Iloprost treatment for refractory Raynaud's phenomenon in two infants.

Raynaud's phenomenon (RP) is rare in young children. We describe two infants with severe RP, manifesting as fingertip necrosis, who were resistant to conventional vasodilators and were treated successfully with iloprost, a prostacyclin analogue. The application of iloprost is safe and should be considered in children with threatening ischemic digits.

Treatment of Achilles tendon calcinosis in juvenile dermatomyositis with external ilizarov fixator.

Calcinosis is a devastating complication of juvenile dermatomyositis and a challenging therapeutic problem. We report the use of an external Ilizarov fixator for the treatment of Achilles tendon calcinosis causing severe disability in a young girl with juvenile dermatomyositis.

Protracted febrile myalgia in children and young adults with familial Mediterranean fever: analysis of 15 patients and suggested criteria for working diagnosis.

OBJECTIVES: To present an analysis of patients with protracted febrile myalgia (PFM), a rarely reported manifestation of familial Mediterranean fever (FMF), and propose clinical criteria for working diagnosis. METHODS: A multicenter retrospective cohort study of children with PFM was performed. Clinical and laboratory data were obtained by medical record review. RESULTS: The study group included 15 patients with PFM. PFM occurred as the presenting sign of FMF in 33%. FMF was diagnosed clinically in all and by genetic analysis in 93%. M694V allelic involvement was noted in 93% of the patients. PFM occurred at a mean age of 9 +/- 3.4 years and was characterized by severe generalized muscle pain in all patients and fever in 71%. Mean duration up to diagnosis was 15.5 +/- 6 days. Mean erythrocyte sedimentation rate was 104 +/- 26 mm/h; mean C-reactive protein was 15.4 +/- 6.3 mg%. Creatine kinase was normal. Treatment included corticosteroids (4 patients) and nonsteroidal anti-inflammatory drugs (NSAIDs) (9 patients) with a symptomatic relief achieved at a mean of 7.7 +/- 4.3 days and 5 +/- 3.8 days, respectively (p = 0.14) (mean severity score 3 and 2.2, respectively, p = 0.075). Symptomatic relief in 2 untreated patients was achieved at a mean of 45.5 days. CONCLUSION: Based on our data, we propose criteria for working diagnosis including: severe disabling myalgia of at least 5 days in a young patient with FMF, associated with fever, elevated levels of inflammatory markers and presence of at least one M694V mutation.

Inhibitory diffusible factor IDF45, a G1 phase inhibitor.

An inhibitory diffusible factor of 45 kDa (IDF45) was isolated from medium conditioned by dense cultures of 3T3 cells. The procedure involved Bio-Gel P150 chromatography and 2 reverse-phase FPLC. After the final step of purification, 60 ng/ml of IDF45 inhibited 50% of alpha-globulin-stimulated DNA synthesis. It was shown that IDF45 acted in the G1 phase of the cell cycle. When added for 8 h in the G1 phase of the cell cycle, it was able to inhibit DNA synthesis in the S phase which followed this G1 phase. Furthermore, IDF45 inhibited the early stimulation of RNA synthesis induced by alpha-globulin.

The treatment of rheumatic carditis: a review and meta-analysis.

We performed a meta-analysis of the literature on the treatment of established rheumatic carditis to determine if corticosteroid therapy is superior to salicylates in preventing the sequela of inflammation--valvular damage. We identified 22 reports of comparative trials published since the introduction of corticosteroids in 1949. Five of the 22 studies met the criteria we established for the meta-analysis, which included using randomization and a 1-year follow-up for the presence of a new pathologic apical systolic murmur. Based on the meta-analysis, the advantage of corticosteroid treatment over salicylates in preventing a pathologic murmur at 1 year posttreatment is not statistically significant (estimated odds ratio 0.88; 95% confidence interval: 0.53 to 1.46). However, the meta-analysis is dominated by 1 large negative trial, and there was significant heterogeneity in the results obtained from the studies in the meta-analysis; thus, the question of whether corticosteroid therapy is marginally superior to salicylates for the prevention of valvular heart disease from rheumatic fever remains open.

Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment.

BACKGROUND: Infantile bilateral striatal necrosis (IBSN) encompasses several syndromes of bilateral symmetric, spongy degeneration of the caudate nucleus, putamen, and globus pallidus. The familial form of IBSN is rare, and inheritance is either autosomal recessive or maternal. METHOD: The authors describe an Israeli Bedouin kindred in which 15 children born to consanguineous parents were affected with familial IBSN. They evaluated the clinical and radiologic evolution of the disease in 11 patients and the cerebral pathologic findings in one patient. Three of the children were treated with oral biotin 100 mg/day. RESULTS: Inheritance was apparently autosomal recessive. The untreated children had a similar clinical picture including developmental arrest beginning at the age of 7 to 15 months, choreoathetosis, and dysphagia. Pendular nystagmus appeared at a late stage. MRI, performed at various stages of the disease, showed severe basal ganglia atrophy. Postmortem study in one patient showed severe atrophy of the lenticular nuclei with gliosis and loss of neurons. Biotin, 100 mg/day, administered to the proband over a period of 15 months, may have slowed progression. In two other children treatment was initiated earlier and appeared to arrest or improve disease. CONCLUSIONS: Familial infantile bilateral striatal necrosis was inherited as an autosomal recessive trait. Clinical features included developmental arrest, dysphagia, and choreoathetosis. Imaging and pathology showed atrophy and degeneration of the basal ganglia. Oral biotin may have benefited three children.

Nuclear and mitochondrial origin of rat liver double-stranded RNA.

We have studied the intracellular location of double-stranded RNA from rat liver. The majority of this dsRNA is associated with nuclear and mitochondrial fractions and the remaining portion is associated with microsomes. Mitochondrial dsRNA hybridizes specifically with purified strands of mitochondrial DNA and seems therefore to arise from transcription of the latter. A fraction of nuclear dsRNA hybridizes with repetitive sequences of nuclear DNA. Because of self-hybridization of dsRNA strands, it was not possible to determine whether another fraction of DSRNA is homologous to nonrepetitive sequences of DNA. Both mitochondrial and nuclear types of dsRNA are not retained on oligo(dT) cellulose columns and therefore seem to lack long poly A sequences. The mechanism of formation of dsRNA is discussed.

Autosomal recessive microcephaly with neonatal myoclonic seizures: clinical and MRI findings.

We describe an infant who was born to a consanguineous couple of Palestinian origin. The patient had severe microcephaly, myoclonic seizures, hypsarrythmia, spasticity, hypertonicity, and profound mental retardation. A similar case was reported in another unrelated Palestinian family, suggesting that this condition may be endemic. The condition resembles early onset myoclonic seizures and spasticity described by Tolmie et al.: Am J Med Genet 27:583-594 [1987]. To the best of our knowledge, only four pairs of sibs have been described with this syndrome; however, to date no magnetic resonance imaging (MRI) findings were reported for this condition. We present the clinical and radiological findings in the patients, including the first report of MRI findings.

Meyer dysplasia in the differential diagnosis of hip disease in young children.

OBJECTIVES: To describe a rare developmental disorder of the femoral capital epiphysis in infants and children that is often misdiagnosed and to suggest an evaluation protocol to differentiate it from other hip problems. DESIGN: Case series. SETTING: Tertiary care center. SUBJECTS: Five consecutive patients referred for evaluation of acute onset of limping between January 1990 and December 1997. INTERVENTION: All clinical and imaging data were collected. RESULTS: Two of the 5 patients were initially diagnosed as having osteomyelitis and 3 as having Perthes disease. The diagnosis of Meyer dysplasia was confirmed by plain film of the pelvis, a negative bone scan, or normal bone marrow findings on magnetic resonance imaging. The limping resolved without treatment in all patients within 1 to 3 weeks. CONCLUSIONS: Meyer dysplasia is a benign condition that should be included in the differential diagnosis of hip disease in infants and children. Awareness of this condition may prevent unnecessary hospitalization and treatment.

Juvenile Behçet's disease in Israel. The Pediatric Rheumatology Study Group of Israel.

OBJECTIVE: Behçet's disease (BD) is a vasculitis mainly observed in young adult males. Juvenile BD is rare and only small series of pediatric cases have been reported. The objective of this study was to define the epidemiology and clinical features of BD among Israeli children. METHODS: A questionnaire was sent to 8 pediatric rheumatology units in Israel and 30 cases of BD diagnosed before the age of 16 years were identified. RESULTS: Fifteen patients fulfilled the International Study Group Criteria for BD, while 15 had an incomplete form of BD. Among the patients with complete BD, stomatitis and skin involvement were the most common manifestations. Other symptoms included genital ulcers, uveitis, CNS involvement, arthritis, and gastrointestinal involvement. A positive family history was elicited in 3 patients. HLA B5 was found in 7 of 12 patients (58%). The 15 patients with incomplete BD all had recurrent stomatitis; other manifestations included uveitis, arthritis, and genital ulcers. HLA B5 was found in 94% of this group. CONCLUSION: Juvenile BD in Israel is not uncommon, and is frequently associated with HLA B5 positivity. This could indicate a genetic susceptibility in our region. Half of the patients in our series had an incomplete form of BD, which may represent a less severe variant of the disease. In any case, careful follow-up is required, since their condition could eventually evolve into complete BD.

Reversible cortical atrophy and cognitive decline induced by valproic acid.

An 18-year-old male suffered from familial progressive myoclonic epilepsy from the age of 7 years. In addition to seizures, there was a marked decline in school performance. At the age of 14 years, sodium valproate was started as add-on therapy; 2 weeks later he was hospitalized in a stuporous state. The serum level of valproate was within the therapeutic range. Cognitive evaluation disclosed moderate mental retardation. No metabolic abnormalities were detected. Valproate was discontinued and during the 4 following months, a slow but significant improvement was documented in cognitive functions. Repeated assessment was within the range of mild mental retardation. Initially, magnetic resonance imaging (MRI) showed mild cortical atrophy. A subsequent MRI study performed 2 years later was normal.

Endometrial suction in luteal phase as a method of late postcoital contraception.

In a pilot study group of 25 women presenting in our clinic after exposure at ovulation to undesired pregnancy, endometrial suction by means of a Pipelle catheter was performed. Sixteen of the 25 women had proven fertility and 9 had never tried to conceive. The women were aged 18 to 38 years. Pathological dating of endometrial sampling verified that the patients were actually post-ovulation in all cases studied. hCG tests were performed 10 to 14 days after endometrial suction and all were negative. We conclude that endometrial suction in the luteal phase is a possible means of postcoital non-hormonal contraception, and we are currently expanding our study.

PIP: The Pipelle disposable endometrial biopsy suction catheter was used on 25 women for postcoital contraception 1-7 days after exposure to unprotected coitus occurring 12-16 days before the next expected menses. 35 women entered the study and were offered estrogen/progestogen, an IUD, or endometrial suction. The 25 women who chose suction were aged 18-38. 16 were fertile. All had informed consent and a pelvic exam but no antibiotics or analgesia. The pipelle catheter was introduced as often as 4 times, until no more tissue was obtained. All patients were followed with beta-hCG at 10-12 days and 3 weeks and were seen at 2 and 4 weeks. All tissue was post-ovulatory as judged by pathology. There were no complications or pregnancies. This method of postcoital pregnancy termination deserves more study, since it is relatively painless and does not require subsequent visits or compliance on the part of the patient.

Pro- and anti-inflammatory cytokines in children with febrile convulsions.

The production of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-10 by peripheral blood mononuclear cells was examined in 13 children with and 11 children without any history of febrile convulsions. The results revealed an increase in all types of cytokine production by lipopolysaccharide-stimulated mononuclear cells from individuals of both groups. However, the secretion of IL-6 and IL-10 in response to lipopolysaccharide was higher in those with a previous history of convulsions. Because IL-1 beta production precedes that of IL-10, a cytokine known to suppress IL-1 beta generation, it is possible that its secretion was inhibited partially by the significantly higher amount of IL-10 found after 24 hours of incubation. If this were the case, these findings may explain the comparable levels of IL-1 beta produced by peripheral blood mononuclear cells from children of both groups. The higher level of IL-1 beta produced by mononuclear cells from children with history of convulsion after 5 hours of incubation with lipopolysaccharide supports this assumption.

Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins.

Acute disseminated encephalomyelitis is a demyelinating syndrome that occurs infrequently in children. Various treatment modalities, such as plasmapheresis or steroids or intravenous immunoglobulins (IVIG), have been prescribed. The article describes the results of combined IVIG and high-dose steroids given for 3 days in the treatment of a patient with atypical encephalomyelitis. The results suggest that this approach may be more beneficial than the application of either drug alone.

Successful treatment of rheumatic chorea with carbamazepine.

Carbamazepine has been used successfully in the treatment of different movement disorders and was recently reported to be effective for nonhereditary chorea. In view of the significant side effects associated with the drugs currently used to treat chorea, we sought to further evaluate the efficacy of carbamazepine in children with rheumatic chorea. The study was prospective and included 10 children with chorea (eight females and two males; age range = 7-16 years) referred to our Pediatric Rheumatology Clinic between 1995 and 1999. Nine had rheumatic fever and one had antiphospholipid antibody syndrome that later evolved to systemic lupus erythematosus. All were treated with carbamazepine. Improvement was evident within 2-14 days of initiation of low doses of carbamazepine (4-10 mg/kg daily). The plasma drug levels were 2.8-8.2 microg/mL (therapeutic antiepileptic range = 8-12 microg/mL). The chorea disappeared within 2-12 weeks. The duration of treatment was 1-15 months. No side effects were observed. Recurrence was observed in three patients who received a second trial of carbamazepine with a good response. We suggest that carbamazepine may serve as a first-line treatment for rheumatic chorea.

Reversible deafness caused by biotinidase deficiency.

We present a child with complete biotinidase deficiency who developed bilateral sensorineural deafness without a response to a maximal stimulus of 90 dB in brainstem acoustic-evoked response. After treatment with 20 mg biotin daily, a repeated brainstem acoustic-evoked response demonstrated an improved hearing threshold of 65 dB, and the child began to talk. The case is a rare example of reversible hearing loss caused by to biotinidase deficiency and highlights the need for immediate replacement therapy once the diagnosis is established.

Carbamazepine-induced Stevens-Johnson syndrome treated with IV steroids and IVIG.

A 17-year-old female is presented who developed antiepileptic drug hypersensitivity syndrome after treatment with carbamazepine. The initial diagnoses were idiopathic thrombocytopenic purpura and toxic shock syndrome. The patient was treated with intravenous immunoglobulin and intravenous steroids. After a severe climax on days 2-4 she recovered completely and was discharged on the eighth day of hospitalization. Although we do not have direct proof, we believe that these treatment modalities, especially the IVIG, shortened and ameliorated the clinical course of the disease.

Neonatal assessment of babies conceived by in vitro fertilization.

PROBLEM: Neonatal outcome of in vitro fertilization (IVF) pregnancies has been described by different authors, but several issues have yet to be resolved. The aim of the present study was to evaluate neonates conceived in vitro and to direct special attention to neonatal morbidity and prevalence of minor abnormalities. The information that has been accumulated so far is scant. METHOD: The first 100 babies conceived in vitro, and subsequently born in our institute, were investigated and compared with the general, spontaneously conceived newborn population. All infants were examined by a senior neonatologist, and the data that were recorded included gestational age at delivery, birth weight, gender, major malformations, minor congenital abnormalities, neonatal mortality, and neonatal morbidity (including asphyxia, jaundice, meconium aspiration, hypoglycemia, and hypocalcemia). RESULTS AND CONCLUSIONS: The data indicate that the IVF neonates assessed had a higher rate of low birth weight (37%), twinning (30%), and preterm birth (20%) in comparison with the general reference population (p < 0.05). However, no differences were encountered either in the rate of small for gestational age infants or the incidence of major malformations and minor abnormalities between these groups of newborns. The overall neonatal morbidity in IVF babies was found to exceed that of the general population. Nevertheless, at birth, there were no clinical pathognomonic signs typical of IVF babies, although more detailed metabolic, endocrine, and neurobehavioral studies are still required to confirm that newborns conceived in vitro do not differ from those conceived spontaneously in any of these respects.

The grand multipara.

Grandmultiparity (GMP) has long been considered an obstetric complication for both mother and fetus, although recent studies indicate that, with proper perinatal care, women with high-parity rates are no longer at high risk. The current study examines the outcome of delivery in 1700 women in their fifth or more delivery, as compared with two control groups: 622 primiparas and 735 multiparas (two to three previous deliveries). Excellent prenatal care was available free of charge to all parturients. Our objectives were to evaluate the management of GMP in contemporary obstetrics and to assess whether grand multiparas are still high-risk patients. The age of the grandmultiparas was significantly higher compared with with the control groups, which may explain the higher incidence among them of antenatal medical disorders, such as diabetes mellitus and hypertensive disease. No significant differences were found among the three groups for preterm or post-term births, small-for-gestational-age infants, polyhydramnios, oligohydramnios, perinatal death, fetal distress, multiple births, placenta previa, abruptio placentae or cord prolapse. Macrosomia was markedly higher in the grandmultiparas and multiparas than in nulliparas. Thus, our results indicate that good perinatal care can ensure better results in grandmultiparas, and that grandmultiparity no longer needs to be considered a high-risk obstetric category in our population.

Great grand multiparity--beyond the 10th delivery.

OBJECTIVE: To investigate the perinatal outcome and obstetric complications of women delivering for the 10th time or more. METHODS: Four hundred twenty women of great grand multiparity were analyzed in a modern health care setting and compared with our general population of obstetric patients, with regard to past history, maternal age, gestational age, mode of delivery, fetal outcome and intercurrent medical/obstetric problems. RESULTS: The study group showed significantly lower rates of low birth weight infants and instrumental delivery. No significant difference was seen in the incidence of cesarean section, pathologic fetal presentation, maternal hypertension, gestational diabetes, hemorrhage, or perinatal morbidity or mortality. There was a slightly higher incidence of twin births compared with the general population. CONCLUSION: It is probable that women capable of reaching their 10th delivery are basically healthy. If offered adequate perinatal care, they are not a high-risk group during subsequent deliveries.