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Biomedical subjects

J Cosin

Publications and source records attributed to J Cosin.

At least 19 recordsLinked to original sources

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.

BACKGROUND: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. METHODS: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. RESULTS: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years). CONCLUSIONS: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

AIDS-Related Opportunistic Infections↗

Thrice-weekly sulfadiazine-pyrimethamine for maintenance therapy of toxoplasmic encephalitis in HIV-infected patients. Spanish Toxoplasmosis Study Group.

An open, randomised, multicentre trial was conducted to evaluate the efficacy of thrice-weekly versus daily therapy with sulfadiazine-pyrimethamine in the prevention of relapses of toxoplasmic encephalitis in HIV-infected patients. Between February 1994 and July 1997, 124 patients with HIV infection were enrolled after resolution of the first acute episode of toxoplasmic encephalitis treated with sulfadiazine-pyrimethamine. Patients were randomly assigned to receive either a daily regimen consisting of sulfadiazine (1 g) twice a day plus 25 mg pyrimethamine and 15 mg folinic acid daily (n = 58), or a thrice-weekly regimen consisting of the same doses of sulfadiazine and folinic acid plus 50 mg pyrimethamine (n = 66). After a median follow-up period of 11 months (range 1-39 months), no differences were found in the incidence of toxoplasmic encephalitis relapses between the groups, there being 14.9 episodes per 100 patient-years (95% CI: 2.8-20.2) in the daily-regimen group versus 14.1 episodes (95% CI: 2.3-17.2) in the intermittent-regimen group. The estimated cumulative percentages of relapse at 12 months were 17% and 19%, respectively (P = 0.91). In a Cox multivariate analysis, not taking antiretroviral therapy was the only variable independently associated with relapse (adjusted risk ratio: 4.08; 95%CI: 1.32-12.66). Baseline CD4+ cell counts, prior AIDS, mental status, sequelae and allocated maintenance therapy regimen were not independent predictors of relapse. No differences were observed in the survival rate (P = 0.42), or in the incidence of severe adverse effects (P = 0.79). The efficacy of the thrice-weekly regimen was similar to that of the daily regimen in the prevention of relapses of toxoplasmic encephalitis. Administration of antiretroviral therapy was the only factor associated with a lower incidence of relapse.

AIDS-Related Opportunistic Infections↗

Treatment of AIDS-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy.

OBJECTIVES: To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML). PATIENTS AND METHODS: The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles. RESULTS: With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74x10(6)/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P<0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result. CONCLUSIONS: This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.

AIDS-Related Opportunistic Infections↗

Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity.

BACKGROUND: Aspirin (acetylsalicylic acid, ASA) is widely used for secondary prevention of ischemic vascular events, although its protection only occurs in 25% of patients. We previously demonstrated that platelet reactivity is enhanced by a prothrombotic effect of erythrocytes in a thromboxane-independent manner. This diminishes the antithrombotic therapeutic potential of ASA. Recent data from our laboratory indicate that the prothrombotic effect of erythrocytes also contains an ASA-sensitive component. In accordance with this observation, intermittent treatment with high-dose ASA reduced the prothrombotic effects of erythrocytes ex vivo in healthy volunteers. In the present study, the effects of platelet-erythrocyte interactions were evaluated ex vivo in 82 patients with vascular disease: 62 patients with ischemic heart disease treated with 200 mg ASA/d and 20 patients with ischemic stroke treated with 300 mg ASA/d. METHODS AND RESULTS: Platelet activation (release reaction) and platelet recruitment (fluid-phase proaggregatory activity of cell-free releasates from activated platelets) were assessed after collagen stimulation (1 microg/mL) of platelets, platelet-erythrocyte mixtures, or whole blood. Platelet thromboxane A2 synthesis was inhibited by >94% by ASA administration in all patients. Importantly, platelet recruitment followed one of three distinct patterns. In group A (n=32; 39%), platelet recruitment was blocked by ASA both in the presence and absence of erythrocytes. In group B (n=37; 45%), recruitment was abolished when platelets were evaluated alone but continued in the presence of erythrocytes, indicating a suboptimal effect of ASA on erythrocytes of this patient group. In group C (n= 13; 16%), detectable recruitment in stimulated platelets alone persisted and was markedly enhanced by the presence of erythrocytes. CONCLUSIONS: In two thirds of a group of patients with vascular disease, 200 to 300 mg ASA was insufficient to block platelet reactivity in the presence of erythrocytes despite abolishing thromboxane A2 synthesis. Platelet activation in the presence of erythrocytes can induce the release reaction and generate biologically active products that recruit additional platelets into a developing thrombus. Insufficient blockade of this proaggregatory property of erythrocytes can lead to development of additional ischemic complications.

Adult↗

Leishmania infection occurring in herpes zoster lesions in an HIV-positive patient.

We report the first case of co-infection with herpes zoster and leishmania in the same lesion, on the face of a 29-year-old female, who was an intravenous drug user and who was HIV positive. The infection was initially resistant to acyclovir and itraconazole, and the patient died due to severe internal complications, not attributed to visceral leishmaniasis. The prevalence of leishmania infection in the Mediterranean countries is increasing among the HIV-positive population because of the existence of human carriers. Paradoxically, most of these patients show mild forms of visceral leishmaniasis.

AIDS-Related Opportunistic Infections↗

Functional and ultrastructural alterations of canine myocardium subjected to very brief coronary occlusions.

The effects of very brief and recurrent coronary occlusions on myocardial regional shortening and its ultrastructure have been analysed. Ultrasonic crystals were implanted in the left ventricular subendocardium of 23 anaesthetized dogs with the thorax open, to measure the shortening fractions of an ischaemic and a control segment. Twenty 2 min total occlusions were provoked in the left anterior descending coronary artery, with 3 min recovery intervals (reperfusion) between occlusions. The shortening fraction decreased progressively with each occlusion, reaching a value 18.9% lower than the basal after the last ischaemic episode (P < 0.05); 32.3% after 4 h of reperfusion (P < 0.01), and 28.6% after 24 h (P < 0.01). Qualitative and quantitative ultrastructural analysis showed an increase in the mitochondrial volume of the ischaemic tissue (158% vs control, P < 0.001) with significant damage to the cell components (7.7-fold increases vs control mitochondria). These results show that when the myocardium is subjected to very brief and repeated coronary occlusions, there is progressive deterioration of systolic function with structural alterations, mainly at the mitochondrial level. These modifications are still observable 24 h after the end of ischaemic stimulation and could be the cause of transitory and/or chronic systolic dysfunctions in the absence of previous heart attack.

Animals↗

Comparison of the effects of amiodarone versus metoprolol on the frequency of ventricular arrhythmias and on mortality after acute myocardial infarction. SSSD Investigators. Spanish Study on Sudden Death.

A randomized trial was conducted to assess the efficacy of amiodarone versus metoprolol or no antiarrhythmic treatment to suppress asymptomatic ectopic activity and improve survival in patients who have had myocardial infarction with a left ventricular ejection fraction of 20 to 45% and > or = 3 ventricular premature complexes per hour (pairs or runs). Patients (n = 368) were randomly assigned to receive amiodarone 200 mg/day (n = 115) 10 to 60 days after the acute episode, and metoprolol 100 to 200 mg/day (n = 130) or no antiarrhythmic therapy (n = 123). After a median follow-up of 2.8 years, mortality in the amiodarone-treated patients (3.5 +/- 2% SEM) did not differ significantly from that of untreated control subjects (7.7 +/- 2.5%, p = 0.19), but was lower than that in the metoprolol group (15.4 +/- 3.5%, p = 0.006). Patients treated with metoprolol had twice the mortality seen in control subjects, even though the differences were not statistically significant. Holter studies performed at 1, 6 and 12 months showed that both amiodarone and metoprolol were equally effective in reducing heart rate, whereas only amiodarone significantly reduced ectopic activity (p < 0.0001). Thus, long-term treatment with amiodarone was clearly safe in patients with an ejection fraction of 20 to 45%, was effective in suppressing arrhythmias, and was associated with a lower mortality than metoprolol; corroboration is required in a larger trial.

Aged↗

AIDS and rheumatic manifestations in patients addicted to drugs. An analysis of 106 cases.

We evaluated the rheumatic manifestations in 106 patients with AIDS whose risk factor is intravenous drug addiction. All were intravenous drug addicts and carriers of the human immunodeficiency virus (HIV). Their average age was 28.36 years; 83 were men and 23 were women; 73 were in stage IV of the HIV infection; 12 were in stage III and 21 in stage II. Rheumatic manifestations were found in 21 patients (20%). Specifically, 13 had arthralgias/myalgias, 2 demonstrated oligoarthritis, 1 had tuberculous arthritis of the knee, and 1 patient showed systemic necrotizing vasculitis. Finally, 6 patients had a history of septic arthritis. There was an absence of the Reiter syndrome/reactive arthritis, a low frequency of symptoms of articular swelling, and the marked presence of histories of septic arthritis. The practices that lead to HIV infection may play a decisive role in the appearance of rheumatic manifestations in patients with AIDS, even more than the presence of the virus itself or the immunological alterations thereby produced.

Acquired Immunodeficiency Syndrome↗

Primary septic arthritis in heroin users: early diagnosis by radioisotopic imaging and geographic variations in the causative agents.

We reviewed 37 cases of septic arthritis in heroin users. Our data confirm the predominance of the fibrocartilaginous joint infections in this group (sacroiliac joint 39%, chondrosternocostal unions 37%). In Spain, Staphylococcus aureus is the most commonly isolated organism (73%). This emphasizes the geographic variations in the causative germs since, in contrast to other reports, we have not identified any gram negative bacillary arthritis in our population of heroin users. Our data show that the 67gallium citrate scintigraphy is positive earlier than the 99mTc-MDP bone scan in the poorly vascularized joints (p less than 0.0005). The early localization of the infectious focus by 67gallium citrate scintigraphy followed by a prompt bacteriologic diagnosis (blood, synovial fluid or tissue cultures) allowed good therapeutic results.

Adolescent↗

Relation between power spectrum time course during ventricular fibrillation and electromechanical dissociation. Effects of coronary perfusion and nifedipine.

To relate the evolution of ventricular fibrillation (VF) to the haemodynamic recovery after cardioversion, we characterized the differences in the ECG power spectrum (PS) time course, among different types of VF: under control conditions, with previous administration of nifedipine and on cardiopulmonary bypass (CPB). In the first few seconds VF showed a PS with a narrow peak between 8 and 15 Hz and its higher harmonics, suggesting some organization and regularity. In the following 40 seconds, the arrhythmia accelerated slightly, maintaining an organized spectrum. Afterwards, the PS became slow and irregular, losing its initial characteristics after 60 seconds. Conversely, VF on CPB maintained its organized PS, over a prolonged period. Previous administration of 0.32, 0.64 mg kg-1 of nifedipine maintained the initial characteristics of the PS for 90 and 150 seconds. Similar results were obtained with previous autonomic blockade. In another group of dogs, defibrillation was performed after successive periods of VF, to study electromechanical dissociation (EMD). In all control dogs, EMD was observed after 90 seconds of VF. Pretreatment with nifedipine postponed EMD until 120-150 seconds and was not observed in dogs on CPB. The PS time course during VF seems a reliable method of analyzing and quantifying the different types of VF. It could be related with the onset of EMD, reflecting the metabolic alterations that happen during VF. Nifedipine could delay the ischaemic effects during VF and increase the possibility of successful cardiac resuscitation.

Animals↗

Reflex cardiovascular response to acute myocardial ischaemia.

The usual cardiovascular response to acute myocardial ischaemia is either pressor, characterised by tachycardia and hypertension or depressor, manifested by bradycardia, hypotension and systemic vasodilatation. We studied the incidence of ectopic arrhythmias, the changes in heart rate, in left ventricular pressure and dP/dt and the changes in plasma level of free fatty acids. Acute anterior ischaemia increased the heart rate, left ventricular dP/dtmax and plasma level of free fatty acids and developed frequent ventricular ectopic arrhythmias. Previous injection of propranolol prevented the elevation of plasma free fatty acids. Acute inferior ischaemia produced a slight decrease in heart rate, no change in plasma level of free fatty acids and a significant decrease in left ventricular dP/dtmax. The experimental model allowed us to study the response to acute myocardial ischaemia in conscious dogs; the results obtained point to a preferential location of the pressor and depressor receptors respectively to the anterior and inferior surfaces of the left ventricle.

Animals↗

Time constant of isovolumic pressure fall: new numerical approaches and significance.

The effects of left ventricular diastolic pressure changes on the values of the time constant (T) of isovolumic pressure fall are controversial. Normally, T is calculated either by linear regression of 1n left ventricular pressure (LVP) vs. time (TL) or by using an exponential model with asymptote (PB, extrapolated base-line pressure to which LVP would fall if decay continued indefinitely). This study, in intact dogs, has been designed to revise the effects that drugs that alter load (angiotensin and nitroprusside, without and with autonomic blockade) and inotropism (isoproterenol and propranolol) might have on the relaxation rate using different numerical methods. We found that 1) the upward or downward translation of the LVP curve had an important effect on the value of TL calculated by the semilogarithmic method; 2) when a model with asymptote was used, the simultaneous changes of T and PB, were not related to the dose of the drug; 3) the values of TL and the -dP/dt values extrapolated to 15 mmHg from a model with PB, were much more sensitive to beta-agonist or antagonist drugs than to others whose action was through load alteration. We feel that some of the earlier studies on relaxation rate determinants should be revised as possibly some of the conclusions have been based on artifacts introduced by the method chosen for the computation of the relaxation parameters.

Angiotensin II↗