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Biomedical subjects

J Dormont

Publications and source records attributed to J Dormont.

At least 19 recordsLinked to original sources

[Good clinical practice:impediment of source of progress?].

On the bases of the Declaration of Helsinki (1964), the law called Huriet-Sérusclat (1988) and several subsequent decrees have clearly defined the appropriate organization and management of clinical trials in France. The law on the Commission de l'informatique et des libertés (1978) and several European regulations have also to be taken into account. This extensive legal and regulatory system has been the source of a major improvement in the scientific quality of clinical trials and in the security of participating persons. Indirectly, it has also improved daily clinical care, as physicians have learned how to inform their patients and have been trained to use protocols and standard operative procedures. However, the legal and regulatory pressure has increased the cost and complexity of trials to such an extent that no clinician with his own resources is now able to be the sponsor of a trial involving more than a few patients. In addition to trials organized by pharmaceutical companies for drug development, health authorities in France and Europe should consider to support major clinical trials on therapeutic strategies with public health implications. A few examples can be acknowledged thus far, but a real policy remains to be defined.

Clinical Trials as Topic↗

Disclosure of HIV seropositivity.

Deciding whether or not to disclose one's HIV-positive status to another person is an important decision: the way each person experiences and copes with the illness is reflected in this choice. We conducted a study of 174 patients (29.3% of women) to examine how the decision to disclose or conceal was made, as well as its subjective and social consequences. We discovered that only 3.5% of the individuals remained silent about their illness. Most spoke about it, regardless of how they had been infected or of the advice they had received to be discrete. The confession often did not bring them the relief they sought. Revealing one's HIV-positive status is not a sign of social responsibility, or of a special trust in someone, but rather a compulsive act to release suppressed tension. Individuals who do not confess need attention; their silence is a sign of their inability to adapt to their illness, as well as of their self-imposed exclusion from society.

Adaptation, Psychological↗

[Antiretroviral treatments in human immunodeficiency virus infection].

Antiretroviral drugs already registered or currently in clinical trials are shortly described, including dideoxynucleosides, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, tat inhibitors and antisens molecules. In a second part, the treatment of patients with the nucleosides already on the market or in a pre-registration phase is reviewed, on the basis of an analysis of available phase III clinical trials. The third part describes the strategy of clinical trials and explains why "surrogate markers" including markers of viral replication cannot yet be the main criteria to evaluate the efficacy of a new drug in a phase III trial.

Animals↗

Hyperchloremic acidosis during grand mal seizure lactic acidosis.

OBJECTIVE: To evaluate the prevalence and the mechanism of hyperchloremic acidosis component (HClA) during lactic acidosis secondary to grand mal seizures. DESIGN: Retrospective study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 35 patients admitted for grand mal seizures with lactic acidosis (pH < 7.35, TCO2 < 20 mmol/l and PaCO2 < 8 kPa). MEASUREMENTS: HClA was defined by the ratio: excess anion gap/HCO3 deficit (delta AG/delta TCO2) < 0.8. A difference in the distribution space of protons and their accompanying anion, i.e., a displacement of chloride from cells by the entering lactate, was evaluated by the ratio natremia/chloremia (Na+/Cl-). RESULTS: Immediately after seizures, a profound lactic acidosis was observed (pH = 7.22 +/- 0.17 (mean +/- SD), AG: 23.8 +/- 7.1 mmol/l, TCO2 = 14.5 +/- 5.3 mmol/l, lactate: 14.6 +/- 6.9 mmol/. HClA was present on admission in 11 patients (31.5%). Its prevalence increased to 73% after recovery. delta AG/delta TCO2 ratios were unrelated to creatinine, level and PaCO2, but dependent on the ratio Na+/Cl- (r = 0.803; p < 0.001, delta AG/delta TCO2 = 6.4 x (Na+/Cl-)-7.9). These data demonstrate that HClA is not a respiratory or renal phenomenon and suggest differences in the distribution spaces of hydrogen ions and their accompanying anions. CONCLUSION: HClA component may be associated with lactic acidosis in grand mal seizures and appears to be secondary to a lactate antiport. This phenomenon could be an immediate physiological response to a sudden metabolic acidosis.

Acid-Base Equilibrium↗

Pancreatic lesions in HIV-infected patients.

The pancreas is frequently involved during HIV infection, especially by disseminated infections or neoplasms. These lesions are generally asymptomatic and are discovered at autopsy. However, hypoglycaemia secondary to massive pancreatic infiltration by a tumour or tuberculous necrosis may occur. The most important cause of pancreatic dysfunction in HIV-infected patients is a drug toxic effect (intravenous pentamidine, didanosine, zalcitabine). Hypoglycaemia, which may or may not be followed by diabetes, can develop during intravenous pentamidine therapy. In cases with increased serum amylase and/or lipase levels, potentially toxic drugs must be promptly discontinued to avoid major pancreatic involvement.

AIDS-Related Opportunistic Infections↗

Future treatment strategies in HIV infection.

UNLABELLED: EFFECTIVENESS OF EARLY TREATMENT WITH ZIDOVUDINE: In terms of progression to AIDS-related complex, AIDS or death, clinical trials have not yet shown any long-term benefit for early compared with deferred treatment with zidovudine. The Concorde trial showed a short-term benefit, as did two of the AIDS Clinical Trials Group studies, but the number of deaths in these short-term trials was too small to draw definitive conclusions. USE OF CD4 CELL COUNTS AS A MARKER OF AIDS: Most trials of zidovudine treatment have shown a slower decline in CD4 cell counts. However, it is still not clear whether these markers can predict long-term survival although they appear to have some value in predicting short-term benefits. SECOND-LINE THERAPY: In patients who are intolerant of or have failed to respond adequately to zidovudine, treatment with didanosine or zalcitabine has shown some short-term benefit, mainly in asymptomatic patients or those with AIDs-related complex. No substantial long-term benefit was observed. Zalcitabine appeared to show a slight increase in survival compared with didanosine. FUTURE PROSPECTS: Treatment strategies still being developed include multidrug combinations, the combination of a nucleoside with a non-nucleoside reverse transcriptase inhibitor, or the use of a combination of drugs that affect different stages of the HIV life cycle, such as proteinase inhibitors. More sensitive assays, such as RNA polymerase chain reaction, may allow treatment to be tailored more closely to the needs of the individual patient.

AIDS-Related Complex↗

[Recurrent thrombocytopenic thrombotic purpura associated to prostatic cancer. A case].

The association between thrombocytopenic thrombotic purpura (TTP) and infectious or multisystem disease, pregnancy, transplantation, drugs and toxins is well known. The onset of TTP in the course of neoplasm is rarely described. The authors report one case of TTP associated with prostatic tumor. TTP preceded the discovery of neoplasm by 12 months. Moreover, TTP showed an original course with four recurrences despite antiplatelet and hormonal therapies; the successive regressions were obtained with less and less effort, as TTP was discovered at an early stage.

Humans↗

[Hyperchloremic acidosis in metabolic acidosis with anion gap excess. Comparison with diabetic ketoacidosis].

The occurrence of hyperchloremia during diabetic ketoacidosis (DKA) recovery and the lack of correlation between anion gap excess (delta AG) and bicarbonate deficit (delta TCO2) on admission suggest an hyperchloremic acidosis (HCLA) component. The hypothesis that this phenomenon is not specific of DKA and can occur in other metabolic acidoses with increased anion gap was tested. HCLA component, defined by the ratio delta AG/delta TCO2 less than or equal to 0.80, was evaluated on admission and during therapy in 31 patients with DKA and 53 patients with non diabetic metabolic acidosis (ND-MA). HCLA component prevalence was similar on admission (32 p. 100 for DKA versus 41 p. 100 for ND-MA), but it increased during therapy only in DKA patients (86 p. 100 at 9 h - P less than 0.001). In view of the significant correlation (r = 0.636; P less than 0.001) observed between delta AG/delta TCO2 and creatinine, kidney acid base defense appears clearly in DKA patients: the more severe the volume depletion, the greater the ketone retention and the less prominent the HCLA. This phenomenon seems to be secondary to a large tubular excretion of ketones. In the 53 ND-MA patients no correlation between delta AG/delta TCO2 and creatinine could be found. A transfer of chloride from cells to the extracellular space secondary to intracellular diffusion of lactate ions could explain the HCLA component.

Acid-Base Equilibrium↗