Effect of pentoxifylline on the phagocytic activity, cAMP levels, and superoxide anion production by monocytes and polymorphonuclear cells.

The effect of pentoxifylline (Trental) on the phagocytic capacity, cAMP levels, and superoxide anion production of human peripheral blood monocytes and polymorphonuclears (PMNs) was studied. The drug inhibited the phagocytosis of latex particles by both monocytes and PMNs in a dose-dependent manner. In addition, superoxide anion production during the phagocytic process was also reduced following incubation of the cells with pentoxifylline. It is suggested that this inhibitory effect is due to the increased intracellular levels of cAMP induced by the drug.

Prevalence of Raynaud's phenomenon in patients with migraine.

We assessed the prevalence of Raynaud's phenomenon (RP) in 111 migrainous patients and 111 controls matched for age and sex. While 29 (26%) of the 111 migrainous patients suffered from RP, its prevalence among the controls was seven (6%) of 111. Raynaud's phenomenon was diagnosed among 13 (33%) of 39 patients with classic migraine and 16 (22%) of 72 patients with common migraine. Drug treatment did not account for the different prevalence in the two groups. We conclude that RP occurs more frequently in patients suffering from migraine than in the non-migrainous population.

Secondary pituitary insufficiency: report of three cases of ectopia or hemiagenesis of the thyroid gland.

Three patients with clinical and laboratory manifestations suggestive of pituitary insufficiency due to the presence of a pituitary tumor were found to have long-standing myxedema. The insidious appearance of the signs of hypothyroidism was explained by the cause of their disease--an ectopic thyroid gland in two patients and hemiagenesis of the thyroid in the third. Early recognition and treatment of such cases is important.

Magnesium therapy for torsades de pointes.

This is the first report of the successful use of magnesium sulfate (MgSO4) in 3 consecutive patients with torsades de pointes (TdP). In 1 patient, TdP was induced by a combination of quinidine and amiodarone, in the second by procainamide, and in the third by an overdose of imipramine. The QT intervals before TdP were 0.70, 0.64 and 0.56 second, respectively. A bolus of 1.0 to 2.0 g MgSO4 25% abolished the TdP in all 3 patients; but in the third patient, because of recurrent TdP, a second bolus of 1.0 g and a continuous 24-hour infusion of 1.0 mg/min were administered, preventing TdP. There was no immediate shortening in the QT interval in any patient after MgSO4. Magnesium can be given safely even in patients with acute myocardial infarction, angina pectoris or systemic hypertension, conditions in which isoproterenol is contraindicated; it can be applied faster than temporary cardiac pacing; and its use for TdP appears worthy of additional trials.

Gastroesophageal dysfunction in Brachmann-de Lange syndrome.

Two children with the Brachmann-de Lange syndrome and severe gastroesophageal reflux are described. Both had esophagitis, recurrent severe anemia, and one had recurrent episodes of aspiration pneumonia and clubbing. Medical treatment failed in both children. One child responded dramatically to surgery, but the other died before surgery could be attempted. Our experience and a review of the literature suggest that early recognition and surgical treatment of gastroesophageal reflux will reduce morbidity and mortality in children with this syndrome.

Infectious endocarditis in idiopathic hypertrophic subaortic stenosis: report of three cases and review of the literature.

Three cases of infective endocarditis (IE) occurringg in patients with idiopathic hypertrophic subaortic stenosis (IHSS) are described. A review of the literature reveals the IE occurs in about 50 percent of the patients suffering from IHSS. It appears to complicate the natural history of the severe cases, at least as it appears from hemodynamic studies, being precipitated by the same factors and caused by the same infective organisms as in valvular heart disease. It has the same clinical picture and outcome, although the appearance of new murmurs was more common than in other types of heart disease complicated by IE, and indicated the same poor prognosis. The infection seems to involve both the aortic and the mitral valve, with equal frequency, and less commonly the ventricular outflow tract. The need for IE prophylaxis in cases of IHSS is stressed.

Inflammatory pseudotumor of the heart with vasculitis and venous thrombosis.

Inflammatory pseudotumor (IPT) is a tumor-like reactive lesion of unknown etiology. An unusual case of intracardiac IPT with multisystemic involvement, including leukocytoclastic vasculitis, polyarthritis, and inferior vena cava thrombosis in a 17-year-old boy is reported. This unique combination may suggest that immune/autoimmune factors are important in the pathogenesis of IPT.

L-dopa is protective against indomethacin-induced small intestinal ulceration in the rat: possible role of an alpha-2-adrenergic mechanism.

Dopaminergic agents ameliorate experimentally induced gastroduodenal mucosal injury, but there is no information about their effect on small intestinal mucosa. We studied the effect of L-dopa and related substances on indomethacin-induced intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg indomethacin, 30 min after refeeding fasted rats. Total ulcer area was measured 24 hrs after indomethacin administration. L-dopa, 5 mg/kg given in two divided doses 5 h apart, starting 30 minutes before administration of indomethacin, was found to protect the small bowel mucosa against indomethacin- induced damage (ulcer area 122 +/- 5.5 vs 224.2 +/- 5.4 mm2, mean +/- SEM, p less than 0.006). Administration of 5 mg/kg haloperidol, a dopa antagonist, did not abolish the protective effect of L-dopa. On the other hand, yohimbine, an alpha-2-adrenoreceptor antagonist, almost completely abolished the protective effect (180.4 +/- 5.3 vs 122 +/- 5.5, p less than 0.004). Clonidine 20 micrograms/kg, an alpha-2-adrenoreceptor agonist, closely mimicked the protective effect of L-dopa (141.5 +/- 10.9 vs 224.2 +/- 5.4, p less than 0.006). All drugs were give i.p. in two divided doses, at the same schedule as described for L-dopa. The results demonstrate that L-dopa has a protective effect on indomethacin-induced small bowel injury in the rat. The protective effect is probably mediated through stimulation of alpha-2-adrenoreceptors.

Total parenteral nutrition-associated cholestasis after selective damage to acinar zone 3 hepatocytes by bromobenzene in the rat.

Total parenteral nutrition is known to cause cholestasis, but the hepatic site of this effect has not been determined. The purpose of our study was to observe the effect of TPN on bile flow and bile salt secretion rate in rats after selective damage to acinar zone 3. Bromobenzene, 3.8 mmol/kg, was injected i.p., and the animals were studied 48 hours later. Experimental groups received either parenteral nutrition or saline for 2 hours. Bromobenzene caused selective damage to acinar zone 3 hepatocytes, and reduced baseline bile flow (23.99 +/- 1.09 vs 37.2 +/- 1.66, mean +/- SEM, microliter/min/kg, p < 0.001). Bromobenzene had no effect on bile salt secretion rate. Total parenteral nutrition decreased bile flow in the bromobenzene treated groups, despite the selective hepatic damage to acinar zone 3 (20.54 +/- 1.07 vs 23.28 +/- 1.63, mean +/- SEM, p < 0.001). Total parenteral nutrition reduced bile salt secretion rate in healthy animals, but this reduction was not seen in bromobenzene treated rats. Our results suggest that bile flow reduction in response to total parenteral nutrition is mediated through an effect on acinar zones 1 and 2, as this reduction is still observed after zone 3 destruction by bromobenzene. Zone 3 hepatocytes may be involved in the effect of parenteral nutrition on bile salt secretion, as the reduction in secretion rate seen in healthy animals was not observed in bromobenzene treated rats.

Effect of pentoxifylline on E-rosette formation and on the mitogenic response of human mononuclear cells.

Pentoxifylline (Trental) has been shown to increase the intracellular cAMP concentration. In the present study we have examined the capacity of the drug to affect E-rosette formation by T lymphocytes. In addition, the mitogenic response of human lymphocytes to phytohemagglutinin (PHA) and concanavalin A (con A) was studied. The drug exerted a dose dependent inhibitory effect on E-rosette formation and on the proliferative response of lymphocytes to PHA and con A. It is suggested that this inhibitory effect is most probably due to the increased intracellular levels of cAMP induced by the drug.

Elevated serum ferritin level in acute myocardial infarction.

Serum ferritin level was determined in 20 patients with acute myocardial infarction (AMI) during the first 10 days post infarction. Starting on the second day, a gradual increase in serum ferritin level was detected, reaching a maximum of four times the initial level on the sixth day after the infarction. In addition, a significant increase in ferritin content was found in the peripheral blood monocytes on the fifth day after the event. The control group comprised six patients suffering from chest pains not due to AMI. In all of them the serum ferritin level was found to be within normal limits. Peripheral blood monocytes derived from healthy individuals incubated with hydrocortisone, showed a significant enhancement of their ferritin content, a finding suggesting that these cells activated by steroids during stress could be a source of the increased serum ferritin level following AMI. It is concluded that measurement of serum ferritin may be used as a complementary tool for confirming the diagnosis of AMI.

Short stature as the major manifestation of celiac disease in older children.

Celiac disease was diagnosed by jejunal biopsy and response to gluten elimination in 11 of 23 children with short stature referred after negative endocrine evaluation. The mean age of the group was 11 years, with a range of 5-16. All had been followed for a mean of 2.5 years at a large pediatric endocrine clinic for the evaluation of growth retardation. Bone age retardation of more than 25 percent of the chronologic age was found in all children. Microcytic anemia and past history of gastrointestinal problems were typical of the celiac group but were not documented in the nonceliac patients. Stool fat excretion was a specific but insensitive test, while the 1-hour blood xylose test was of no value in differentiating between the two groups. Close cooperation between pediatric endocrinology and gastroenterology clinics may be fruitful in the identification of celiac patients, especially in a group of older children with short stature, bone age retardation, and microcytic anemia.

The effect of cisapride on total parenteral nutrition-associated cholestasis in rats.

BACKGROUND: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown. OBJECTIVES: To study the effect of cisapride on TPN-induced cholestasis in a rat model. METHODS: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups. At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct. RESULTS: At the end of the third hour, TPN caused a significant reduction in bile flow (P < 0.02) and bile salt secretion rate (P < 0.001) (61.24 vs. 50.74 microliters/min/kg, and 1.173 vs. 0.799 mumol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN. CONCLUSIONS: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

The role of Helicobacter pylori and gastritis in children with recurrent abdominal pain.

BACKGROUND: Recurrent abdominal pain is a common pediatric diagnostic problem. Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology. OBJECTIVES: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP. PATIENTS AND METHODS: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months. RESULTS: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P < 0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P < 0.01 between the H. pylori-associated gastritis and each of the other groups). CONCLUSIONS: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

Chronic hepatitis B virus in children in Israel: clinical and epidemiological characteristics and response to interferon therapy.

OBJECTIVE: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy. METHODS: We retrospectively studied 51 patients (34 males, 17 females), aged 2-18 years, from several medical centers in Israel. RESULTS: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3-6 MU/m2). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P < 0.05). CONCLUSIONS: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B.

The effect of serum from patients with acute myocardial infarction on in vitro lymphocyte reactivity. II. Inhibition of IL-2 production.

Culture supernatants from concanavalin-A (con-A)-activated peripheral blood lymphocytes from healthy controls grown in the presence of sera from 20 patients 24 hours and 1 week after acute myocardial infarction (AMI) were tested for their mitogenic activity and for the presence of interleukin-2 (IL-2). Binding of exogenous IL-2 to activated lymphocytes from 10 patients was also determined. In supernatants prepared in the presence of patients' as compared to control sera, a significantly decreased mitogenic activity and IL-2 content were found. The mitogenic activity and IL-2 content in culture supernatants prepared with patients' sera collected 24 hours after the AMI (AMI I) and one week thereafter (AMI II) were significantly suppressed, and the degree of suppression in the 24-hour sera was significantly higher than in those collected after one week. No significant differences were observed in the binding capacity to exogenous IL-2 of activated patients' and control lymphocytes. The possibility is that immunosuppressive factors in the patients' sera, including cortisol, may suppress the patients' immune response acting through inhibition of IL-2 production.

The effect of serum from patients with acute myocardial infarction on in vitro lymphocyte reactivity. I. Inhibition of mitogen stimulation.

Sera from 20 patients obtained within 24 hours and one week after acute myocardial infarction (AMI) were tested for their immunomodulating effect on concanavalin-A (con-A) stimulated lymphocyte cultures from 11 healthy unrelated donors. Individual control sera from 21 healthy donors and 5 pools of control sera were used for comparison. Cortisol levels were tested in patients' and controls' sera. A significantly higher suppressive effect was seen in the presence of patients' sera taken at 24 hours than corresponding sera taken one week later. However, the suppressive effect after one week was increased as compared to control sera. A significant correlation between the degree of suppression and the cortisol level in corresponding sera was observed. An increased immunosuppression was observed with increased cortisol levels.