Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant

The objective of the study was to determine whether administering doxapram by infusion to the very low birthweight infant, prior to extubation during the first 3 weeks of life, would increase the incidence of successful extubation. The study patients, 56 infants of less than 1251 g birthweight and less than 30 weeks' gestation, were entered in the first 3 weeks of life when lung disease had started to improve. A randomized blinded trial was performed, with infants receiving 3.5 mg kg⁻¹ doxapram bolus, followed by an infusion at 1 mg kg⁻¹ h⁻¹, or placebo. Weaning from positive pressure ventilation was standardized and extubation occurred after a 12 h trial of an intermittent mandatory ventilation (IMV) rate of 6 breaths min⁻¹, if PCO₂ < 55 mmHg, pH > 7.26, and FiO₂ < 0.45. Study drug was continued for 48 h postextubation, and the infants were placed on nasopharyngeal continuous positive airway pressure (CPAP) for 72 h postextubation. Extubation failure within the first 72 h after extubation was objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO₂ > 55 mmHg), excessive oxygen requirement (FiO₂ > 0.8) or frequent apnoea (more than three in 12 h, or more than two requiring face mask IMV in 24 h). No difference was noted in the frequency of successful extubation between the groups. Fifteen infants in each group were successfully extubated before the 10th day of the study. In conclusion, when given in accordance with this protocol doxapram does not increase the likelihood of successful extubation in the very low birthweight infant. Increasing successful extubations in this group of infants will require other strategies.     

Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy

Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plasmodium falciparum infection and disease. We have previously described the use of peptides to define malaria-specific CTL epitopes. To determine whether these peptide epitopes are processed intracellularly from the whole antigen we have developed recombinant vaccinia viruses (rVV) expressing three malaria antigens: thrombospondin-related adhesive protein (TRAP), Pfs16 and the C- terminal half of liver-stage antigen (LSA)-1. Target cells infected with recombinant viruses were lysed by malaria-specific CTL from semi- immune African donors. We also tested the ability of cells infected with these recombinant vaccinia viruses to re-stimulate malaria- specific CTL in peripheral blood lymphocytes from malaria immune adults. Two other pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC, a canarypox virus, both expressing malaria antigens were also evaluated for their ability to stimulate malaria-specific CTL in contrast to peptide, none of these viruses successfully re- stimulated CTL from the peripheral blood lymphocytes of semi-immune donors. The ability of human CTL from naturally exposed individuals to recognize processed antigen supports the relevance of these cells in protective immunity to malaria.      

Posturally induced vasoconstriction in diabetes mellitus

In healthy subjects, standing elicits a reduction in blood flow to the skin of the foot. In adults with insulin dependent diabetes this posturally induced response is deficient, resulting in capillary hypertension when the foot is in the dependent position (that is, below heart level). Such functional abnormalities of the microcirculation in diabetes may precede any evidence of clinically detectable microangiopathy. This study investigates the posturally induced change in blood flow to the skin of the foot in prepubertal and postpubertal patients with insulin dependent diabetes. Laser Doppler fluximetry was used to assess the postural change in blood flow at the pulp of the great toe. Postural vasoconstriction (dependent flux value/supine flux value x 100) was greater after puberty in normal subjects (median (range) 60.4 (7.0-164.9)% prepubertal v 20.5 (5.9-101.0)% postpubertal). Prepubertal children with diabetes did not differ from their healthy peers (69.8 (7.2-192.7)% with diabetes v 60.4 (7.0-164.9)% controls); however postpubertal children with diabetes had a significantly impaired postural vasoconstriction (40.6 (7.9-140.2)% with diabetes v 20.5 (5.9-101.7)% controls). Abnormalities in the normal reduction of blood flow on standing occurred in young postpubertal children with diabetes, most of whom were free of complications.     

Virus‐Associated Trichodysplasia Spinulosa

A 46‐year‐old hepatitis C‐positive African American woman presented with a several month history of worsening, well‐marginated, erythematous, dusky plaques on the dorsum of her feet and ankles. After an initial skin biopsy showed spongiotic dermatitis, she was treated with emollients, high potency topical steroids, and keratolytics, all of which were of no benefit. A punch biopsy from the dorsum of her foot showed acanthosis, individual keratinocyte necrosis, confluent upper epidermal necrosis, and a superficial and deep perivascular lymphocytic infiltrate. Given the patient's positive hepatitis C status and clinicopathological correlation, a diagnosis of necrolytic acral erythema was rendered. Empiric therapy with oral zinc sulfate was initiated despite a normal plasma zinc level, and the skin lesions resolved with post‐inflammatory hyperpigmentation. Necrolytic acral erythema, considered one of the necrolytic erythemas, is a cutaneous manifestation of hepatitis C virus infection. A total of nine cases have been reported in the literature, seven from Egypt and two from the United States. All reported patients have been hepatitis C positive. This case represents the third reported patient from the US with necrolytic acral erythema.     

Normal instability of the hip in the neonate: US standards

In recent years, the use of real-time ultrasonography (US) has enabled dynamic evaluation of the infant hip through a range of motion and stress. Preliminary experience has suggested that a certain amount of instability in the hips of newborns is normal, but no standards have been established. In this study, a group of term neonates whose physical examinations were normal were examined with US on the 1st and 2d days of life. Each hip was imaged in the transverse plane in nonstressed and stressed positions, and movement of the femoral head under stress was quantitated. This displacement under stress was used to establish a normal range of hip instability in neonates. Patterns of hip laxity in boys and girls are identical, and in most infants hip instability diminishes between the 1st and 2d days of life. Our method of quantitating hip instability produces consistent results, with intraobserver 95% confidence intervals of +/- 1.2 mm for each measurement.