Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children.

The effect of a 14-valent pneumococcal polysaccharide vaccine on morbidity from acute lower respiratory tract infection (ALRI) was determined in a randomized double-blind controlled trial in children under the age of 5 years living in the Paupa New Guinea highlands. The vaccine did not protect against mild ALRI. Vaccine efficacy in the study as a whole was 28% for moderate/severe ALRI, which was not statistically significant though consistent with the significant effect on mortality. Children entered the trial in five separate cohorts 4 months apart. The incidence of disease and vaccine efficacy varied between cohorts and with age. There was no vaccine effect in the first cohort, which had a much higher proportion of older children. The effect was greatest and statistically significant among those groups encountering an epidemic of moderate and severe ALRI at a young age. It was therefore in children at the most vulnerable age in times of greatest incidence of disease that the vaccine had its most potent effect. It is postulated that the efficacy of pneumococcal vaccine is dependent on the predominant invading serotypes in the period after vaccination, the age at which children develop immunocompetence to specific vaccine serotypes, and the levels of naturally acquired specific immunity already present in children at the time of vaccination, and that for all of these conditions there will be a cohort effect.     

Therapist features in sexual offender treatment: their reliable identification and influence on behaviour change

In the first of the two studies reported here, we established that trained judges could reliably identify 18 therapist features that occurred with reasonable frequency. In the second study 17 of these features were examined to determine how well they related to changes in sexual offenders with treatment. Five videotapes from each of five different prison programs were rated for the presence of these 17 features and correlational analyses examined their relationship with changes in 44 measures of treatment targets. The primary findings indicated that empathy and warmth displayed by the therapists and their directive and rewarding behaviours, were the features that most strongly predicted therapeutic benefits. The results are discussed in terms of their clinical and research implications. Copyright © 2002 John Wiley & Sons, Ltd.     

Partially hepatectomized rats: a model for the study of the effect of toxins on the plasma protein profiles of nascent hepatocytes.

A useful framework is proposed for unifying the synthesis of plasma proteins and their degradation by, or release from, liver cells of intact and partially hepatectomized rats, in which synthesis and release of acute-phase plasma proteins occur in synchrony with the internalization and catabolism of plasma and extracellular proteins. The catabolism of proteins and other hepato-intracellular glycoproteins during sepsis or trauma is essential to provide constituent amino acids and carbohydrates for the synthesis of acute-phase plasma proteins. Increases in the plasma levels of acute-phase response proteins in sham-operated rats reached a maximum between 1 and 2 d after mock surgery, and had returned virtually to control levels within 6 d. By contrast, acute-phase proteins in the plasma of partially hepatectomized rats were decreased by 10-20% of their initial values after 24 h. A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively. This delayed response suggests that the nascent liver cells had inherited the capacity of the parent cells to respond to inflammatory signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame for the application of toxin to nascent hepatocytes is suggested. An increased activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver tissue 19 h post partial hepatectomy suggested that hepatic regenerating factor(s) were produced in liver tissue via the hepatic bound and/or free neuraminidase-mediated desialylation of humoral substrates. By contrast, circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D-glucosaminidase were increased marginally after 24 h but had returned nearly to control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute-phase plasma proteins.     

Influence of political power, medical provincialism, and economic incentives on the rationing of surgical intensive care unit beds.

OBJECTIVE: To determine factors influencing rationing decisions in a surgical ICU during a temporary nursing shortage when two to six of the unit's 16 beds were closed. DESIGN: Blinded, concurrent data collection, retrospective chart review. SETTING: Surgical ICU. PATIENTS: All patients (n = 308) for whom a surgical ICU bed was requested were studied during a 3-month period. MEASUREMENTS AND MAIN RESULTS: Admitting patterns did not change and no attempts were made to limit admissions to more severely ill patients during times of the greatest shortage of surgical ICU beds. Contrary to findings in previous reports, the severity of illness of patients admitted to the surgical ICU decreased as bed availability and bed census decreased. Bed allocation across surgical services was influenced by factors other than medical suitability. Of major users, cardiothoracic surgery experienced the highest percentage (59%) of all patient admissions and lowest percentage (1.6%) of all denied admissions. General surgery experienced the lowest percentage (15%) of all admissions and highest percentage (10.4%) of all denied admissions, although these patients had the highest average Acute Physiology and Chronic Health Evaluation (APACHE II) scores for all patients admitted (17.7) and for patients denied admission (15.8). CONCLUSIONS: Surgical attending physicians rarely used other open inhouse ICU beds when surgical ICU beds were unavailable. Political power, medical provincialism, and income maximization overrode medical suitability in the provision of critical care services.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Predicting survival and recurrence in localized melanoma: A multivariate approach

Several clinical and pathologic factors appear to affect melanoma recurrence and survival. While much attention has been directed at identifying prognostic factors, few researchers have developed predictive models for survival and recurrence. Two major clinical questions are of interest in the management of melanoma: 1) what is the patient's chance of surviving for a given period, e.g., 5 or 10 years, after diagnosis of melanoma; and 2) after a patient has been disease free for a period of time, e.g., 5 years, what is his or her chance of melanoma recurrence or death in the following interval, e.g., 5 years or 10 years. In this paper, a generalized multivariate prognostic model to address both of these clinical questions is presented.Tables of the estimated probabilities of melanoma recurrence and death for prognostic subgroups are shown to facilitate prediction of an individual patient's outcome. The model was based on a database of 4,568 patients with localized melanoma, one of the largest melanoma databases in the world with detailed clinical and pathologic information, and long-term follow-up. Tumor thickness at diagnosis was the single most important prognostic factor for all outcomes. Tumor ulceration, Clark's level, lesion location, and sex had an impact on overall survival from diagnosis for some of the subgroups defined by tumor thickness. Tumor thickness at diagnosis was strongly indicative of melanoma recurrence and death even after a disease free interval of 2, 5, or 10 years. Lesion location and ulceration were of prognostic importance after disease free intervals up to 5 years, but their impact on melanoma recurrence and death diminished after longer disease free intervals.Prediction models for melanoma outcome at diagnosis and after a disease free period can provide useful information to clinicians in the management of melanoma patients. Utilization of the model will be valuable in identifying patients at high risk for melanoma recurrence and death.

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Resumen Diversos factores clínicos y patológicos parecen afectar las tasas de recurrencia y mortalidad del melanoma. En tanto que se ha dispensado bastante atención en cuanto a identificar factores de pronóstico, pocos investigadores han desarrollado modelos de predicción de sobrevida y de recurrencia. Dos interrogantes principales son de interés en cuanto al manejo del melanoma: 1) cual es la probabilidad del paciente de sobrevivir un determinado período, por ejemplo 5 o 10 años, después del diagnóstico de melanoma; y 2) después de que el paciente se ha mantenido libre de enfermedad por un período de tiempo, por ejemplo 5 años, cual es su probabilidad de recurrencia del melanoma o de muerte en el siguiente período de tiempo, por ejemplo 5 o 10 años. En este artículo se presenta un modelo generalizado y multivariable de pronóstico para enfrentar estos interrogantes clínicos.Se presentan tablas para estimar las probabilidades de recurrencia y de muerte en divesos subgrupos de pronóstico que facilitan la predicción del destino final de un individuo. El modelo se fundamentó en una base de datos de 4568 pacientes con melanomas localizado, una de las más grandes bases de datos de melanoma existentes en el mundo, con detallada información clínica y patológica y con seguimiento a largo plazo. El espesor del tumor en el momento del diagnóstico apareció como el factor individual de pronóstico de mayor importancia. La ulceración del tumor, el nivel de Clark, la ubicación de la lesión y el sexo exhibieron importancia en cuanto a la sobrevida para algunos de los subgrupos definidos según el espesor del tumor. El espesor del tumor en el momento del diagnóstico fue un factor fuertemente indicativo de recurrencia y de muerte, aún después de un intervalo libre de enfermedad de 2, 5 o 10 años. La ubicación de la lesión y la ulceración aparecieron como de importancia en cuanto el pronóstico después de intervalos libres de enfermedad hasta de 5 años, pero tal importancia disminuyó después de intervalos libres de enfermedad de mayor duración.Los modelos de predicción del resultado final en el melanoma aplicados en el momento del diagnóstico y después de un período libre de enfermedad pueden proveer información útil para el manejo clínico de pacientes con melanomas. La utilización del modelo es de valor en la identificación de pacientes con mayor riesgo de recurrencia y muerte por melanoma.

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Résumé Plusieurs facteurs cliniques et anatomopathologiques semblent déterminer la récidive et la survie des mélanomes. De nombreux auteurs se sont intéressés à l'identidification des facteurs de pronostic, mais peu d'équipes ont essayé d'élaborer un modèle permettant de prédire survie et récidive. Deux problèmes restent à résoudre dans le traitement des mélanomes: 1) quelles sont les chances de survie après le diagnostic de mélanome pour un patient donné, pendant une période donnée, par exemple 5 à 10 ans et 2) quels sont les risques de récidive ou de décès dans les 5 à 10 ans qui suivent une période donnée (par exemple 5 ans) où un patient semblait en rémission. Dans cet article, nous avons créé un modèle d'évaluation pronostique multifactorielle pour tenter de répondre à ces 2 questions.Des tables montrant les probabilités de récidive et de décès par mélanome, calculées à partir de sous groupes différents, peuvent aider à déterminer le pronostic. Ce modèle repose sur une banque de données de 4568 patients atteints de mélanome non disséminé. Il s'agit d'une des plus grandes banques de données au monde contenant des informations cliniques, anatomopathologiques et sur l'évolution à long terme. L'épaisseur de la tumeur au moment du diagnostic était le facteur pronostic le plus important pour déterminer l'évolution. Le caractère ulcéré, le stade de Clark, la localisation de la lésion et le sexe avaient tous une importance pronostique, influant sur la survie globale liée à l'épaisseur de la tumeur. L'importance de l'épaisseur de la tumeur au moment du diagnostic était un facteur de récidive et mortalité même après un intervalle long de 2, 5 ou 10 ans. Le site de la tumeur et son caractère ulcéré étaient également des facteurs associés à un risque de récidive tumorale ou de décès après une rémission de 5 ans. L'influence de ces facteurs diminuait en cas de rémission plus prolongée.Les modèles permettant d'évaluer l'évolution du mélanome malin au moment du diagnostic et apreès un intervalle de rémission sont utiles au cours du traitement du mélanome. Ils doivent permettre d'identifier les patients à risque de récidive et de décès.

     

Antiarrhythmic activity of 17 beta-aminoestratrienes. Comparison of 3-ols and 3-acetates with the corresponding 3-(3-amino-2-hydroxypropyl) ethers

The antiarrhythmic efficacy of 17 beta-amino- and 17 beta-amino-16 alpha-hydroxyestratrien-3-ols and 3-acetates (group 1) was compared with the efficacy of corresponding 3-[2-hydroxy-3-(isopropylamino)propyl] and 3-[2-hydroxy-3-(tert-butylamino)propyl] ethers (group II), substituents which are usually associated with beta-adrenoceptor blocking activity. Group I compounds exerted potent antiarrhythmic activity against both aconitine-induced arrhythmias in mice and ischemia-induced arrhythmias in rats and reduced the maximum following frequency of isolated guinea pig atria. Electrophysiological studies indicated that their mechanism of action is due to an ability to reduce the fast inward sodium current in cardiac cells (class I antiarrhythmic action). Group II compounds were inactive in the aconitine and atrial tests and electrophysiological studies confirmed that they were devoid of class I activity. However, these compounds, like both class I antiarrhythmic and beta-adrenoceptor blocking drugs, were active against ischemia-induced arrhythmias. Group II compounds, unlike group I compounds, exerted nonspecific beta-adrenoceptor blocking actions, which may account for their activity in the rat test. It was concluded that introduction of the 3-substituted ether group did not confer any advantage over the parent 3-ol or 3-acetate compounds.     

Kupffer cell modulation of the systemic immune response

The effects of global hepatic injury and of Kupffer cell activation on systemic immunity were studied in an in vivo rat model, using the diameters of the delayed-type hypersensitivity (DTH) response to keyhole limpet hemocyanin and of a subcutaneous Staphylococcus aureus abscess as measures of systemic immunoresponsiveness. Hepatic injury with carbon tetrachloride resulted in significant suppression of the DTH score (5.5 +/- 0.7 vs 8.8 +/- 0.8 mm). Kupffer cell activation with intraportal Escherichia coli was likewise suppressive (DTH score, 4.4 +/- 0.5 vs 6.1 +/- 0.4 mm for animals receiving systemic E coli); the magnitude of this suppression correlated with the numbers of organisms extracted by the liver. Conversely, Kupffer cell ablation with carrageenan lessened the immunosuppressive effects of anesthesia and surgery (DTH score, 8.5 +/- 0.9 vs 6.8 +/- 0.6 mm for controls; S aureus abscess, 4.1 +/- 0.4 vs 5.7 +/- 0.4 mm for controls). These results indicate that Kupffer cells can modulate the systemic immune response and suggest that gram-negative portal bacteremia with resultant Kupffer cell activation may contribute to the immunologic derangements characteristic of trauma and critical surgical illness.