The relationship between haptoglobin polymorphism and serum ceruloplasmin ferroxidase activity.

The antioxidative potential of haptoglobin is type dependent; Hp2-2 has much lower antioxidative capacity than Hp1-1 or Hp2-1. It is therefore possible that other antioxidants may compensate for decreased antioxidative capacity in Hp2-2 individuals. Haptoglobin polymorphism was correlated with ceruloplasmin ferroxidase activity in a sample population of unrelated black Jordanians. Hp2-1 was the predominant type, occurring at a frequency of 0.518 and Hp2 was the common allele, occurring at a frequency of 0.6455; no Hp0-0 individuals were observed in the sample population. In general, haptoglobin concentration was highest among Hp1 homozygotes and lowest among Hp2 homozygotes, while ceruloplasmin ferroxidase activity was highest among Hp2 homozygotes and lowest among Hp1 homozygotes. Furthermore, ceruloplasmin ferroxidase activity was higher at haptoglobin concentrations >85 mg/dl compared with that at haptoglobin concentrations of 30-85 mg/dl, which was also higher than at haptoglobin concentrations <30 mg/dl, irrespective of haptoglobin type. These results suggest that ceruloplasmin ferroxidase activity is both haptoglobin type and concentration dependent.

Endocarditis due to Streptococcus acidominimus.

It has been reported in recent years that the causative microorganisms, affected population, and clinical presentation of infective endocarditis have changed. We report on a 15-year-old boy with ventricular septal defect who was diagnosed with Streptococcus acidominimus endocarditis.

Age group-associated variations in the pattern of Hp type distribution in Jordanians.

The relationship between haptoglobin (Hp) type and life expectancy was investigated by determining the pattern of Hp type distribution in 790 unrelated Jordanians divided into four age groups: A (1-19 years), B (20-39 years), C (40-59 years) and D (60-85 years). While the frequency of Hp 2-2 gradually decreased from 0.576 in A to 0.393 in D, the frequency of Hp 2-1 gradually increased from 0.348 in A to 0.526 in D. Hp2 allele decreased from 0.750 in A to 0.656 in D while that of Hpl allele increased from 0.250 in A to 0.344 in D. Hp type distribution in A, B and D age groups was in agreement with the Hardy-Weinberg equilibrium (HWE). These findings demonstrate that the pattern of Hp polymorphism varies in different age groups, indicating that life expectancy might be Hp phenotype-associated. Additionally, the results suggest that Hp 2-2 phenotype might be an age-associated risk factor.

The prevalence of type II diabetes mellitus is haptoglobin phenotype-independent.

Haptoglobin (Hp) phenotype distribution and the association between Hp polymorphism and type II diabetes mellitus was investigated in a Jordanian sample population consisting of 618 nondiabetics and 265 diabetics. In nondiabetics, Hp 2-2 was the most predominant type occurring at a frequency of 0.529 followed by Hp 2-1 occurring at a frequency of 0.387. In diabetics, the Hp 2-2 frequency was 0.540 while that of Hp 2-1 was 0.381. No statistically significant variation was detected in Hp type distribution between the two groups. The Hp2 allele occurred at a frequency of 0.722 in nondiabetics and 0.730 in diabetics. In both groups, the Hp type distribution was in agreement with the Hardy-Weinberg equilibrium calculations. These results suggest that type II diabetes mellitus is Hp phenotype-independent.

Kawasaki disease: a diagnostic challenge.

Kawasaki disease (KD) is an acute, self-limited, febrile, multi-system vasculitis that predominantly affects the the pediatric population, and is the leading cause of acquired heart disease in children. No etiologic agent for the disease has been identified, there are no diagnostic tests available, and the diagnosis is established by fulfilling a defined set of clinical criteria. We report on a 9-year-old boy who presented initially with symptoms felt to represent a streptococcal infection. He was subsequently shown to meet the criteria for KD, developed cardiac complications of the disease and subsequently demonstrated recovery over a year's period of time. The diagnostic criteria for KD, differential diagnosis, pitfalls in diagnosis, therapeutic recommendations and outcomes are discussed with relevance to this case. Recent print and electronic information sources and references are provided.

Case series: clonidine has no systematic effects on PR or QTc intervals in children.

This study retrospectively examined the effects of clonidine, both alone and combined with psychostimulants, on the electrocardiograms (ECGs) of children and adolescents. Two pediatric cardiologists, blinded to treatment condition, examined pre- and posttreatment ECGs in 42 subjects treated with clonidine for attention-deficit/hyperactivity or tic disorder. While ECG variability was found, it did not appear to be related to any systematic effect of clonidine, either alone or in combination with psychostimulants. These data do not rule out the possibility of rare idiosyncratic reactions to clonidine with or without psychostimulants, though none occurred in this sample.

A possible clonidine-trazodone-dextroamphetamine interaction in a 12-year-old boy.

A 12-year-old boy on a dextroamphetamine-clonidine-trazodone treatment regimen had a recurrence of insomnia, and his bedtime trazodone dose was doubled from 50 mg to 100 mg. Within 45 mins after taking the first 100-mg trazodone dose on an empty stomach, the patient had a syncopal episode associated with hypotension, bradycardia, and sedation. The drug reaction could have resulted from either trazodone or clonidine, but it is more likely to have resulted from a pharmacodynamic clonidine-trazodone interaction, presumably aggravated by rapid absorption (on an empty stomach) of a recently increased dose of trazodone. It is conceivable but less likely that the psychostimulant was a clinically significant factor. However, a drug interaction between clonidine and D-amphetamine does not need to be postulated to explain this child's syncopal reaction. The authors advise that (1) if trazodone and clonidine are used concurrently, the doses of both agents should be changed slowly, (2) blood pressure and pulse should be carefully monitored at baseline and then periodically during treatment, and (3) administration of trazodone on an empty stomach, and especially dose increases on an empty stomach, should be avoided. Physicians should remain aware that trazodone has the potential to produce hypotension and sedation, especially when combined with other agents (such as clonidine) that might produce the same adverse effects.

Intrauterine infection with coxsackievirus: is it a cause of congenital cardiac malformations?

BACKGROUND: Although maternal infections with coxsackievirus during pregnancy are relatively common, fetal infections are quite rare. Coxsackievirus infection in utero has been associated with myocarditis, but has not been proven a teratogen. CASE: A patient whose fetus had structural cardiac anomalies and hydrops was found to have an intrauterine infection with Coxsackie B-1 virus, proven by virus isolation from the amniotic fluid. This infection led to increasing intrauterine hydrops and subsequent neonatal death. CONCLUSION: This interesting association of intrauterine infection with Coxsackie B virus and structural cardiac anomalies in the fetus warrants further investigation.

The changing pattern of infective endocarditis in childhood.

Forty-eight cases of infective endocarditis (IE) that occurred in 42 patients with congenital heart disease were reviewed from 1970 through 1990 and were compared with a 20-year review of 108 cases diagnosed between 1953 and 1972. The review demonstrates that the natural history of IE in children has changed over the last 2 decades, with half of the cases occurring after surgery for congenital heart disease. In the postoperative group, 46% of patients had undergone valve replacement and 7 of these (29%) had a right ventricular to pulmonary artery valved conduit as the site for IE, suggesting significant additional risk in this setting. Among patients with nonsurgically treated congenital heart disease and IE, mitral valve prolapse has emerged as an important underlying heart lesion occurring in 29% of patients. The bacterial spectrum has shifted, with a significant increase in the incidence of uncommon causative organisms. Mortality has continued to decline with survivorship of 90% in this series.

Sites of preferential induction of cyclobutane pyrimidine dimers in the nontranscribed strand of lacI correspond with sites of UV-induced mutation in Escherichia coli.

An approach utilizing fluorescence-activated DNA sequencing technology was used to study the position and frequency of UV-induced lesions in the lacI gene of Escherichia coli. The spectrum of sites of UV damage in the NC+ region of the gene was compared with a published spectrum of UV-induced mutation in lacI (Schaaper, R.M., Dunn, R.L., and Glickman, B.W. (1987) J. Mol. Biol. 198, 187-202). On average, the frequency of UV-induced lesions in the nontranscribed strand was higher than that in the transcribed strand in the region analyzed. A large fraction of mutations occurs at sites of UV-induced lesions in the nontranscribed strand, but not in the transcribed strand. This bias is reduced in an excision repair deficient (UvrB-) strain. In addition, mutations occur overwhelmingly at sites where a dipyrimidine sequence is present in the nontranscribed strand. This bias is also markedly reduced in the UvrB- strain. In light of recent work Mellon and Hanawalt (Mellon, I., and Hanawalt, P.C. (1989) Nature 342, 95-98) describing the preferential removal of cyclobutane dimers from the transcribed strand of the expressed lacZ gene in E. coli, our data suggest that preferential strand repair may have a significant effect on mutagenesis.

Colony hybridisation in Escherichia coli: a rapid procedure for determining the distribution of specific classes of mutations among a number of preselected sites.

Colony probe oligonucleotide hybridisation was used for the unambiguous identification of DNA alterations and the determination of distributions and frequencies of forward mutation at the molecular level. To demonstrate the reliability and versatility of this technique, distributions of spontaneous and ethyl methanesulfonate (EMS)-induced mutations have been reproduced using a battery of oligonucleotide probes complementary to specific sites and classes of mutation. These studies are indicative of the diagnostic potential of oligonucleotide colony hybridisation to the characterisation of mutation; oligonucleotide hybridisation used in conjunction with a well studied mutational target provides a rapid and reliable alternative to DNA sequencing for the characterisation of all classes of mutations.