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J Padilla

Publications and source records attributed to J Padilla.

At least 37 records · Page 2Linked to original sources

Peroxisome proliferator activator receptor-gamma agonists and 15-deoxy-Delta(12,14)(12,14)-PGJ(2) induce apoptosis in normal and malignant B-lineage cells.

The research described herein evaluates the expression and functional significance of peroxisome proliferator activator receptor-gamma (PPAR-gamma) on B-lineage cells. Normal mouse B cells and a variety of B lymphoma cells reflective of stages of B cell differentiation (e.g., 70Z/3, CH31, WEHI-231, CH12, and J558) express PPAR-gamma mRNA and, by Western blot analysis, the 67-kDa PPAR-gamma protein. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), a PPAR-gamma agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [(3)H]thymidine and 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assays. Only PPAR-gamma agonists (thiazolidinediones), and not PPAR-alpha agonists, mimicked the effect of 15d-PGJ(2) on B-lineage cells, indicating that the mechanism by which 15d-PGJ(2) negatively affects B-lineage cells involves in part PPAR-gamma. The mechanism by which PPAR-gamma agonists induce cytotoxicity is via apoptosis, as shown by annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay. Interestingly, addition of PGF(2alpha), which was not known to affect lymphocytes, dramatically attenuated the deleterious effects of PPAR-gamma agonists on B lymphomas. Surprisingly, 15d-PGJ(2) induced a massive increase in nuclear mitogen-activated protein kinase activation, and pretreatment with PGF(2alpha) blunted the mitogen-activated protein kinase activation. This is the first study evaluating PPAR-gamma expression and its significance on B lymphocytes. PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of other PGs, namely PGE(2), which promotes B cell differentiation. Finally, the use of PGs, such as 15d-PGJ(2), and synthetic PPAR-gamma agonists to induce apoptosis in B-lineage cells may lead to the development of novel therapies for fatal B lymphomas.

Animals↗

Temporal development of autoreactive Th1 responses and endogenous presentation of self myelin epitopes by central nervous system-resident APCs in Theiler's virus-infected mice.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a chronic-progressive, immune-mediated CNS demyelinating disease and a relevant model of multiple sclerosis. Myelin destruction is initiated by TMEV-specific CD4(+) T cells targeting persistently infected CNS-resident APCs leading to activation of myelin epitope-specific CD4(+) T cells via epitope spreading. We examined the temporal development of virus- and myelin-specific T cell responses and acquisition of virus and myelin epitopes by CNS-resident APCs during the chronic disease course. CD4(+) T cell responses to virus epitopes arise within 1 wk after infection and persist over a >300-day period. In contrast, myelin-specific T cell responses are first apparent approximately 50-60 days postinfection, appear in an ordered progression associated with their relative encephalitogenic dominance, and also persist. Consistent with disease initiation by virus-specific CD4(+) T cells, CNS mononuclear cells from TMEV-infected SJL mice endogenously process and present virus epitopes throughout the disease course, while myelin epitopes are presented only after initiation of myelin damage (>50-60 days postinfection). Activated F4/80(+) APCs expressing high levels of MHC class II and B7 costimulatory molecules and ingested myelin debris chronically accumulate in the CNS. These results suggest a process of autoimmune induction in which virus-specific T cell-mediated bystander myelin destruction leads to the recruitment and activation of infiltrating and CNS-resident APCs that process and present endogenous myelin epitopes to autoreactive T cells in a hierarchical order.

Amino Acid Sequence↗

Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis.

To clarify the role of tumor necrosis factor (TNF) in the inflammatory aspects of autoimmunity vs its potential role in the apoptotic elimination of autoreactive effector cells, we assessed the roles of the p55 (TNFR1/Tnfrsf1a/CD120a) and p75 (TNFR2/Tnfrsf1b/CD120b) TNF receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE). TNFR p55/p75(-/-) double knockout mice were completely resistant to clinical disease. TNFR p55(-/-) single knockout mice were also totally resistant to EAE, exhibiting reduced MOG(35-55)- specific proliferative responses and Th1 cytokine production, despite displaying equivalent DTH responses. Importantly, IL-5 was significantly increased in p55(-/-) mice. In contrast, p75(-/-) knockout mice exhibited exacerbated EAE, enhanced Th1 cytokine production, and enhanced CD4(+) and F4/80(+) CNS infiltration. Thus, p55/TNFR1 is required for the initiation of pathologic disease, whereas p75/TNFR2 may be important in regulating the immune response. These results have important implications for therapies targeting p55 and p75 receptors for treating autoimmune diseases.

Animals↗

Effect of neuropeptide Y on the sympathetic contraction of the rabbit central ear artery during cooling.

In order to analyse the effect of neuropeptide Y (NPY) on the cutaneous vascular response to sympathetic nerve stimulation during cooling, the isometric response of isolated 2-mm segments of the rabbit central ear (cutaneous) artery was recorded at 37 degrees C and during cooling (30 degrees C). Electrical field stimulation (4-16 Hz) at 37 degrees C produced a frequency-dependent contraction, which was reduced during cooling (45% for 16 Hz) and potentiated by NPY (10(-8), 3x10(-8) and 10(-7) M), this potentiation being greater at 30 degrees C than at 37 degrees C. The NPY-induced potentiation of the contraction elicited by electrical field stimulation (8 Hz) was abolished by an antagonist of Y1 subtype NPY receptors, BIBP3226 (10(-6) M), at 37 degrees C and 30 degrees C, reduced by phentolamine (10(-6) M) at 30 degrees C but not at 37 degrees C, was not modified by the purinoceptor antagonist PPADS (3x10(-5) M) and was reduced by application of both phentolamine and PPADS at both temperatures. Both NiCl2 (10(-3) M) and verapamil (10(-5) M) abolished the potentiating effect of NPY at 37 degrees C and reduced it at 30 degrees C. Neither application of an inhibitor of nitric oxide synthesis, L-Nomega-nitro-arginine (L-NOARG, 10(-4) M), nor endothelium removal modified the potentiating effect of NPY at 37 degrees C or 30 degrees C. NPY (10(-8), 3x10(-8) and 10(-7) M) potentiated in a concentration-dependent way the arterial contraction in response to exogenous noradrenaline (10(-8)-10(-4) M) at 30 degrees C but not at 37 degrees C, and it increased the response to ATP (10(-4)-10(-2) M) at both temperatures. Therefore, in cutaneous (ear) arteries: (1) NPY potentiates the sympathetic response at 37 degrees C and at 30 degrees C, (2) this potentiating effect of NPY was more marked at 30 degrees C than at 37 degrees C, probably because of greater potentiation of the alpha-adrenoceptor response during cooling, and (3) the potentiating effect of NPY at both temperatures is mediated by NPY receptors of the Y1 subtype, is dependent of Ca2+ channels and is independent of the release of endothelial nitric oxide.

Adenosine Triphosphate↗

[Small-cell nonanaplastic bronchogenic carcinoma. The new stage I].

OBJECTIVE: To validate updated guidelines for stage I classification of patients with differentiated small-cell bronchogenic carcinoma. METHODS: Seven hundred seventeen tumors of differentiated small-cell bronchogenic carcinoma were resected in our hospital and given a TNM classification of stage I based on guidelines recently issued by the Spanish Society of Pneumology and Chest Surgery (SEPAR). Survival was calculated using the Kaplan-Meier method and curves were compared with a log-rank test. The Cox proportional hazards model was used to analyze multiple variables. RESULTS: One hundred forty-two cases were classified as stage IA and 575 as stage IB. Survival was significantly longer for stage IA than for stage IB (p = 0.0021). The prognosis was significantly better for stage IA patients who were asymptomatic (p = 0.0380) or who had tumors < or = 2 cm in diameter (p = 0.0431). In stage IB, histologic grade (p = 0.0104) and tumor diameter (p = 0.0002) significantly affected survival. A noteworthy finding was the 82% survival at five years in a group of 66 patients with a maximum tumor diameter of 3 cm classified as T2N0M0 due to invasion of the visceral pleura or to proximal involvement of a lobar bronchus at a site > 2 cm from the carina; that survival rate was not significantly different from survival for stage IA (p = 0.1573). Multivariate analysis showed that tumor diameter (p = 0.0272) was of prognostic importance in stage IA, while tumor diameter (p = 0.0005) and histologic grade (p = 0.0092) were relevant in stage IB. CONCLUSION: The new staging guidelines for differentiated small-cell bronchogenic carcinoma are nearer to prognostic reality given that survival for stage IA patients is significantly longer than for stage IB patients. However, the method continues to have shortcomings in that it fails to achieve one of its main objectives, namely prognostic homogeneity for each subgroup, as indicated by problems related to variables of tumor extension such as diameter, involvement of the visceral pleura or bronchial location, apart from other factors that affect survival.

Carcinoma, Bronchogenic↗

The Severity of Dependence Scale (SDS) as screening test for benzodiazepine dependence: SDS validation study.

AIMS: To assess the validity of the Severity of Dependence Scale (SDS) as a screening test to detect benzodiazepine dependence in regular benzodiazepine users. METHOD: One hundred regular benzodiazepine users, recruited from neurotic benzodiazepine users attending the Mental Health Outpatient Services of the Canary Islands Health Service, were administered the SDS and responses were compared with the Composite International Diagnostic Interview (CIDI) diagnosis of benzodiazepine dependence. Receiver Operating Characteristic (ROC) analysis was used to determine which cut-off score on SDS allowed the best trade-off between sensitivity and specificity. RESULTS: SDS was shown to have high diagnostic utility, and a score higher than six on the scale appears to be an appropriate threshold for problematic benzodiazepine use. The SDS had a specificity of 94.2% and a sensitivity of 97.9%, and the area under the curve was of 0.991. CONCLUSION: The SDS was found to be a valid brief self-report questionnaire for the assessment of benzodiazepine dependence in patients using benzodiazepines.

Adolescent↗

PPAR-gamma-mediated regulation of normal and malignant B lineage cells.

Prostaglandins of the E-series stimulate B lymphocytes by enhancing immunoglobulin-class switching and antibody production. Little is known about whether or not other prostaglandins affect B lineage cells and perhaps counterbalance the stimulatory effects of PGE2. PGD2 is a major product of cyclooxygenase in bone marrow and in macrophages, suggesting a role for this lipid product in immunological responses. PGD2 undergoes dehydration to the biologically active prostaglandin 15-deoxy-delta 12,14-PGJ2 (15d-PGJ2) that binds to the nuclear receptor known as peroxisome proliferator-activated receptor gamma (PPAR-gamma). We found that normal mouse B cells and a variety of B lymphoma cells (e.g., 70Z/3, WEHI-231, CH12, and J558) express PPAR-gamma mRNA and the 67-kDa PPAR-gamma protein. 15d-PGJ2 had a dose-dependent antiproliferative/cytotoxic effect on normal and malignant B cells, as shown by 3H-thymidine and MTT assays. Only PPAR-gamma agonists (i.e., thiazolidinediones) mimicked the effect of 15d-PGJ2 on B lineage cells, indicating that the mechanism by which 15d-PGJ2 negatively affects B lineage cells involves PPAR-gamma. The mechanism whereby PPAR-gamma agonists induced cytotoxicity is via apoptosis, as shown by Annexin V assay. PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of PGE2, which promotes B-cell differentiation. The use of prostaglandins, such as 15d-PGJ2, and synthetic PPAR-gamma agonists to induce apoptosis in B lineage cells may lead to the development of therapies for fatal PGE2-resistant B lymphomas.

Animals↗

[The "quality of life" concept in medical students and postgraduate residents in a university hospital].

We investigated the quality of life's concept and its uses by both residents and interns as well as last year medical students in the University Hospital in Caracas (HUC). A random sample by strata, without replacement of 123 persons, completed a self administered questionnaire which included a set of closed questions and one of open questions related to the quality of life's concept. The mean age was 29 years for both sexes (3.55 standard deviation or SD). There was not a statistically significant difference between males and females. More than 50% read about quality of life in either newspapers, journals and fiction literature. There was no difference among the groups (p = 0.25). Only 68% had heard in a different sort of academical institution the term "quality of life" such as in the school of medicine, highschool or in some discussion groups with no differences among the groups (p = 0.15). However, there was no agreement as from whom and where they learned about quality of life (p < 0.001). Although everybody considered that the quality of life was an important element in medical actions such as diagnostic or therapeutics, its importance was reduced for diagnosis compared to treatment (p < 0.0001). All the elements that were considered as part of the concept were also considered as important, regardless of the group and was statistically significant (p < 0.05). The open question analysis showed that the non-medical definitions represent 85.15% of the group, 50% out of them included terms of potentiality or condition. Among the elements included in the definition was the social in 27.65%, psychological in 23.53% and, the economical in 12.35% of the questionnaires. The great majority of the "quality of life" definitions did not include a clearly defined subject and in many cases it was exclusively related to ill persons. Finally, there is an informal and not well oriented form of learning about "quality of life" in residents, interns and last year medical students with a lack of a good applicability in the medical practice. Therefore, there is a need for a formal training on quality of life along the medical studies and its uses in the medical practice in general and with special emphasis on diagnosis and therapeutics.

Adult↗

Viral hyperinfection of the central nervous system and high mortality after hematopoietic stem cell transplantation for treatment of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

Theiler's murine encephalomyelitis virus (TMEV) establishes a persistent infection in the central nervous system (CNS) leading to an inflammatory demyelinating disease of the CNS in which the histology and clinical course is similar to multiple sclerosis (MS). Disease pathogenesis is primarily due to T-cell-mediated destruction of myelin, which has been attributed to cytopathic effects of the virus, but immune-mediated destruction of myelin mediated via both virus-specific and myelin-specific T cells appear to play the major role. To determine if bone marrow transplantation would be an effective therapy for a virus-initiated autoimmune disease and to better separate viral cytopathic effects from immune-mediated demyelination, we ablated the immune system of TMEV-infected animals with 1,100 cGy total body irradiation, and then the animal's immunity was reconstituted by transplantation of disease-susceptible SJL/J mice with syngeneic marrow or disease-susceptible DBA/2J with marrow from disease-resistant (C57Bl/6 x DBA/2)F1 (B6D2) donors. Hematopoietic transplant performed after onset of disease resulted in 42% mortality in SJL/J syngeneic transplants, 47% mortality in diseased DBA2 recipients restored with marrow from naive B6D2 donors, and 12% in diseased DBA2 recipients receiving marrow from B6D2 donors previously infected with TMEV. Delayed type hypersensitivity (DTH) to both virion and myelin proteins was decreased in surviving mice that underwent transplantation; however, CNS viral titers were significantly elevated compared with nontransplanted controls. We conclude that a functional immune system with appropriate T-cell responses are important in prevention of lethal cytopathic CNS effects from TMEV. Relevant to the clinical use of bone marrow transplantation, attempts to ablate the immune system in viral-mediated immune diseases or virus-initiated autoimmune disease may have acute and lethal consequences. Our results raise concern about the attempted use of autologous hematopoietic transplantation in patients with MS, an autoimmune disease with a suspected virus etiology, particularly if the graft is aggressively depleted of lymphocytes.

Animals↗

Translation to Spanish, reproducibility, and cross-cultural adaptation of the Miller-Rahe Recent Life Change Questionnaire in Venezuela.

OBJECTIVE: To translate into Spanish a version of the Miller-Rahe Recent Life Change Questionnaire and to adapt it to Venezuelan cultural values. METHODS: The Spanish version and cross-cultural adaptation of the Miller-Rahe Recent Life Change Questionnaire was done following recently proposed guidelines to preserve semantic, idiomatic, and conceptual equivalence in translations of health assessment instruments. We performed one or more translations into the new language, as well as back-translation, test-retest reliability, and weighting score for the translated instrument. RESULTS: A Spanish version of the Recent Life Change Questionnaire was obtained. Validity of translations was demonstrated with a significant agreement for the nonliteral translations (kappa value = 0.97, P < 0.05). The conceptual equivalence was demonstrated by significant agreement in the back-translations (kappa value = 0.84, P < 0.05). The translated instrument met acceptable levels of reliability, as assessed by Spearman's rank correlation coefficients (> 0.60 for all categories of the questionnaire). The cross-cultural adaptation of the translated instrument required addition and exclusion of items as well as changes of the ranking and scaling of life units in the original questionnaire. CONCLUSION: A valid and reliable Spanish version of the Miller-Rahe Recent Life Change Questionnaire was produced and adapted to Venezuelan cultural values.

Adult↗

Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial.

In 1989, we began a multicenter study to evaluate the potential benefit of preoperative chemotherapy with cisplatin, ifosfamide and mitomycin over surgery alone in CT-visible N2 non-small-cell lung cancer. We present here a 7-year assessment of this randomized trial. Sixty patients were randomized to receive either surgery alone or three cycles of mitomycin 6 mg/m2, ifosfamide 3 g/m2 and cisplatin 50 mg/m2, given intravenously on day 1 of each cycle at 3-week intervals and followed by surgery. All patients received thoracic irradiation after surgery. The resected tumors were evaluated for the presence of K-ras gene point mutations. Treatment arms were well-balanced in characteristics such as gender, age, histology, and tumor size. Mediastinoscopy and/or mediastinotomy (Chamberlain procedure) with a biopsy was performed in all patients with N2 stage detected by CT scan of the chest (83% of the patients in the preresectional chemotherapy arm and 63% of those in the surgery arm). In eight of the 25 patients (32%) who had mediastinoscopy in the preresectional chemotherapy arm, the initially positive mediastinal lymph nodes were downstaged. For the 30 patients who received preresectional chemotherapy, overall median survival was 22 months (95% CI, 13.4 30.6). Of the 30 patients who received surgery alone, overall median survival was 10 months (95% CI, 7.4-12.6; P = 0.005 by the log rank test). Updated survival data reveals a plateau in the preresectional chemotherapy group, and this still significant long-term survival benefit prompts us to hypothesize that even with short-term preresectional chemotherapy, the natural history of still resectable CT-visible N2 non-small cell lung cancer is favorably altered. The results of our study mirror the long-term survival recently reported in the MD Anderson randomized study.

Adult↗

[The prognosis following surgical resection of small-cell nonanaplastic bronchogenic carcinoma according to the new staging guideline: an analysis of 1433 patients].

OBJECTIVE: To validate current guidelines for staging bronchogenic lung carcinoma. METHODS: Between 1969 and 1996, small-cell non-anaplastic tumors of bronchogenic carcinoma classified by the recently proposed TNM guidelines of the Spanish Society of Pneumology and Chest Surgery (SEPAR) were resected from 1,433 patients. We used the Kaplan-Meier method to calculate survival and compared the curves using a log-rank test. RESULTS: A stage IA classification was given to 142 patients and IB to 575. Thirty-seven cases were classified IIA and 336 were IIB. Of the latter, 177 were T2N1M0 and 159 were T3N0M0. Two hundred forty-eight patients were in stage IIIA, 54 T3N1M0, 23 T1N2M0, 120 T2N2M0 and 51 T3N2M0. Ninety-five stage IIIB patients were classified as follows: 37 T4N0M0, 35 T4N1M0, and 23 T4N2M0. Five-year survival for IA patients, at 75% was significantly better than the 60% rate for IB patients (p = 0.0021). Likewise, the prognosis for stage IIA, where five-year survival was 57%, was significantly better than for IIB at 39% (p = 0.0434). The prognosis for patients classified as T1NM0 was better than for those classified as T2N1M0, which was 38% (p = 0.0320). The survival of those classified as T3N0M0 (42%) was not significantly different from that of T1N1M0 (p = 0.1754) or T2N1M0 (p = 0.5360) patients. We found no significant difference between T1N1M0 and stage IB (p = 0.3847) patients. Among stage III patients, we observed no difference in survival between stage IIIA and IIIB (p = 0.1914). In stage IIIA, patients classified as T3N2M0 had a significantly lower rate of survival (p = 0.0399). The presence of mediastinal ganglia in stage IIIB was associated with a lower survival rate (p = 0.0328). CONCLUSION: The new guidelines for staging non-small cell anaplastic lung carcinoma do not provide consistent prognoses for homogeneous groups of patients, at least not in certain categories.

Carcinoma, Bronchogenic↗

[Resection of bronchogenic carcinoma invading the diaphragm].

The prognosis for survival when small cell non-anaplastic bronchogenic carcinoma (SCN-ABC) invades the diaphragm has not been clearly established because the diagnosis is rare. We report a series of eight patients who underwent full resection of SCN-ABC with diaphragm invasion. One died during the postoperative period. Mean survival was eight months for the remaining seven and no patient lived five years. All died as a result of remote metastasis. Given these results, we question whether surgery is the most appropriate treatment for these patients.

Aged↗

Effects of vasopressin on the sympathetic contraction of rabbit ear artery during cooling.

In order to analyse the effects of arginine-vasopressin on the vascular contraction to sympathetic nerve stimulation during cooling, the isometric response of isolated, 2-mm segments of the rabbit central ear (cutaneous) artery to electrical field stimulation (1-8 Hz) was recorded at 37 and 30 degrees C. Electrical stimulation (37 degrees C) produced frequency-dependent arterial contraction, which was reduced at 30 degrees C and potentiated by vasopressin (10 pM, 100 pM and 1 nM). This potentiation was greater at 30 than at 37 degrees C and was abolished at both temperatures by the antagonist of vasopressin V1 receptors d(CH2)5 Tyr(Me)AVP (100 nM). Desmopressin (1 microM) did not affect the response to electrical stimulation. At 37 degrees C, the vasopressin-induced potentiation was abolished by the purinoceptor antagonist PPADS (30 microM), increased by phentolamine (1 microM) or prazosin (1 microM) and not modified by yohimbine (1 microM), whilst at 30 degrees C, the potentiation was reduced by phentolamine, yohimbine or PPADS, and was not modified by prazosin. The Ca2+-channel blockers, verapamil (10 microM) and NiCl2 (1 mM), abolished the potentiating effects of vasopressin at 37 degrees C whilst verapamil reduced and NiCl2 abolished this potentiation at 30 degrees C. The inhibitor of nitric oxide synthesis, L-NOARG (100 microM), or endothelium removal did not modify the potentiation by vasopressin at 37 and 30 degrees C. Vasopressin also increased the arterial contraction to the alpha2-adrenoceptor agonist BHT-920 (10 microM) and to ATP (2 mM) at 30 and 37 degrees C, but it did not modify the contraction to noradrenaline (1 microM) at either temperature. These results suggest that in cutaneous (ear) arteries, vasopressin potentiaties sympathetic vasoconstriction to a greater extent at 30 than at 37 degrees C by activating vasopressin V1 receptors and Ca2+ channels at both temperatures. At 37 degrees C, the potentiation appears related to activation of the purinoceptor component and, at 30 degrees C, to activation of both purinoceptor and alpha2-adrenoceptor components of the sympathetic response.

Adenosine Triphosphate↗

Double-blind, randomized, placebo-controlled assessment of chloroquine/primaquine prophylaxis for malaria in nonimmune Colombian soldiers.

To improve upon the efficacy of primaquine prophylaxis for malaria (94%, Plasmodium falciparum malaria; 85%, Plasmodium vivax malaria), we administered chloroquine (300 mg weekly) in combination with primaquine (30 mg daily) to nonimmune Colombian soldiers during 16 weeks of patrol in a region of endemicity and for a further 1 week in base camp. The occurrence of symptomatic parasitemia was determined during those 17 weeks and during a further 3 weeks in base camp. The protective efficacy for the chloroquine/primaquine treatment group of 100 subjects, compared with that for the placebo treatment group of 51 subjects, was 88% (95% confidence interval [CI], 76-94) against all types of malaria, 89% (95% CI, 61-97) against P. falciparum malaria, and 88% (95% CI, 58-93) against P. vivax malaria. Two chloroquine/primaquine recipients had severe gastrointestinal distress. Comparison of these data with data from a previous study indicates that the addition of chloroquine did not increase the prophylactic efficacy of primaquine.

Antimalarials↗

Primaquine prophylaxis against malaria in nonimmune Colombian soldiers: efficacy and toxicity. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Primaquine had a prophylactic efficacy of 90% to 95% against infection with Plasmodium falciparum and P. vivax in Indonesian settlers. OBJECTIVE: To evaluate the efficacy of primaquine prophylaxis for protecting nonimmune persons from malaria. DESIGN: Randomized, double-blind, placebo-controlled field study. SETTING: A malaria-endemic area in Colombia. PATIENTS: 176 healthy, young, nonimmune adult male soldiers. INTERVENTION: Primaquine, 30 mg/d, or matching placebo during 15 weeks of patrol in the endemic area and 1 week afterward. MEASUREMENTS: Symptomatic parasitemia was determined over the 16-week intervention period and for 3 weeks in base camp. RESULTS: Protective efficacy in the primaquine group (122 participants) was 89% (95% CI, 75% to 96%) against all types of malaria, 94% (CI, 78% to 99%) against P. falciparum malaria, and 85% (CI, 57% to 95%) against P. vivax malaria. Six primaquine recipients had mild to moderate gastrointestinal distress, and three had severe distress. CONCLUSIONS: For prophylaxis against P. falciparum malaria, primaquine has an efficacy and toxicity competitive with those of standard agents. A potential advantage of primaquine is that prophylaxis may be discontinued 1 week after the recipient has left the endemic area.

Adolescent↗