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Biomedical subjects

M Berkovitch

Publications and source records attributed to M Berkovitch.

At least 37 records · Page 2Linked to original sources

Hypertension and abdominal pain: uncommon presentation after exposure to a pine caterpillar.

UNLABELLED: The pine caterpillar Thaumatopoea wilkinsoni is found in pine woods all over Israel. Contact with its hair usually results in local reactions. Systemic reactions after contact with caterpillar hairs are known in other caterpillar species, but have been described only once after contact with T. wilkinsoni. We describe a group of adolescents who were exposed to T. wilkinsoni while camping in a pine wood. Three of them were referred to an emergency department. They had severe pruritus, pain and edema at the contact sites, with papular and urticarial rashes. Two of the patients had abdominal pain and one patient had hypertension for several hours. The hypertension resolved spontaneously. CONCLUSION: Skin eruptions are the most common manifestations of T. wilkinsoni contact, however, although systemic manifestations are rare, abdominal pain and hypertension may occur.

Abdominal Pain↗

Neutropenia as a complication of intravenous immunoglobulin (IVIG) therapy in children with immune thrombocytopenic purpura: common and non-alarming.

UNLABELLED: Following reports on adult patients with neutropenia as a result of administration of intravenous immunoglobulin (IVIG) we have investigated the incidence and consequences of neutropenia following IVIG treatment in children with immune thrombocytopenic purpura (ITP). The medical records of 14 children with ITP who received IVIG as inpatients were reviewed. Past and present history, age, previous medications, complete blood count and differential before and after treatment with IVIG were recorded for each patient. The patients, aged 5.5 +/- 3.5 (0.5-11.5) years [mean +/- SD; range] received one or more courses of IVIG. Neutropenia (total neutrophils < 2000/mm3) was observed within 24 h after the first course of IVIG in five children (36%). The pretreatment neutrophil count in this group was not significantly different from that observed in the patients without IVIG-induced neutropenia (p = 0.98). The condition resolved spontaneously and without complications in all patients within 48 h. In a preliminary experiment in which bone marrow derived mononuclear cells were assayed for the clonogenicity in methylcellulose, there was no suppressive effect of IVIG on the number of CFU-GM colonies. CONCLUSIONS: Since IVIG is currently administered in a vast number of medical indications, neutropenia following IVIG administration may not be an uncommon finding. It seems to be transient and self limited.

Child↗

The effect of diazepam in the recovery of rabbits from acute acetaminophen intoxication.

We have recently shown that diazepam can reduce mortality of acute iron overdose in rats. The mechanism for that effect is not yet defined. Our objective in the present study was to assess whether diazepam can similarly reduce mortality of experimental acute acetaminophen intoxication. Survival of rabbits was compared among four groups receiving 3 g/kg (body weight) of acetaminophen (LD40) orally each, followed by: 1) nothing (group I), 2) one oral dose of 140 mg/kg N-acetylcystein (NAC) an hour later (group II), 3) intramuscular injection of 7 mg/kg diazepam (group III), 4) intramuscular injection of 7 mg/kg diazepam and one oral dose of 140 mg/kg NAC an hour later (group IV). 37.5% of rabbits in group I died after 16 hours, whereas none of the rabbits in group III died, (p = 0.04). No animal died during the 96-hour observation period in groups II and IV. Two and four hours post drug administration, acetaminophen plasma concentrations (APC) were significantly lower among rabbits in group III than in group I (p = 0.0007 and 0.01, respectively) and significantly lower among rabbits in group IV than in those in group II (p<0.0001 and p = 0.03, respectively). Acetaminophen plasma concentrations 2 hours after drug administration were also significantly lower among rabbits in group III than in those in group II (p = 0.0002). Seven and 24 hours after dosage, APC tended to be higher among rabbits in group III than in those in group I, but not significantly so. Administration of diazepam without NAC did not prevent liver and renal dysfunction. We conclude that early administration of diazepam in acute experimental acetaminophen overdose in rabbits reduced APC and mortality, probably by slowing intestinal motility, which resulted in delayed acetaminophen absorption from the gastrointestinal tract.

Acetaminophen↗

Sodium potassium adenosine triphosphatase activity in preterm and term infants and its possible role in sodium homeostasis during maturation.

AIM: To investigate sodium (NA(+)) potassium (K(+)) adenosine triphosphatase (ATPase) activity in newborn infants at different gestational ages, to elucidate the mechanism underlying poor renal sodium conservation in preterm infants. METHODS: Fifty three healthy newborn infants, gestational age 30-42 weeks, were studied. Umbilical cord red blood cell Na(+) K(+)ATPase activity, plasma renin activity, and plasma aldosterone activities were measured in all of them. Red blood cell Na(+) K(+)ATPase activity was re-examined in eight preterm infants, one and two weeks after birth. Total and ouabain sensitive ATPase activity was measured spectrophotometrically using a method that couples ATP hydrolysis with NADH oxidation. RESULTS: Red blood cell Na(+) K(+)ATPase activity was significantly lower (p<0.01) in preterm babies with a gestational age below 35 weeks, compared with those with aged 35 weeks and above: 2.3 (0.8) and 6.7 (1.3) nmol NADH/minute/mg protein, respectively. There was no correlation between gestational age, Na(+) K(+)ATPase, plasma renin activity and aldosterone values either in the preterm or term babies. Two weeks after birth, irrespective of gestational age, the enzyme activity of the preterm babies increased to values similar to those observed in the term neonates at birth. CONCLUSION: The differences in sodium homeostasis between term and preterm babies are modulated via changes in Na(+) K(+)ATPase activity.

Gestational Age↗

Abnormal visual evoked potentials in children with "Alice in Wonderland" syndrome due to infectious mononucleosis.

Visual illusions characterized by distortion of form, size, reciprocal position of objects, movement, or color, labeled as "Alice in Wonderland" syndrome, were discussed in children with infectious mononucleosis, as well as in other clinical conditions, such as migraine, epilepsy, use of certain hallucinogenic drugs, etc. The purpose of our study was to investigate for the first time visual evoked potential results in children with "Alice in Wonderland" syndrome associated with infectious mononucleosis. Five children with "Alice in Wonderland" syndrome associated with infectious mononucleosis underwent visual evoked potential studies during and after their clinical symptoms. Visual evoked potential results during the disease demonstrated statistically significant high amplitudes of P100-N145 in all children compared to the control group. A few weeks later, repeated studies after the resolution of the complaints were normal. Since the same findings can be observed in patients with migraine, we postulate that a common pathophysiologic underlying abnormality, which can cause transient focal decreased cerebral perfusion, could be involved in the disease process of these two conditions.

Adolescent↗

Acute iron intoxication: the efficacy of deferiprone and sodium biocarbonate in the prevention of iron absorption from the digestive tract.

To determine whether enteral deferiprone given after a loading dose of liquid iron interferes with iron absorption from the digestive tract, prospective randomized animal study was initiated using Sprague-Dawley rats. The rats were given 20 mg elemental iron/kg as a ferrous sulfate solution + 1 mEq sodium bicarbonate/kg, and then dosed orally with 150 mg deferiprone/kg immediately or after 15 min. Serum iron levels were measured at 1, 3, 5 and 24 h; feces were collected for 24 h. The 20 mg elemental iron/kg caused a significant and rapid increase in serum iron levels to > 350 micrograms/dL within 20 min of oral dosing. Deferiprone, if given immediately after the iron, produced a significant decrease in serum iron levels and a 2-fold increase in iron excretion in feces. Effectiveness was delayed when the deferiprone was given 15 min after the iron dosing. Enteral deferiprone might be useful in preventing cases of acute iron intoxication.

Animals↗

Steady-state pharmacokinetics of isotretinoin and its 4-oxo metabolite: implications for fetal safety.

Isotretinoin is the most potent human teratogen on the market. Women for whom contraception fails may conceive during or soon after discontinuing isotretinoin therapy, making its elimination kinetics a crucial determinant of fetal safety. The steady-state pharmacokinetics of isotretinoin and its major 4-oxo metabolite were studied in 16 adult patients treated for acne who were receiving doses that ranged from 0.47 to 1.7 mg/kg daily. This is the first study of the pharmacokinetics of isotretinoin in women of childbearing age (n = 11). The clinical efficacy and tolerability of isotretinoin was investigated, and the correlation between these data and steady-state serum concentrations of isotretinoin was tested. The concentration-time data best fitted a two-compartment open model with linear elimination. There was no correlation between efficacy and tolerability of isotretinoin and steady-state serum concentrations. There was no correlation between dose of isotretinoin and steady-state concentration, due to the large variability in apparent clearance. Values for elimination half-life (t1/2) of isotretinoin and its metabolite were 29+/-40 hours and 22+/-10 hours, respectively. These data suggest a longer elimination t1/2 of the parent drug than previously reported. This is probably due to the longer sampling time used in this study (as long as 28 days). This study suggests that a greater variability exists in the safe time after discontinuation of the drug for onset of conception.

Abnormalities, Drug-Induced↗

Hereditary insensitivity to pain with anhidrosis.

Hereditary sensory neuropathy type IV is an autosomal-recessive disorder characterized by congenital insensitivity to pain and anhidrosis and resulting in recurrent hyperpyrexia, self-mutilation, recurrent infections, chronic osteomyelitis, bone and joint deformities, and limb amputations. Described is a child with signs as well as skin and nerve biopsy results compatible with this disease, emphasizing the importance of early diagnosis and appropriate medical and educational care to prevent complications.

Biopsy↗

Trying to improve compliance with prophylactic penicillin therapy in children with sickle cell disease.

AIMS: To evaluate compliance with prophylactic penicillin therapy in sickle cell disease (SCD) in children. METHODS: Forty-five children aged 37 +/- 19 (9-84) months [mean +/- s.d; range] with homozygous SCD were recruited. After a baseline period of 2 months the patients were randomized to either the intervention or non-intervention group. The intervention consisted of a slide show explaining the pathogenesis of sickle cell disease and its complications; weekly phone calls by the clinic social worker; and a calendar. Compliance was again evaluated after the 2 month intervention period and after a further 2 month monitoring period without intervention. Compliance was monitored using the Medication Event Monitoring System. At the end of the 6 months, parents in both groups completed a questionnaire the aims of which were to determine knowledge and understanding of sickle cell disease and previous experience with infection. Patient admissions to the hospital during the study were recorded. RESULTS: Compliance during the 2 month baseline assessment was 66.0 +/- 32.5 (1.3-98.2)% and 69.3+25.4 (19.8-96.5)% in the intervention (n = 13) and non-intervention (n = 10) groups respectively (P = 0.79). During the next 2 months, compliance in the intervention group (n = 11) was 79.0 +/- 31.4 (11.0-100.0)% and in the non-intervention group (n = 9) was 66.0 +/- 20.2 (42.2-96.8)% (P = 0.297). In the final 2 month monitoring period compliance was 82.0 +/- 34.7 (3.8-100.0)% and 65.8 +/- 25.3 (25.0-98.2)% in the intervention (n = 7) and the non-intervention (n = 6) groups respectively (P = 0.366). No statistically significant differences were found when comparing compliance between the groups. CONCLUSIONS: Compliance with prophylactic antibiotic therapy in children with sickle cell disease is highly variable and its evaluation is problematic.

Administration, Oral↗

Infection due to Yersinia enterocolitica in a series of patients with beta-thalassemia: incidence and predisposing factors.

Over 15 years, 14 patients with yersiniosis in two North American comprehensive thalassemia clinics (0.6 cases per 100 patient-years) presented with fever (100%), diarrhea (86%), right-lower-quadrant abdominal pain (71%), bacteremia (57%), a palpable abdominal mass (36%), and pharyngitis (28%). Clinically apparent infection occurred within 10 days of blood transfusion in 57% of patients. Nine patients (64%) had only a modest elevation in serum level of ferritin (< 2,000 micrograms/L). Patients with focal abdominal findings had a higher body iron burden, as estimated by the serum ferritin level, and significant intraabdominal suppurative complications. Two patients were not receiving iron-chelating therapy with deferoxamine; one patient was receiving the experimental chelator deferiprone (L1). Iron-loaded patients with beta-thalassemia are at greatly increased risk for severe yersiniosis, even when their body iron burden (as indicated by the serum ferritin level) is only moderately elevated and they are not receiving iron-chelating therapy with deferoxamine.

Adolescent↗

Clinical relevance of therapeutic drug monitoring of digoxin and gentamicin in the saliva of children.

Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often difficult. In 11 children treated with digoxin for various cardiac conditions, and in 24 children treated with gentamicin (14 patients were administered gentamicin three times a day, and 10 once-daily), drugs levels were measured in plasma and saliva. There was no correlation between plasma total or free digoxin concentrations and saliva levels, precluding the clinical use of the saliva test for digoxin. No correlation was found between plasma gentamicin concentrations and saliva levels when the drug was administered three times a day; however, good correlation was found when the drug was administered once-daily (r2 = 0.89, p < 0.0001). Saliva may be used as a noninvasive method of measuring gentamicin serum concentrations to guide dosage adjustments in patients administered the drug once-daily.

Anti-Bacterial Agents↗

The efficacy of diazepam in the treatment of acute iron overload in rats.

While conducting studies on the prevention of mortality from acute iron intoxication in rats, diazepam, given to prevent animal suffering, was observed to be associated with reduced mortality in a limited number of animals. The objective was to assess whether diazepam reduces mortality following acute iron intoxication in rats. Survival of rats was compared among groups receiving (i) orally 612 mg/kg iron alone (LD60), (ii) iron with a subcutaneous injection of 2.5 mg/kg diazepam (DZ), or (iii) iron, DZ with 800 mg/kg deferiprone intraperitoneal injections. The administration of DZ decreased mortality from 60 to 16% (p < 0.001). The addition of deferiprone to DZ resulted in zero mortality (p < 0.05 compared with the DZ group) over the study period. The administration of DZ was not associated with decreased iron absorption or increased urinary iron excretion, whereas the administration of deferiprone did result in urinary iron excretion. Microscopic examination suggests that diazepam administration may be associated with lower intracellular accumulation of iron. In conclusion, diazepam reduces mortality from iron overdose in rats through a yet unidentified mechanism, although the drug does not inhibit iron absorption or enhance urinary iron removal.

Acute Disease↗

Heliox therapy for pneumothorax: new indication for an old remedy.

STUDY OBJECTIVE: To evaluate a new method of treating pneumothorax: having the subject breathe a helium/oxygen mixture (heliox). METHODS: We conducted a prospective, randomized, controlled study of nine white rabbits weighing 2.5 to 3.5 kg. Experimental pneumothorax was induced in all rabbits with the injection of 20 mL of air into the pleural space. The rabbits then breathed heliox, oxygen, or room air for 2 hours. Chest radiography was performed 5 minutes after induction of pneumothorax, then at 1 and 2 hours. We determined pneumothorax size on the chest radiograph by measuring the interpleural distance and expressing it as a percentage of the hemithorax. RESULTS: At 2 hours the pneumothoraces in the heliox group had diminished from 17.50% +/- .50% to .17% +/- .29%; in the oxygen-breathing group they had diminished from 17.83% +/- 2.25% to .50% +/- .50%; and in the air-breathing group they had diminished from 18.50% +/- 3.12% to 17.33% +/- .25%. The difference between the air-breathing and the oxygen-breathing or heliox-breathing animals was highly significant; no significant difference was found between the oxygen and heliox groups (P<.0001). CONCLUSION: Heliox, a safe and convenient therapy, is as effective as oxygen in reducing the volume of an experimental pneumothorax in rabbits.

Animals↗

Immune function in patients with beta thalassaemia receiving the orally active iron-chelating agent deferiprone.

Short-term deferiprone may reduce body iron in some patients with thalassaemia major. Concerns regarding potential immunosuppressive effects of deferiprone have been raised from results of animal studies and case reports in humans. We studied immune function in 57 thalassaemia patients: 36 treated with deferiprone (L1; CP020) and 21 treated with desferrioxamine (DFO). Circulating B lymphocytes were increased in all patient groups. No differences were detected between treatment groups in percentages of circulating lymphocytes, concentrations of IgG, IgM or IgA, specific antibody titres, complement levels, or in vitro lymphocyte proliferation. No clinically important infections were observed in any patient. These data suggest that no clinical or laboratory changes consistent with immuno-suppression or immunodeficiency are observed during deferiprone therapy.

Adolescent↗

Salivary measurement of deferiprone concentrations and correlation with serum levels.

Deferiprone (L1) is the first clinically available oral iron chelator and it has been proven to be effective for the treatment of transfusional iron overload in thalassemic patients. Because many of these patients have impaired compliance with their medications, effective means of continuous monitoring of compliance are crucial. Saliva drug monitoring has the potential advantage of an easy, noninvasive approach, assuming that it represents serum levels. However, drugs have variable correlations between saliva and serum concentration. We compared serum and saliva levels of L1 at various time points after ingestion of a 75 mg/kg/day dose in nine thalassemic patients. A highly significant correlation between serum-free L1 and saliva levels (r = 0.97, p = 0.0003) was found. Pharmacokinetic profiles were similar using serum and saliva monitoring. We conclude that saliva can be substituted for serum in monitoring L1 levels.

Deferiprone↗

Acute iron intoxication: significant differences between sexes.

Iron, one of the common medications in use among children and adults, is the leading cause of pediatric unintentional ingestion fatalities and is not an uncommon poisoning among adults. Accidental ingestion is common because iron-containing compounds are readily available, brightly colored, often sugar coated, and frequently considered harmless vitamins. There are no data on differences between sexes with regard to iron intoxication, and the management of iron overdose is the same for females and males. After oral administration by gavage of the LD50 of iron to Wistar rats, the pharmacokinetics of iron, baseline and peak serum iron levels, and mortality rates were compared between sexes. Prepubertal females died significantly more than males (p < 0.01), pubertal females died significantly earlier than males (p < 0.04), and the same was true among adult rats (p = 0.02). Baseline serum iron levels were not significantly different between prepubertal female and male rats, but female pubertal rats had significantly higher baseline iron levels than males (p = 0.006). After iron administration, females had significantly higher peak serum iron concentrations (p < 0.03). Mechanisms of iron absorption are still not completely known and, probably, there are differences in iron absorption between sexes, which may account for the differences in serum iron levels and mortality rates. While the therapeutic approach in cases of intoxication is individual, iron intoxication, as may be true for other poisonings also, treatments administered to females may need to be different from that given to males.

Administration, Oral↗