Estudios de cohortes especiales / Special cohort studies

Resumen Como se comentó en el artículo anterior (Estudios de cohortes. 1ª parte. Descripción, metodología y aplicaciones), los estudios de cohortes se caracterizan por ser observacionales, longitudinales y analíticos; y en todos ellos se debe considerar una exposición o "factor de exposición", un período de seguimiento, eventuales pérdidas de seguimiento y el desenlace de un resultado. Se han propuesto modificaciones y variantes al diseño del estudio de cohortes tradicional. Se describen de forma resumida, las características principales de los estudios de cohortes con base poblacional, de cohortes bidireccional o ambispectivo; y de otras variantes: según número de cohortes (única y múltiple), de acuerdo al tipo de reclutamiento de la población a estudio (cerrada y abierta), según el tipo de exposición (fija y dinámica); estudio de casos y controles anidado, cohorte-caso; y cohortes ocupacionales (simple con población de referencia externa, simple con grupo de referencia interna y de cohortes múltiples). Finalmente, se desarrollan algunos ejemplos de la literatura de las variantes de cohortes más frecuentes. El objetivo de este manuscrito fue generar un documento de estudio referente a las modificaciones y variantes del diseño del estudio de cohortes.

As we mentioned in a previous article (Cohort studies. 1st part. Description, methodology and applications), cohort studies are characterized by being observational, longitudinal and analytical studies; and in all of them an exposure, a follow-up period, eventual loss of follow-up; and an outcome should be considered. A number of modifications and variants to the traditional cohort study design have been proposed. A summary with the main characteristics of population-based cohort studies, bidirectional cohorts, and of other variants according: to the number of cohorts (single and multiple), to the recruitment of the study population (closed and open), to the exposure (fixed and dynamic); nested case-control study, cohort-case, and occupational cohorts (simple with external reference population, simple with internal reference group and multiple cohorts), are described. Finally, examples of the literature of the most frequent cohort variants are developed. The aim of this manuscript was to generate a study document referring to some of the modifications and variants of cohort studies.

Functional human sperm capacitation requires both bicarbonate-dependent PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases.

In all mammalian species studied so far, sperm capacitation correlates with an increase in protein tyrosine (Tyr) phosphorylation mediated by a bicarbonate-dependent cAMP/protein kinase A (PKA) pathway. Recent studies in mice revealed, however, that a Src family kinase (SFK)-induced inactivation of serine/threonine (Ser/Thr) phosphatases is also involved in the signaling pathways leading to Tyr phosphorylation. In view of these observations and with the aim of getting a better understanding of the signaling pathways involved in human sperm capacitation, in the present work we investigated the involvement of both the cAMP/PKA and SFK/phosphatase pathways in relation to the capacitation state of the cells. For this purpose, different signaling events and sperm functional parameters were analyzed as a function of capacitation time. Results revealed a very early bicarbonate-dependent activation of PKA indicated by the rapid (1 min) increase in both phospho-PKA substrates and cAMP levels (P < 0.05). However, a complete pattern of Tyr phosphorylation was detected only after 6-h incubation at which time sperm exhibited the ability to undergo the acrosome reaction (AR) and to penetrate zona-free hamster oocytes. Sperm capacitated in the presence of the SFK inhibitor SKI606 showed a decrease in both PKA substrate and Tyr phosphorylation levels, which was overcome by exposure of sperm to the Ser/Thr phosphatase inhibitor okadaic acid (OA). However, OA was unable to induce phosphorylation when sperm were incubated under PKA-inhibitory conditions (i.e. in the absence of bicarbonate or in the presence of PKA inhibitor). Moreover, the increase in PKA activity by exposure to a cAMP analog and a phosphodiesterase inhibitor did not overcome the inhibition produced by SKI606. Whereas the presence of SKI606 during capacitation produced a negative effect (P < 0.05) on sperm motility, progesterone-induced AR and fertilizing ability, none of these inhibitions were observed when sperm were exposed to SKI606 and OA. Interestingly, different concentrations of inhibitors were required to modulate human and mouse capacitation revealing the species specificity of the molecular mechanisms underlying this process. In conclusion, our results describe for the first time the involvement of both PKA activation and Ser/Thr phosphatase down-regulation in functional human sperm capacitation and provide convincing evidence that early PKA-dependent phosphorylation is the convergent regulatory point between these two signaling pathways.

[Morphological features of the nasal mucosa in healthy children exposed to different concentrations of atmospheric pollution]. / Características morfológicas de la mucosa nasal en niños sanos expuestos a differentes concentraciones de contaminación atmosférica.

OBJECTIVE: During the last decades the impact of pollution in big cities on the upper respiratory tract of children has become an issue of interest. The purpose of the present study was to determine if exposure of healthy children to different concentrations of atmospheric pollution alters morphologically the nasal respiratory epithelium. MATERIAL AND METHODS: In this randomised, prospective, open clinical trial we included 71 healthy children matched for age and sex and divided them into 3 groups: Group I, 31 children from Mexico City. Group II, 21 children from Tula, Hidalgo a moderate polluted area, and Group III, 19 children from Contepec, Michoacán, a rural non-polluted area. We took a nasal biopsy from the lower turbinate and performed nasal cytology in all children. The samples were examined twice by a pathologist with a double-blind technique. Ozone measurements were taken during 1992. RESULTS: Nasal symptoms (nasal obstruction, pruritus and dryness) were present in 96.8%, 71.4% and 52.6% of patients in groups I, II and III respectively (p = 0.001). We also found bilateral hypertrophy turbinates in 100% of children in group I versus 81% and 73% in groups II and III (p = 0.009). Citologic examination disclosed no significant differences among the study groups, although p values were 0.06 respecting inflammation and abnormal goblet cells when we compared group I versus group II and III. Respecting histological examination we found significant differences when comparing group I versus II and III in squamous metaplasia (p = 0.02) and pseudoepitheliomatous hyperplasia (p = 0.003), with not significant differences among keratinization (p = 0.06) and dysplasia (p = 0.06). CONCLUSIONS: The results of this study indicate that exposure to a polluted atmosphere is followed by severe changes in the histology and cytology of the nasal mucosa in healthy children, with these changes being more frequent and severe in the more polluted areas. These findings implicate that we must put more attention on the long term effects of atmospheric pollution in order to establish stronger control measures.

Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children.

OBJECTIVE: To assess the effect of zinc supplementation on respiratory tract disease, immunity and growth in malnourished children. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A day-care center in Quito, Ecuador. SUBJECTS: Fifty children (12-59 months old) recruited by height-for-age and weight-for-age deficit. INTERVENTIONS: Twenty-five children (supplemented, S group) received 10 mg/day of zinc as zinc sulfate, and 25 (nonsupplemented, NS group) received a placebo during 60 days. All were also observed during a 60-day postsupplementation period. Two children of the S group dropped out. Daily the clinical presence of cough, respiratory tract secretions, and fever, was recorded. On days 0,60 and 120, the cutaneous delayed-type hypersensitivity (DTH) to multiple antigens, and anthropometric parameters were assessed. On days 0 and 60 serum zinc levels were also measured. RESULTS: On day 60, DTH was significantly larger (20.8 +/- 7.1 vs 16.1 +/- 9.7 mm), and serum zinc levels were significantly higher (118.6 +/- 47.1 vs 83.1 +/- 24.5 micrograms/dl) in the S group than in the NS group (P <0.05 for each). The incidence of fever [relative risk (RR): 0.30, c.i. = 0.08- 0.95, P =0.02], cough (RR): 0.52, c.i. = 0.32-0.84, P = 0.004) and upper respiratory tract secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001) was lower in the S group than in the NS group at day 60. At the end of the postsupplementation observation period (day 120), the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups. The incidence of cough was higher at day 120 in the S group than in the NS group (RR): 2.28, c.i. = 1.37-3.83, P = 0.001). CONCLUSIONS: This study supports a role for zinc in immunity, and immunity to respiratory infections, while pointing out the need for larger studies.

Dermatitis de contacto alergica por colorantes en calcetines. / Alergic contact dermatitis to dyes in socks

La dermatitis de contacto alergica por colorantes en calcetines, constituye un problema cronico e incapacitante, su diagnostico no siempre es sencillo y a menudo se confunde con otras dermatosis que afectan los pies.Los agentes etiologicos principales son los colorantes azoicos derivados del aminoazobenceno y otros colorantes de tipo antraquinonico que pueden jugar tambien un papel importante. El diagnostico preciso puede efectuarse unicamente por medio de pruebas epicutaneas con los colorantes utilizados en la tincion de acetato, nylon y poliester, asi como con fragmentos de las prendas sospechosas, lo cual permite identificarlas, facilitando las alternativas adecuadas para el uso de calcetines que pueden ser tolerados por el paciente. Es importante completar el estudio inmunologico con otras substancias que pueden originar dermatitis de contacto en los pies como son materiales del calzado y medicamentos topicos

[Absence of bacteremia after dental extractions]. / Inexistencia de bacteriemia consecutiva a la odontectomía

A study was made on 100 subjects of both sexes between the ages of 3 and 15 years to detect the presence of bacteria in the circulation after performing dental extractions. Two groups were formed of 42 and 57 subjects respectively. One of these groups was subjected to preoperative antisepsis of the region to be operated on, the rest of the conditions were similar for both groups. All the patients were submitted to a preoperative gingival smear and 5 c.c. of blood taken for cultures. Two postoperative blood cultures, one immediately after the operations and another 24 hrs. later were also done in all patients. All the extracted teeth presented severe infections at the root level and some showed complicated infection such as osteomyelitis. All blood cultures performed 24, 48, 72 hrs. and 21 days after the operation, were negative; therefore, there is no justification based on the study, to assume the existance of focal infection related to the presence of bacteremia.