Maurice Levy

Outcome after maternal varicella infection in the first 20 weeks of pregnancy.

BACKGROUND Infection with the varicella-zoster virus during pregnancy can produce an embryopathy characterized by limb hypoplasia, eye and brain damage, and skin lesions. The risk is greatest when infection occurs during the first 20 weeks of pregnancy, but the magnitude of the risk is uncertain. METHODS We studied 106 women with clinically diagnosed varicella infection in the first 20 weeks of pregnancy and compared the outcomes with those in 106 age-matched, nonexposed controls. RESULTS Among the women with varicella, there was a trend toward more elective terminations of pregnancy (14 percent, vs. 7.5 percent among the controls; P = 0.1), corresponding to a significantly higher perception of teratogenic risk (P = 0.03). The proportions of miscarriages and live births and the mean birth weights were similar in the two study groups; there were more premature births (< or = 37 weeks) among the women with varicella infection (14.3 percent vs. 5.6 percent, P = 0.05). Congenital defects occurred in four infants born to the women with varicella (varicella embryopathy, hydrocephalus, meningocele and clubfeet, and hammer toe) and two infants born to the controls (ventricular septal defect and hip dislocation). The risk of varicella embryopathy after infection in the first 20 weeks was 1.2 percent (95 percent confidence interval, 0 to 2.4 percent). When we pooled our results with those from other prospective studies, the mean risk of embryopathy after infection with varicella-zoster virus in the first trimester was 2.2 percent (95 percent confidence interval, 0 to 4.6 percent). CONCLUSIONS The absolute risk of embryopathy after maternal varicella infection in the first 20 weeks of pregnancy is about 2 percent.

Colchicine: a state-of-the-art review.

Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule‐dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3′,5′‐adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half‐lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine‐induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long‐term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Downs syndrome, the agent should not be used by pregnant women.

Tissue plasminogen activator for the treatment of thromboembolism in infants and children

We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding.

Propylthiouracil Hepatotoxicity A Review and Case Presentation

Propylthiouracil (PTU) is widely used to treat patients with hyperthyroidism. In rare cases, this drug has been found to have severe toxic effects on the liver. The case of a 14-year-old girl treated with PTU for hyperthyroidism who developed jaundice, severe hepatocellular dysfunction, and hepatomegaly is reported. Her condition gradually deteriorated, and she developed paranoid ideation, profound lethargy, and peripheral edema. After three weeks of prednisone therapy, clinical and laboratory signs of improvement were observed. This patient was one of only five pediatric cases among the 16 reported cases of PTU liver toxicity reported to date. Her history and the fatal outcome in some reported cases demonstrate the high degree of sensitivity required to recognize this potential complication in patients treated with PTU, particularly since its immediate discontinuance and steroid-therapy intervention may lead to recovery.

Neonatal withdrawal syndrome: associated drugs and pharmacologic management.

Use of addicting drugs among women during pregnancy exposes newborns to potentially serious disorders. A group of symptoms referred to as neonatal withdrawal syndrome (NWS) may occur in infants born to mothers addicted to certain drugs because, at birth, the infants suddenly are cut off from the drug supply. Classes of drugs that cause NWS are those that produce addiction in adults, including the opioids (heroin, methadone, morphine), barbiturates, alcohol, and benzodiazepines. Many of the manifestations of NWS occur regardless of the class of drug, including irritability, hyperactivity, abnormal sleep pattern, high‐pitched cry, tremor, vomiting, diarrhea, weight loss, and failure to gain weight. The fact that these symptoms are nonspecific makes it difficult to identify NWS unless it is specifically looked for. The onset, duration, and severity of the disorder differ based on such factors as the addictive drug used, time and amount of mothers last dose, and rate of elimination of the drug from the newborn. Pharmacologic intervention may be required to control severe symptoms and signs. The most common drugs used to modify withdrawal are phenobarbital, paregoric, chlorpromazine, and diazepam. Treatment is complicated by conflicting information on the effectiveness of various agents.

Mycoplasma Pneumoniae Infections and Stevens-Johnson Syndrome Report of Eight Cases and Review of the Literature

On the basis of a literature review and eight cases of our own, we analyzed 37 cases of Mycoplasma pneumoniae (MP) infection and Stevens-Johnson syndrome (SJS). Our clinical and laboratory findings do not differ from those reported in the literature for MP infection with no exanthem or for SJS of various etiologies. Eighty percent of the children presented with symptoms of upper respiratory tract infection (URTI) (cough, fever, sore throat, malaise, headache), with a mean of 10 days (range 1 to 30) before skin rash broke out. Skin manifestations occurred in 94.2% of the patients after 3 to 21 days (mean 10.3 days) of fever. The exanthem, composed predominantly of maculopapular and vesicular, was distributed chiefly on the trunk and extremities and lasted less than 14 days in 87.8% of the patients. Stomatitis was observed in 91.6% of the patients and conjunctivitis in 50%. No consistent pattern seems to emerge by which one could predict the existence of MP infection causing SJS. The complications of SJS associated with MP seem less frequent (2.7%) and much less severe than in cases where SJS arises from other reported causes. Because coincidence cannot be excluded from the assessments of the degree and rate of improvement for the few patients treated with corticosteroid, from the low frequency of complications, and from the mortality rate of zero in this series of patients, the use of corticosteroids for SJS associated with MP infection is questionable.

Diseases That Mimic Meningitis Analysis of 650 Lumbar Punctures

A retrospective review of charts for 650 children who had lumbar puncture for suspected meningitis was undertaken to determine the characteristics of patients with and without meningitis, identify other conditions suggesting meningitis, and evaluate the predictive value of signs and symptoms of meningitis. The incidence of positive lumbar punctures increased with patient age. Younger infants did not present with classical features of meningitis. Bulging fontanel, lethargy, and irritability were nonspecific symptoms. Vomiting and headache, although not specific, proved to be more sensitive indicators of meningeal infection. Most patients with meningitis (75%) had at least one sign of meningeal irritation, but so did 25% of patients without meningitis. Brudzinskis sign was not specific. In contrast, nuchal rigidity and Kernigs sign had high predictive value. Up to age five, the diseases most often suggesting meningitis were right-sided pneumonia, gastroenteritis, otitis, tonsillitis, exanthema subitum, and urinary tract infections. Of 171 patients with febrile convulsion, one (0.5% ) had bacterial meningitis and four had aseptic meningitis.

Xanthogranulomatous Pyelonephritis in Children Etiology, Pathogenesis, Clinical and Radiologic Features, and Management

matous pyelonephritis was likely first described by Schlagenhaufer’ in 1916, and the term itself was coined by Osterlind’ in 1944. It is a chronic inflammatory lesion of the kidney characterized by destruction of the renal parenchyma, which is replaced by granulomatous tissue containing lipid-laden macrophages (foam cells). Once regarded as uncommon, the condition has been reported with increasing frequency in the last few

Simple measurement of captopril in plasma by high-performance liquid chromatography with ultraviolet detection.

Captopril is an orally active inhibitor of angiotensin-converting enzyme. A rapid, accurate, and sensitive high-performance chromatography (HPLC) method is described for measuring plasma concentrations of captopril. Captopril was stabilized by forming an adduct with p-bromophenacyl bromide. This adduct was measured by HPLC using a C-18 reverse-phase column and monitoring the column effluent by ultraviolet absorption at 260 nm. The method proved to be linear in the clinical range of 10–1,000 ng/ml. The plasma levels of captopril in a young patient given a small oral dose were determined by this method.

Diseases That Mimic Meningitis

A retrospective review of charts for 650 children who had lumbar puncture for suspected meningitis was undertaken to determine the characteristics of patients with and without meningitis, identify other conditions suggesting meningitis, and evaluate the predictive value of signs and symptoms of meningitis.The incidence of positive lumbar punctures increased with patient age. Younger infants did not present with classical features of meningitis. Bulging fontanel, lethargy, and irritability were nonspecific symptoms. Vomiting and headache, although not specific, proved to be more sensitive indicators of meningeal infection. Most patients with meningitis (75%) had at least one sign of meningeal irritation, but so did 25% of patients without meningitis. Brudzinskis sign was not specific. In contrast, nuchal rigidity and Kernigs sign had high predictive value. Up to age five, the diseases most often suggesting meningitis were right-sided pneumonia, gastroenteritis, otitis, tonsillitis, exanthema subitum, and...