Purpura fulminans induced by disseminated intravascular coagulation following infection in 2 unrelated children with double heterozygosity for factor V Leiden and protein S deficiency.

Purpura fulminans is associated with homozygous protein C and homozygous protein S deficiency or may follow bacterial or viral infections. We present 2 children from 2 unrelated Arab families with purpura fulminans who were double heterozygotes for factor V Leiden inherited from their fathers and protein S deficiency inherited from their mothers. No previous thrombotic events have occurred in either patient or their respective family members. In one patient sepsis accompanied by disseminated intravascular coagulation appeared to be the trigger of purpura fulminans. In the other patient varicella infection preceded purpura fulminans and was also associated with disseminated intravascular coagulation. This report emphasizes the need for evaluation of hereditary defects in the inhibitory mechanisms of blood coagulation in patients with purpura fulminans at any age.

Prevalence of antibodies to Chlamydia pneumoniae in an Israeli population without clinical evidence of respiratory infection.

AIMS: To estimate the occurrence of recent, past, and "persistent" infections with Chlamydia pneumoniae--as indicated by serology--in an Israeli population without clinical evidence of respiratory infection. METHODS: Serum samples from 402 subjects (172 children and 230 adults), without known respiratory symptoms, were collected. Antibodies to C pneumoniae (IgG, IgA, and IgM) were evaluated using the microimmunofluorescence (MIF) assay. Antibody prevalence and indication of recent, past, and persistent infections were calculated and their distribution determined according to age, sex, and season. RESULTS: Antibodies to C pneumoniae were detected in 53 children (31%) and 171 adults (74%). Recent infection was indicated in only one of 50 children under 5 years of age, in nine of 122 older children, and in 19 of 230 adults. IgM antibodies were detected in nine children, but only in three adults. Past infection was indicated in six of 96 young children (aged 1-10 years), in 28 of 76 teenagers, and in 128 of 230 adults. Persistent infection was indicated in three young children, in six teenagers, and in 24 adults, with a significantly higher frequency (p = 0.012) in men (18 of 117) than in women (six of 113). No seasonal differences could be detected. CONCLUSIONS: Infection with C pneumoniae was detected serologically in children and adults without clinical signs of respiratory disease. These results should serve as a basis for studies on the role of C pneumoniae infections and their sequelae in Israel and contribute to the general understanding of asymptomatic infection with C pneumoniae.

Hyperthermia-induced cardiac arrest in dogs and monkeys.

The pattern of dying from immersion hyperthermia was documented in 8 dogs, 9 rhesus monkeys and 12 pigtail monkeys. Under light general anesthesia and spontaneous breathing, the animals were immersed into water of 45 degrees C, which was subsequently adjusted to control brain (parietal epidural) temperature at 42 +/- 0.5 degrees C. Transient initial hypertension, tachycardia, tachypnea and hypocarbia were followed by progressive hypotension with decreasing central venous pressure and pulmonary artery occlusion pressures (measured in three dogs only), bradycardia and bradypnea. Cardiac arrest occurred in the dogs after immersion of 288 +/- 66 min and more rapidly (P less than 0.02) in the rhesus monkeys (at 137 +/- 75 min) and pigtail monkeys (at 178 +/- 26 min). EEG silence occurred in the monkeys at MAP 40 mmHg and in the dogs at MAP 25 mmHg. Cardiac arrest occurred in form of sudden ventricular fibrillation (2/5 dogs, 2/9 rhesus monkeys, 3/12 pigtail monkeys), or later in electromechanical dissociation leading to electric asystole (3/5 dogs, 7/9 rhesus monkeys, 9/12 pigtail monkeys). The mean blood glucose levels decreased to less than 30 mg/dl (P less than 0.002), whereas hematocrit, serum osmolality, lactate and potassium levels increased. Necropsies revealed macroscopic petechial hemorrhages in all extracerebral organs, but not in the brain. There was no gross evidence of cerebral edema. Death seemed to be the result of primary cardiovascular failure leading to secondary (ischemic) cerebral failure (EEG silence) and apnea, which coincided with pulselessness.

Delayed death after uncomplicated hot tub bathing in dogs and monkeys.

Prolonged heat exposure as in hot tub bathing, although frequently practiced, has occasionally resulted in fatalities that have been explained by an underlying disease. We explored the tolerance of hot water immersion of 60 min in five previously healthy animals (three dogs and two monkeys). With invasive monitoring, experimental body immersion in water at 40-45 degrees C, with core temperature kept at 40-42 degrees C for 60 min, caused no significant cardiovascular, pulmonary or metabolic changes during hyperthermia or for 2 h after return to normothermia. Then secondary deterioration occurred with progressive hypotension, petechial hemorrhages throughout the viscera, gross gastrointestinal hemorrhages and irreversible (hypovolemic) shock. These effects occurred earlier in the monkeys than in the dogs. This shock state did not respond to standard resuscitation attempts. One dog survived the secondary shock state. We conclude that during and after hot tub immersion, good initial tolerance to heat exposure can, several hours after return of normothermia, result in delayed secondary deterioration and death. We recommend that the mechanism of this delayed shock state with apparent capillary leakage be clarified.

Role of dopamine and GABA in the control of motor activity elicited from the rat nucleus accumbens.

The application of 1.2 and 12.0 micrograms/side of the GABAA receptor agonist 3-aminopropane sulphonic acid bilaterally into the nucleus accumbens (Acb) of rats nonsignificantly depressed locomotor activity as assessed in automated Animex activity cages, while the highest dose (60 micrograms/side) significantly stimulated activity. The GABAA receptor antagonists picrotoxinin (0.0625 and 0.125 micrograms/saide) and bicuculline (0.895 micrograms/side) produced forward locomotion around the cage accompanied by a number of other behaviours. The GABAB agonist baclofen (0.023 and 0.092 micrograms/side) induced a short-lasting (18 min) locomotor depression. None of the GABAB antagonists tested (2-hydroxysaclofen 2.6 micrograms/side, two novel beta-(benzo[b]furan) analogues of baclofen 9G or 9H each 6.8 micrograms/side, 4-aminobutylphosphonic acid 1.32 micrograms/side and phaclofen 0.535 and 2 micrograms/side) significantly affected locomotor activity. In rats pretreated with reserpine and alpha-methyl-p-tyrosine, picrotoxinin (0.0625 and 0.125 micrograms/side) did not significantly alter locomotor activity. Furthermore, when picrotoxinin (0.0625 micrograms/side) was combined with either the selective dopamine (DA) D1 agonist SKF38393 or the selective D2 agonist quinpirole, no significant alteration in locomotor function occurred. When SKF38393 and quinpirole were coadministered, significant stimulation occurred which was further enhanced by the addition of picrotoxinin. It is concluded that GABAA receptors, together with D1 and D2 receptors, play a major role in modulating the control of motor function by the Acb of rats.

Heliox use in the treatment of acute hyperammonemia.

The objective of this study was to evaluate a new method for the treatment of acute hyperammonemia with a helium-oxygen mixture (heliox). We conducted a prospective, randomized, controlled study of male Sprague-Dawley rats. Experimental hyperammonemia was induced by 7 days of a high-ammonia diet. Subsequently, the animals were randomly divided into two groups: the study group treated with heliox breathing for 24 hours and a control group breathing room air for 24 hours. A prospective, randomized, controlled laboratory animal study was conducted at an animal research facility. The baseline plasma ammonia level was 9.49 +/- 10.96 micromol/L. After 7 days of a high-ammonia diet, the plasma ammonia level rose to 31.53 +/- 8.86 micromol/L. There was a significant statistical difference between the plasma ammonia level following 24 hours of heliox therapy (23.14 +/- 13.97 micromol/L) and the ammonia level in the control group (42.31 +/- 24.25 micromol/L) (P < .05). Heliox breathing was found to be an efficient treatment modality for decreasing plasma ammonia levels in an animal model. Further studies are required to evaluate its potential application in the treatment of patients with hyperammonemia.

Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy.

A 20-month-old boy of Jewish-Turkish origin presented with severe metabolic acidosis. He was born prematurely and had bacteremia during the neonatal period. Scaly skin eruption, developmental delay, generalized muscular hypertonia, and mild ventriculomegaly were noted during the 1st year. Holocarboxylase synthetase deficiency was diagnosed, and biotin and carnitine were administered. The skin rash and the organic aciduria resolved within several days, and at 30 months, his psychomotor development was appropriate for age. Metabolic evaluation should be performed in patients with combined neurologic and dermatologic symptoms even when medical history suggests a nonmetabolic etiology.

Midazolam in treatment of epileptic seizures.

Midazolam (Versed), the first water-soluble benzodiazepine, has had widespread acceptance as a parenteral anxiolitic agent. Its antiepileptic properties were studied in adult patients with good results. Midazolam was administered intramuscularly to 48 children, ages 4 months to 14 years, with 69 epileptic episodes of various types. In all but 5 epileptic episodes, seizures stopped 1-10 min after injection. These results suggest that midazolam administered intramuscularly may be useful in a variety of epileptic seizures during childhood, specifically when attempts to introduce an intravenous line in convulsing children are unsuccessful.

Postural stability by computerized posturography in minor head trauma.

Mild head injuries are very common among young children. Often, these injuries are followed by a variety of subjective complaints termed posttraumatic syndrome. Posturography (balance test) was performed immediately after the trauma in 21 children who had sustained mild head injury. Significant difference in performance was observed in head-injured children in all subparts of the test as compared with a control group. We conclude that posturography may serve as a simple cost-effective method in qualifying the posttraumatic imbalance.

Peripheral facial nerve paralysis in children: the value of routine diagnostic work-up studies.

Acute facial nerve paralysis is a relatively common pediatric disorder. Idiopathic facial nerve palsy (Bell's palsy) has to be distinguished from other etiologies. Retrospective review of the results of routine diagnostic work-up studies of our patients, failed to reveal any clinically significant abnormalities and did not provide more data as far as etiology or indication for management. Significant history and positive findings on physical examination should direct the physician towards specific diagnostic procedures.

"Alice in wonderland" syndrome: a manifestation of infectious mononucleosis in children.

The association between "Alice in Wonderland" Syndrome (AWS) and infectious mononucleosis (IM) has been previously described in three patients.We describe two additional cases in children, where in one case, the visual symptoms of AWS appeared during the course of active IM and in the second, 2 weeks following a clinically mild, but serologically proven attack.

Oral blast injury caused by an accident.

Blast trauma within the oropharyngeal cavity may be associated with superficial or deep injuries. Superficial injury generally needs only observation; deeper injury that violates the retropharyngeal space may produce dissecting emphysema into the neck and mediastinum followed by prevertebral soft tissue infections and mediastinitis. Injury involving the parapharyngeal space might damage vital cervical vessels. Life-threatening complications may result unless treatment is adequate. Three children who sustained oropharyngeal blast injury are presented. The direct cause was the blast effect of a new, spoiled, orange-flavor beverage just released on the market. The bottle cap of the soft drink and its effervescent liquid "exploded" into their mouths while they were trying to open the bottle with their teeth. Obviously, the failure to observe due precautions, as frequently happens among children, contributed to the occurrence of the accidents. This paper describes the diagnosis, management, and relevant educational and preventive measures of the problem.

Airway obstruction in neonates and children: surgical treatment.

OBJECTIVE: This review of 54 infants and children with airway obstruction who were treated surgically emphasizes the importance of the surgical indications with respect to various anomalies causing airway obstruction and the surgical approach to their management. PATIENTS: There were 4 etiologic groups of airway obstruction. Group A comprised 12 infants with subglottic stenosis; Group B--20 infants with tracheomalacia; 21 patients (Group C) with anatomic narrowing of the trachea; and 1 infant (Group D) with laceration of a main bronchus. METHODS: The surgical procedures performed included anterior laryngotracheal decompression in 12 infants, aortopexy in 19; 1 pulmonary arteriopexy; tracheal stenting with an autologous rib graft in 3 and with Marlex mesh in 1. Tracheal widening, using a free tibia autologous graft, was performed in 3 patients; transbronchoscopic excision in 12; anterior tracheal wedge resection in 4, and segmental tracheal resection and anastomosis in 1 patient. The lacerated bronchus was repaired with fine Dexon sutures. RESULTS: There were no operative deaths. With respect to the original indications for surgery, there were 3 failures--2 in Group A and 1 in Group C. Two patients died from causes unrelated to the procedures--one 10 days postoperatively, and the other 3 months after surgery. CONCLUSIONS: The surgical approach to tracheal obstruction in infants and children offers effective treatment, with no operative mortality, a low complication rate, and good long term survival.

Snakebite poisoning in children--a call for unified clinical guidelines.

In Israel, there are no uniform guidelines for the treatment policy of children snake-bitten by the Vipera palaestinae, the most abundant venomous snake in the country. We conducted a retrospective study aiming to compare treatment policies in two different medical centers. We found significant differences regarding admission and steroid administration criteria. Although the differences between the centers regarding anti-venom administration did not reach statistical significance, there were substantial differences. Neither of the centers had a well-established policy for the treatment of snake envenomation in children. In the era of cost containment, a policy of routine admission of children to the PICU service following V. palaestinae envenomation is unjustified, especially since the introduction of a specific monovalent anti-venom into the therapeutic armamentarium.

Vipera palaestinae snake envenomations: experience in children.

In Israel, Vipera palaestinae (V. palaestinae) is the most common venomous snake, accounting for 100-300 reported cases of envenomation every year. However, V. palaestinae snakebites in children have not been extensively investigated. The demographic features, treatment and outcome of V. palaestinae envenomation in 37 children treated in two medical centers over a 9 year period were retrospectively reviewed. The victims age ranged from 2-18 years with a mean age of 8.9 years. Twenty-nine children were males and eight were females. Twenty-one patients resided in rural areas, and 16 children were living in urban areas. Twenty-three (63%) of the patients were bitten on the lower limb; Twelve (33%) on the upper limb, and two on the head or neck (4%). Using a grading scale of one to three from minimal to severe envenomation, 15 (40.5%), 15 (40.5%) and 7 (19%) patients had mild, moderate and severe envenomation, respectively. Major complications of envenomation that were manifested after arrival consisted of compartment syndrome (two patients) and respiratory dysfunction (two patients). Specific monovalent antiserum for the treatment of V. palaestinae bite was given to 16 children (43%) of whom, four patients were in the severe group, seven and five in the moderate and mild groups respectively. No patient suffered a significant infection, tissue loss, permanent disability or death. We conclude that early ICU admission along with close monitoring and antivenom therapy is important in reducing morbidity and mortality in children systemically envenomed by V. palaestinae.

Elevated serum creatine kinase. Following febrile seizures.

Serum creatine kinase (CK) was determined in 52 children admitted following an episode of febrile convulsions. Enzyme levels correlated with the estimated duration of the seizure. Twenty-four hour values were significantly higher than those observed 1 hour after the convulsive episode. Serum CK levels are frequently used for diagnostic purposes, so the questionable validity of this test when drawn after a convulsive episode must be considered.

Talismans and amulets in the Pediatric Intensive Care Unit: legendary powers in contemporary medicine.

BACKGROUND: For centuries talismans and amulets have been used in many cultures for their legendary healing powers. METHODS: We asked the parents of every child (Jews and Arabs) admitted to the Pediatric Intensive Care Unit over a 2 month period to complete a questionnaire, which included demographic data on the patient and the family, the use of talismans or other folk medicine practices, and the perception of the effects of these practices on the patient's well-being. A different questionnaire was completed by the ICU staff members on their attitude toward the use of amulets. RESULTS: Thirty percent of the families used amulets and talismans in the ICU, irrespective of the socioeconomic status of the family or the severity of the patient's illness. Amulets and talismans were used significantly more by religious Jews, by families with a higher parental educational level, and where the hospitalized child was very young. The estimated frequency of amulet use by the children's families, as perceived by the staff, was significantly higher than actual use reported by the parents. In Jewish families the actual use of amulets was found to be 30% compared to the 60% rate estimated by the medical staff; while in Moslem families the actual use was zero compared to the staff's estimation of about 36%. Of the 19 staff members, 14 reported that the use of amulets seemed to reduce the parents' anxiety, while 2 claimed that amulet use sometimes interfered with the staff's ability to carry out medical treatment. CONCLUSIONS: The use of talismans in a technologically advanced western society is more frequent than may have been thought. Medical and paramedical personnel dealing with very ill patients should be aware of the emotional and psychological implications of such beliefs and practices on patients and their families.

Do standard monitoring sites affect true brain temperature when hyperthermia is rapidly induced and reversed.

BACKGROUND: Accurate measurements of brain and core temperatures during warming and cooling of the whole organism, accidentally or therapeutically, are important for studies of thermoregulation and cerebral insults and resuscitation. HYPOTHESIS: During steady states and normal circulation, temperatures in the brain, nasopharynx, esophagus and rectum (the latter are core temperatures) equilibrate quickly; and that during rapid cooling or warming, slight temperature gradients occur, with esophageal core temperature reflecting brain temperature better than rectal temperature. METHODS: We evaluated 5 mongrel dogs and 12 pigtail monkeys. The animals were exposed to total body hyperthermia by immersion into water at 45 degrees C to achieve cerebral temperature 42 degrees C which was maintained until cardiac arrest. In monkeys, at cardiac arrest, surface cooling and cardiopulmonary resuscitation were attempted for up to 30 min to determine resuscitability at 38.5 degrees C. Continuously monitored were brain (epidural) (Tep), esophageal (Tes), rectal (Tre) and nasopharyngeal temperatures (Tnp). Also monitored were mean arterial pressure and intracranial pressure. RESULTS: At normothermia, in dogs and monkeys, Tep, Tre, Tes and Tnp correlated well. In the dogs, during heating, Tes, Tnp and Tre at first correlated well. Vigorous panting started as Tep reached 41 degrees C, which immediately lowered Tnp and Tep to increase less steeply than Tes and Tre. After about 40 min of panting, with cerebral perfusion pressure still normal, Tep decreased sharply and reached the levels of Tnp, while Tre remained high. In the monkeys during heating, Tep, Tes and Tre correlated well. When cerebral perfusion pressure decreased below 50 mmHg, Tep declined significantly as compared with Tre, which continued to be high in severe arterial hypotension. Tes at that time achieved levels between Tep and Tre. During cooling in monkeys, the decline in Tre was slower as compared with the decline in Tes and Tep. CONCLUSIONS: In normal dogs and monkeys, rectal, esophageal and nasopharyngeal temperatures are almost identical with brain temperatures; but during rapid external warming or cooling, brain temperature is reflected in nasopharyngeal temperature, somewhat in higher esophageal temperature, but not in even higher rectal temperature. For clinical monitoring during temperature changes, one should use primarily esophageal temperature and, if feasible, brain (epidural) temperature as well.

Hyperthermia-induced cardiac arrest in monkeys: limited efficacy of standard CPR.

BACKGROUND: Successful resuscitation from heatstroke cardiopulmonary arrest has been only partially explored and the data covering the post resuscitation pathophysiology leading to secondary arrest is, in most cases, insufficient. HYPOTHESIS: Following heatstroke-cardiopulmonary arrest, successful resuscitation may be achieved by standard CPR with surface cooling and administration of glucose. We ponder the sequence of early circulatory responses and the pathophysiological changes following successful resuscitation. METHODS: We exposed 12 pigtail monkeys to total-body hyperthermia (cerebral T 42 degrees C) until cardiac arrest ensued. Standard external CPR with surface cooling and glucose 5% IV were administered for up to 30 min. Control group A (n = 6) was compared with experimental group B (n = 6), which received additional steroid, glucagon and hypertonic glucose during CPR attempts. RESULTS: No significant differences were found between the outcome of the two groups. The 30-min CPR attempt succeeded in restoration of spontaneous circulation (ROSC) in 8/12 monkeys-5 animals from group A and 3 in group B. The animals in whom resuscitation was unsuccessful had significantly prolonged periods of rectal temperature exceeding 42.5 degrees C (p < 0.05), and significantly higher rectal temperatures at the end of 30 min of CPR and cooling (p < 0.05). All the resuscitated animals later rearrested at 158 +/- 68 (95-228) min after ROSC; pulmonary edema occurred in 6/8 animals. CONCLUSIONS: We conclude that experimentally-induced heatstroke can be transiently reversed by standard resuscitative procedures, but is followed by a delayed, irreversible, secondary shock state, which could not be prevented by the treatment we employed. We were, however, able to document in detail the pathophysiologic processes involved in the resuscitation, and the irreversible shock one sees after "successful" CPR.

[Aortopexy for tracheomalacia in infants and children].

During the past 12 years (1985-1998), 28 infants and children were operated on here for tracheomalacia. The diagnosis was made in all using rigid bronchoscopy. During the examination the infants breathed spontaneously, but the trachea collapsed on forced expiration. Indications for surgery were repeated cyanotic spells ("dying spells") in 22, recurrent pneumonia, and inability to extubate (in 8). In 11 there were more than 1 indications. Age at surgery was from 7 days to 3 years (average 11.7 months). All 28 children underwent bronchoscopy and guided aortopexy via a left-third intercostal approach. The ascending aorta and aortic arch (and in 6 the proximal innominate artery as well) were lifted anteriorly, using 3-5 non-absorbable sutures (5.0). The sutures were placed through the adventitia of the great vessels and then passed through the sternum. Respiratory distress was significantly improved in 21. Another 2 required external tracheal stenting with autologous rib grafts, and in 1 other an internal Palmaz stent was introduced for tracheal stability. In 4 aortopexy failed, 1 of whom had tracheobronchomalacia throughout, and another 3 had laryngomalacia which required tracheostomy to relieve the respiratory symptoms. Postoperative complications were minor: pericardial effusion in 1 and relaxation of the left diaphragm in another. 1 infant subsequently died, of unknown cause 10 days after operation, after having been extubated on the 1st postoperative day. On long-term follow-up (6 months to 12 years) 25 were found free of residual respiratory symptoms and 3 remained with a tracheostomy. Thus, infants and children with severe tracheomalacia associated with severe respiratory symptoms, can be relieved by bronchoscopic guided suspension of the aortic arch to the sternum.