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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 217 records · Page 12Linked to original sources

AIDS: calcification of the basal ganglia in infants and children.

CT or postmortem examination demonstrated calcification of the basal ganglia in eight infants and children with acquired immune deficiency syndrome. Serial CT studies documented progression of both bilateral symmetric calcium densities and cerebral atrophy. Clinical features included progressive encephalopathy with dementia, and pyramidal tract signs. Postmortem examination of four children revealed variable degrees of calcific vasopathy of the basal ganglia, involving predominantly the putamen and globus pallidus.

Acquired Immunodeficiency Syndrome↗

Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne.

Abnormalities in plasma lipids are a recognized side effect of isotretinoin therapy for nodulocystic acne. We studied 60 patients during 20 weeks of isotretinoin therapy, to measure changes in plasma lipids and lipoproteins, to compare plasma lipid responses in men and women, and to determine whether there are alterations in levels of lipoprotein lipase or hepatic triglyceride lipase that could explain the development of isotretinoin-induced hypertriglyceridemia. Mean triglyceride levels rose in men and women, with maximum mean increases of 46.3 mg per deciliter (P less than 0.0001) and 52.3 mg per deciliter (P less than 0.002), respectively. The maximum level was reached by 4 weeks of therapy in men but not until the 12th week in women. Nine of 53 patients (17 per cent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter. Both men and women had significant increases in mean plasma levels of cholesterol and low-density-lipoprotein cholesterol and decreases in mean levels of high-density-lipoprotein cholesterol. There were no significant changes in mean levels of lipoprotein lipase or hepatic triglyceride lipase. Plasma lipid and lipoprotein levels returned to base line by eight weeks after discontinuation of the drug. If sustained over a long period, the change in the ratio of low-density-lipoprotein cholesterol to high-density-lipoprotein cholesterol that we observed, from 2.4 to 3.0 (P less than 0.0001), would predict an increased risk of cardiovascular disease.

Acne Vulgaris↗

Immunoaffinity isolation of apolipoprotein E-containing lipoproteins.

Discrete apolipoprotein E-containing lipoproteins can be identified when EDTA plasma is fractionated on columns of 4% agarose. The present study has demonstrated, by physical and metabolic criteria, that these apolipoprotein E-containing lipoprotein subclasses may be further isolated by immunoaffinity chromatography. Whole plasma was first bound to an anti-apolipoprotein E immunoadsorbent prior to gel filtration on 4% agarose. After elution from the affinity column and dialysis, the bound fraction was chromatographed on 4% agarose. Discrete subfractions of apolipoprotein E could be demonstrated within elution volumes similar to those observed in the original plasma. When whole plasma was first submitted to gel filtration and the apolipoprotein E-containing lipoproteins of either intermediate- or of high-density lipoprotein (HDL) size were subsequently bound to anti-apolipoprotein E columns, the bound eluted fractions maintained their size and physical properties as shown by electron microscopy and by rechromatography on columns of 4% agarose. The metabolic integrity of apolipoprotein E-containing very-low-density lipoproteins (VLDL) was examined by coinjection into a cynomolgus monkey of 125I-labeled apolipoprotein E-rich and 131I-labeled apolipoprotein E-deficient human VLDL which had been separated by immunoaffinity chromatography. The plasma specific activity time curves of the apolipoprotein B in VLDL, intermediate-density (IDL) and low-density (LDL) lipoproteins demonstrated rates of decay and precursor-product relationships similar to those obtained after injection of whole labeled VLDL, supporting the metabolic integrity of VLDL isolated by immunoaffinity chromatography.

Animals↗

Neurological complications in infants and children with acquired immune deficiency syndrome.

Neurological complications occurred in 6 children, aged 6 months to 5 years, with acquired immune deficiency syndrome who were followed for 14 months. The most frequent manifestations included encephalopathies, acquired microcephaly, and pyramidal tract signs. Computed tomographic examinations showed variable degrees of cortical atrophy with ventricular dilatation and calcification. Electrophysiological abnormalities were demonstrated. Two children had documented central nervous system infections. Neurological deterioration resulted in dementia in 3 children. Cognitive impairment and developmental delays were evident in the other 3. Postmortem examination of the 3 children who died showed subacute cytomegalovirus encephalitis in 1; nonspecific hemispheric white matter changes, calcific vasopathy of the basal ganglia, and striking bilateral corticospinal tract degeneration in the second; and extensive calcific vasopathy of the basal ganglia and frontal centrum semiovale, and bilateral attenuation of the frontopontine and corticospinal tracts in the third.

Acquired Immunodeficiency Syndrome↗

Inhibition of lymphocyte response to mitogens by dipyridamole: preliminary findings.

It has been recently noted that dipyridamole (DP) may be involved in certain immunological reactions, in addition to its antiplatelet action. In the present investigation the mitogenic response of human lymphocytes from three groups of subjects to 3 different lectins was examined. In both the experimental group treated over a short period and in the controls a highly significant decrease in the mean lymphocyte response to all 3 mitogens was noted following 3 days of DP administration. The response remained low after an additional 3 days of treatment. Discontinuation of drug administration was followed by a significant increase in response to two mitogens, concanavalin A (Con A) and pokeweed mitogen (PWM). The response to phytohaemagglutinin (PHA) extent only increased to a small, non-significant. No change in the mean mitogenic response was detected in the group undergoing long-term treatment. The mechanism by which DP alters lymphocyte activity is as yet unknown.

Adult↗

Serum lactate dehydrogenase levels in adults and children with acquired immune deficiency syndrome (AIDS) and AIDS-related complex: possible indicator of B cell lymphoproliferation and disease activity. Effect of intravenous gammaglobulin on enzyme levels.

Twenty-seven of 33 patients with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex (16 adults and 17 children) demonstrated significant elevation of serum lactate dehydrogenase activity, occurring in the isomorphic distribution. Serum lactate dehydrogenase activity was the highest in all nine patients with acute Pneumocystis carinii pneumonitis, in seven of whom extensive interstitial pulmonary infiltrates with lymphocytes and plasma cells were documented. Lactate dehydrogenase activity was also significantly elevated on a long-term basis in all 17 pediatric patients with non-Pneumocystis lymphoid interstitial pneumonitis. Clinical resolution of Pneumocystis carinii pneumonitis was associated with a decline in lactate dehydrogenase activity. Periodic intravenous gammaglobulin was more effective than conventional therapy (trimethoprim/sulfamethoxazole and pentamidine) in achieving clinical and immunologic improvement and reduction of serum lactate dehydrogenase activity in patients with Pneumocystis carinii pneumonitis. Intravenous gammaglobulin was also more effective in patients with AIDS and non-Pneumocystis carinii pneumonitis and lymphoid interstitial pneumonitis. Lactate dehydrogenase activity declined to normal, at least temporarily, in nine of 12 intravenous gammaglobulin-treated patients as compared with only two of 12 untreated patients. Six adult patients with AIDS or AIDS-related complex and no interstitial pneumonitis exhibited normal lactate dehydrogenase levels. These findings suggest that serum lactate dehydrogenase activity in patients with AIDS or AIDS-related complex may be a useful indicator of pulmonary interstitial inflammation. As such, it may be utilized to predict disease course and monitor response to intravenous gammaglobulin treatment.

Acquired Immunodeficiency Syndrome↗

Defective humoral immunity in pediatric acquired immune deficiency syndrome.

Specific antibody production was assessed in six young children with the acquired immune deficiency syndrome (AIDS). All patients were immunized with bacteriophage phi X 174, a T cell-dependent neoantigen. In addition, antibody responses to pneumococcal vaccine and tetanus toxoid, lymphocyte responses to mitogens, and serum immunoglobulin levels were determined. Polyclonal hypergammaglobulinemia was documented in three patients. Responses to bacteriophage phi X 174 were abnormal in all patients: primary responses were blunted, secondary responses were markedly decreased, and the class switch (IgM-IgG) was absent in five of six patients. Antibody formation to pneumococcal vaccine and tetanus toxoid was also diminished. Lymphocyte mitogenic responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, and staphylococcal Cowan A were generally decreased. These findings confirm that pediatric patients with AIDS have significant abnormalities in humoral immunity. Dysfunction of both T cells and B cells plays a role in the resultant poor specific antibody production.

Acquired Immunodeficiency Syndrome↗

Developmental abnormalities in infants and children with acquired immune deficiency syndrome (AIDS) and AIDS-related complex.

Children with acquired immune deficiency syndrome (AIDS) display two types of clinical picture: a full-blown AIDS characterized by the presence of opportunistic infections and/or Kaposi's sarcoma and a prodromal stage now identified as AIDS-related complex (ARC). Neurological complications have been identified in infants and children with the disease. This paper discusses the developmental abnormalities in 16 pediatric patients, seven with AIDS and nine with ARC, ranging in age from six months to six years. In all cases, the mothers of these children either had ARC, AIDS and/or used intravenous drugs. Developmental histories showed delayed acquisition of milestones in most children following the diagnosis of AIDS or ARC, with delayed motor milestones consistently noted in both groups. Several children with AIDS actually lost milestones as their illness progressed; this has not occurred in the ARC group. Psychometric testing revealed more severe cognitive dysfunction in the group with AIDS. Involvement of the central nervous system was documented clinically, radiologically, and/or electrophysiologically in all patients with AIDS. In the ARC group the course of the illness has shown greater variability. Medical and social factors that may contribute to the developmental abnormalities are discussed.

Acquired Immunodeficiency Syndrome↗

Treatment of blood hyperviscosity with calcium dobesilate in patients with diabetic retinopathy.

This double-blind randomized trial was carried out on 37 patients with diabetic retinopathy and blood hyperviscosity. 19 patients received calcium dobesilate in capsules of 500 mg 3 times daily for 3 months and 18 patients took 3 placebo capsules daily during the same period. Calcium dobesilate was found to reduce whole-blood viscosity in a statistically significant manner which was accompanied by a diminution of the albumin/globulin ratio and a significant reduction of fibrinogen and cholesterol levels. A statistically significant diminution of capillary fragility was also observed in the calcium dobesilate-treated group. These results indicate that calcium dobesilate, by restoring the integrity of the microvessels, and by lowering blood viscosity, could act favorably on the evolution of diabetic retinopathy.

Adult↗

Effect of heparin-induced lipolysis on the distribution of apolipoprotein e among lipoprotein subclasses. Studies with patients deficient in hepatic triglyceride lipase and lipoprotein lipase.

In normal subjects, apolipoprotein E (apo E) is present on very low density lipoproteins (VLDL) (fraction I) and on particles of a size intermediate between VLDL and low density lipoproteins (LDL) (fraction II). The major portion of apo E is, however, on particles smaller than LDL but larger than the average high density lipoproteins (HDL) (fraction III). To investigate the possible role of the vascular lipases in determining this distribution of apo E among the plasma lipoproteins, we studied subjects with primary deficiency of either hepatic lipase or of lipoprotein lipase and compared them with normal subjects. Subjects with familial hepatic triglyceride lipase deficiency (n = 2) differ markedly from normal in that fraction II is the dominant apo E-containing group of lipoproteins. When lipolysis of VLDL was enhanced in these subjects upon release of lipoprotein lipase by intravenous heparin, a shift of the apo E from VLDL into fractions II and III was observed. In contrast, apolipoproteins CII and CIII (apo CII and CIII, respectively) did not accumulate in intermediate-sized particles but were shifted markedly from triglyceride rich lipoproteins to HDL after treatment with heparin. In subjects with primary lipoprotein lipase deficiency (n = 4), apo E was confined to fractions I and III. Release of hepatic triglyceride lipase by heparin injection in these subjects produced a shift of apo E from fraction I to III with no significant increase in fraction II. This movement of apo E from large VLDL and chylomicron-sized particles occurred with little hydrolysis of triglyceride and no significant shift of apo CII or CIII into HDL from triglyceride rich lipoproteins. When both lipoprotein lipase and hepatic triglyceride lipase were released by intravenous heparin injection into normal subjects (n = 3), fraction I declined and the apo E content of fraction III increased by an equivalent amount. Either moderate or no change was noted in the intermediate sized particles (fraction II). These data strongly support the hypothesis that fraction II is the product of the action of lipoprotein lipase upon triglyceride rich lipoproteins and is highly dependent on hepatic triglyceride lipase for its further catabolism. In addition, the hydrolysis by hepatic triglyceride lipase of triglyceride rich lipoproteins in general results in a preferential loss of apo E and its transfer to a specific group of large HDL.

Adult↗

Acquired immunodeficiency syndrome (AIDS) in infants and children: report of nine cases.

We report here nine children with AIDS. The risk factors of these patients were hemophilia in one, blood transfusions in four, maternal intravenous drug use in three and paternal AIDS in one. One baby was also of Haitian parentage. The major clinical symptoms included failure to thrive, hepatomegaly, lymphadenopathy, interstitial pneumonia, recurrent bacterial and viral infections and persistent oral thrush. Three infants had chronic recurrent parotitis. Five infants developed opportunistic infections primarily Pneumocystis carinii pneumonia and all five died of bacterial sepsis. None of the infants were lymphopenic but all had reversed T4/T8 ratios and poor in vitro lymphocyte responses to pokeweed mitogens. Although many of the clinical and laboratory features of pediatric and adult AIDS are similar, there are some unique features for pediatric AIDS such as the absence of lymphopenia and the high prevalence of recurrent bacterial infections and sepsis.

Acquired Immunodeficiency Syndrome↗

Fetal transmission of AIDS through the mother's womb.

The obstetrician and pediatrician must be alert to the potential development of AIDS in children born to mothers with AIDS/ARC or to healthy mothers who belong to a risk group for AIDS. Serologic studies for HTLV-III should be conducted during pregnancy. In the future it may be possible to identify the AIDS virus or antibodies to it in amniotic fluid obtained by diagnostic amniocentesis. In the interim, sonographic studies during pregnancy in women at risk for AIDS may be helpful in identifying fetal intrauterine growth retardation and may help raise our level of suspicion for congenital AIDS. There is no definitive cure for pediatric AIDS yet. However, recent studies suggest that intravenous gammaglobulin with or without specific antibodies to HTLV-III may arrest disease progression. Under these circumstances, early institution of treatment may alter the disease course favorably.

Acquired Immunodeficiency Syndrome↗

Evidence for non-equilibrating pools of apolipoprotein C-III in plasma lipoproteins.

Using immunoaffinity chromatography to isolate apoC-III from radiolabeled lipoproteins for direct determination of specific radioactivity, we have studied the metabolism of human apoC-III in VLDL and in HDL following the bolus injection of 125I-labeled VLDL. Transfer of apoC-III radioactivity from VLDL to HDL was detected in the plasma sample drawn 5 min after injection of the tracer. However, the specific radioactivity of apoC-III in VLDL was found to be higher than that in HDL, with this difference being maintained throughout the sampling period (48-72 hr). The ratios of the respective specific activities ranged from 1.2 to 1.9 in six subjects studied (two normolipidemics and four hypertriglyceridemics). When 125I-labeled HDL was injected as the tracer, however, the higher apoC-III specific radioactivity was associated with the HDL fraction. This lack of complete equilibration of apoC-III between VLDL and HDL in vivo was further characterized by in vitro studies using either 125I-labeled VLDL or 125I-labeled HDL. All incubations were carried out for 3 hr at 37 degrees C followed by 16 hr at 4 degrees C and the apoC-III specific activity in each lipoprotein fraction was directly determined after immunoaffinity chromatography. In a study of plasma from a mildly hypertriglyceridemic subject in which 125I-labeled VLDL was incubated with unlabeled HDL, apoC-III specific activities in VLDL remained 30% greater than that in HDL. When 125I-labeled HDL (from the same subject) was incubated with unlabeled VLDL of apoC-III, final specific activity in VLDL was less than 10% of that of HDL apoC-III. Differences in specific activities were also demonstrated when radiolabeled purified apoC-III was exchanged onto VLDL prior to its incubation with HDL. A consistent difference in apoC-III specific activities in VLDL and HDL was observed after isolation of the particles either by molecular sieve chromatography or by ultracentrifugation. These studies demonstrated that, while the exchange of apoC-III between VLDL and HDL may be very rapid, this equilibration is not complete. Pools of apoC-III that do not participate in the equilibration process are present in both the VLDL and HDL fractions and could account for 30-60% of the total apoC-III mass in each lipoprotein fraction.

Adult↗

Rapid gas chromatographic assay for monitoring valproic acid and valpromide in plasma.

A gas chromatographic (GC) method for monitoring valproic acid and valpromide in plasma was developed. The procedure involved a single solvent extraction of drugs from acidified plasma samples, followed by a GC injection of the organic phase. This rapid, sensitive, specific, and reproducible method is a key factor in pharmacokinetic and stability studies of valpromide. Pharmacokinetic application of the new GC method is presented by a simultaneous plasma monitoring of valpromide and valproic acid levels obtained after intravenous administration of valpromide to a dog.

Chromatography, Gas↗

Pharmacokinetics of valpromide after oral administration of a solution and a tablet to healthy volunteers.

The pharmacokinetics of valpromide, a primary amide of valproic acid, was investigated in 6 healthy, adult male volunteers, each of whom was given 900 mg as a marketed, enteric-coated tablet and a solution. Valpromide was biotransformed to valproic acid after the administration of the tablet and the solution with a bioavailability of 0.79 +/- 0.24 and 0.77 +/- 0.12, respectively, relative to a marketed tablet of valproic acid. The absorption of valpromide was not rate-limited by dissolution. As a solid, nonhygroscopic, neutral prodrug of valproic acid, valpromide may be a good alternative to valproic acid and sodium valproate.

Adult↗

Babesiosis in asplenic hosts.

A case of babesiosis in an asplenic individual is reported. A course characterized by fever, haemolysis, hepatitis, depressed mental status and non-cardiac pulmonary oedema was observed. Studies performed on the patient's lymphocytes revealed profound depression in mitogenic responses during her acute disease which returned to normal with recovery. Serum factor(s) were implicated in causing these changes. Review of the literature on babesiosis in asplenic hosts revealed European patients with disease caused by bovine species of Babesia are at significantly higher risk of a fatal outcome than North Americans with disease caused by murine species.

Adult↗