Upon heat stress processing of ribosomal RNA precursors into mature rRNAs is compromised after cleavage at primary P site in Arabidopsis thaliana.

Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.

Implementing a hospital based injury surveillance system: a case study in Nigeria.

A pilot study of violent injury surveillance was implemented in two hospitals in Kano, Nigeria, in two phases: a formative evaluation including training and arranging the collection of hospital information, followed by a 6 month prospective data collection. Road traffic injuries constituted about 80 per cent of the cases, gunshot injuries were the commonest in victims of interpersonal violence (IPV). The causes and context of IPV, the relationship of victims and perpetrators, and the place, related activities and anatomical site of injuries from IPV are summarized.

Bloqueo caudal combinado versus anestesia general en pacientes pediátricos / Caudal blockade versus combined general anesthesia in pediatric patients

Contexto: El bloqueo caudal para anestesia regional en cirugía pediátrica ofrece la posibilidad de reducir los requerimientos de agentes inhalados y mejorar el control de dolor postoperatorio. Objetivo: Evaluar el consumo de anestésico inhalatorio y el efecto analgésico postoperatorio obtenido con bloqueo caudal combinado. Diseño: Ensayo clínico controlado no aleatorizado. Lugar y sujetos: 40 niños (1 a 10 años) atendidos en el Hospital "Eugenio Espejo" de la ciudad de Quito y programados para cirugía de miembros inferiores, hernioplastia inguinal, orquidopexia y circuncisión. Intervención: Anestesia general inhalatoria con halotano (AG) vs. Bloqueo caudal combinado (BC) mediante bupivacaína (al 0.25 a 2 mg/kg) + anestesia inhalatoria. Mediciones Principales: Requerimientos del anestésico inhalatorio evaluados a los 20, 40 y 60 minutos de instaurado el bloqueo. Dolor postoperatorio valorado a la primera hora de finalizada la intervención. Resultados: En el grupo BC la necesidad de halotano transoperatorio fue significativamente menor (0.5% a 1.0%) en comparación a los requerimientos del grupo AG (1.5% a 2.5%). A la primera hora del periodo posoperatorio el 80% (n=16) de pacientes del grupo BC no presentó dolor y el 20% (n=4) tuvo dolor de leve. En el grupo AG el dolor varió desde leve hasta muy severo. La presencia de dolor fue significativamente diferente entre los grupos(20% vs. 100%; p<0.05). El tiempo de recuperación anestésica fue similar. Se registraron como complicaciones en el grupo sometido a bloqueo caudal: taquicardia (n=2) y retención urinaria (n=2). Conclusiones: El bloqueo caudal combinado es una buena alternativa en la cirugía menor pediátrica, reduce los requerimientos de anestésico inhalatorio en el transoperatorio y disminuye el dolor postoperatorio inmediato.

Comparative prevalence of sensitization to common animal, plant and mould allergens in subjects with asthma, or atopic dermatitis and/or allergic rhinitis living in a tropical environment.

BACKGROUND AND OBJECTIVES: Current information suggests that the expression of allergic diseases is determined by the exposure and nature of the allergen. The objectives of the present study were to determine if the nature of allergenic exposition to animal, plant or fungal allergens influenced the clinical manifestations of atopic dermatitis (AD), allergic rhinitis (AR) or asthma (AS) in patients living in a tropical environment. The prevalence and degree of sensitization to these allergens were analysed by age and gender. SUBJECTS AND METHODS: A total of 1496 atopic cases, grouped according to the primary diagnosis of AD or AR or AS, were skin tested using a standardized allergen panel. Participants were categorized by age groups. The atopic index (AI) and mean weal diameter (MWD) as well as the prevalence of positive skin tests were determined for each of the patient groups and compared by age groups. RESULTS: The prevalence of atopy as well as the AI and the MWD peaked at 6-15 years of age and declined thereafter. In all the patients tested, the prevalence of sensitization was, in decreasing order; dust mites 94.3%, cockroach 41.5%, pets 31.5%, plant allergens 31.1% and fungal 19.4%. Eight hundred and ninety-three atopic patients were exclusively sensitized only to animal allergens. Of these, 38.4% had AD, 31.3% had AR and 30.5% with AS. CONCLUSION: These data demonstrate that for patients with AD, AR and AS living in a tropical environment, the prevalence of positive skin reactions to animal allergens is highest followed by plant and fungal allergens. We did not observe any association between the type of allergen and clinical manifestations. The index of atopy was similar for both sexes. The prevalence and degree of sensitization were shown to peak in young adults independent of the allergen in AD and AR patients.

The dynamics of tuberculosis in response to 10 years of intensive control effort in Peru.

Improved tuberculosis (TB) case detection and cure rates are expected to accelerate the decline in incidence of TB and to reduce TB-associated deaths. Time series analyses of case reports in Peru showed that the per capita TB incidence rate was probably steady before 1991. Case reports increased between 1990 and 1992 as a result of improved case detection. Although diagnostic efforts have continued to increase since 1993, the incidence of new pulmonary TB cases has declined in every department of the country, with a national rate of decline > or =5.8% per year (range, 1.9%-9.7%). This elevated rate of decline suggests that 27% (19%-34%) of cases (158,000) and 70% (63%-77%) of deaths (91,000) among smear-positive patients were averted between 1991 and 2000. This is the first demonstration that a significant number of TB cases can be prevented through intensive short-course chemotherapy in a high-burden country.

The effect of alcohol on the risk of lung cancer in Uruguay.

A hospital-based case-control study of the association between alcohol drinking and lung cancer was carried out in Uruguay between January 1988 and December 1990. The sample included 327 men with lung cancer and 350 male controls. Personal interviews were conducted in the Institute of Oncology by trained personnel using a structured questionnaire. The results showed a significant positive association between beer intake and the risk of lung cancer. The odds ratio for beer drinkers in the highest quartile was 3.4 (95% confidence limits, 1.3-6.6) after adjustment for tobacco. The association between beer and lung cancer was consistent for all the cell types, analyzed separately. A moderate effect for total alcohol consumption was also observed, with a relative risk of 2.2 for those subjects in the highest quartile.

Prospective study of Lewis antigen alterations in the gastric precancerous process.

A prospective study with two gastric biopsies taken several years apart was carried out in 117 subjects with intestinal metaplasia who are of the Lewis(a-b+) phenotype. They are residents of a rural Andean region in Colombia displaying very high rates of gastric cancer. The anomalous expression of Lewis(a) antigens in the metaplastic epithelium carried a significantly increased risk of colonic metaplasia and dysplasia. Such risk was much higher when the simultaneous expression of sulfomucins and Lewis(a) antigen was observed.

Lewis antigen alterations in gastric cancer precursors.

To explore the dynamics of the progressive loss of cell differentiation observed in the gastric precancerous process, the abnormal expression of Lea antigen in the gastric epithelium was investigated. Gastric biopsy specimens of 122 subjects with Le(a-b+) phenotype who had intestinal metaplasia of the gastric mucosa were studied. The subjects are residents of a rural area in the Colombian Andes with very high risk of gastric cancer. The abnormality was detected with increasing frequency in lesions with other markers of progression of the precancerous process, namely, colonic-type of morphology of the metaplastic cells, expression of sulfomucins, and dysplastic changes. The concomitant expression of the abnormal Lea antigen and sulfomucins was found to be a more reliable marker of more advanced lesions such as colonic metaplasia and dysplasia than either marker alone.

Black tobacco, maté, and bladder cancer. A case-control study from Uruguay.

A case-control study of bladder cancer involving interviews with 111 incident cases and 222 controls was carried out in Montevideo, Uruguay. The analysis was conducted separately for each sex. Point estimates of relative risk associated with smoking variables, ingestion of infusions of the herb Ilex paraguariensis (maté), and selected dietary items were obtained by stratified and logistic regression analysis. Among men, smokers of black tobacco showed a relative risk (RR) 2.7 higher than blond tobacco smokers and maté exposure showed a significant dose-response, after adjustment for age, residence, social class, hospital, type of tobacco, smoking intensity, smoking duration, and vegetable consumption, with a seven-fold increase in risk for heavy consumers. Joint exposure to type of tobacco and maté consumption showed a multiplicative effect. Women showed a similar increase in risk with maté consumption. The results suggest that the high mortality rates of bladder cancer observed in Uruguay could be explained by the combined effect of black tobacco smoking and maté ingestion.

Urinary excretion of nitrate, N-nitrosoproline, 3-methyladenine, and 7-methylguanine in a Colombian population at high risk for stomach cancer.

Urinary excretion levels of nitrate and N-nitrosoproline were determined in 160 individuals in a Colombian population at high risk for gastric cancer. In 156 of these subjects urinary levels of 3-methyladenine and 7-methylguanine were determined. Gastric biopsy specimens were obtained from 118 individuals and were histologically characterized according to pathological criteria into the following groups: normal, superficial gastritis, chronic atrophic gastritis, chronic atrophic gastritis with intestinal metaplasia, and dysplastic. The histological changes were correlated with the four variables listed above. There were no significant differences in the excretion of nitrate, N-nitrosoproline, 3-methyladenine, or 7-methylguanine in subjects with different pathological changes. A statistically significant correlation was present between nitrate and N-nitrosoproline excretion in the total population group (r = 0.297, P = 0.0001). A highly significant correlation (r = 0.56, P = 0.0002) was noted for urinary nitrate and N-nitrosoproline excretion in individuals with intestinal metaplasia and dysplasia. An increase in the urinary excretion of 3-methyladenine and 7-methylguanine was associated with tobacco smoking in the total population group.

Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks.

This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. The highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. In the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. The prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Children's Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection.

Gastric precancerous process in a high risk population: cross-sectional studies.

The gastric precancerous process is evaluated in 1788 participants in a gastroscopy survey in the population of Nariño, Colombia, which has one of the highest gastric cancer incidence rates on record. A detailed histological classification is used, and a hierarchical distribution of lesions is described with the main stages being gland neck hyperplasia, atrophy (gland loss), intestinal metaplasia and dysplasia. Acute inflammation was not found to be a specific stage in the sequence but rather a common finding in all stages of the precancerous spectrum. Indices of disease progression for the different steps are calculated and found to increase with gastric pH and nitrate and nitrite content of the gastric juice. The effects of high pH and nitrite content are intimately correlated. Relative risks of specific lesions, namely, hyperplasia, atrophy, metaplasia, and dysplasia, increase linearly with higher pH, nitrate, and nitrite values in the gastric juice. The severity of atrophy correlates with the prevalence of metaplasia, suggesting a sequential relationship between the described stages, a finding supported by all parameters examined. The model of progression described may serve as a basis for comparisons with populations at different levels of gastric cancer risk but it fails to provide information concerning the time required for each change, which should be provided by follow-up (cohort) studies.

Gastric precancerous process in a high risk population: cohort follow-up.

In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Columbia, have been followed from 3-16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.

Pediatric cancer in New Orleans.

Rates for pediatric cancer in the Greater New Orleans area were compared with rates from the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Program. The same patterns observed nationally were seen in New Orleans over a 10-year period. Rates were comparable with the exception of cancers of the brain and central nervous system for which New Orleans children displayed higher rates. Using the large number of cases in the SEER Program, three etiological patterns of childhood cancer were apparent based on the age at diagnosis.

Risk factors of gastric precancerous lesions in a high-risk Colombian population. I. Salt.

A case-control study for stomach cancer was conducted in a high-risk population in Nariño, Colombia to determine the risk of gastric precancerous lesions associated with salt intake measured by sodium-to-creatinine ratio of a single urine sample. Gastric biopsies and urine samples were collected from 263 individuals. Urinary sodium-to-creatinine ratios were studied in relation to histological data from the biopsies. Significantly high odds ratios for precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) were associated with higher sodium-to-creatinine ratios. Adjusted odds ratios (OR) of 2.50 for chronic atrophic gastritis and 7.24 for dysplasia were found. The association with intestinal metaplasia was weaker and not significant (OR = 1.57). Furthermore, an excess risk associated with adding salt to food at the table was found among patients with precancerous lesions (OR = 1.80). These findings support the two-step involvement of salt in the process of gastric precancerous lesions.

Risk factors of gastric precancerous lesions in a high-risk Colombian population. II. Nitrate and nitrite.

Gastric nitrite content was studied in relation to precancerous lesions of the stomach in a case-control study conducted in a high-risk Colombian population. The proportion of detectable nitrite in gastric juice and the mean pH were significantly higher among those with precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) than among the controls (normal and superficial gastritis); the proportion and mean pH increased with the progression of histological changes from normal to dysplasia. Nitrite was not detectable in gastric juice with a pH less than 5.0. A positive association was found between the proportion of detectable nitrite and the risk of gastric precancerous lesions. Odds ratios of 4.39 for intestinal metaplasia and 24.72 for dysplasia remained significant after controlling for confounders. This finding suggests that nitrite may be a precursor of a mutagen that targets gastric epithelial cells.

Alcohol drinking and tobacco smoking in gastric cancer. A case-control study.

This study compares 210 cases of cancer of the stomach (138 males and 72 females) with 630 controls (414 males and 216 females) afflicted with a wide variety of diseases. All patients (cases and controls) were admitted for treatment at the University Hospital of Montevideo, Uruguay in the time period July 1985-December 1988. They were submitted to the same detailed questionnaire by 3 social workers unaware of the objectives of the study. The analysis was performed at the Louisiana State University of New Orleans, using multiple logistic regression. The variables analyzed were cigarette smoking, alcohol ingestion, salted meat intake, total vegetable consumption, total fruit consumption and "mate" ingestion. Strong positive associations were found in both sexes for low fruit and vegetable consumption, high intake of salted meat and "mate" ingestion. Only males showed significantly elevated OR's for tobacco smoking and alcohol drinking. Of the main tobacco variables, time-dependent one's (age at start, duration) displayed significant gradients of increasing risks. Thus, a prolonged exposure seems more important than the amount smoked per day for the risk of developing gastric carcinoma. Both wine and hard liquor carried increased OR's, but heavy drinkers of wine displayed a six-fold increase in risk, replicating previous reports from France.

Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans.

The sympathetic response to hypoxia depends on the interaction between chemoreceptor stimulation (CRS) and the associated hyperventilation. We studied this interaction by measuring sympathetic nerve activity (SNA) to muscle in 13 normal subjects, while breathing room air, 14% O2, 10% O2, and 10% O2 with added CO2 to maintain isocapnia. Minute ventilation (VE) and blood pressure (BP) increased significantly more during isocapnic hypoxia (IHO) than hypocapnic hypoxia (HHO). In contrast, SNA increased more during HHO [40 +/- 10% (SE)] than during IHO (25 +/- 19%, P less than 0.05). To determine the reason for the lesser increase in SNA with IHO, 11 subjects underwent voluntary apnea during HHO and IHO. Apnea potentiated the SNA responses to IHO more than to HHO. SNA responses to IHO were 17 +/- 7% during breathing and 173 +/- 47% during apnea whereas SNA responses to HHO were 35 +/- 8% during breathing and 126 +/- 28% during apnea. During ventilation, the sympathoexcitation of IHO (compared with HHO) is suppressed, possibly for two reasons: 1) because of the inhibitory influence of activation of pulmonary afferents as a result of a greater increase in VE, and 2) because of the inhibitory influence of baroreceptor activation due to a greater rise in BP. Thus in humans, the ventilatory response to chemoreceptor stimulation predominates and restrains the sympathetic response. The SNA response to chemoreceptor stimulation represents the net effect of the excitatory influence of the chemoreflex and the inhibitory influence of pulmonary afferents and baroreceptor afferents.

Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans.

We compared the effects of isocapnic hypoxia (IHO) and hyperoxic hypercapnia (HC) on sympathetic nerve activity (SNA) recorded from a peroneal nerve in 13 normal subjects. HC caused greater increases in blood pressure (BP), minute ventilation (VE), and SNA [53 +/- 14% (SE) during HC vs. 21 +/- 7% during IHO; P less than 0.05]. Even at equivalent levels of VE, HC still elicited greater SNA than IHO. However, apnea during HC caused a lesser (P less than 0.05) increase in SNA (91 +/- 26% compared with apnea on room air) than apnea during IHO (173 +/- 50%). Hypercapnic hypoxia resulted in a greater absolute increase in VE (23.6 +/- 2.8 l/min) than the additive increases due to HC alone plus IHO alone (18.0 +/- 1.8 l/min, P less than 0.05). SNA also increased synergistically by 108 +/- 23% with the combined stimulus compared with the additive effect of HC alone plus IHO alone (68 +/- 19%; P less than 0.05). We conclude that 1) HC causes greater increases in VE and SNA than does hypoxia; 2) for the same increase in VE, hypercapnia still causes a greater increase in SNA than hypoxia; however, during apnea, hypoxia causes a much greater increase in SNA than hypercapnia; 3) the inhibitory influence of ventilation on SNA is greater during hypoxia (i.e., predominantly peripheral chemoreceptor stimulation) than hypercapnia (i.e., predominantly central chemoreceptor stimulation); and 4) combined hypoxia and hypercapnia have a synergistic effect on SNA as well as on VE.