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.     

Chronic Bullous Dermatosis of Childhoo Immonopathologic Studies

Chronic bullous dermatosis of childhood (CBDC) is a distinctive subepidermal blistering disorder that characteristically involves the lower face, neck, lower trunk, and diaper area. Nearly all affected patients have a continuous linear band of IgA at the dermoepidermal junction by direct immunofluorescence and many have circulating IgA antibasement membrane antibodies. Few ultrastructural studies have been performed to determine the location of these IgA autoantibodies. We examined an infant with the typical clinical, histopathologic, and immunopathologic features of CBDC in whom a circulating, lamina lucida-reactive IgA autoantibody was identified with a new, more sensitive, split-skin indirect immunofluorescence technique.     

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.     

Biological correlates of deliberate self-harm behaviour: a study of electroencephalographic,biochemical and psychological variables in parasuicide

Clinical, electroencephalographic and biochemical variables were measured in 40 patients who attempted suicide and 27 age-matched controls. Patients had significantly higher scores for depression, hopelessness, neuroticism and psychoticism and lower scores for extraversion than controls. They also had significantly lower contingent negative variation (CNV), higher postimperative negative variation and lower whole blood serotonin values than controls. Within the patient group, vulnerability to parasuicide, as determined by previous or repeated acts of deliberate self-harm, was associated with higher scores for hopelessness and suicide intent, lower scores for extraversion and decreased CNV. Factor analysis revealed significant correlations between psychological variables and auditory evoked potential amplitudes for the vulnerable group. A profile of variables associated with increased risk of self-harm in patients presenting with attempted suicide is proposed from our data.     

Views of problem drinking among Native American,Hispanic, and Anglo children

Native American, Hispanic, and Anglo sixth graders reacting to an example of teenage problem drinking expressed similar beliefs and attitudes in many respects. However, Native American children viewed the problem as less serious, subscribed more to a disease theory of alcoholism, attributed less causal responsibility to the individual, and adopted a less aggressive approach toward treatment than did Hispanic, and especially Anglo, children. Their less conventional value orientations accounted for all these differences except their stronger endorsement of a disease theory of problem drinking.     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Anesthesia and/or Sedation for Pulsed Dye Laser Therapy

One of the most exciting developments in pediatric dermatology has been the use of the flashlamp-pumped, 585-nm, pulsed dye laser for treatment of vascular birthmarks. In many cases the results are miraculous. The increase in self-esteem and happiness of many children and adolescents has been overwhelming; for some, depression has been lifted, stuttering has ceased, social involvement has increased, and antidepressants have been discontinued. There are many success stories to tell.
Despite the remarkable effects of the pulsed dye laser and the medical and psychosocial indications for its use, the issue of pain control remains significant. We have no perfect outpatient pediatric anesthetic. Most methods carry either some risk or, if not hazardous, often are not very effective for controlling pain. Needless to say, a diversity of opinions exist on how to manage discomfort from this treatment modality. Therefore, we thought it would be useful to share the experiences and opinions of several dermatologists who have extensive experience with the pulsed dye laser.