[Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial]. / Medicación preanestésica con dexmedetomidina intranasal y midazolam oral como ansiolítico. Un ensayo clínico.

INTRODUCTION: Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. MATERIAL AND METHODS: A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. RESULTS: A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. CONCLUSIONS: Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients.

Eryptosis and oxidative damage in type 2 diabetic mellitus patients with chronic kidney disease.

It has been suggested that oxidative stress may participate in the progression of diabetes and its complications. Long-term complications of type 2 diabetes mellitus (T2DM) include retinopathy, atherosclerosis, shortened life span of erythrocytes, nephropathy, and chronic kidney disease (CKD). Oxidative damage has been associated with erythrocyte apoptosis induction in other pathological conditions. Our aim was to study the presence of eryptosis and its possible relationship with oxidative damage in patients with T2DM without CKD (T2DM/CKD(-)) and in patients with T2DM and CKD (T2DM/CKD(+)).Oxidative damage of lipids erythrocytes were increased in diabetic patients. The highest lipoperoxidation was found in T2DM/CKD(+). Likewise, the lower plasma total antioxidant capacity, GSH/GSSG ratio, and GSH in erythrocytes were found in T2DM/CKD(+) patients. A negative correlation was found between plasma total antioxidant capacity and oxidative damage. Phosphatidylserine (PS) externalization was measured in erythrocytes to evaluate eryptosis. Annexin binding in erythrocytes of T2DM/CKD(+) patients was higher than in healthy subjects and T2DM/CKD(-) patients. A positive correlation between lipoperoxidation and PS externalization in erythrocytes was found. This work showed that the erythrocytes of diabetic patients have increased oxidative damage, a reduction of antioxidant systems and more erythrocyte PS externalization. The duration of diabetes and the presence of CKD increase both oxidative damage and eryptosis. It is possible that a longer time of evolution induces an increase in erythrocyte oxidative damage and the consumption of blood antioxidant systems, adding to the osmotic stress in CKD and so contributes to an increase in PS externalization in diabetic patients.

Processing of the circumsporozoite protein in infected hepatocytes is not dependent on aspartic proteases.

CD8(+) T cells play a major role in the protective immune response against the liver stage of malaria. It was previously shown that the circumsporozoite protein (CSP) is processed and presented to specific T cells by both traversed and infected hepatocytes, but their respective antigen processing requirements were not completely defined. In the present study, we show that in vitro processing of the Plasmodium berghei CSP by infected mouse primary hepatocytes is exclusively dependent on proteasomes, while aspartic proteases are also needed in the case of traversed hepatocytes.

IL-12p40-independent induction of protective immunity upon multiple Plasmodium berghei irradiated sporozoite immunizations.

Both IFN-gamma and IL-12 play critical roles in defence against malaria. In a previous study, using Plasmodium yoelii model, C57BL/6 IFN-gamma receptor deficient mice (IFN-gammaR-/-) failed to develop protective immunity after a single immunization with irradiated sporozoites, but were protected after multiple immunizations. In contrast, in another study, BALB/c IFN-gamma gene knockout mice (IFN-gamma-/-) and BALB/c IL-12-deficient mice (IL-12p40-/- and IL-12p35-/-) were unable to mount protective immune response even after multiple immunizations with the same irradiated parasites. To better define the role of IFN-gamma and IL-12p40 in sterile protection, we selected the C57BL/6 model. Wild-type and IL-12p40-/- mice were immunized with a single or multiple doses of P. berghei irradiated sporozoites. While the wild-type mice were able to rapidly produce IFN-gamma and mount a protective immune response after a single immunization with irradiated sporozoites, IL-12p40-/- mice were neither able to produce IFN-gamma nor were protected. However, both strains of mice were able to produce IFN-gamma and were protected after three doses of irradiated sporozoites. Protection was partially and largely mediated by CD4+ T cells and CD8+ T cells, respectively. Thus, IL-12p40 plays an important role in mediating early protection by irradiated sporozoite immunization but is dispensable for protective immunity induced by several immunizations with irradiated sporozoites. Moreover, treatment of hyperimmune IL-12p40-/- mice with rhIL-18 bp-Fc, an inhibitor of IL-18 activity, did not abrogate protection indicating that IL-18 is not required for the effector phase of the immune response; it remains possible, however, that IL-18 may compensate for the lack of IL-12p40 in the induction phase of the immune response.

CD1d-restricted NK T cells are dispensable for specific antibody responses and protective immunity against liver stage malaria infection in mice.

Immunization with a single dose of irradiated sporozoites is sufficient to induce protection against malaria in wild-type mice. Although this protection is classically attributed to conventional CD4+ and CD8+ T cells, several recent reports have suggested an important role for CD1-restricted NK T cells in immunity to malaria. In this study, we directly compared the ability of C57BL/6 wild-type and CD1-deficient mice to mount a protective immune response against Plasmodium berghei sporozoites. Our data indicate that CD1-restricted NK T cells are not required for protection in this model system. Moreover, specific IgG antibody responses to the P. berghei circumsporozoite repeat sequence were also unaffected by CD1 deficiency. Collectively, our data demonstrate that CD1-restricted NK T cells are dispensable for protective immunity to liver stage P. berghei infection.

Generation and characterization of malaria-specific human CD8(+) lymphocyte clones: effect of natural polymorphism on T cell recognition and endogenous cognate antigen presentationby liver cells.

CD8(+) cytolytic T lymphocytes (CTL) play a fundamental role in the clearance of malaria parasites from the liver in mouse models. In humans, however, only low levels of parasite-specific CD8(+) T lymphocytes have been observed in individuals living in endemic areas. In the present study, we identified high levels of circulating CD8(+) T lymphocytes specific for a previously described HLA-A2-restricted CTL epitope of the circumsporozoite (CS) protein of Plasmodium falciparum in an adult living in Burkina Faso, as evidenced by IFN-gamma ELISPOT assay and MHC-tetramer technology. After cloning by limiting dilution culture, T cell recognition of natural CS variants of P. falciparum was studied. The results demonstrate that naturally occurring variations drastically affect residues critical for T cell recognition as only two out of nine sequences analyzed were efficiently recognized by the CTL clones. These clones were also used to analyze T cell recognition of the endogenously presented cognate antigen. We observed efficient antigen recognition of both HLA-A*0201-transfected murine antigen presenting cells and liver cells from HLA-A*0201/K(b)-transgenic mice upon infection with recombinant vaccinia virus encoding the CS protein (WR-CS). More importantly, we demonstrate for the first time efficient recognition of WR-CS-infected human liver cells.

[Accumulated probability of hypertension in diabetes and of diabetes in hypertension]. / Probabilidad acumulada de hipertensión en diabéticos y de diabetes en hipertensión.

OBJECTIVE: To determine the cumulative probability of hypertension in type 2 diabetic patients, and of diabetes in patients with essential arterial hypertension. METHODS: A 15-years follow-up study of 308 subjects, 156 with type 2 diabetes and 152 with arterial hypertension. Time zero (T0) was the date in which the diabetes or the hypertension were established. The time in years from T0 up to diagnosis of hypertension in diabetics or diabetes in hypertensives was determined. The cumulative probability was calculated with the method of Kaplan and Meier. RESULTS: The incidence of hypertension in the diabetics was 4.36 patient-year, and that of diabetes in hypertensives of 1.23 patient-year (p = < 0.00001; Cl95% 4.8-14.7). After the first 5 years, 40% of the diabetics had hypertension and 12% of the hypertensives developed diabetes; at 15-years follow-up, these figures were 71% and 21% respectively (p < 0.001). CONCLUSIONS: The probability of essential arterial hypertension in type 2 diabetes was significantly higher than the incidence of diabetes in hypertensive subjects. In both instances, the risk was greater for men than for women.

[Prevalence of arterial hypertension and related factors in a marginated rural population]. / Prevalencia de hipertensión arterial y factores asociados en la población rural marginada.

OBJECTIVE: To determine the prevalence and risk factors related to systemic arterial hypertension (SAH) in the rural marginated population of Durango, Mexico. MATERIAL AND METHODS: A comparative cross-sectional study was performed in 627 rural communities, approximately 90% of which have 250 inhabitants or less. The arterial pressure and sociodemographic variables were determined. RESULTS: A total of 5,802 subjects were studied, 4,452 women (76.7%) and 1,350 men (23.3%). SAH was found in 1,271 individuals (21.9%; CI 95% 20.8-23.0) of which 1,011 were women (22.71%; CI 95% 21.5-23.9) and 260 were men (19.26%; CI 95% 17.2-21.4). Of the target population, 3,018 individuals (52.0%) live in communities of less than 250 inhabitants, 2,080 (60.9%) women and 938 (31.1%) men. In this group, SAH was identified in 445 cases (14.74%; CI 95% 13.5-16.0) of which 326 are women (15.7%; CI 95% 14.1-17.3) and 119, men (12.7%; CI 95% 10.6-14.9). The main risk factors related to SAH were obesity, type 2 diabetes, alcohol and tobacco consumption. CONCLUSIONS: The prevalence of SAH in the rural marginated population is apparently related to the degree of development of the communities.

[Postoperative analgesia using epidural administration of bupivacaine plus lidocaine]. / Analgesia postoperatoria con administración epidural de bupivacaína + lidocaína.

OBJECTIVE: To compare the postoperative analgesia of bupivacaine + lidocaine versus lidocaine in lower abdominal surgery. DESIGN: Randomized clinical trial. METHODS: Thirty patients, scheduled for lower abdominal surgery and epidural anesthesia (EA) were randomly assigned to receive EA with 30 mg of bupivacaine plus 240 mg of lidocaine (group A) or 300 mg of lidocaine (group B). A lumbar epidural catheter in L1-L2 or L2-L3 was inserted, and a bolus with total dose was given. The periods of latency and postoperative analgesia, the hemodynamic variable and the preoperative, intraoperative and postoperative data were recorded. RESULTS: Fifteen patients per group were included. There were no differences intergroup in age, height, weight, hemodynamic variables and surgical data. The period of latency was similar in the groups but postoperative analgesia was longer in group A and the postoperative pain scores were higher in group B in the first 120 minutes after surgery. There were no serious complications. In newborns of cesarean section, the Apgar scores at 1 and 5 minutes after delivery were similar in both groups. CONCLUSIONS: The mixture of bupivacaine + lidocaine proved be an effective alternative for epidural use in lower abdominal surgery.

[Folic acid deficiency and its association with neural tube defects in northern Mexico]. / Deficiencia de folatos y su asociación con defectos de cierre del tubo neural en el norte de México.

OBJECTIVE: To evaluate folic acid deficiency and other risk factors and their relationship with the occurrence of neural tube defects (NTD), in the rural population of northern Mexico (Chihuahua, Durango and Zacatecas). MATERIAL AND METHODS: A multicentric case-control study was performed. Cases were both live and stillborn with NTD, and controls were healthy newborns without congenital malformations. Exposure to known risk factors was determined, establishing its association with NTD using multiple logistic regression analysis. RESULTS: Risk factors associated to NTD were: folic acid deficiency (OR 11.1; CI 95% 1.2-106.2, p = 0.04); the antecedents of previous NTD pregnancies (OR 3.3; CI 95% 1.1-18.8, p = 0.05) and stillbirths (OR 7.1; CI 95% 1.1-46.3, p = 0.04). CONCLUSIONS: Folic acid deficiency is one of the major risk factors associated to NTD among the rural population of northern Medico. Further investigations are necessary to determine the role of involved risk factors and implement adequate preventive measures.

[Importance of family support in the control of glycemia]. / Importancia del apoyo familiar en el control de la glucemia.

OBJECTIVE: To determine the importance of family support in the control of glucemia in non-insulin-dependent diabetes mellitus patients. MATERIAL AND METHODS: A case and control study was designed where cases were patients with glycemia < 140 mg/dl and controls, patients with glycemia > or = 140 mg/dl. Family support was determined using the questionnaire Environmental Barriers to Adherence Scales which estimates the support lent by the family to the patient to follow therapeutic indications. The study consisted of 32 cases and 50 controls. RESULTS: Family support received by the patient is significantly associated to the presence of glycemia < 140 mg/dl (OR = 3.9; 95% C.I. 1.4-11.1). Other variables did not show significant association. CONCLUSIONS: Family support lent to patients influences the control of glycemia.

Regular production of infective sporozoites of Plasmodium falciparum and P. vivax in laboratory-bred Anopheles albimanus.

One of the major constraints for studies on the sporogonic cycle of the parasites causing human malaria, and on the protective efficacy of pre-erythrocytic vaccines, is the scarcity of laboratory-reared Anopheles mosquitoes as a source of infective sporozoites. The aim of the present study was to reproduce the life-cycles of Plasmodium falciparum and P. vivax in the laboratory and so develop the ability to produce infective sporozoites of these two species regularly under laboratory conditions. Colonized Anopheles albimanus, of Buenaventura and Tecojate strains, were infected by feeding either on Plasmodium-infected blood, from human patients or experimentally inoculated Aotus monkeys, or on gametocytes of the P. falciparum NF-54 isolate grown in vitro. The monkeys were infected with the blood stages of a Colombian P. vivax isolate and then, after recovery, with the Santa Lucia strain of P. falciparum from El Salvador. Although both of the mosquito strains used were successfully infected with both parasite species, the Buenaventura strain of mosquito was generally more susceptible to infection than the Tecojate strain, and particularly to infection with the parasites from the patients, who lived where this strain of mosquitoes was originally isolated. Monkeys injected intravenously with the P. vivax sporozoites produced in the mosquitoes developed patent sexual and asexual parasitaemias; the gametocytes that developed could then be used to infect mosquitoes, allowing the development of more sporozoites. However, experimental infections failed to establish after the P. falciparum sporozoites were used to inoculate monkeys. The ability to reproduce the complete life cycle of P. vivax in the laboratory, from human to mosquito and then to monkey, should greatly facilitate many studies on vivax malaria and on the efficacy of candidate malaria vaccines. The availability of the sporogonic cycles of P. falciparum from three different sources should also permit a variety of biological studies.

[The prevalence of non-insulin-dependent diabetes mellitus in the rural population of Durango, Mexico]. / Prevalencia de diabetes mellitus no insulinodependiente en la población rural de Durango, México.

This study was carried out to determine the prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in rural inhabitants of Durango, Mexico, and some of the risk factors for the disease. A random samples of 30,996 individuals aged 30 years and over was selected from 627 rural communities in Durango. These persons were interviewed between November 1993 and December 1994 to obtain information on several sociodemographic variables. A capillary blood sample was collected from each individual to determine his or her glucose level after 10-12 hours of fasting. Measures of central tendency and dispersion were calculated, and percentage distributions for the study variables were determined. Comparisons among proportions were made utilizing the chi-square test, and means were compared using Student's t test. The strength of associations was estimated with odds ratios, and 95% confidence intervals (CI 95%) were calculated for proportions. The final sample consisted of 31,028 persons, of whom 22,890 (73.8%) were women and 8,138 (26.2%) were men. A total of 1,004 cases of NIDDM were detected (3.2%; CI 95%:3.0 to 3.4), 767 in women and 237 in men. Only 9.2% of the study population was obese. The highest frequency of NIDDM was documented in persons 60 to 69 years of age. Family history of NIDDM was identified in 59.5% of the persons with the disease (CI 95%: 58.9 to 60.0) and in 26.3% of the healthy persons (CI 95%: 25.8 to 26.8). The low prevalence of NIDDM found in this study may be related to the low level of obesity in the population surveyed.

[Survival analysis in cirrhotic patients]. / Análisis de supervivencia en pacientes cirróticos.

BACKGROUND: Hepatic cirrhosis (HC) is a chronic and progressive disease that, independently of its etiology, favors the presence of some complications that impair the survival of patients. AIMS: To determine the frequency, etiology, and main decompensation factors, as well as analyse survival curves in HC of a population of Durango, México. METHODS: Cirrhotic patients of both sexes from the Hospital General del IMSS in Durango were included. The etiology of cirrhosis, the factors of decompensation and the grade of portal hypertension (PHT) were determined. A 39 month follow-up was done, registering complications and cause of death. STATISTICAL ANALYSIS: Fisher's exact test, Friedman's variance analysis, Mantel-Haenzsel chi-square test and Kaplan-Meier methods were used. RESULTS: Fifty patients were studied, 30 female and 20 male. The mean age was 54.3 years old (range 32-74 years). The more frequent etiology was alcoholic in 42% patients (19 male and 2 female). Forty three patients (86%) had decompensation by ascitis; 19 (38%) had variceal bleeding, 18(36%) had encephalopathy and 16(32%) were icteric. Twenty six patients (52%) had PHT III, and 30 (60%) were Child-Pugh class B. CONCLUSIONS: Survival in the decompensated group at 19.8 months follow-up was 62% and 73% in the total group, 20% died. Statistical significance (p < 0.05) was found between PHT grade and Child-Pugh functional class; hepatic reserve correlated inversely with bleeding (p < 0.05) and encephalopathy (p < 0.05) probability. The advanced grade of PHT directly correlated with bleeding encephalopathy and mortality (p < 0.05). We did not find any association between the etiology of cirrhosis and the incidence of complications.

[Prevalence of risk factors associated with hepatitis C in blood donors in the municipality of Durango, Mexico]. / Prevalencia y factores de riesgo asociados a hepatitis "C" en donadores de sangre en el municipio de Durango, México.

OBJECTIVE: To determine the prevalence of anti-viral hepatitis C antibodies (HCV-Ab+) in voluntary blood donors and to identify the main risk factors associated with it. MATERIAL AND METHODS: A case-control study was conducted over a 20-month period beginning in June 1993. A clinical history was obtained from all blood donors seen at the Centro Estatal de la Transfusión Sanguínea (State Blood Transfusion Center) and the Instituto Mexicano del Seguro Social in Durango, Mexico. HCV-Ab+ was determined in 5 915 serum assays using the second generation enzymatic immunoassay (UBI HCV EIA). RESULTS: The prevalence of HCV-Ab+ was 1.47 per 100 donors. The HCV-Ab+ prevalence was similar for urban and rural donors (1.54% and 1.34%) with no history of work migration. The main risk factors associated with HCV were a history of transfusions, (odds ratio -OR- 14.80, 95% confidence interval -CI-4.97-47.17) and sexual promiscuity or intercourse with prostitutes, (OR 6.53, 95% CI 2.61-16.54). CONCLUSIONS: The high prevalence of HCV-Ab+ may be explained by the lack of epidemiological surveillance of the population at risk. These data underscore the need for routine screening of HCV-Ab among voluntary blood donors and male or female prostitutes.

CD8+ T-cell protective immunity induced by immunization with Plasmodium berghei CS protein-derived synthetic peptides: evidence that localization of peptide-specific CTLs is crucial for protection against malaria.

Immunization of BALB/c mice (H-2d) with a mixture of major histocompatibility complex (MHC) class I- and MHC class II-restricted synthetic peptides emulsified in incomplete Freund's adjuvant (IFA) induced a high level of specific cytotoxic T lymphocyte (CTL) activity. Peptides 249-260 or 252-260, derived from the circumsporozoite protein of Plasmodium berghei and representing a H-2Kd-restricted CTL epitope, were injected twice subcutaneously or intraperitoneally in BALB/c mice in combination with the tetanus toxin-derived universal T-helper peptide P30 in IFA. No protection was observed after exposure of immunized mice to infected mosquitoes. In contrast, when peptide 252-260-specific CTLs were expanded in vitro and adoptively transferred into naive recipient, mice were partially protected (64%) against a subsequent sporozoite challenge. Furthermore, direct transfer of lymph nodes or spleen cells from mice immunized with the peptide PbCS 252-260 also conferred protection to recipient mice. This protection was long-lasting and similar to that obtained with irradiated sporozoites.

Induction of a cytotoxic T cell response by co-injection of a T helper peptide and a cytotoxic T lymphocyte peptide in incomplete Freund's adjuvant (IFA): further enhancement by pre-injection of IFA alone.

We have previously demonstrated that it is possible to induce a consistent and strong cytolytic T lymphocyte (CTL) response to synthetic peptides, corresponding to poorly immunogenic malaria CTL epitopes, by co-injecting them with peptides representing defined T helper (Th) epitopes in incomplete Freund's adjuvant (IFA). In this study we have tested different immunization protocols to improve further the elicitation of the CTL response. We show that the CTL response to a mixture of Th + CTL peptides administered in IFA was further enhanced by a previous injection of the Th epitope peptide in IFA. Moreover, we found that the response could be significantly augmented by a pre-injection of IFA alone. This enhancement was observed only if the Th epitope was also present in the second injection. The number of lymph node cells recovered was 2-3-fold higher in mice pre-injected with IFA, but the increase in specific CTL activity, expressed as lytic units per animal, by pre-injection of IFA was at least 10-20-fold. Thus, pre-injection of IFA clearly increases the magnitude of a subsequent CTL response.

Development of sporogonic cycle of Plasmodium vivax in experimentally infected Anopheles albimanus mosquitoes.

The sporogonic cycle of Plasmodium vivax was established and maintained under laboratory conditions in two different strains of Anopheles albimanus mosquitoes using as a parasite source blood from human patients or from Aotus monkeys infected with the VCC-2 P.vivax colombian isolate. Both the Tecojate strain isolate from Guatemala and the Cartagena strain from the colombian Pacific coast were susceptible to infections with P.vivax. A higher percentage of Cartagena mosquitoes was infected per trial, however the Tecojate strain developed higher sporozoite loads. Intravenous inoculation of Aotus monkeys with sporozoites obtained from both anopheline strains resulted in successful blood infections. Animals infected with sporozoites from the Tecojate strain presented a patent period of 21-32 days whereas parasitemia appeared between days 19-53 in monkeys infected with sporozites from Cartagena strain.

[Seminal vesicle cyst and ipsilateral renal agenesis: frequent association]. / Quiste de vesícula seminal y agenesia renal ipsilateral: asociación frecuente.

Presentation of a new case of cyst of the seminal vesicle in one patient with ipsilateral renal agenesis, stressing the frequency of this association. The cyst become evident following confirmation of renal agenesis, and presented an unusual communication to the bladder due to previous surgery (transurethral resection). This diagnosis was only suspected in the computerized tomography and cystoscopy and later confirmed by deferentovesiculography. The relevance of exploring any possible dysplasia of the seminal tract in the presence of renal agenesis is stressed. From an embryological point of view, the close relationship during development of both urinary and reproductive systems appear to explain the coexistence of these two anomalies. The primary symptoms of the condition, including the unspecific ones, as in the present cases, are discussed. Differential diagnosis from other deep pelvic cysts is referred. Following a literature review and based in our personal experience, already published, our views on the different embryological, clinical, diagnostic and therapeutic considerations are established.