Alveolitis in the pulmonary syndrome of Wilson and Mikity.
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Female↗
Biomedical subjects
A Rubinstein
Publications and source records attributed to A Rubinstein.
Pharmacokinetics of valpromide in dogs after various modes of administration.
Valpromide-Dipropylacetamide was administered to five dogs via five modes: Three oral formulations (solution, capsule, and enteric-coated tablet), intravenous and intramuscular injections. No significant change in the terminal half-life of valpromide could be observed after the various modes of administration in each dog. Valpromide was more rapidly absorbed after the administration of an oral solution than after i.m. injection. Similar data also were obtained for its metabolite--valproic acid. It was shown that valpromide in the dogs was partly biotransformed to valproic acid. The average fraction of valpromide that was transformed to valproic acid (fm) ranged from 30-55 per cent after all the oral and parenteral administrations, except for the enteric-coated tablet, which showed a very low bioavailability of valpromide.
Administration, Oral↗
Microbially controlled drug delivery to the colon.
The human gastrointestinal tract consists of a highly complex ecosystem of aerobic and anaerobic microorganisms that plays a significant role in the metabolism of nutrients as well as drugs. In the colon, bacteria ferment various types of substrates that are not susceptible to digestion in the small intestine. This arouses interest in specific drugs, drug delivery systems, and prodrugs that escape small bowel digestion, arrive intact, and are absorbed or degraded in the large bowel. For the past forty years, experience has been gained with the azo prodrug of 5-amino salicylic acid, salazopyrine, which is cleaved by colonic bacteria to its parent drug. Some laxative drugs were also reported to degrade into active metabolites in the colon. Lately equally interesting and more sophisticated microbial controlled delivery systems, have been developed based on similar principles.
Animals↗
Diagnostic bronchoalveolar lavage in children with AIDS.
Between October, 1985 and May 1987, 29 children (mean age 22 +/- 22 months, range 2-54 months) with AIDS or ARC developed acute respiratory illness. The initial diagnostic procedure was flexible fiberoptic bronchoscopy, with bronchoalveolar lavage (BAL). BAL was positive for Pneumocystis carinii in 14 and for respiratory syncytial virus, Staphylococcus aureus, and Escherichia coli in 3 additional patients. Subsequent lung tissue analysis and/or clinical course suggested no false negative lavages. Complications possibly related to the procedure occurred in two patients. We find BAL an effective diagnostic technique in these patients, offering a less invasive alternative to open lung biopsy.
AIDS-Related Complex↗
Corticosteroid treatment for pulmonary lymphoid hyperplasia in children with the acquired immune deficiency syndrome.
Five children with positive serology for human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay and Western blot were followed for chronic pulmonary disease. Lung biopsies were performed in all patients, and confirmed the diagnosis of pulmonary lymphoid hyperplasia. All children demonstrated progressive hypoxia and increasing alveolar capillary oxygen gradients over at least 1 year of follow-up. All children were on periodic intravenous gamma globulin treatment for a B-cell defect prior to the initiation of corticosteroid therapy. Prednisone was initially given at a dose of 2 mg/kg daily and was subsequently tapered to an alternate day regimen. All children showed improvement in oxygenation. No deterioration in immune function was noted, and there was no increase in bacterial infection. This study indicates that corticosteroids can successfully reverse the severe hypoxia that may result from pulmonary lymphoid hyperplasia in pediatric AIDS patients.
Acquired Immunodeficiency Syndrome↗
Rapid healing of diabetic foot ulcers with meticulous blood glucose control.
Fifteen diabetic patients, with neuropathic food ulcers refractory to conventional treatment, were found to be poorly balanced and were put on meticulous regimens; some on continuous subcutaneous insulin infusion and others on split mixed doses. Once diabetes was controlled, the wound healed rapidly in 11 of the patients within 4 to 13 weeks. In 4 patients amputation was necessary. The outcome was better in patients with good peripheral pulses. We suggest that tight control of diabetes promotes healing of diabetic foot lesions.
Adult↗
Opportunistic lymphoproliferations associated with Epstein-Barr viral DNA in infants and children with AIDS.
Two types of lymphoproliferative disease associated with Epstein-Barr viral (EBV) DNA--central-nervous-system lymphoma and chronic lymphocytic interstitial pneumonitis (LIP)--were recognised in children with human T-lymphotropic virus type III/lymphadenopathy virus infection and the acquired immunodeficiency syndrome (AIDS). Eight of ten lung biopsy specimens from children with LIP contained EBV DNA. EBV DNA was not identified in lung biopsy specimens with Pneumocystis carinii, cytomegalovirus, or atypical mycobacteria but without LIP, nor was EBV found in lung biopsy specimens from five adults with AIDS. Children with these EBV-associated complications had raised serum antibody titres to the replicative EBV antigens, but most of them lacked antibody to the component of the EB nuclear antigen encoded by the Bam HI K fragment. EBV-associated lymphoproliferative disease is a common and important complication of childhood AIDS.
Acquired Immunodeficiency Syndrome↗
Enhanced biorecognition and internalization of HPMA copolymers containing multiple or multivalent carbohydrate side-chains by human hepatocarcinoma cells.
N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing pendant saccharide moieties (galactosamine, lactose, and triantennary galactose) were synthesized. The relationship between the content of saccharide moieties and three-dimensional arrangement of galactose residues and their biorecognition and internalization by human hepatocarcinoma HepG2 cells was investigated. The results obtained clearly indicated preferential binding of the trivalent galactose and the lactose-containing copolymers to these cells. The higher the saccharide moieties content in HPMA copolymers, the higher the levels of binding. The biorecognition of the glycosylated HPMA copolymers by HepG2 cells was inhibited by free lactose. The data on the internalization and subcellular trafficking of HPMA copolymer conjugates obtained by confocal fluorescence microscopy correlated well with the flow cytometric analysis of their biorecognition by target cells. Structural features of the glycosides responsible for the specific recognition of the HPMA copolymers have been identified. The results underline the potential of glycosylated HPMA copolymers for delivery of pharmaceutical agents to hepatocarcinoma cells.
Biological Transport↗
Bacterial infection in the acquired immunodeficiency syndrome of children.
We have followed 46 children with acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. Twenty-six patients had at least one episode of serious bacterial infection. Twenty-seven episodes of sepsis were documented in 21 patients. Soft tissue infection was common in both the presence and the absence of documented bacteremia. Urinary tract infection commonly presented as worsening diarrhea in the absence of sepsis. Organisms commonly isolated included Streptococcus pneumoniae, Haemophilus influenzae and Salmonella sp. Staphylococcal infection accompanied episodes of cellulitis/abscess. Escherichia coli commonly caused urinary tract infection in the absence of sepsis. Enteric and nosocomial sepsis was limited to hospitalized, instrumented patients or to individuals who had received prior antibiotic therapy as outpatients. We conclude that bacterial infection causes serious morbidity in acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex and may be further evidence for altered humoral immunity in the disorder.
Acquired Immunodeficiency Syndrome↗
Apo E-containing lipoproteins in low or high density lipoprotein deficiency.
Apolipoprotein (apo) E-containing subfractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) have been described in normolipidemic and hyperlipidemic subjects. These lipoproteins exist, however, in the presence of large amounts of apo A-I- and apo B-containing lipoproteins so that it has been difficult to assess the independence of these apo E-containing subclasses from the major lipoprotein classes. The present study has approached this question by taking advantage of three hypolipidemic states in which one or more of the major apolipoproteins is deficient or absent. After separating lipoproteins from whole plasma by molecular sieve chromatography followed by radioimmunoassay of column fractions, we found that two subjects with abetalipoproteinemia had no apo E-containing lipoproteins the size of VLDL or IDL and all the plasma apo E was in a fraction of large HDL. Two subjects with Tangier disease and two with familial apo A-I/C-III deficiency had extremely low levels of HDL cholesterol and of apo A-I-containing lipoproteins. In spite of the absence of classical HDL, a major fraction of apo E-containing lipoproteins was reproducibly observed at the elution volume characteristic of large HDL and was identical to that found in normal subjects. These data thus suggest the existence of apo E-containing lipoproteins that are the size of HDL and are not dependent upon the presence of either apo B or apo A-I. While studies in normal subjects indicate that apo E is associated with other apolipoproteins in HDL, further investigations will be needed to determine the full composition of these apo E-containing lipoproteins in the lipoprotein-deficient patients described in this report.
Abetalipoproteinemia↗
Plasma lipoprotein distribution of apolipoprotein E in familial hypercholesterolemia.
Although familial hypercholesterolemia (FH) has been well characterized in terms of the etiology of the major lipoprotein abnormality, that of low density lipoproteins (LDL), less information is available on changes in other lipoproteins which could influence the atherogenic process in this disorder. The present study has focused on such potential abnormalities by studying in detail the lipoprotein association of apolipoprotein E (apo E) in a large group of subjects homozygous for FH. Total plasma apo E levels in homozygous subjects were significantly elevated (p less than 0.001) relative to heterozygous subjects which were, in turn, significantly greater (p less than 0.001) than controls (137.6 micrograms/ml, 69.4 micrograms/ml, 46.5 micrograms/ml respectively). After separation of plasma lipoproteins by 4% agarose chromatography, an increased mass of apo E in lipoproteins of intermediate size was present; this may reflect the absence of LDL receptors that normally mediate their clearance. Homozygous FH subjects also demonstrated an increased mass of apo E-enriched high density lipoproteins (HDL) of large size, but a reduction in HDL cholesterol and apo A-I. The increase in the potentially atherogenic remnant lipoproteins and the decrease in HDL are associated with an increased risk for atherosclerosis, even in the absence of the LDL elevation, which is characteristic of FH. The increase in apo E-enriched HDL could reflect a compensatory mechanism that permits reverse cholesterol transport in the absence of LDL receptors.
Apolipoprotein C-III↗
Latency of auditory nerve response in neonates one to eight hours old.
Recording the response of the auditory nerve (W1) in neonates can contribute to the diagnostic distinction between audiological-otological versus neurological pathology. If W1 latency were subject to relatively rapid shortening in the hours directly after birth, inconsistencies in the literature might be clarified. The purpose of this research was to study W1 in neonates one to eight hours old in order to determine if significant latency changes occur during this period. Auditory nerve-brainstem responses were recorded in 40 full-term neonates and in 12 normal adults. W1 latency in 1- to 3-hour-old neonates was 1.81 +/- 0.28 ms and 1.77 +/- 0.18 ms in 7- to 8-hour-old neonates. This difference was not significant. In adults, W1 latency was significantly shorter (1.36 +/- 0.06 ms). These findings indicate that auditory nerve latency is about 0.43 ms longer at birth than in the adult and that the latency does not shorten significantly during the first hours after birth.
Adult↗
Clinical and immunologic effects of lipid-based parenteral nutrition in AIDS.
The effect of lipid-based parenteral nutrition was assessed in eight patients with AIDS and weight loss of 10% or greater. All patients received home parenteral nutrition consisting of a lipid-based system with 50% of nonprotein calories given as fat. Measurements were made of body weight, serum albumin, and immune function as assessed by mitogen responses, P24 antigen levels and T-cell counts. Over a period of 2 months, weight gain and improved well-being were noted in all patients. An improved in vitro lymphocyte mitogenic response to phytohemagglutinin and to concanavalin A was also noted. No change in T-cell subsets was observed. Viral cultures and P24 serum levels also remained unchanged. Lipid-based parenteral nutrition is safe and probably efficacious in AIDS.
Acquired Immunodeficiency Syndrome↗
Hyperglycemia preceding stroke.
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Cerebrovascular Disorders↗
Platelet-associated IgG in pediatric HIV infection.
Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluates for the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children.
Antibody Specificity↗
Elevated tumor necrosis factor-alpha in association with severe anemia in human immunodeficiency virus infection and Mycobacterium avium intracellulare infection.
Mycobacterium avium intracellulare (MAI) infection is a serious opportunistic infection that occurs in children with human immunodeficiency virus (HIV) infection. In MAI the hematologic system is profoundly affected. In the present study the hematologic manifestations of MAI in 37 HIV-infected infants and children were reviewed. Anemia was the predominant feature in all patients, with severe anemia (hemoglobin < 6 g/dL) occurring in 7 of 34 (21%) patients. This was followed by leukopenia (79%), monocytosis (82%), thrombocytopenia (59%), leukoerythroblastic reaction (68%), and neutropenia (41%). Serum tumor necrosis factor (TNF)-alpha was markedly elevated in all patients with MAI with an X +/- SE of 702 +/- 182 pg/mL. There was an association between elevated TNF-alpha and anemia in these patients.
AIDS-Related Opportunistic Infections↗
Hypertriglyceridemia may cause a subclinical peripheral neuropathy.
Recently few patients with a painful neuropathy, attributed to extremely high triglyceride levels, were reported. In a prospective study, we evaluated 16 patients with marked hypertriglyceridemia without other causes of neuropathy, using nerve conduction and autonomic function tests. Six subjects (37%) showed mild signs of an asymptomatic motor and/or sensory and/or autonomic axonal polyneuropathy. The study demonstrates, that hypertriglyceridemia may be associated with a mild axonal polyneuropathy, usually subclinical, in significantly more patients than previously considered.
Action Potentials↗
Human immunodeficiency virus within the brains of children with AIDS.
Infants and children with symptomatic human immunodeficiency virus (HIV) infection frequently develop neurologic disease with symptoms and signs of acquired microcephaly, developmental delays, encephalopathy, pyramidal tract signs, and less often, movement disorders and ataxia. However, clinical courses vary and, based upon progression of neurologic findings, we have classified them into 2 broad categories; progressive (loss of previously acquired language and cognitive skills) and plateau (failure to acquire additional developmental skills). We have used immunocytochemistry to localize HIV within the brains of neurologically involved children with AIDS. Interestingly, the brains of those children with a progressive neurologic course showed readily detectable HIV antigen, while those with a plateau course showed little or no detectable HIV. These findings suggest that in children with symptomatic HIV infection, the progressive neurologic deterioration is due to continued presence of HIV within deep white matter and gray matter, while the plateau neurologic course is due to HIV induced damage followed by either limited penetration of virus into the central nervous system, or clearance of virus below detectable limits.
AIDS Dementia Complex↗