[Focus on smoking].
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Biomedical subjects
Publications and source records attributed to A Gervais.
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beta 2-Microglobulin and lysozyme were determined in paired serum and cerebrospinal fluid samples from 137 patients, using immunofluorometry and ELISA, respectively. Of these patients, 54 were infected by human immunodeficiency virus type 1 (HIV1) (including 20 AIDS dementia patients), 73 were HIV1-seronegative with neurological diseases (meningitis (n = 10), multiple sclerosis (n = 29), other neurological diseases (n = 34)) and 10 were controls. Intrathecal synthesis of beta 2-microglobulin occurred in each group. Conversely, lysozyme intrathecal synthesis was found only in meningitis (10/10) and in HIV1-infection (24/54). A pathological increase in beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) was observed in 45 patients (34 HIV1-infected patients and 11 HIV1-seronegative patients with neurological diseases). Serum concentration and intrathecal synthesis of beta 2-microglobulin were correlated only in the 20 AIDS dementia patients. The cerebrospinal fluid beta 2-microglobulin and lysozyme concentrations were correlated in the 54 HIV1-infected patients only. Blood CD4 + T-cell count was correlated negatively with beta 2-microglobulin intrathecal synthesis but not with lysozyme intrathecal synthesis. These data suggest that in the absence of any central nervous system opportunistic process the increase of beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) may be a reliable marker of central nervous system involvement in HIV1-infected patients. Intrathecal synthesis of lysozyme was related principally to HIV1-encephalitis and central nervous system opportunistic processes.
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We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy.
We report on a patient who presented with a Pneumocystis carinii pneumonia. Intravenous pentamidine (4 mg/kg/day) was given for 14 days without the occurrence of adverse effects. During this treatment, the mean (+/- SD) serum pentamidine trough concentration was 94 +/- 16 ng/ml. Three days later, the patient was admitted because of fever, and pentamidine (4 mg/kg/day) was again started. Fasting hypoglycemia and azotemia then occurred; the mean serum trough pentamidine level was 190 +/- 10 ng/ml during this week of treatment. We conclude that the occurrence of hypoglycemia and azotemia during pentamidine therapy may not be idiosyncrasic, but seemed associated in our patient with high levels of serum pentamidine.
15N uniformly labeled lac repressor and lac repressor headpiece were prepared. 15N NMR spectra of lac repressor were shown resolution inadequate for detailed study while the data showed that the 15N labeled N-terminal part of the protein is quite suitable for this type of study allowing future investigation of the specific interaction of the lac repressor headpiece with the lac operator. We report here the total assignment of proton 1H and nitrogen 15NH backbone resonances of this headpiece in the free state. Assignments of the 15N resonances of the protein were obtained in a sequential manner using heteronuclear multiple quantum coherence (HMQC), relayed HMQC nuclear Overhauser and relayed HMQC-HOHAHA spectroscopy. More than 80 per cent of residues were assigned by their 15NH(i)-N1H(i + 1) and 15NH(i)-N1H(i - 1) connectivities. Values of the 3JNH alpha splitting for 39 of the 51 residues of the headpiece were extracted from HMQC and HMQC-J. The observed 15NH(i)-C beta H cross peaks and the 3JNH alpha coupling constants values are in agreement with the three alpha-helices previously described [Zuiderweg, E.R.P., Scheek, R.M., Boelens, R., van Gunsteren, W.F. and Kaptein, R., Biochimie 67, 707 (1985)]. The 3JNH alpha coupling constants can be now used for a more confident determination of the lac repressor headpiece. From these values it is shown that the geometry of the ends of the second and third alpha-helices exhibit deviation from the canonical alpha-helix structure. On the basis of NOEs and 3JNH alpha values, the geometry of the turn of the helix-turn-helix motif is discussed.
Trimethoprim-sulfamethoxazole (TMP-SMZ) and pentamidine are both licensed for the treatment of Pneumocystis carinii pneumonia (PCP). However, their use is associated with various adverse side effects. In this prospective study, 26 AIDS patients with 32 episodes of PCP were treated with pentamidine (4 mg/kg/d). Each patient was treated for 12 to 21 days, depending on the rapidity of onset of the clinical response. During the 32 PCP episodes, hypoglycemia occurred in 16 instances, azotemia in 12, liver toxicity in 10, and leukopenia in 8. The occurrence of thrombopenia, leukopenia, and liver toxicity was not related to age, pentamidine levels, or other complications. However, patients who had hypoglycemia during pentamidine treatment had higher serum pentamidine levels than patients who did not have hypoglycemia (107 +/- 40 versus 70 +/- 26 ng/ml, p less than 0.004). In addition, we observed that patients with azotemia showed higher pentamidine levels during treatment (120 +/- 35 versus 64 +/- 22 ng/ml, p less than 0.001). In fact, 100% (11/11) of patients with serum pentamidine concentration greater than 100 ng/ml had fasting hypoglycemia and/or azotemia, while 33% (7/21) of those with pentamidine levels less than 100 ng/ml had these side effects (p less than 0.001). The relative risk of these complications with pentamidine levels greater than 100 ng/ml was 3 (95% confidence interval, 1.6 to 5.5). Fine-tuning the dose of pentamidine may eventually prove useful to avoid toxicity and optimize therapy.
A questionnaire was developed to assess adult recall for a range of transpersonal experiences throughout childhood and adolescence (mystical experience, out-of-body experience, lucid dreams, archetypal dreams, ESP), as well as nightmares and night terrors as indicators of more conflicted, negative states. In two exploratory studies this questionnaire was administered to subjects with high estimated levels of early transpersonal experiences and practising meditators, with respective undergraduate controls. A cognitive skills/precocity model of early transpersonal experience was contrasted with a vulnerability of self model by comparisons of these groups on questionnaire categories, imaginative absorption, neuroticism, and visual-spatial skills, with some support found for both models depending on experience type, age of estimated recall, and adult meditative practice.
The assessment of proteins intrathecal synthesis (ITS) is an essential step in the CSF analysis. It can be established qualitatively by different ratios and quantitatively by empirical formulae. Schuller and Sagar's formula was proposed 10 years ago for the calculation of IgG ITS. From this calculation, the antibody specific activity of intrathecal immunoglobulins may be also evaluated. The same principle may be used for complement components and for different other CSF proteins. Two examples (concerning Fibronectin and prealbumin ITS) demonstrate the usefulness of this approach, which can be programmed by a computer.
OBJECTIVE: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). PARTICIPANTS: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. INTERVENTION: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of 5 doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. RESULTS: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and 5 occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P less than 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. CONCLUSION: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia.
A new methodology, using electroimmunodiffusion, has been described for the determination of fibronectin (Fn) in plasma and CSF. Fn was determined in the plasma of 35 normal subjects, and in the plasma and the CSF of 86 patients: 10 controls, 17 definite MS, 15 other inflammatory processes, 11 degenerative diseases, 13 peripheral neuropathies and 20 other neurological diseases. The normal mean was 354 +/- 53 micrograms/ml in plasma, not influenced by sex or age, and in the CSF 2.3 +/- 0.85 micrograms/ml. A significant increase of plasma Fn was observed in each of the patients-group. In the CSF an increase of Fn was observed predominantly in inflammatory processes but not in MS. An intrathecal synthesis of Fn was established in 24/76 patients, most often in inflammatory (9/15) processes but rarely (3/17) in MS. The intrathecal synthesis was suspected from the CSF Fn/CSF Albumin ratio and calculated using a formula derived from the principles previously described for IgG intrathecal synthesis. It represents the principal source of Fn increase in the CSF. In all inflammatory processes (including MS) the eventual influence of corticoids, immunosuppressive or anti-inflammatory drugs has not been established. The significance of the CSF Fn level in MS is discussed with regard to the recent demonstration of its presence within MS lesions and on macrophages in plaques.
Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.
A new mouse monoclonal antibody that recognizes alpha- and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin was obtained. The 125I- and 111In-labelled antibody, and its F(ab')2 and Fab fragments localize in isoproterenol induced infarcted rat heart, with the F(ab')2 fragment showing the highest uptake. Comparison with 99Tc-pyrophosphate uptake in infarcted dog heart, induced by selective obstruction of a coronary artery, suggest that the 111In-labelled F(ab')2 localizes specifically in infarcted myocardium only.
Ribbon against drop (R.A.D.) ribbons exhibit a polycrystalline texture similar to that of most melt-grown ribbons; we review here the defects of as-grown materials as well as after the solar cells' production.
Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings.
Falsely elevated serum digoxin values have recently been reported in patients with liver disease. Since not all patients have circulatory digoxin-like immunoreactive substance (DLIS) in their serum, we compared the clinical and laboratory findings in patients with and without DLIS. Thirty-two patients with liver disease were studied. The only parameter that was significantly different in the two groups was serum bilirubin. In the group of patients with DLIS, significant correlations were obtained between DLIS and bilirubin and DLIS and creatinine. We postulate that increased levels of DLIS in serum are due to an abnormality of DLIS excretion.
The bronchodilating response to two doses of 100 micrograms of salbutamol introduced into an extension device (Aero-chamber [AC]), each followed by four tidal breaths, was compared with the nebulization of 2.5 mg of salbutamol in a saline solution during tidal breathing in a crossover study of ten patients with reversible airway obstruction. The forced expiratory volume in one second (FEV1) and the forced vital capacity 30 min after the drug administration improved significantly with both methods (p less than .001). The improvement of FEV1 with the AC (52.1 percent) compared with the nebulization (55.7 percent) was similar (p greater than .05).