Caring for patients with asthma. Guidance on routine self monitoring is not satisfactory.
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Biomedical subjects
Publications and source records attributed to M Levy.
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BACKGROUND: Infection with the varicella-zoster virus during pregnancy can produce an embryopathy characterized by limb hypoplasia, eye and brain damage, and skin lesions. The risk is greatest when infection occurs during the first 20 weeks of pregnancy, but the magnitude of the risk is uncertain. METHODS: We studied 106 women with clinically diagnosed varicella infection in the first 20 weeks of pregnancy and compared the outcomes with those in 106 age-matched, nonexposed controls. RESULTS: Among the women with varicella, there was a trend toward more elective terminations of pregnancy (14 percent, vs. 7.5 percent among the controls; P = 0.1), corresponding to a significantly higher perception of teratogenic risk (P = 0.03). The proportions of miscarriages and live births and the mean birth weights were similar in the two study groups; there were more premature births (< or = 37 weeks) among the women with varicella infection (14.3 percent vs. 5.6 percent, P = 0.05). Congenital defects occurred in four infants born to the women with varicella (varicella embryopathy, hydrocephalus, meningocele and clubfeet, and hammer toe) and two infants born to the controls (ventricular septal defect and hip dislocation). The risk of varicella embryopathy after infection in the first 20 weeks was 1.2 percent (95 percent confidence interval, 0 to 2.4 percent). When we pooled our results with those from other prospective studies, the mean risk of embryopathy after infection with varicella-zoster virus in the first trimester was 2.2 percent (95 percent confidence interval, 0 to 4.6 percent). CONCLUSIONS: The absolute risk of embryopathy after maternal varicella infection in the first 20 weeks of pregnancy is about 2 percent.
FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity had higher FK506 whole-blood and plasma levels (27.5 +/- 3.2 ng/ml and 1.44 +/- 0.14 ng/ml) than patients with stable liver function (15.2 +/- 2.1 ng/ml and 0.98 +/- 0.15 ng/ml, P < 0.05 and P < 0.01, respectively). Patients with acute rejection had FK506 whole-blood and plasma levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 +/- 6.8 ng/ml and 3.9 +/- 1.4 ng/ml) in comparison with patients with mild-to-moderate neurotoxicity (18.1 +/- 2.4 ng/ml and 1.1 +/- 0.13 ng/ml) (P = 0.048 and P < 0.001, respectively). Long-term use of FK506 was associated with a significant reduction in glomerular filtration rate at 1-year posttransplant in patients on primary FK506 treatment (33%, P < 0.001). The reduction in glomerular filtration rate correlated with the yearly mean FK506 plasma but not with whole-blood levels or FK506 dose. There was a correlation between FK506 whole-blood and plasma levels (r = 0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 whole-blood and plasma levels were 14.1 +/- 0.26 ng/ml and 0.96 +/- 0.75 ng/ml, respectively. There was a large intra- and interpatient variability in the ratio between whole-blood and plasma levels (range 1.0-73.5), with a mean ratio of 18.0 +/- 0.28 (+/- SEM). In conclusion, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.
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In 30 patients with osteonecrosis of the hip (12 idiopathic, 18 secondary), we assessed the role of hypofibrinolysis mediated by high levels of plasminogen activator inhibitor (PAI). We evaluated hypofibrinolysis as a common, potentially reversible, pathophysiologic cause of idiopathic osteonecrosis. In all 18 patients with secondary osteonecrosis, PAI was normal, as was the ability to activate fibrinolysis. Nine of the 12 patients with idiopathic osteonecrosis had exceptionally high PAI levels and could not normally elevate tissue plasminogen activator (tPA-Fx), the major stimulator of fibrinolysis, after 10 min of venous occlusion at 100 mm Hg. The group of 12 patients with idiopathic osteonecrosis, compared to the 18 with secondary osteonecrosis, had low mean stimulated tPA-Fx (1.92 vs. 7.6 IU/ml, P < or = .001) and very high stimulated PAI-Fx (70 vs. 7.6 U/ml, P < or = .01). Three of the 12 patients with idiopathic osteonecrosis had both normal PAI and normal stimulated tPA-Fx. These three patients and 14 of the 18 with secondary osteonecrosis had high lipoprotein (a) [Lp(a)] (> 20 mg/dl). Mean Lp(a) was much higher (60 mg/dl) in the patients with secondary osteonecrosis than Lp(a) (16 mg/dl, P < or = .001) in the 12 patients with idiopathic osteonecrosis. These findings suggest that hypofibrinolysis mediated by high PAI is a common cause of idiopathic osteonecrosis, whereas high Lp(a) may play an etiologic role in secondary osteonecrosis. Prospective studies of patients with high PAI and/or high Lp(a) should be carried out to assess further their apparently causal roles in osteonecrosis.
Hemodynamic responses to three standard laboratory stressors (i.e., postural change, video game, forehead cold) were evaluated in 341 children (170 males) who had a mean age of 11.2 +/- 2.6 years. Inter-task consistency was evaluated for five physiological parameters for all stressor pairings. Evidence of consistency in systolic and diastolic blood pressure, heart rate, cardiac output, and total peripheral resistance responses to all three stressors was observed. The highest and most consistent correlations across stressors were observed for cardiac output and total peripheral resistance responses. The need for clarification in the categorization of laboratory stressors used to measure reactivity is discussed.
Respiratory pumping in Aplysia is a spontaneously occurring behavior whose neural circuitry has been explored, but whose natural functions are incompletely understood. Respiratory pump rate was examined in freely behaving pairs of Aplysia fasciata, to determine whether it is modified by the occurrence of mating and other behaviors. The background rate of respiratory pumping was approximately 2/hour. This rate was maintained while animals were immobile, moving in place, crawling, or feeding. The rate was increased to over 8/hour during courtship and to approximately 4/hour during female mating and was reduced to approximately 1/hour during male-mating. These data suggest that respiratory pumping has a reproductive function, perhaps in dispersal of pheromones that are released during female-mating and courtship. Respiratory pumping never occurred while animals were swimming, suggesting that respiratory pumping and swimming may be mutually incompatible behaviors. Respiratory pumping was less common by night than by day.
Two days after an elective Caesarean section, a 30-year-old woman suffered a pulmonary oedema. The diagnosis of cardiomyopathy was obtained with echocardiography, right heart catheterization and a myocardial biopsy. Peripartum cardiomyopathy is defined as a heart failure occurring in the last trimester of pregnancy or up to the third postpartum month and the lack of another etiology. The cause of myocarditis resulting in peripartum cardiomyopathy remains yet unknown. An immunosuppressive therapy can be associated with the treatment of the congestive heart failure.
In Aplysia fasciata, the sea hare, shock paired with moderate increases or decreases in the seawater concentration leads to pairing-specific increases in the respiratory pump rate in response to the same solutions an hour later. A common neural circuit underlies learned changes to increased and decreased seawater concentration, as shown by complete generalization of learning between these stimuli. Different neural circuitry controls learning after pairing a shock with pH 7 seawater, as shown by a lack of generalization of learning to this stimulus. Preexposure to strong changes in the seawater leads to sensitization of respiratory pumping. The hypothesis was tested that associative learning and sensitization arise from activation of common pathways. However, patterns of generalization of sensitization elicited by preexposure to altered seawaters differ from those produced by associative learning.
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Itraconazole is a new triazole antifungal agent. Active orally, this drug is effective against a wide range of fungal pathogens that includes Aspergillus species, and its use in leukemic and AIDS patients is currently on the increase. Oral itraconazole absorption presents up to threefold interindividual variation in man and is reduced in AIDS patients. Consequently an individual itraconazole adjusting dosage is necessary to ensure adequate clinical antifungal activity. Itraconazole undergoes extensive metabolism and the main isolated metabolite, hydroxyitraconazole, is found in plasma at concentrations 2-3-fold higher than parent drug and presents in vitro the same antifungal activity. At present, despite the contribution of this metabolite to the overall activity of the drug, no well-documented assay was reported in the literature for the codetermination of itraconazole and hydroxyitraconazole in plasma. Due to the wide variety of coadministered drugs to patients receiving itraconazole, the purpose of the developed method was to obtain a specific assay sensitive enough for itraconazole therapeutic monitoring. Therefore, a three-step liquid-liquid extraction procedure following by reversed-phase chromatography and spectrofluorimetric detection was performed. This assay allowed determination of 20 ng/ml of both itraconazole and its active metabolite with an acceptable precision using a 0.5-ml plasma sample; no analytic interference was encountered from 45 coadministered drugs tested.
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Since the original description of composite replacement of the aortic valve and ascending aorta by Bentall in 1968, several modifications of the technique have been described. In order to evaluate the results of these different techniques, we have retrospectively reviewed our results with 140 consecutive patients who underwent Bentall operations between October 1986 and March 1994, using three different anastomotic techniques: Classic, n = 30; Button, n = 95, and Cabrol, n = 15. Overall hospital mortality was 5%. In univariate analysis, acute type A dissection, rupture, new preoperative neurological symptoms, and the Cabrol technique were associated with a higher hospital mortality, but by multivariate analysis no independent risk factors were demonstrated. Overall rates of reoperation did not differ among the three techniques (Classic 4.1%/pt-yr, Button 2.7%/pt-yr, Cabrol 0%/pt-yr; p = 0.44). The actuarial freedom from reoperation was 87% at 5 years. The 5-year actuarial survival for all patients was 79% (Classic 85%, Button 82%, Cabrol 52%): the poorer results with the Cabrol modification are likely due to patient selection, complicated by a higher early mortality in this small group of patients. The presence of dissection was associated with a higher mortality in Marfan patients (50% vs 8%, p = 0.03). The rate of aortic valve-related complications was 3.6%/pt per year. Actuarial event-free survival was 67% at 5 years. Current indications for an elective Bentall procedure include an ascending aortic diameter of 6 cm or greater, with significant aortic valvular dysfunction, and dilatation of the ascending aorta greater than 5 cm in patients with Marfan syndrome or a bicuspid aortic valve. The routine procedure of choice is the Button Bentall technique, with the Classic Bentall and the Cabrol variation reserved for use under special circumstances.
Current surgical techniques in operations on the thoracic aorta frequently require exclusion of the cerebral circulation for varying periods. During these periods, hypothermic circulatory arrest (HCA), selective cerebral perfusion (SCP), and retrograde cerebral perfusion (RCP) can be used for cerebral protection. Hypothermia is the principle component of these methods of protection. The main protective effect of hypothermia is based on reduction of cerebral energy expenditures and largely depends on adequate suppression of cerebral function. It is most effective at deep hypothermic levels (13 degrees C to 15 degrees C). Measures that preserve autoregulation of cerebral blood flow help increase the margin of safety with all methods of protection. There is solid experimental and clinical data indicating the safe limits and outcome following HCA. Current applications of SCP and RCP are fairly recent developments and do not have comparable supporting data. SCP can be used without deep hypothermia and allows prolonged periods of cerebral protection, but is complex in application. RCP is simpler, but always requires deep hypothermia. Present clinical data do not allow separation of its protective effect from that of HCA alone. Recent modifications in the application of HCA include monitoring of cerebral O2 extraction, and selective use of supplemental SCP to limit arrest times to less than 50 minutes, or RCP to prevent embolic strokes, as indicated. These changes appear to have reduced the overall mortality, the severity of embolic strokes, and stroke-related mortality.
An investigation of an outbreak of Legionnaires' disease in 1992 in Fairfield, a municipality of Sydney, was carried out to determine the source of the outbreak. Cases of Legionnaires' disease with onset of symptoms between 11 and 20 April 1992 were included. Definite cases were individuals with a history consistent with Legionnaires' disease, confirmed by direct fluorescent antibody testing plus serology or culture. There were two control groups: patients admitted to the same hospital as the cases, matched for age and sex, and patients admitted to hospital with a presumptive diagnosis of legionnaires' disease, in whom the diagnosis was subsequently excluded. There were 26 definite cases with onset of symptoms between 11 and 20 April 1992. Six (23 per cent) died. Twenty-two cases (85 per cent) reported visiting the Fairfield business district during the ten days prior to the onset of symptoms. They were 20 times more likely to have visited Fairfield than were matched controls. Matching of Legionella pneumophila serogroup 1 from environmental and clinical samples was achieved by cytogenetic fingerprinting. Fourteen cases were linked to a single environmental sample. The epidemiological findings were consistent with a point source of Legionella in the Fairfield business district. It is most likely that the exposure occurred on 10 April 1992.
Cyclic GMP (cGMP) dependent vasodilating agents (natriuretic peptides, nitric oxide) inhibit secretion of endothelin-1 (ET-1) in cultured endothelial cells. However, in circulatory conditions associated with acute hypotension, a marked increase in plasma ET-1 has repeatedly been observed. Therefore, after administration of cGMP-dependent agents in hypotensive dose, the net effect of these opposing influences on ET-1 release may shed light on the mechanisms determining circulating levels of this peptide. We have studied the effect of a hypotensive dose of atrial natriuretic peptide (n = 16), 8-Br-cGMP (n = 5), and papaverin (n = 7) on plasma ET-1 in anesthetized dogs. All agents produced marked increases in the peptide level at the end of infusion (178, 280, and 240% of the last preinfusion level, respectively) and a mean arterial blood pressure (MAP) decrease of 19, 18, and 42 mmHg (1 mmHg = 133.3 Pa), respectively. In all three protocols, plasma ET-1 continued to rise when the hypotensive agent was discontinued and remained elevated for 2-3 h postinfusion, even though MAP was normalized. There was a close positive correlation between the maximal increment in plasma ET-1 and the maximal decrease in MAP (r = 0.67, p < 0.001). These results show that acute hypotension due to directly acting vasodilators is a potent stimulus for systemic release of ET-1, even when due to agents known to inhibit ET-1 production in cultured endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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