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Biomedical subjects

P Gajdos

Publications and source records attributed to P Gajdos.

At least 55 records · Page 3Linked to original sources
PubMed1998

Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet-size dependent phenomenon.

Myotonic dystrophy (DM) is caused by an expansion of a CTG triplet repeat sequence in the 3'-noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. Impaired glucose penetration into brain tissues has been described in DM patients and is a phenomenon that remains unexplained. The present study shows that altered brain glucose metabolism is triplet repeat dependent. We studied brain glucose metabolism (CMRGlu, mumol/100 g/min) by the use of positron emission tomography and 18F-fluoro-2-deoxy-D-glucose in 11 ambulatory non-obese DM patients and in 11 age and sex matched healthy subjects. All subjects underwent a glucose tolerance test with plasma insulin determinations. The expansion of CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. As compared to controls, in DM patients, the CMRGlu was significantly decreased (26.26 +/- 5.05 vs. 33.43 +/- 2.18, mumol/100 g/min, P = 0.004), and after oral glucose loading, plasma insulin levels were significantly higher and plasma glucose levels remained unchanged (respectively, F = 11.21, P = 0.004 and F = 0.20, P = 0.66). Subsequently, the glucose/insulin ratio was significantly lower in DM patients (F = 6.25, P = 0.02). The length of the expansion of the CTG repeats correlated negatively with the CMRGlu (r2 = 0.63, P = 0.003) and positively with the area under the curve for insulin changes over time after oral glucose (r2 = 0.49, P = 0.016). We conclude that, in DM patients, the brain metabolism of glucose is impaired in a repeat dependent manner.

Activities of Daily Living↗
PubMed1998

Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve.

AIMS: To investigate the relationship between adrenal gland function and pressor response to noradrenaline in septic shock. METHODS: Basal cortisol level, noradrenaline--mean arterial pressure dose-response curve and cortisol response to intravenous corticotrophin bolus were obtained in nine patients fulfilling usual criteria for septic shock and in six normal volunteers. In patients with septic shock, dose-response curve to noradrenaline was determined a second time 60 min after a 50 mg intravenous hydrocortisone bolus. RESULTS: As compared with controls, patients with septic shock had increased basal cortisol levels (mean+/-s.d.: 1564+/-818 vs 378+/-104 nmol l(-1) , P=0.002, 95% confidence interval for difference in means: [452, 1920]) and a blunted cortisol response to corticotrophin (403+/-461 vs 1132+/-195 nmol l(-1), P=0.008, [-1163, -2951). Five patients had impaired adrenal function reserve. As compared with controls, septic patients displayed a moderate and non significant decrease in pressor sensitivity to noradrenaline (P=0.112). As compared with patients with adequate adrenal response, patients with impaired adrenal function reserve showed a significant decrease in pressor sensitivity to noradrenaline (P=0.038). In septic patients, hydrocortisone improved pressor response to noradrenaline (P=0.032). This effect was more marked in patients with impaired adrenal function reserve so that, as compared with patients with adequate response, the difference was no longer significant (P=0.123). CONCLUSIONS: In septic shock, impaired adrenal function reserve may partly be accounted for by the depressed pressor sensitivity to noradrenaline. The latter may be substantially improved by physiological doses of hydrocortisone.

Adrenal Gland Diseases↗
PubMed1998

[Long-term ventilation at home in adults with neurological diseases].

Respiratory handicap due to neurological diseases is often underestimated. Given clinical signs are either mild or absent, systematic measurement of the vital capacity is the best mean to detect in practice the restrictive syndrome. The onset of home mechanical ventilatory support should be decided at steady state, apart from episodes of acute respiratory failure. Two types of indications should be distinguished. Necessary ventilation aims at supplying over day and night the respiratory insufficiency incurred by the paralysis of respiratory muscles. Although the criteria for the use of such a supply differ according to the neurological disease, a daytime hypercapnia above 45 mmHg is widely accepted in the literature. It is otherwise established to use first a non invasive technique, while tracheostomy is secondarily proposed in case of failure of these techniques. The application of this therapeutic strategy in Duchenne de Boulogne muscular dystrophy showed that, given that tracheostomy will become necessary in this evolutive disease, proposal of an early tracheostomy is not nonsensical. By contrast, preventive ventilation aims at preventing from the aggravation of the restrictive syndrome in those patients with no criterion for necessary ventilation. It has been proved ineffective in Duchenne muscular dystrophy through a controlled clinical trial.

Adult↗
PubMed1997

Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group.

We have conducted a trial to randomly assess the efficacy and tolerance of intravenous immunoglobulin (i.v.Ig) or plasma exchange (PE) in myasthenia gravis (MG) exacerbation and to compare two doses of i.v.Ig. Eighty-seven patients with MG exacerbation were randomized to receive either three PE (n = 41), or i.v.Ig (n = 46) 0.4 gm/kg daily further allocated to 3 (n = 23) or 5 days (n = 23). The main end point was the variation of a myasthenic muscular score (MSS) between randomization and day 15. The MSS variation was similar in both groups (median value, +18 in the PE group and +15.5 in the i.v.Ig group, p = 0.65). Similar efficacy, although slightly reduced in the 5-day group was observed with both i.v.Ig schedules. The tolerance of i.v.Ig was better than that of PE with a total of 14 side effects observed in 9 patients, 8 in the PE group and 1 in the i.v.Ig group (p = 0.01). Although our trial failed to show a pronounced difference in the efficacy of both treatments, it exhibited a very limited risk for i.v.Ig. i.v.Ig is an alternative for the treatment of myasthenic crisis. The small sample sizes in our trial, however, could explain why a difference in efficacy was not observed. Further studies are needed to compare PE with i.v.Ig and to determine the optimal dosage of i.v.Ig.

Adult↗
PubMed1997

Association of the AChRalpha-subunit gene (CHRNA), DQA1*0101, and the DR3 haplotype in myasthenia gravis. Evidence for a three-gene disease model in a subgroup of patients.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction having multigene control. HLA-linked loci and the HB*14 micro-satellite marker located within the CHRNA gene which encodes the muscular acetylcholine receptor (AChR) alpha-subunit, the target self-antigen, were previously associated with MG. Combined analysis of these loci revealed a significant increase of DQA1*0101 alleles in HB*14+ vs. HB*14- patients and of DQA1*0501 alleles in HB*14/DQA1*0101 patients. Importantly, the effect of DQA1*0101 was independent of allelically associated DQB1 and DRB1 genes. In contrast, the effect of DQA1*0501 could not be dissociated from that of DRB1*03 and DQB1*0201 on the extended DR3 haplotype. These results indicate that a combination of three genes, of which two are linked to HLA, contributes to disease susceptibility in a subgroup of MG patients.

Adult↗
PubMed1997

No evidence for an association of AChR beta-subunit gene (CHRNB1) with myasthenia gravis.

Using a polymorphic dinucleotide repeat, we have investigated the contribution of the gene encoding the beta-subunit of the muscle acetylcholine receptor (CHRNB1), the target autoantigen, to the susceptibility to myasthenia gravis (MG). We have combined a case-control study (comparing 143 patients and 162 controls) and a transmission-disequilibrium test bearing on 35 simplex families with heterozygous parents. There was no evidence for an association of CHRNB1 with MG, even after subgrouping patients according to thymus histology, or other clinical criteria. Interestingly however, the shortest four variants of the CHRNB1 microsatellite were seen only in patients with thymus hyperplasia and in none of the control subjects (P < 0.0025).

Adult↗
PubMed1997

[Importance of neuromuscular "jitter" under stimulation in the diagnosis of myasthenia gravis].

Ninety five patients with global muscular weakness or purely extraocular weakness were included in a retrospective study. Electrical micro stimulation and single fiber electromyography were performed in all, for neuromuscular jitter evaluation in myasthenia gravis diagnosis. In our study, increased jitter was more often present (70% of generalised myasthenia gravis and 57% of ocular myasthenia gravis) than decrement after repetitive nerve stimulations (58% of generalised myasthenia gravis and 14% of ocular myasthenia gravis). Increased jitter was also found in non-myasthenic patients. With the aim of a better sensitivity and specificity of the electrophysiological diagnosis for myasthenia gravis a protocol is described.

Adult↗
PubMed1997

Rapid shift in peak melatonin secretion associated with improved performance in short shift work schedule.

We studied the performance and adaptability of 40 nurses (median age 35 years), 20 on permanent day shift and 20 on permanent night shift with fast rotation of work and days off, matched for age, gender, and socio-familial responsibilities. For 15 days prior to the study, subjects maintained sleep logs and trained for performance tests. Questionnaires were administered to evaluate adaptability to shift work. During the experimental phase, sleep/wake patterns were monitored using sleep logs and activity/inactivity with wrist actigraphy. Performance levels were measured with the four choice reaction time and memory test for seven letters, eight times/day during the wake period, days on and off. On the last day of work and first day off, 6-sulfatoxy-melatonin levels were assayed from urine samples collected every 2 hours. Estimated total sleep time during the 15-day experimental period was not significantly different in the dayshift and nightshift nurses. Night nurses shifted regularly to daytime activities on days off and, as a group, were significantly sleep deprived on work days with napping on the job in 9 of the 20 night shift nurses (mean of 114+/-45 minutes per shift) and a significant performance decrement during the work period. Further analysis revealed two subgroups of night nurses: The majority (14 nurses) had a mean peak of 6-sulfatoxy-melatonin at 0718 hours on days off and no peak during night work while the other 6 night shift nurses presented a fast melatonin shift with two clear peaks on both work and days off. Comparison of performance scores revealed that all nurses performed similarly on days off. Daytime nurses and fast-shifting night nurses had similar scores on work days, while nonshifting night nurses had significantly lower scores at work. Despite similar gender, age, social conditions, and light exposure levels, a minority of the nurses studied possessed the physiological ability to adapt to a fast-shifting sleep-wake schedule of more than 8 hours and were able to perform appropriately in both conditions. This shift was associated with a change in the acrophase of 6-sulfatoxy-melatonin.

Adult↗
PubMed1996

[Iatrogenic air embolism].

The incidence of iatrogenic air embolism can only be estimated since many accidents are not recognized. Clinical manifestations, essentially neurological or cardiovascular disorders vary greatly. Air embolism may occur during coronary or cerebral arteriography, cardiopulmonary bypass, venous catheterism, various types of surgery or blood transfusion among other situations. Once air has entered the arterial circulation, the bubble of gas follows the blood flow until it is blocked by a smaller calibre vessel. The progressive diffusion of the air reduces the size of the embolus which then migrates on to smaller and smaller vessels. Subsequent pathological manifestations of air embolism result from mechanical obstruction leading to ischemia and inflammatory reactions to air acting as a foreign body. The sudden onset signs of neurological impairment with or without a cardiopulmonary component in patients in a high-risk situation leads to clinical diagnosis. Treatment must be started immediately although brain CT scan or echocardiography may help confirm the diagnosis. The source of the air must be immediately identified and removed and the vital functions controlled. Mechanical or facial mask ventilation with pure oxygen is indicated. Hyperbaric oxygen therapy should be instituted. Morbidity and mortality after iatrogenic air embolism is high but major improvements have been achieved with oxygen therapy. Neurological sequellae have been estimated to reach 19 to 50% of the patients. A personal controlled prospective study revealed 14% mortality after hyperbaric oxygen therapy given within 12 hours of the accident.

Embolism, Air↗
PubMed1996

[Respective indications of plasma exchange and high-dose immunoglobulins in polyradiculoneuritis and myasthenia gravis].

The main purpose of plasma exchange is to remove toxic substances. The mechanisms involved appear to be complex. The primary aim of immunoglobulins is to compensate for immunodeficiency, but when given intravenously at high doses, immunoglobulins can also have unexpected immunomodulation effects. Routine therapeutic use of these methods raises the problem of cost and potential morbidity. Two therapeutic trials have demonstrated that plasma exchange in Guillain-Barré syndrome improves outcome when given early. In chronic polyradiculonevritis, plasma exchange and intravenous immunoglobulins have been shown to be equally effective although plasma exchange would give less satisfactory results in patients with polyradiculonevritis and monoclonal IgG. The effect of intravenous immunoglobulins is being evaluated. Plasma exchange has become the gold standard for acute crisis of myasthenia gravis. Recent results suggest that intravenous immunoglobulins could be equally effective in these diseases. Though useful therapeutic tools, the respective indications and optimal doses for these methods remains to be defined.

Humans↗
PubMed1996

Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema.

BACKGROUND: Converting enzyme inhibitors meet most of the criteria required to be used in acute pulmonary edema. However, they could also induce deleterious effects on renal function and electrolytes. The purpose of this study was to evaluate the efficacy and safety of a single intravenous 2-hour infusion of enalaprilat (1 mg) after an acute pulmonary edema. METHODS AND RESULTS: This was a placebo-controlled, randomized, double-blind study performed in 20 congestive heart failure patients (New York Heart Association class III or IV). Systemic and regional hemodynamic parameters, biological parameters, and blood gases were measured before and repeatedly after the onset of infusion. Compared with placebo, enalaprilat decreased pulmonary capillary wedge pressure (-37% versus -10%, P = .001), diastolic and mean systemic blood pressures (-21% versus 0%, P = .009, and -18% versus -1%, P = .026, respectively), diastolic and mean pulmonary blood pressures (-21% versus -8%, P = .040; -18% versus -9%, P = .046), and brachial and renal resistances (-44% versus -14%, P = .017, and -22% versus -2%, P = .014, respectively); increased brachial and renal blood flows (+77% versus +8%, P = .036, and +12% versus 0%, P = .043, respectively), arterial oxygen tension (+2% versus -16%, P = .041), and arterial oxygen saturation (+1% versus -2%, P = .045); and tended to decrease rate-pressure product (-19% versus -7%, P = .076), increase brachial artery diameter (+13% versus 0%, P = .081), and improve intrapulmonary shunt (-18% versus +16%, P = .080). Enalaprilat did not affect cardiac output or carotid or hepatosplanchnic hemodynamics. CONCLUSIONS: Early administration of enalaprilat is effective and well tolerated in acute pulmonary edema.

Acute Disease↗
PubMed1996

Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon.

BACKGROUND: In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. METHODS AND RESULTS: In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39 +/- 0.39 versus 4.00 +/- 0.67, P = .00003) and regional (anterior, 2.39 +/- 0.64 versus 3.87 +/- 0.92, P = .002; septal, 2.60 +/- 0.48 versus 4.00 +/- 0.70, P = .0003; lateral, 2.26 +/- 0.58 versus 4.16 +/- 1.11, P = .0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size (r = -.77, P = .009). CONCLUSIONS: The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Adult↗