated to blood pressure increase. It is also shown that both natriuretic and kaliuretic actions of zinc depend on AT1 receptor activation. Whatever should be the mechanism(s) related to the central effects of zinc here evidenced, the functional integrity of calcium channels is required.
Angiotensin II↗
Infusion therapy team and dressing changes of central venous catheters.
OBJECTIVE: To determine whether central venous catheter (CVC) dressing changes could be performed by ward nurses rather than by the infusion therapy team (ITT) nurses without increasing the risk of catheter-related infection. DESIGN: Retrospective cohort study using prospectively collected data. The study extended from January 1995 to June 1996. SETTING: The University of Texas M.D. Anderson Cancer Center, a referral cancer center. PATIENTS: The study group was a random sample of 483 patients who received CVC dressing changes by ward nurses during the study period. A random sample of 483 patients who received CVC dressing changes by the ITT constituted the control group. RESULTS: The risks of catheter-related septicemia were 1.7% among cases and 1.4% among controls (risk ratio, 1.14; 95% confidence interval [CI95], 0.26-6.42; P=.70). There also were no significant differences between the two groups in the risks of catheter-related site infection (risk ratio, 0.50; CI95, 0.02-4.12; P=.25) or any catheter-related infection (risk ratio=1.00; CI95, 0.27-3.64; P=.59). CONCLUSIONS: Provided that aseptic techniques (including maximal barrier precautions during insertion) are maintained, the responsibility of CVC dressing changes could be delegated to the ward nurses without increasing the low risk of CVC-related infection, resulting in an estimated cost saving in excess of $90,000 per year.
Adult↗
Central lead administration induces natriuretic and kaliuretic effects in rats.
The aim of the present experiments was to discern whether central acute lead injections affect brain control of renal function. Adult Wistar male rats received third-ventricle injections of lead acetate in three different doses (0.03, 0.3, and 3.0 nmol/rat). Lead acetate induced a significant increase in renal excretion of sodium and potassium. Pretreatment with losartan, a selective angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central lead injection), inhibits lead-induced natriuretic and kaliuretic effects. In addition, pretreatment with gadolinium, a calcium-channel blocker (0.3 nmol/rat into the third ventricle 20 min before central lead administration), reversed the increase in renal excretion of sodium and potassium provoked by central lead administration. Taken together, the data presented here suggest that lead injected into the third ventricle increases renal excretion of sodium and potassium by a mechanism that depends on the functional integrity of central angiotensin II AT1 receptors and calcium channels.
Angiotensin II↗
Natriuretic and kaliuretic effects of central acute cadmium administration in rats.
We studied the acute effects of cadmium third ventricle injections on renal excretion of water, sodium and potassium in rats previously submitted to an oral water load equivalent to 10% of their body weight. Injections of cadmium chloride (0.03, 0.3, and 3.0 nmol/rat) significantly increased sodium and potassium renal excretion without changing urine flow. Pretreatment with losartan, an angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central cadmium administration) inhibits the natriuretic effect of this metal, being unable to reverse its kaliuretic effect. Pretreatment with gadolinium, a calcium-channel blocker (0.3 nmol/rat into the third ventricle 20 min before central cadmium administration) abolishes both the natriuretic and the kaliuretic response of cadmium. The data clearly show that cadmium injections into the third ventricle disturb central regulation of renal function leading to an increased renal loss of sodium and potassium. It is also evident that the natriuretic action of the metal depends on an increase in brain angiotensin II release. Also, the functional integrity of calcium channels is required for the expression of both the natriuretic and the kaliuretic effects of the metal.
Angiotensin Receptor Antagonists↗
Opiatergic participation in the thirst-inhibiting effect of acute third ventricle injections of cadmium (Cd2+) and lead (Pb2+).
We have previously demonstrated that acute third ventricle injections of both lead and cadmium prevent the dipsogenic response elicited by dehydration or by central injections of dipsogenic agents such as angiotensin II, carbachol and isoproterenol in rats. We have also shown that the antidipsogenic action of cadmium may be due, at least in part, to activation of thirst-inhibitory central serotonergic pathways. In the present paper we show that in Wistar male rats the antidipsogenic effect of both lead acetate (3.0 nmol/rat) and cadmium chloride (3.0 nmol/rat) may be partially dependent on the activation of brain opiatergic pathways since central injections of naloxone (82.5 nmol/rat), a non-selective opioid antagonist, blunt the thirst-inhibiting effect of these metals. One hundred and twenty minutes after the second third ventricle injections, dehydrated animals (14 h overnight) receiving saline + sodium acetate displayed a high water intake (7.90 +/- 0.47 ml/100 g body weight) whereas animals receiving saline + lead acetate drank 3.24 +/- 0.47 ml/100 g body weight. Animals receiving naloxone + lead acetate drank 6.94 +/- 0.60 ml/100 g body weight. Animals receiving saline + saline drank 8.16 +/- 0.66 ml/100 g body weight whilst animals receiving saline + cadmium chloride drank 1.63 +/- 0.37 ml/100 g body weight. Animals receiving naloxone + cadmium chloride drank 8.01 +/- 0.94 ml/100 g body weight. It is suggested that acute third ventricle injections of both lead and cadmium exert their antidipsogenic effect by activating thirst-inhibiting opioid pathways in the brain.
Animals↗
A comparison between laddermill and treadmill maximal oxygen consumption.
Maximal O2 consumption (VO2max) is an index of the capacity for work over an 8 h workshift. Running on a treadmill is the most common method of eliciting it, because it is an easy, natural exercise, and also, by engaging large muscle masses, larger values are obtained than by other exercises. It has been claimed, however, that climbing a laddermill elicits a still higher VO2max, probably because more muscle mass is apparently engaged (legs + arms) than on the treadmill (legs only). However, no data in support of this claim have been presented. To see if differences exist, we conducted progressive tests to exhaustion on 44 active coal miners, on a laddermill (slant angle 75 degrees, vertical separation of rungs 25 cm) and on a treadmill set at a 5% gradient. The subjects' mean (range) age was 37.4 (31-47) years, height 174.3 (164-187) cm, body mass 82.2 (64-103) kg. Mean (range) VO2max on the laddermill was 2.83 (2.31-3.64) l x min(-1) and 2.98 (2.03-4.22) l x min(-1) on the treadmill (P < 0.01, Student's paired t-test). Mean (range) of maximal heart rate f(cmax) (beats x min(-1)) on the laddermill and on the treadmill were 181.0 (161-194) and 181.3 (162-195), respectively (NS). Laddermill:treadmill VO2max was negatively related to both treadmill VO2max x kg body mass(-1) (r = -0.410, P < 0.01) and body mass (r = -0.409, P < 0.01). Laddermill:treadmill f(cmax) was negatively related to treadmill VO2max x kg body mass(-1) (r = -0.367, P < 0.02) but not to body mass (r = -0.166, P = 0.28). Our data would suggest that for fitter subjects (VO2max > 2.6 l x min or VO2max kg body mass(-1) > 30 ml x min(-1) x kg(-1)) and/or higher body masses (> 70 kg), exercise on the laddermill is not dynamic enough to elicit a VO2max as high as on the treadmill. For such subjects, treadmill VO2max would overestimate exercise capacity for jobs requiring a fair amount of climbing ladders or ladder-like structures.
Adult↗
Cardiac tamponade after a systemic-pulmonary shunt complicated by serous leakage.
A newborn baby with complex congenital heart disease had severe persistent pericardial effusion after a systemic-pulmonary shunt. Pericardiocentesis and pericardiotomy could not stop pericardial leakage. At reoperation, topical application of a fibrin glue resulted in resolution of the leak and avoided replacement of the graft.
Blood Vessel Prosthesis↗
Antiemetic activity of ondansetron in acute gastroenteritis.
BACKGROUND: The mechanism of nausea and vomiting associated with gastroenteritis is unknown. The role of 5-HT3 receptors in emesis associated with gastroenteritis was investigated in paediatric patients. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted in three groups of 12 patients each, receiving either a single i.v. dose of ondansetron (0.3 mg/kg), metoclopramide (0.3 mg/kg) or placebo (sterile saline). Food was restricted and oral rehydration was administered for 4 h. RESULTS: During 0-24 h, the number of emetic episodes experienced was significantly greater (P = 0.048) with placebo (mean = 5) than ondansetron (mean = 2) and the proportion of patients experiencing no emesis was significantly greater (P = 0.039) with ondansetron (58%) than placebo (17%). A numerical difference, in favour of ondansetron, was observed between ondansetron and metoclopramide groups for both of the above parameters. Fewer treatment failures were observed with ondansetron (17%) than placebo (33%) and metoclopramide (42 %). More diarrheal episodes were observed in the groups receiving anti-emetic treatment. All three treatments were well tolerated. CONCLUSIONS: Ondansetron, a 5HT3 receptor antagonist, was significantly superior to placebo in preventing emesis associated with acute gastroenteritis, in paediatric patients. Therefore, serotonin, acting through 5HT3 receptors, may play a role in this form of emesis.
Acute Disease↗
Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early atherogenesis.
Probucol is a potent inhibitor of atherosclerosis in animal models. However, the mechanism of its antiatherogenic effect is not known. To investigate the effects of probucol on gene expression of VCAM-1, MCP-1, and M-CSF in vivo during the early stages of atherogenesis, we determined gene expression in 12 control WHHL rabbits and 12 WHHL rabbits fed 1% probucol from age 3 weeks. Three animals from each group were killed at 6, 9, 12, and 18 weeks of age. Two intimal/medial segments of the thoracic aorta, each comprising the orifices of a pair of intercostal arteries, were analyzed by semiquantitative RT-PCR using GAPDH as an internal standard. A third segment located between these two segments was studied by immunocytochemistry. A basal level of VCAM-1 gene expression was observed in lesion-free aortas of both treated and untreated WHHL rabbits (and in normal NZW aortas). Immunocytochemistry showed some VCAM-1 protein in normal arteries and confirmed that VCAM-1 protein expression generally correlated with gene expression. In the untreated WHHL rabbits, a marked upregulation of VCAM-1 expression was observed at 18 weeks. To correlate gene expression with intimal monocyte/macrophages in each animal, the macrophage area was determined by morphometry of immunostained sections. In addition, a scoring system of lesions was used. VCAM-1 expression showed a highly significant correlation with the extent of intimal macrophage presence (P < .001). A lesser degree of correlation between gene expression and macrophage accumulation was also seen for MCP-1. In contrast, M-CSF expression remained constant over the entire study period and showed no correlation with the intimal macrophage accumulation. Probucol treatment completely prevented lesion formation in all animals up to 18 weeks of age. Probucol reduced the level of basal VCAM-1 expression and prevented its upregulation. MCP-1 expression was not affected by probucol treatment, whereas M-CSF expression was significantly lowered by probucol. Our results support the idea that VCAM-1 plays an important role in early atherogenesis and suggest that the antiatherogenic effect of probucol may in part be due to a downregulation of VCAM-1. Reduction of the basal level of M-CSF gene expression by probucol treatment may also contribute to its ability to inhibit atherogenesis.
Animals↗
Lead (Pb2+) and cadmium (Cd2+) inhibit the dipsogenic action of central beta-adrenergic stimulation by isoproterenol.
We have previously demonstrated that acute third ventricle injections of both Pb2+ and Cd2+ impair the dipsogenic response elicited by three different situations: dehydration and central cholinergic or angiotensinergic stimulation. beta-Adrenergic activation is part of the multifactorial integrated systems operating in drinking behavior control in the central nervous system. In the present study acute third ventricle injections of Pb2+ (3, 30 and 300 pmol/rat) or Cd2+ (0.3, 3 and 30 pmol/ rat) blocked the dipsogenic response induced by third ventricle injections of isoproterenol (ISO; 160 nmol/rat) in a dose-dependent manner. Normohydrated animals receiving ISO + NaAc (sodium acetate) or saline (controls) displayed a high water intake after 120 min (ISO+saline = 5.78 +/- 0.54 ml/100 g; ISO+NaAc = 6.00 +/- 0.6 ml/100 g). After the same period, animals receiving ISO but pretreated with PbAc at the highest dose employed (300 pmol/rat) drank 0.78 +/- 0.23 ml/100 g while those receiving ISO and pretreated with the highest dose of CdCl2 (30 pmol/rat) presented a water intake of 0.7 +/- 0.30 ml/100 g. Third ventricle injections of CdCl2 (3 nmol/rat) or PbAc (3 nmol/rat) did not modify food intake in rats deprived of food for 24 h. Thus, general central nervous system depression explaining the antidipsogenic action of the metals can be safely excluded. It is concluded that both Pb2+ and Cd2+ inhibit water intake induced by central beta-adrenergic stimulation.
Adrenergic beta-Antagonists↗
Low intensity physical training in older subjects.
BACKGROUND: This study was designed to evaluate the effects of a low intensity general training program (< 50% of heart rate reserve) on physical fitness of healthy older subjects, by comparing maximal and submaximal indices of training response. METHODS: Twenty-two volunteers over 60 years of age participated in the present study. The sample was randomly divided in an experimental group of 13 older subjects (3 men and 10 women, mean age 63.5 +/- 3 years) while the remaining 9 subjects (3 men and 6 women, mean age 64.2 +/- 4 years) served as inactive control group. After medical screening all participants were evaluated before and after 12 weeks in which the experimental subjects underwent a low intensity training. Each subjects-either inactive or active-performed two treadmill tests at two-days interval, to measure maximal and submaximal responses to exercise, respectively. Heart rate (HR), oxygen uptake (VO2) and pulmonary ventilation (VE) were measured using a telemetric apparatus. RESULTS: The major finding of the study was the significant improvement in submaximal response to exercise of experimental subjects, expressed by the reduction in HR, VO2 VE while VO2 max did not change. CONCLUSIONS: Thus, it appears that a low intensity general training similar to that followed in the present study may represent a good means to improve physical fitness in healthy elderly people. Similarly, this study supports the effectiveness of evaluation tests based on submaximal responses to exercise in this population.
Aging↗
Cardiac frequency in miners recorded during four to five work shifts.
Cardiac frequency (fc) was recorded in 101 coal-face miners [mean age 32.7 (range 21-49) years, mean height 169.6 (range 150-185) cm, mean body mass 76.9 (range 54-106) kg, mean maximal cardiac frequency (fcmax) 180.2 (range 154-197) beats min-1, mean maximal oxygen uptake (VO2max) 2.93 (range 1.9-4.0) 1.min-1] with a small-size, nonintrusive fc counter, during the five (n = 76) or at least four (n = 25) work-shifts in a week. The femax and VO2max were determined during a progressive test to exhaustion on a treadmill. Overall (four to five work-shifts) mean work-time fc(fc) was 97.7 (range 74.9-122.4) beats.min-1, resting fc (fcrest) 59.1 (range 50-75) beats.min-1, work-time increase in fc (fc-fcrest) 38.5 (range 21.1-55.8) beats.min-1 and percentage of fe reserve used (fcreserve = fcmax-fcrest) 32.0 (range 18.5-50.9). Multiple regression analysis showed that fc and fc-fcrest, as dependent variables, correlated with predicted percentage of CO lung diffusion capacity, (DLCOSB%) (r = - 0.334 and r = -0.273, respectively) but not with age, fcmax, VO2max, VO2max kg-1 body mass, effort test delta oxygen uptake/delta fe or percentage of forced expiratory volume in 1 s as independent variables. The percentage of fcreserve used as dependent variable, correlated with DLCOSB (r = -0.265) and fcmax (r = -0.227) but not with any of the other variables listed. Individual differences in worktime fc are thus large and virtually unpredictable. Other physiological variables not taken in account here (i.e. sense of effort, fatigue perception) as well as psychological ones (work satisfaction, motivation) may have played a role in those differences. At peaks of effort, some subjects reached fc values within the range of femax.
Adult↗
Vascular dynamics in isolated systolic arterial hypertension.
With a growing elderly population, the incidence of isolated systolic hypertension (ISH) has increased. This study characterizes dynamic vascular changes that occur with advanced age and with ISH. Fifty-five healthy individuals and seven with ISH were distributed in seven age groups from the second to the seventh decade. An index of aortic stiffness (delta P/delta V) was derived using a mercury sphygmomanometer to obtain pulse pressure, and ultrasonographic measurements were used to estimate aortic volumes applying the "cylinder formula." The mathematic derivation of this formula is explained in detail. Pulse pressure showed no significant change with age, but showed a significant increase with ISH. A decrease in volume change from systole to diastole was found with advanced age. Normotensive subjects aged 65 +/- 2 years had a 2.6-fold increase in aortic stiffness compared with young individuals. Elderly patients with ISH had a 7-fold increase in aortic stiffness compared with Group 1 (15 +/- 2 years) (p < 0.001) and a 2.7-fold increase compared with Group 6 (normotensive subjects aged 65 +/- 2 years). A strong correlation between systolic pressure and arterial stiffness was observed (r = 0.953) (p < 0.001). The proposed stiffness index was compared with the one described by Hirai, obtaining a high correlation, that is, r = 0.989 (p < 0.001). When compared with Stefanadis' index of distensibility, our index showed a correlation of r = 0.932 (p < 0.003). It is concluded that while systolic pressure is a main determinant of arterial stiffness, the delta P/delta V is a more sensitive method to estimate dynamic changes in elastic arteries such as the aorta.
Adolescent↗