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The survival rate of very preterm, low birth weight infants (weighing less than 1500 g) is 85 per cent in the USA and is ever increasing, while 42 to 75 per cent of extremely premature infants (weighing 751-1000 g) survive. Of great concern is the lack of consistent decrease in neurological syndromes and associated visual impairments. Because of short gestations, these infants have not had time to accrue up to 80 per cent of magnesium normally present at term. These very preterm infants are at highest risk for cerebral hypoxia/ischemia (H/I), intracranial hemorrhage (ICH), periventricular leukomalacia (PVL) or cystic PVL (CPVL), and possible sequelae, cerebral palsy (CP) and mental retardation (MR). These syndromes are associated with damage to optic structures and the visual pathways which traverse the brain. Visual defects are common in surviving preterm infants. Increased levels of harmful neurochemical mediators that have been reported in these conditions include oxygen free radicals, excitatory amino acids, tumor necrosis factor-alpha (TNF-a), and thromboxane A2 (TXA2) which are aggravated in magnesium deficiency and may be ameliorated by magnesium. We review the published data concerning the effects of prenatal magnesium supplementation on ICH, CPVL, CP and MR and available reports concerning survival. Further considerations on the safety and efficacy of magnesium sulphate administration given prenatally to the preterm neonate await the outcome of three trials that are continuing for more than a year on three continents.

Objective: Status asthmaticus with respiratory failure is a potentially fatal complication of bronchial asthma. To prevent a fatality in status asthmaticus with respiratory failure, treatment with intravenous isoproterenol or mechanical ventilation has been advocated. These interventions also have serious potential complications, however, and while continuous inhalation of beta agonists has shown promise, the optimal therapy of severe status asthmaticus remains unclear. This paper describes our experience with a treatment protocol used in status asthmaticus with respiratory failure that seeks to avoid intravenous isoproterenol or assisted ventilation., Study Design: Case series of pediatric intensive care patients with severe respiratory failure due to status asthmaticus. Six children and adolescents experienced a total of nine episodes of severe respiratory failure due to status asthmaticus., Results: In seven of the nine episodes the patients were managed without either intravenous isoproterenol or mechanical ventilation. Hypercarbia persisted for an average of 25 hours (range 17 to 40 hours) in these seven episodes. All subjects recovered without notable sequelae. In two episodes, clinical and blood gas deterioration led to mechanical ventilation. Ventilation was required for 112 and 42 hours, respectively, in these episodes and the patients developed either pneumothorax or pneumomediastinum during ventilation., Conclusion: Using a protocol initiated in 1978 for correction of hypoxia and acidemia, many patients with severe respiratory failure from status asthmaticus can be treated without isoproterenol or mechanical ventilation. Since those treatments have significant risks, consideration should be given to this intervention before resorting to them.

A double-blind, placebo-controlled trial was undertaken to assess the safety and efficacy of once daily cetirizine in alleviating the symptoms of perennial allergic rhinitis. Subjects were adults with perennial allergic rhinitis, characterized by nasal congestion, postnasal discharge, sneezing, rhinorrhea, nasal itching, lacrimation, ocular itching, and itching of the roof of the mouth, and a total pretreatment symptom severity score of greater than or equal to 8. Patients were randomized to treatment with 10 mg cetirizine, 20 mg cetirizine, or placebo for 4 weeks. Efficacy was assessed in 215 patients and safety in 216. Cetirizine in once daily dosages of 10 or 20 mg proved to be effective in relieving the overall symptoms of perennial allergic rhinitis and particularly postnasal discharge and sneezing. The 10-mg dose afforded optimal symptomatic relief, and the 20-mg dose provided little or no additional benefit. Cetirizine was well tolerated, and the frequency of somnolence was not significantly greater in patients receiving this drug than in those given placebo.

The safety and efficacy of pentigetide (Pentyde) nasal solution, administered as 1 mg into each nostril four times daily, was compared with placebo for controlling symptoms associated with seasonal allergic rhinitis. This was a randomized, multicenter, double-blind, parallel-group trial involving 431 patients divided equally between pentigetide and placebo treatment. The study was conducted during the 1986 spring allergy season and consisted of 1 week of baseline followed by 2 weeks of treatment. Physicians evaluated the frequency and severity of nasal symptoms at study entry (day 1) and the final visit (day 22). Physicians and patients assessed the global condition of the patient at the end of the study and patients also recorded the severity of symptoms in a daily diary. Pentigetide-treated patients showed a statistically significant greater reduction in the frequency (P = .004) and severity (P = .05) of total nasal symptom score (sneezing, nasal congestion, and rhinorrhea) and in the individual nasal symptom scores compared with placebo-treated patients. Diary results showed consistently lower total nasal symptom scores on each treatment day for pentigetide-treated patients (P = .02). Both the physicians and patients globally rated more pentigetide-treated patients improved than placebo-treated patients. The incidence and types of adverse experiences were similar between treatment groups and there were no reports of sedation or fatigue in the pentigetide group. No clinically significant changes occurred for laboratory tests, physical examination parameters or vital sign measurements. Pentigetide nasal solution was safe and effective for the treatment of seasonal allergic rhinitis.

An improved and simplified high-performance liquid chromatographic method is presented for the simultaneous determination of theophylline and dyphylline in serum. The internal standard, beta-hydroxyethyltheophylline (20 microliters of a 100 micrograms/ml solution) is added to 50 microliters of serum. Serum proteins are precipitated by the addition of 30 microliters of 40% trichloroacetic acid solution. The mobile phase consists of a sodium acetate buffer with 6% acetonitrile. Chromatogram run time is 6 min. The sensitivity limit for both compounds is 0.25 micrograms/ml. This method is interference-free from the major metabolites of theophylline and other drugs commonly coadministered with theophylline.

Recertification offers a method of evaluating a diplomate's cognitive knowledge of allergy and immunology. In 1983 candidates for the American Board of Allergy and Immunology recertification examination were offered the entire certifying examination but were informed that they would, for recertification purposes, be held responsible only for a subset of questions judged to be particularly clinically relevant. All 40 candidates elected to take the entire certifying examination. Differences between the performance of certifying and recertifying candidates on the recertifying questions were small. Except for the five-choice questions, the differences in performance between the two groups on the remaining questions were also small in an absolute sense. Recertification performance was not related to the time of original certification. Ninety-eight percent of the candidates completed a questionnaire after the examination. Ninety percent stated that they would encourage their colleagues to participate in the recertification process.

A girl had opportunistic infections and was found to have T-cell dysfunction. During a period of months, recurrent staphylococcal infections, polyclonal hyperglobulinemia, eosinophilia, and peripheral, necrotizing, cutaneous lesions developed. Circulating immune complexes were demonstrated, and abnormal suppressor-cell function was found. At age 36 months, the child died of a staphylococcal pneumonia. At postmortem examination, the thymus gland was found to be histologically abnormal, lacking corticomedullary differentiation. We propose that this patient had a syndrome in which lymphocyte abnormalities and dysfunction of suppressor T cells permitted hyperresponsiveness of antibody-forming cells. Large amounts of circulating antibody and immune complexes were formed, and their deposition led to peripheral tissue injury.

The IgG antibody (Ab) response achieved with specific venom immunotherapy was explored in 32 patients with Hymenoptera hypersensitivity. Venom-specific IgG Ab was quantitated before and after 1 year of immunotherapy using two solid phase radioimmunoassay (SPRIA) methods. An agarose-based test using 125I-Staphylococcus aureus Protein A (SPRIA) was used to determine specific IgG for five Hymenoptera species: yellow jacket (YJ), honeybee (HB), yellow-faced hornet (YH), white-faced hornet (WFH), and Polistes (POL). A cellulose disk test using 125I-anti-IgG (IgG RAST) was available only for YJ and HB venoms. Acceptable agreement (90% concordance) was observed with IgG anti-HB levels measured in the two assays. For the YJ-IgG, however, 17/69 (25%) of sera positive in the SPRIA were negative in the IgG RAST, whereas the converse was not observed. This result suggests that the IgG RAST is insufficiently sensitive to detect YJ-IgG responses in all patients on maintenance level immunotherapy. Using the Protein A SPRIA, there was excellent agreement between the venom used for immunotherapy and the specificity of the IgG Ab response. In 31 patients treated with a total of 90 venom species, 90/90 venom IgG levels were increased or maintained at high pretreatment levels in response to immunotherapy. In the same patients venom IgG levels obtained for venom species not included in therapy were undetectable or declined in 55/60 cases; in 4 cases treatment with YJ venom stimulated a WFH and/or YH IgG response, the remaining case, YJ venom stimulated a small rise in POL IgG. These apparent discrepancies can be explained by variable cross-reactivity among vespid and POL venoms. Among 32 patients with a combined total of 87 positive venom skin tests, 1 year of specific immunotherapy resulted in greater than 5 micrograms/ml of venom-specific IgG in 61 instances. In 25 instances, the level of venom IgG was detectable but less than 5 micrograms/ml, and in 1 case venom IgG could not be detected. Based on recent analyses by Golden et al., some or all of these latter 26 cases may represent suboptimal therapy despite a standard immunotherapy regimen. We conclude that venom IgG measurements can provide a specific and quantitative assessment of the immunologic response to venom therapy, and that such assessment may be clinically useful in detecting instances of suboptimal immunotherapy.

A six-year-old girl with sickle cell disease and severe asthma was treated for status asthmaticus on several occasions. Sickle cell crises appeared to be precipitated by the asthmatic episodes. The interactions between these two disease processes are discussed and a treatment protocol for the rare patient with both of these diseases is proposed.

This manuscript presents a four year follow-up of a review of the issues in the management of status asthmaticus that are often controversial. A combination of previous considerations and experience is mixed with a review of the recent literature to formulate current recommendations. The reasons to use epinephrine, sodium bicarbonate, theophylline, corticosteroids, oxygen, hydration, intravenous adrenergic agents and controlled ventilation are discussed. Death from status asthmaticus should be preventable.

Honey bee and vespid venom immunotherapy have been practiced for the past 10 years. Several studies have evaluated the short-term effects of this therapy. The current study evaluated the long-term effects using venom-specific IgG4 determinations. Forty-six patients ranging in age from 3 to 67 years were followed for periods up to 6 1/2 years. All patients included in the study demonstrated Hymenoptera sensitivity on intradermal testing using 0.2 mL of venom extract at concentrations of 0.01 microgram/mL, 0.1 microgram/mL, or 1 microgram/mL. IgE-specific venom antibody levels were tested and found to be elevated. During the first year following institution of venom immunotherapy, 46/46 patients demonstrated an increase in venom-specific IgG4. After the first year of treatment, values reached a plateau. The IgG4 venom-specific antibodies remained relatively constant over the second and third years of the study. Thirty of the 46 patients were followed for more than 3 years. All of the 30, treated greater than 3 years with continuous immunotherapy, demonstrated a gradual decline in IgG4 levels. Despite very low or negligible levels of venom-specific IgG4 antibodies, six patients accidentally stung were still clinically protected. This study suggests that long-term immunity is not mediated in the same manner as that of short-term protection.

To assess interrelationships between asthma, corticosteroid therapy, growth, and zinc status in children, measurements of height, zinc and copper in serum and hair, taste acuity, and dietary intakes of energy, protein, zinc,and copper were analyzed for 29 asthmatic, 11 prednisone-treated asthmatic, and 21 non-asthmatic subjects, 6 to 20 years old. Reduced height attainment was significant only for the prednisone-treated asthmatic group and was not correlated with clinical or dietary indexes of zinc status. Dietary intake data were similar for all three groups; in comparison with the RDAs, daily intakes were adequate for both energy and zinc (80% to 90%), high for protein (185% to 225%), and low for copper (35% to 60%). Results confirmed earlier reports of growth retardation in corticosteroid-treated asthmatics; significant indications that reduced food intake or impaired zinc status played a major part were not evident.

Ten ambulatory subjects with asthma experienced a seizure while they were receiving oral theophylline preparations and were evaluated prospectively according to a set protocol. The protocol included a lumbar puncture that permitted the simultaneous determination of plasma and cerebrospinal fluid (CSF) theophylline concentrations. A constant relationship was observed between the plasma theophylline concentration and that of the CSF. It was found that the theophylline concentrations in these two biologic fluids could be characterized by the regression equation y = 0.41 X + 0.7 where y is the CSF theophylline concentration and X is the plasma theophylline concentration. Two infants with hydrocephalus treated by ventriculoperitoneal shunt were also simultaneously evaluated for plasma and CSF theophylline concentrations. These infants demonstrated greater than expected entry of theophylline into the CSF. Some central nervous system abnormalities may be characterized by increased theophylline entry into the CSF.

A high-performance liquid chromatographic technique is presented for simultaneous determination of theophylline, 3-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid and caffeine in serum using beta-hydroxyethyltheophylline (BHET) as an internal standard. An aliquot of a serum sample (100 microliters) was added to 40 microliters of an internal standard solution (BHET; 100 micrograms/ml) and vortexed. A 20% trichloroacetic acid solution (60 microliters) was then added; the mixture was vortexed, centrifuged and 100 microliters were injected onto a C8 column maintained at 45 degrees C. Inter- and intra-day variability of the assay for all compounds was less than 4.3%. Sensitivity ranged from 10 ng/ml for 1-methyluric acid to 25 ng/ml for theophylline. Drugs commonly coadministered with theophylline did not interfere with the assay.

Slit-lamp examinations were performed on 24 children and adolescents with severe asthma, all of whom had received steroids for at least 365 days. Posterior subcapsular cataracts (PSCC) were detected in 7 (29.1%). None of the patients had been treated with beclomethasone. All 7 of the patients with PSCC were in the subgroup of 14 patients who had been on the highest doses of corticosteroid, 10 mg or more per day, for the longest period of time. The 7 children with PSCC were all below the fifth percentile for height and had fallen away from their normal growth curve. Of the 17 children in whom PSCC were not detected, only 1 was below the fifth percentile for height. It would seem from our results that the steroid-requiring asthmatic who is growth-suppressed is at an increased risk for developing PSCC. We have documented the reversal of PSCC in 2 children. Both of these children had been placed on beclomethasone, which allowed for the discontinuation of daily prednisone in one case and a reduction to less than 10 mg per day of prednisone in the other. The reversal occurred within 6 months of starting on beclomethasone.

A high-performance liquid chromatographic technique is presented for the simultaneous determination of theophylline, 3-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid, and caffeine in urine using beta-hydroxyethyl theophylline (BHET) as an internal standard. Following centrifugation of the sample, 2 mL of urine was placed onto a Sep-Pak C18 cartridge (Waters Associates, Milford, MA, USA) that was prepared with 5 mL of methanol followed by 10 mL of distilled water. The compounds were eluted with 2.5 mL of a methanol:water (50:50) mixture. An aliquot of the filtered urine sample (100 microL) was added to 40 microL of an internal standard solution (BHET; 100 micrograms/mL). Distilled water (60 microL) was added to yield a volume of 200 microL. The mixture was vortexed and centrifuged, and 100 microL was injected onto a C8 column maintained at 55 degrees C. Inter- and intraday variability of the assay for all compounds was less than 5.7%. Sensitivity ranged from 0.10 microgram/mL for caffeine to 0.68 microgram/mL for 1-methyluric acid. Drugs commonly coadministered with theophylline did not interfere with the assay.

Recent reports note decreased T cell function in association with certain atopic conditions in man. This study was performed to determine whether numbers of circulating T cells are decreased in atopic children and adolescents in comparison with nonatopic age-matched control subjects. The subjects were not selected on the basis of a particular atopic diagnosis, but relatively more had allergic rhinitis and/or asthma (52) than had atopic eczema (7). Numbers of circulating T cells were not found to be significantly different in allergic children aged 2 to 10 yr than in control subjects. Atopic children and adolescents over age 10 yr had significantly fewer T cells in relative percentages (p less than 0.05), but when absolute numbers were considered significance was lost. Atopic children aged 2 to 10 years had significantly more B cells in both relative percentages and absolute numbers than did control subjects (p less than 0.02 and p less than 0.05, respectively). When those subjects treated with corticosteroids were separated from the total atopic group, there were no significant differences between the atopic and control subjects. The effects of corticosteroids, bronchodilators, antihistamines, and immunotherapy were considered and could be shown to produce no consistent effect on lymphocyte subpopulations.

The disposition of theophylline was examined in seven children with asthma on two occasions before and on one occasion after chronic phenobarbital dosing (2 mg/kg/day). There was little intrapatient variability in apparent theophylline clearance between the two baseline assessments (0.081 versus 0.073 L/hr/kg). After 19 days of phenobarbital therapy, there was a significant increase in apparent theophylline clearance (0.104 versus 0.077 L/hr/kg), accompanied by a 30% decrease in the mean steady-state serum theophylline concentration (12.0 versus 8.4 micrograms/ml). The inducing effect of phenobarbital on theophylline metabolism may require theophylline dosage adjustment in patients with asthma who receive both drugs concurrently to maintain a given average steady-state theophylline concentration.

Several reports have suggested that asthmatic children may be particularly vulnerable to viral respiratory infections, in addition to this, abnormal cellular regulation has been suggested as an explanation for the increased IgE levels in atopy. Despite such evidence there have been few studies evaluating cellular immune function in asthmatic children. This study has examined in vivo and in vitro aspects of cellular immune function in twenty-six atopic asthmatic children and compared them with nineteen age-matched non-atopic control subjects. In vivo cellular immunity was assessed by quantitating the cutaneous delayed hypersensitivity (CDH) response to four ubiquitous antigens. Lymphocyte responsiveness to three polyclonal mitogens was measured in vitro. The serum IgE level was determined in all study subjects. The results indicate that CDH to Candida antigen is significantly diminished among the asthmatic subjects and lessened to streptokinase/streptodornase. Lymphocyte mitogen response did not differ significantly between the study groups. No correlation could be shown between in vitro lymphocyte responsiveness and IgE level. These studies suggest that a subtle cellular immune defect may exist in asthmatic children and support the need for further studies of this question.

Diphtheritic neuritis was produced in rabbits and guinea pigs by injection of underneutralized toxin-antitoxin mixtures. The disease is a progressive, ataxic paresis related in severity to the dose of injected toxin-antitoxin. Cerebrospinal fluids of rabbits with this disease showed "albuminocytologic dissociation" similar to that found in the same disease in man. Histologically the disease is a progressive demyelination of the peripheral nervous system, un-accompanied by axis cylinder damage or inflammation. It involves the spinal roots and sensory ganglia in the rabbit, the peripheral nerves in the guinea pig. Diphtheritic neuritis can be distinguished from experimental allergic neuritis in the rabbit and guinea pig on both clinical and histological grounds. The rabbit disease is however an excellent model of diphtheritic neuritis in man. In the animals with diphtheritic neuritis, studied in the present work, there was vigorous production of circulating antitoxin and infrequently complement-fixing antibody to horse serum proteins. No antibody against rabbit spinal cord or sciatic nerve was demonstrated. Skin reactivity to both rabbit nerve suspension and diphtheria toxoid was present at 1 to 2 weeks following inoculation and reached a maximum well before the peak of antitoxin response. These reactions did not seem to be typical delayed reactions. No correlation existed between the development of diphtheritic polyneuritis and any of these immunologic events or the circulating complement level, either in time or in degree. Treatment of rabbits with 400 r whole body irradiation 48 hours before inoculation resulted in severe leukopenia lasting about 3 weeks, delay of antitoxin formation with considerable reduction of peak titers, and some decreased skin reactivity to toxoid. It had no effect on the disease process. It is concluded that diphtheritic polyneuritis is produced by a non-immunologic mechanism, e.g., direct toxicity.