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Biomedical subjects

L Baker

Publications and source records attributed to L Baker.

At least 19 recordsLinked to original sources
PubMed1992

Difluorodeoxycytidine (dFdC)--gemcitabine: a phase I study.

Difluorodeoxycytidine (dFdC) demonstrated broad spectrum activity in preclinical models. A phase 1 study utilizing twice weekly injections was conducted in 50 eligible and evaluable patients. Twenty-nine patients received drug by 30 minute infusion at doses of 5-90 mg/m2 and 22, by 5 minute bolus at 30-150 mg/m2. The primary dose limiting toxicities were marrow suppression and flu-like symptomatology. Thrombocytopenia was dose limiting at 75 mg/m2 on the infusion schedule and 150 mg/m2 on the 5 minute schedule. Flu-like symptoms with fever, rigors and malaise occurred the day of injection in many patients. One patient with renal cell carcinoma attained a partial response. Evaluation of the drug's efficacy and schedule dependency continue.

Adult↗
PubMed1992

Attention deficit disorder with and without hyperactivity: a review and comparison of matched groups.

This paper compares attention deficit disorder (ADD) with hyperactivity (ADDH) and without hyperactivity (ADDWO). The literature is outlined, revealing the areas of possible differences to be not only the core symptoms, but also associated conduct and emotional symptoms, social relations functioning, learning, medical disorders, family history, and course and outcome of the disorder. Empirical data are presented comparing age and sex matched groups of children from a speech/language clinic sample with ADDH (N = 40) and ADDWO (N = 40). Although the methods of the present study are different from those of previous studies, they nonetheless support a number of previous findings, and, further, give support to the external validity of the ADDWO diagnostic category.

Adolescent↗
PubMed1992

Malevolence, splitting, and parental ratings by borderlines.

Malevolent object relations as well as splitting have long been considered by psychodynamic theorists as central features of borderline personality disorder. We tested the hypotheses that borderlines would a) perceive their parents more negatively than both nonborderline major depressive patients and nonpatient normal controls, and b) split their representations of their parents into opposites more than the comparison subjects. Borderlines (N = 31), who were identified by the Diagnostic Interview for Borderlines, Research Diagnostic Criteria major depressives (N = 15), and nonpatient controls (N = 14) were asked to rate each parent on the Adjective Check List (ACL; Gough and Heilbrun, 1983). Seven ACL scales were studied: Favorable, Unfavorable, Critical Parent, Nurturing Parent, Nurturance, Aggression, and Dominance. Correlations were performed between scores for mother and father on the various scales for each of the three cohorts. Analysis of variance and one-way t-tests with Bonferroni correction were used to test group differences. Borderlines rated their parents, especially their fathers, not only as more unfavorable on negative scales than depressives or normals, but as less favorable on positive scales than the comparison groups. Analysis of covariance revealed that a significant portion of the variance in father scores, but not in mother scores, was related to age of respondent and history of sexual abuse. While borderlines did not appear to split their parents into one good and one bad parent, they did show significantly less correlation between parents on the Favorable scale when compared with either depressives or normal subjects. The results imply that borderlines have a greater tendency to view the world in negative, malevolent ways than to split their object representations.

Adult↗
PubMed1991

A dose-intensive regimen of 5-fluorouracil for the treatment of metastatic colorectal carcinoma.

5-Fluorouracil (5-FU) was delivered in a dose-intensive schedule to 23 patients with metastatic or unresectable colorectal carcinoma. The schedule consisted of bolus single-dose 5-FU therapy 400 to 500 mg followed by 4-day infusion of 5-FU, 600 to 800 mg/m2/day, followed by a 17-day to 24-day infusion of 200 to 250 mg/m2/day. Partial remissions were seen in 22% of all eligible patients. Significant toxicity, including mucositis, diarrhea, and hand-foot syndrome, necessitated dose reductions in most patients. The authors conclude that 5-FU given in this moderately intensive schedule is associated with a moderate level of response, as easily achieved with more conventional schedules or with 5-FU-leucovorin combinations. Tumor responsiveness to dose intensive 5-FU regimens may be limited.

Adult↗
PubMed1991

Ammonia-induced astrocyte swelling in primary culture.

The effect of ammonia on water space of astrocytes in culture was determined as a means of studying the neurotoxicity of ammonia in fulminant hepatic failure (FHF). Treatment of primary astrocyte cultures obtained from neonatal rat cortices with 10 mM NH4Cl for 4 days resulted in a 29% increase in astrocytic water space, as measured by an isotopic method utilizing 3-O-methyl-[3H]-glucose. This effect was time- and dose-dependent. The ammonia-induced swelling was reversible as the water space in cultures treated with 10 mH NH4Cl for 3 days, and then returned to normal culture media for 1 day, was similar to control cultures. These findings suggest that elevated levels of ammonia lead to astrocyte swelling and may contribute to the brain edema in FHF.

3-O-Methylglucose↗
PubMed1991

Familial and sporadic hyperinsulinism: histopathologic findings and segregation analysis support a single autosomal recessive disorder.

We evaluated the possible genetic contribution to hyperinsulinism in a series of patients seen during the past 15 years. Of 26 families, 5 (19%) had more than one child affected (multiplex family). There were no apparent differences between patients in the 5 multiplex and 21 simplex families, clinically, biochemically, or on histologic examination of the pancreatic specimens. The families studied had a total of 63 offspring; the 26 index patients had 37 siblings, 6 of whom were affected. After four patients with hyperinsulinism caused by adenoma were excluded from the study, segregation analysis was carried out to test the data for agreement with results expected if familial and isolated hyperinsulinism represented a single disease with recessive mode of inheritance and a segregation ratio of 0.25. Excellent agreement was found between the observed number of affected siblings (20) and the expected number (19.65), with a segregation ratio of 0.254. The results were consistent with the hypothesis that in most or all cases, hyperinsulinism is inherited as an autosomal recessive disease. There was no evidence of distinct familial and sporadic types.

Family Characteristics↗
PubMed1991

Low interleukin-2 synthesis by type 1 diabetics is regulated at the pretranslational level.

Insulin-dependent diabetes mellitus (IDDM) is believed to be a consequence of an autoimmune attack on beta cells by T cells. We have previously reported that T cells from the majority of patients with IDDM produced decreased levels of interleukin-2 (IL-2) following activation with phytohemagglutinin. In this study we began to characterize the basis for this defect. First, we tested whether the decreased IL-2 synthesis was due to the secretion of a factor which inhibited the ability of indicator cells to respond to IL-2 or which inhibited IL-2 release by responder cells. Second, we examined steady-state levels of IL-2 mRNA in IDDMs and controls. To make this feasible, given the limited number of peripheral blood lymphocytes (PBL) available from our patients, we depended upon an approach which enabled the generation of large numbers of resting T cells, called G0/G1 cells, from small numbers of PBL. Preliminary experiments demonstrated that G0/G1 cells from IDDMs reproduced the IL-2 defect seen originally with PBL. Our results suggested that the secretion of inhibitory factors could not explain the IL-2 defect. A comparison of steady-state levels of IL-2 mRNA from activated T cells of IDDMs and age-matched controls, however, demonstrated lower levels of IL-2 mRNA in IDDMs compared to controls. Finally, we observed that the IL-2 mRNA in IDDM T cells was less stabile than that in the control cells, suggesting a possible mechanism for the defect.

Adolescent↗
PubMed1991

Association between attention deficit-hyperactivity disorder and learning disorders.

This article discusses the relationship between attention deficit-hyperactivity disorder (ADHD) and learning disability (LD). The relevant literature is outlined, and empirical data are presented from a prospective follow-up study of 600 speech/language-impaired children. The data show an increased prevalence of both LD and ADHD among children with early speech/language impairments. Furthermore, LD was strongly associated with ADHD in both the initial and follow-up samples. Also, the children with LD had increased rates of other psychiatric disorders (e.g., behavior disorders, mood disorders, anxiety disorders). The implications of these data are discussed with regard to the possible etiology of the ADHD-LD association, treatment for children with LD and ADHD, and promising hypotheses for future research.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Hearing loss in chronic renal failure-hearing threshold changes following haemodialysis.

The prevalence of sensorineural hearing loss, measured by pure tone audiometry, was determined in 66 patients with chronic renal failure and threshold changes following haemodialysis were measured in 31 patients. The incidence of hearing loss was 41% in the low, 15% in the middle and 53% in the high frequency ranges respectively. No correlations with weight changes, haematocrit, metabolic bone disease or ototoxic drug history were found. Of 62 ears studied, 38% had a decrease in low frequency threshold after dialysis and 9% had an increase. Threshold in 22/31 ears with pre-existing low frequency loss altered after dialysis with little change in other frequencies and no correlation with weight changes. In conclusion, we find a high incidence of low and high frequency hearing losses in chronic renal failure patients. Fluctuation in low frequencies with dialysis is common. Possible mechanisms include treatment induced changes in fluid and electrolyte composition of endolymph.

Adult↗
PubMed1990

The sheep growth hormone receptor: molecular cloning and ontogeny of mRNA expression in the liver.

Two overlapping cDNA clones encoding the sheep growth hormone (GH) receptor were isolated from a sheep liver cDNA library. The translated amino acid sequence predicts a polypeptide precursor of 634 amino acids with a calculated molecular weight of 70,799. The mature GH receptor comprises an extracellular domain of 242 amino acids, a hydrophobic transmembrane region of 24 amino acids, and a cytoplasmic domain of 350 amino acids. The nucleotide and translated amino acid sequences display extensive similarity with sequences established for GH receptors from a number of other mammalian species. A prominent transcript of 4.5 kb and a minor transcript of 1.9 kb are detected following Northern blot hybridization of poly(A)+ RNA isolated from sheep liver. The onset of GH receptor mRNA expression in the liver is developmentally regulated: GH receptor transcripts are first detected by Northern blot hybridization in liver taken from a term (145 days of gestation) fetus and reach maximum levels within one week following birth. Ribonuclease protection assays reveal heterogeneity within the 5' untranslated region of GH receptor mRNA transcripts detected in liver and a number of other tissues. At least one transcript appears to be expressed in a liver-specific fashion, supporting a role for alternative RNA splicing in the tissue-specific regulation of sheep GH receptor expression.

Amino Acid Sequence↗
PubMed1990

Myo-inositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos.

Neural tube defects in infants of diabetic mothers constitute an important and frequent cause of neonatal mortality/morbidity and long-term chronic handicaps. The mechanism by which normal neural tube fusion occurs is not known. The failure of rostral neural tube fusion seen in mouse embryos incubated in the presence of excess-D-glucose can be significantly prevented by the supplementation of myo-inositol to the culture medium. This protective effect of myo-inositol is reversed by indomethacin, an inhibitor of arachidonic acid metabolism leading to prostaglandin synthesis. Prostaglandin E2 added to the culture medium completely protects against the glucose-induced neural tube defect. These data suggest that the failure of neural tube fusion seen in diabetic embryopathy is mediated through a mechanism involving abnormalities in both the myo-inositol and arachidonic acid pathways, resulting in a functional deficiency of prostaglandins at a critical time of neural tube fusion.

Animals↗
PubMed1990

How good are clinical MEDLINE searches? A comparative study of clinical end-user and librarian searches.

The objective of this study was to determine the quality of MEDLINE searches done by physicians, physician trainees, and expert searchers (clinicians and librarians). Its design was an analytic survey with independent replication in a setting of self-service online searching from medical wards, an intensive care unit, a coronary care unit, an emergency room, and an ambulatory clinic in a 300-bed teaching hospital. Participating were all M.D. clinical clerks, house, and attending staff responsible for patients in the above settings. Intervention for all participants consisted of a 2-h small group class and 1-h practice session on MEDLINE searching (GRATEFUL MED) before free access to MEDLINE. Search questions from 104 randomly selected novice searches were given to 1 of 13 clinicians with prior search experience and 1 of 3 librarians to run independent searches (triplicated searches). Measurements and main results from these unique citations of the triplicated searches were sent to expert clinicians to rate for relevance (7-point scale). Recall (number of relevant citations retrieved from an individual search divided by the total number of relevant citations from all searches on the same topic) and precision (proportion of relevant citations retrieved in each search) were calculated. Librarians were significantly better than novices for both. Librarians had equivalent recall to, and better precision than, experienced end-users. Unexpectedly, only 20% of relevant citations were retrieved by more than one search of the set of three, with the conclusion that novice searchers on MEDLINE via GRATEFUL MED after brief training have relatively low recall and precision. Recall improves with experience but precision remains suboptimal. Further research is needed to determine the "learning curve," evaluate training interventions, and explore the non-overlapping retrieval of relevant citations by different searchers.

Evaluation Studies as Topic↗
PubMed1990

Serum myoinositol concentrations in premature infants fed human milk, formula for infants, and parenteral nutrition.

Myoinositol concentration was studied in serum of 65 neonates and their mothers at the time of birth, in samples of various types of feedings for infants, and in serial serum samples of 15 premature infants receiving human milk, formulas for infants, or parenteral nutrition over a 3-wk period. At birth the serum concentration of myoinositol was greater in neonates than in their mothers (108 +/- 10 vs 52 +/- 6 mumol/L, respectively, means +/- SEM, p less than 0.01). In feedings for infants, the concentrations of myoinositol were significantly greater in human milk than in formulas or parenteral nutrition solutions (1840 +/- 451 vs 420 +/- 110 vs 100 +/- 8 mumol/L, respectively, p less than 0.001). Over a 3-wk period the serum concentration of myoinositol increased in infants receiving human milk but not in those receiving formulas or parenteral nutrition. Serum concentrations of myoinositol in neonates are greater than in adults and are directly influenced by myoinositol intake.

Adult↗
PubMed1990

Sublingual nitroglycerin administered by spray versus tablet: comparative timing of hemodynamic effects.

The comparative timing of hemodynamic alterations by sublingual nitroglycerin administered by spray vs. tablet has not been studied. Similarly, the directly measured comparative effects on left ventricular pressures have not been reported. To investigate these issues, we analyzed 49 patients undergoing elective diagnostic cardiac catheterization who were randomized to receive 0.4 mg sublingual nitroglycerin by either spray or tablet. Before administration of contrast medium, control determinations of left ventricular end-diastolic and systolic pressures and heart rate were done. These parameters were then evaluated at half-minute intervals for 5 min. Left ventricular end-diastolic pressure was reduced similarly in both groups, with the reduction achieving significance at 1.5 min in the spray and 2.0 min in the tablet group. Lowering of the left ventricular systolic pressure was also similar in the two groups, reaching significance at 2.5 min with spray and 2.0 min with tablet. Heart rate increased significantly by 2.0 min in the tablet group but did not change in the spray group. These findings were not altered by the level of resting left ventricular end-diastolic pressure or use of chronic nitrates. Thus, we found nitroglycerin to be similarly effective in timing and extent of response whether administered by spray or tablet, though the difference in heart rate responses remains unexplained.

Administration, Sublingual↗
PubMed1990

Impaired metabolic function and signaling defects in phagocytic cells in glycogen storage disease type 1b.

Patients with glycogen storage disease (GSD) type 1b (1b), in contrast to patients with GSD type 1a (1a), are susceptible to recurrent bacterial infections suggesting an impairment in their immune system. In this study, phagocytic cell (neutrophil and monocyte) respiratory burst activity, as measured by superoxide anion generation, oxygen consumption, and hexose monophosphate shunt activity, was markedly reduced in both neutrophils and monocytes from GSD 1b patients as compared with either GSD 1a patients or healthy adult control cells. Degranulation, unlike respiratory burst activity, was not significantly different in neutrophils from GSD 1b patients as compared with controls. Both neutrophils and monocytes from GSD 1b patients showed decreased ability to elevate cytosolic calcium in response to the chemotactic peptide f-Met-Leu-Phe. In addition, calcium mobilization in response to ionomycin was also attenuated suggesting decreased calcium stores. Thus, reduced phagocytic cell function in GSD 1b is associated with diminished calcium mobilization and defective calcium stores. Defective calcium signaling is associated with a selective defect in respiratory burst activity but not degranulation.

Calcium↗