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Biomedical subjects

H Goldstein

Publications and source records attributed to H Goldstein.

At least 91 records · Page 5Linked to original sources

Comparison of idiom comprehension of normal children and children with mental retardation.

This study compared the comprehension of 20 idioms of normal children with children exhibiting mild mental retardation. Sixty-six children comprised three groups: normal 9-year-olds, 9-year-old children with mild mental retardation, and younger normal children matched with the mentally retarded children by receptive vocabulary age. The assessment included both literal and idiomatic contexts with accompanying picture stimuli. The three groups demonstrated high accuracy with the literal contexts. On the idiomatic contexts, the normal children comprehended significantly more idioms than the children with mental retardation, and the mentally retarded children performed significantly better than the younger normal children.

Child↗

Cellular and antibody responses directed against the HIV-1 principal neutralizing domain in HIV-1-infected children.

The principal neutralizing domain (PND) for antibody response is located within the V3 variable region of gp120 and can also stimulate T-cell responses. In some adults infected with human immunodeficiency virus (HIV) an HIV-1-specific T-cell response can be detected by demonstrating in vitro proliferation to HIV-1 proteins and peptides. In other HIV-1 infected adults an HIV-1-specific T-cell response can involve interleukin 2 (IL-2) secretion in the absence of T-cell proliferation. To elucidate the T-cell responses to PND in children, we examined the proliferative and the IL-2 secretory responses of peripheral blood lymphocytes from 19 HIV-1-infected children toward a peptide which contained a highly conserved sequence of the principal neutralizing domain of HIVMN (PND-MN). Stimulation with PND-MN induced proliferation of lymphocytes from 2 of the children and IL-2 secretion by lymphocytes from 5 of the children. In a 3-month-old infant, the in vitro cellular response to the PND-MN indicated HIV-1 infection prior to the detection p24 antigen in her serum. Although antibodies directed against PND-MN were detected in all but one of the children examined, the presence of high-affinity/avidity antibodies to the PND-MN correlated with the presence of a cellular response to PND-MN. Thus, in HIV-1-infected children an HIV-1 specific T-cell response in the absence of a proliferative response can be assessed by determination of the IL-2 secretory response and correlates with the generation of high-affinity/avidity antibodies.

Amino Acid Sequence↗

Characterization of IgG and IgG subclass antibodies present in paired maternal and fetal serum which are directed against HIV-1 proteins.

Passive immunity is conferred to the fetus by maternal antibodies, the majority of which are transported across the placenta during the third trimester of pregnancy. To determine the placental transport of anti-HIV-1 antibodies, serum from 5 women infected with human immunodeficiency virus (HIV) and their abortuses were examined for anti-HIV-1 antibodies. The gestational age of the abortuses ranged from 18 to 24 weeks and following polymerase chain reaction amplification, HIV-1 gag DNA was detected in tissue from 2 of the abortuses. The concentration of total IgG antibodies present in cord blood ranged from 2.9% to 12.5% of maternal levels. Antibodies directed against the envelope proteins, gp160 and gp120, the reverse transcriptase protein, p66, and the capsular protein, p24, were present in fetal and maternal serum. Although IgG1 was the predominant subclass antibody generated in response to HIV-1 proteins, IgG2, IgG3, and IgG4 directed against HIV-1 proteins were also detected. There were large differences in the antigens recognized by the antibodies produced in the mothers, and the IgG subclasses of the antibodies produced. HIV-1 proteins recognized by antibodies present in cord blood were similar to those recognized by paired maternal serum and IgG1, IgG2, IgG3 recognizing HIV-1 proteins were detected in fetal serum. However, there was a dichotomy in placental transport of IgG subclass antibodies to HIV-1 proteins. The role of these antibodies in prevention of vertical transmission of HIV-1 has yet to be determined.

DNA, Viral↗

Inhibition of HIV-1 infection by alkylureas.

The risk of infection by HIV-1 through transfusion of contaminated blood products has been markedly decreased but not eliminated by serological screening of donors. Methods are required to further minimize or eliminate the risk of infection of blood product recipients. We therefore examined the capacity of alkylureas to inhibit infectivity of HIV-1. Incubation of free HIV-1 virions with alkylureas suppressed their infectivity, and the minimal inhibitory concentration of the alkylureas was related to the length of the alkyl chain. Butylurea, the most potent inhibitor of HIV-1, inhibited the infectivity of 10(5) median tissue culture infective dose (TCID)50 of HIV-1, chronically HIV-1-infected H9 cells and mononuclear cells from two HIV-1-infected patients. Size fractionation of HIV-1 following incubation with butylurea indicated that the structure of the virus was disrupted by butylurea. This study demonstrates that butylurea, at a concentration that has been shown not to affect red blood cell function, can inhibit infectivity of extracellular and intracellular HIV-1. Since the HIV-1 inhibitory capacity of the alkylureas increases with the length of the alkyl side chain, it is likely that hydrophobic interactions between the alkylureas and HIV-1 are responsible for the observed effect.

Cell Line↗

Effects of ranitidine and sucralfate on ketoconazole bioavailability.

Ketoconazole is an oral imidazole antifungal agent useful in the treatment of opportunistic fungal infections. Gastrointestinal absorption of this agent is variable and dependent on the presence of gastric acid. This study compared the effects of concomitant sucralfate administration with ranitidine administration on the pharmacokinetic disposition of a 400-mg ketoconazole dose. Six healthy male volunteers were randomized to receive 400 mg of ketoconazole alone, 1.0 g of sucralfate concomitantly with a 400-mg ketoconazole dose, or ranitidine, administered 2 h prior to a 400-mg ketoconazole dose to titrate to a gastric pH of 6. All subjects received all three regimens in crossover fashion. Gastric pH was measured continuously for 4 h after ketoconazole administration in all subjects by using a Heidelberg radiotelemetry pH capsule. Relative ketoconazole bioavailability was compared between treatments. With sucralfate, five of six subjects demonstrated a decrease in the peak drug concentration in serum as well as an increase in the time to peak concentration, indicating a delay in ketoconazole absorption. The mean area under the concentration-time curve from 0 to 12 h for ketoconazole following gastric alkalinization was significantly different from that of either ketoconazole alone or ketoconazole with sucralfate (P less than 0.01). Continuous gastric pH monitoring allowed correlation between the decrease in ketoconazole bioavailability observed with ranitidine and the increase in gastric pH. The apparent decrease in ketoconazole bioavailability observed with sucralfate appears to be caused by an alternative mechanism since a change in gastric pH was not observed. On the basis of these findings, separating the administration of ketoconazole and sucralfate should be considered to decrease the potential for interaction of sucralfate on ketoconazole bioavailability.

Adult↗

Incidence of fetal chromosome abnormalities in insulin dependent diabetic women.

In order to screen for fetal neural tube defects and chromosome abnormalities, amniocentesis was carried out in 334 women with insulin-dependent diabetes mellitus (IDDM) between 1979 and 1987. Two cases (0.6%; 95% confidence limits 0.1-2.2%) of fetal chromosome abnormality were found: one case of Klinefelter's syndrome and one case of de novo translocation. This is comparable to the overall incidence of chromosome abnormality found at birth and is also comparable to the incidence of fetal chromosome abnormality (1.0%) found by amniocentesis at our Department in a group of 2,264 young non-diabetic women with little risk of contracting genetic disorders. The results suggest that maternal IDDM does not increase the risk of fetal chromosome abnormality and consequently screening by amniocentesis for chromosome abnormalities among diabetic women does not seem to be indicated.

Adult↗

Divergent activities of protein kinases in IL-6-induced differentiation of a human B cell line.

Lymphokines including IL-2, IL-4, and IL-6 are involved in the induction of Ig production by activated B cells. We have investigated the role of protein kinases in IL-6-induced IgM secretion by SKW6.4 cells, an IL-6 responsive B cell line. IL-6-stimulated IgM production was inhibited by elevated intracellular cAMP induced either by the addition of dibutyryl cAMP or cholera toxin. The inhibitory effect of elevated intracellular cAMP was blocked by n-(2-(Methylamino)ethyl)-5-isoquinolinesulfonic dihydrochloride (H8), an inhibitor of protein kinase A. H8 did not affect IgM secretion induced by IL-6. In contrast, the addition of 1-(5-isoquinolinesulfonyl)-2-methylpiperizine dihydrochloride (H7), an inhibitor of protein kinase C activity, markedly inhibited IL-6-stimulated IgM production by SKW6.4 cells. H7 and elevated intracellular cAMP inhibited IgM mRNA expression and subsequent IgM synthesis by SKW6.4 cells. SKW6.4 proliferation, as determined by [3H]thymidine incorporation, was not markedly affected by IL-6, dibutyryl cAMP, cholera toxin, H7 or H8. PMA, an activator of protein kinase C, directly stimulated significant IgM secretion by SKW6.4 cells. When added to PMA-stimulated SKW6.4 cells, IL-6 stimulated additional IgM production. This observation suggested that IL-6 could stimulate differentiation without activating protein kinase C. This was confirmed by demonstrating that IL-6 did not stimulate production of diacylglycerol, did not induce the translocation of protein kinase C from the cytosolic compartment to the plasma membrane and could induce SKW6.4 cells to produce IgM after depletion of their cellular protein kinase C by PMA. Taken together these results suggests that IL-6-stimulated IgM production requires utilization of an H7-inhibitable protein kinase that can be inhibited by a protein kinase A-dependent pathway. Despite the fact that PMA can stimulate IgM production in SKW6.4 cells, IL-6 appears to use a protein kinase pathway other than protein kinase C to induce IgM production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Women's experience of chorionic villi biopsy and its significance for the course of pregnancy. A qualitative study].

Twenty-nine pregnant women and their families were questioned about how they experienced chorion villus biopsy in order to illustrate the significance of the test for the pregnancy. Semistructured interviews were carried out immediately after the test, one week later when the result was available and at ultrasonic scanning at the 18th-20th weeks of pregnancy, and these results form the basis for this study. One woman had a foetus with Down's syndrome. The remaining foetuses had normal chromosomes. The main interpretation of early foetal diagnosis and of a living foetus was positive. For the pregnant woman and her family, the main advantages were that the time of waiting for the result was reduced (as compared to the waiting time following amniocentesis) the psychological relief that the investigation can be performed early in pregnancy and that a possible termination could take place under full anaesthesia.

Adult↗

Effects of a pragmatic teaching strategy for requesting information by communication board users.

The effects of a pragmatic teaching strategy on 4 nonspeaking children's abilities to initiate requests for information (i.e., who, what, and where) using manual communication boards were investigated. A teaching strategy based on milieu teaching and time-delay procedures was developed and embedded in naturally structured communication tasks to evoke information requests. Results indicated that information requests using the communication board occurred only after the pragmatic teaching strategy was applied sequentially to the three request types during the experimental condition. This effect was demonstrated repeatedly across the 4 subjects. Although generalization across request types was not demonstrated, substantial generalization was found across partners and environments. A social validation measure confirmed the treatment effectiveness. Independent raters perceived significant differences when viewing before- and after-training videotapes on 7 of 10 communication variables for all subjects.

Child↗

Generalized learning of receptive and expressive action-object responses by language-delayed preschoolers.

This study examined the effectiveness of matrix-training procedures in teaching action + object utterances in both the receptive and expressive language modalities. The subjects were 4 developmentally delayed preschool boys who failed to produce spontaneous, functional two-word utterances. A multiple baseline design across responses with a multiple probe technique was employed. Subjects were taught 4-6 of 48 receptive and 48 expressive responses. Acquisition of a word combination rule was facilitated by the use of familiar lexical items, whereas subsequent acquisition of new lexical knowledge was enhanced by couching training in a previously trained word combination pattern. Although receptive knowledge was not sufficient for the demonstration of corresponding expressive performance for most of the children, only minimal expressive training was required to achieve this objective. For most matrix items, subjects responded receptively before they did so expressively. For 2 subjects, when complete receptive recombinative generalization had not been achieved, expressive training facilitated receptive responding. The results of this study elucidate benefits to training one linguistic aspect (lexical item, word combination pattern) at a time to maximize generalization in developmentally delayed preschoolers.

Child, Preschool↗

A cost-benefit analysis of prenatal diagnosis by amniocentesis in Denmark.

A cost-benefit analysis of amniocentesis has been performed using both the excess-cost- and the replacement methods and several replacement and discount rates. In Denmark, amniocentesis is offered free of charge to various groups of pregnant women at risk for genetic disorders of the foetus. Most important is age greater than or equal to 35 years. The analysis is based on incidence and survival rates for Down syndrome (trisomy 21), Patau's syndrome (trisomy 13) and Edward's syndrome (trisomy 18), and on incidence and survival rates of children with neural tube defects. If amniocentesis were offered to all pregnant women independent of age, with a supposed participation rate of 75% and if only tangible costs and benefits were included, the analysis shows a benefit:cost ratio greater than 1.0 using discount rates of 4% and 7% (both for the excess-cost- and replacement method); a benefit:cost ratio less than 1.0 is found using 10%. The ratio is approximately 1.0, if pregnant women aged 15-19 and 20-24 years are excluded, using the discount rate 10%. Calculations for other participation rates have also been performed. If intangible costs and benefit are included, the results are uncertain.

Adult↗

Which types of perinatal events are predictable? A look at a risk score model.

This study describes the association of a risk factor model for complicated delivery, perinatal morbidity and perinatal mortality with each of various types of delivery complications, types of perinatal morbidity and causes of perinatal mortality. The material comprises a total cohort, 4,066 pregnant women with singletons in a Danish county, and their newborn infants, of whom 494 (12%) had clinical morbidity during the first 5 days of life; 28 (0.7%) died perinatally. A set of 20 risk factors, identifiable before pregnancy, at any time during the pregnancy or at term, was devised by joining existing models for prediction of complicated delivery and of perinatal morbidity and mortality. Metabolic and disproportion-related events were well predicted by the model, inertia-related ones less so, and placental conditions not at all, except for abruption. All types of neonatal morbidity (except sepsis) were well predicted, as were deaths. The strongest predictors of perinatal death were signs of hydramnios (RR = 16.1) and growth retardation (RR = 7.2). The 20 risk factors affected 43% of the population, predicting 57% of the unfavorable perinatal events.

Cohort Studies↗

One year of health and social services for adolescents with Down's syndrome. A calculation of costs in a representative area of Denmark.

The costs of the public health and social security system supporting adolescents 14-20 years old with Down's syndrome (DS) over 1 year (1985) were investigated in the county of Aarhus, representing about 10% of the Danish population. Seventy-eight percent of the probands lived in private homes; the rest were institutionalized. No controls lived in an institution. The average yearly price of a DS adolescent living in a private home was Dkr 217,194 (US$ 24,213 or Br.pounds 6,811). If the DS individual was institutionalized, the amount was Dkr 383,271 (US$ 42,728 or Br.pounds 29,665). The average yearly price for a control was: Dkr 33,352 (US$ 3,718 or Br.pounds 2,581).

Adolescent↗

Modeling longitudinal mandibular growth: percentiles for gnathion from 6 to 15 years of age in girls.

Growth of the cephalometric landmark gnathion is modeled mathematically with multilevel statistical techniques. The findings, pertaining to a mixed longitudinal sample (N = 772) of 105 girls, 6 to 15 years of age, provide the most accurate descriptions of longitudinal mandibular growth presently available. Polar, rather than rectangular, coordinates are used to better distinguish between the amount and direction of growth. The velocity curve for sella-gnathion includes growth spurts during childhood (7.5 years) and adolescence (12.7 years). Growth direction of gnathion changes regularly throughout the age range, indicating a relative increase of vertical over horizontal growth. These reference standards serve as a basis for comparing and better understanding abnormal growth patterns.

Adolescent↗

Living conditions of an adolescent population with Down's syndrome during a one-year period.

The living conditions during 1985 of 43 probands with Down's syndrome and 55 controls in the Danish county of Aarhus were investigated. All patients and all controls were born January 1, 1965 to December 31, 1970. The mean age on census day (December 31, 1985) was 17.6 years for probands and 17.4 years for controls. On census day, 30 (70%) of the probands lived in private homes, and 13 (30%) were institutionalized. Controls lived in various places of residence, but none were institutionalized. All probands and all controls had a daily occupation during at least part of 1985. Twenty-seven (63%) probands and 25 (46%) controls attended evening classes during 1985. All but one proband, and all controls participated in recreation activities or entertainment during 1985. More than 75% of the probands went outside their permanent residence at least twice a week (school/work excluded). During 1985, 9 (60%) out of 15 probands institutionalized received an average of 6.5 visits; an average of 20.1 phone calls were made to the staff to inquire about the well being of 7 (47%) out of 15 probands.

Adolescent↗

Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin.

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.

Adult↗

Effects of imitation on language comprehension and transfer to production in children with mental retardation.

This study investigated the effects of verbal imitation on the comprehension of novel object-location responses and subsequent transfer of these responses to production. A matrix training procedure was used to teach 2 children with moderate mental retardation syntactic rules for combining known and unknown words into two-word utterances. An alternating treatments design was used with two conditions: receptive teaching with imitation of the target phrase and no imitation of the phrase. Findings suggested that the use of imitation facilitated both generalized receptive learning and transfer to production in both subjects.

Child↗

Using self-monitoring to reduce disfluencies in speakers with mild aphasia.

This study assessed the effects of treatment designed to teach mildly aphasic individuals to monitor disfluencies--revisions, repetitions, audible pauses--in their connected speech. Treatment effects were evaluated using a multiple baseline design across 3 subjects. All subjects showed immediate and dramatic reductions in the frequency of target behaviors in a picture description task when self-monitoring was introduced. Two subjects simultaneously reduced untargeted disfluencies, and all 3 generalized their improved speech to another discourse task. Treatment effects were unrelated to the accuracy of self-monitoring. Subjects' improved speech was characterized by a slower speaking rate, but more efficient communication as reflected by longer uninterrupted utterances. Although standardized test scores were unchanged, unfamiliar listeners found perceptible improvement between baseline and posttreatment audiotapes of subjects' discourse. Self-monitoring treatment shows promise in reducing distracting and inefficient disfluencies in the speech of mildly aphasic individuals.

Aged↗