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Biomedical subjects

L Baker

Publications and source records attributed to L Baker.

At least 91 records · Page 5Linked to original sources
PubMed1994

Response rates--an evolution.

The documented frequency of response of cancers to common chemotherapy agents and combinations appears to have decreased over the decades. Multiple reasons exist for this decline including: changes in eligibility and evaluability criteria; changes in the type of patients entered onto trial; and, altered criteria for response and methods for response assessment. The disinclination to publish negative results also permits a bias in a favor of overestimating a drug's efficacy. Circumspection now is advised in assessing data from older trials.

Antineoplastic Agents↗
PubMed1994

Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer.

The use of mitomycin for metastatic colorectal cancer has been limited by mitomycin's myelosuppressive potential. The objective of this randomized study was to determine whether WR-2721 would decrease the hematologic toxicity of mitomycin in patients with colorectal cancer resistant to fluorouracil-based therapy. Ninety-seven patients with refractory colorectal cancer were randomized to receive either mitomycin 20 mg/m2 only or the same dose of mitomycin after pretreatment with WR-2721, 910 mg/m2. The principal toxicity in both groups was thrombocytopenia. The platelet nadirs were lower in patients receiving single-agent mitomycin (P = 0.026). Surprisingly, no clinical complete or partial responses were noted in either group, and survival was not different between the two groups. Thus, while WR-2721 decreased the thrombocytopenia associated with mitomycin therapy, mitomycin was ineffective in the treatment of refractory colorectal carcinoma.

Adult↗
PubMed1994

Spouse similarity in attitudes, personality, and psychological well-being.

The study of the origin of spouse similarity is interesting because the extent to which spouse similarity reflects genetic resemblance between husbands and wives affects the genetic structure of a population. The sources of observed spouse similarity in attitudes, personality, and psychological well-being are discussed. Analyses based on data collected from an American adult sample assessed longitudinally showed that spouse correlations were high for attitudes and low to moderate for personality and psychological well-being. Four competing explanations to spouse similarity were compared: initial similarity, attrition, convergence, and age covariation. The results did not support the latter three explanations, indicating that initial similarity may be an appropriate interpretation of observed spouse similarity. The findings are consistent with those of other comparable studies.

Adaptation, Psychological↗
PubMed1994

Strict metabolic control and retinal blood flow in diabetes mellitus.

The effects of strict diabetic control on retinal haemodynamics were studied to elucidate whether such effects are associated with retinopathy changes. In 28 patients with poorly controlled insulin dependent diabetes mellitus and non-proliferative retinopathy, retinal haemodynamics were investigated at baseline, 5 days, 2 months, and 6 months after the institution of strict diabetic control using the bidirectional laser Doppler velocimetry technique and monochromatic fundus photography. Changes in retinal blood flow measured in a major retinal vein (Q) on the fifth day of strict diabetic control correlated significantly with changes in retinopathy level observed at the end of the 6 months of this study (rank correlation 0.65, p < 0.01). On the fifth day of strict diabetic control, 16 out of 20 eyes that showed no progression (NP) of retinopathy at the end of the study had decreases in Q, whereas six out of eight eyes that showed progression (P) had increases in Q. The difference in these changes in Q between P and NP eyes was statistically significant (one way analysis of variance, p = 0.001). No significant changes in Q were detected at 2 months or 6 months. Following the institution of strict diabetic control, no significant changes in time were detected in the regulatory response to 100% oxygen breathing characterised as the percentage decrease in Q at 4-6 minutes of oxygen breathing (analysis of variance, p = 0.36). Changes in Q following institution of strict diabetic control are associated with progression of retinopathy. Measurements described in this study may help identify diabetic patients at risk of progression when their metabolic control is improved.

Adolescent↗
PubMed1994

In vitro and in vivo effects of granulocyte colony-stimulating factor on neutrophils in glycogen storage disease type 1B: granulocyte colony-stimulating factor therapy corrects the neutropenia and the defects in respiratory burst activity and Ca2+ mobilization.

Children with glycogen storage disease (GSD) type 1b are susceptible to recurrent bacterial infections and have chronic neutropenia accompanied by phagocytic cell dysfunction including decreased superoxide anion (O2-) generation, calcium (Ca2+) mobilization, and chemotactic activity. Granulocyte colony-stimulating factor (G-CSF), a cytokine that corrects neutropenia in other diseases, in vitro enhances f-Met-Leu-Phe-triggered neutrophil O2- generation. Short-term pretreatment (15 min) of GSD 1b neutrophils with G-CSF increased the rate of O2- production (p < 0.01); however, this rate was still significantly below the rate of O2- production in control neutrophils. Recombinant human G-CSF (5 micrograms/kg/d) was administered s.c. to a GSD 1b patient. Before treatment, absolute neutrophil counts were < 500/mm3. Two d after G-CSF administration, the absolute neutrophil counts increased to 1333 and remained in the normal range during a 12-mo follow-up period. In vivo, G-CSF therapy increased f-Met-Leu-Phe-stimulated O2- production to 52% of control after 1 mo, and by mo 4, O2- production reached control levels. Our previous studies (J Clin Invest 56:196-202, 1990) demonstrated that decreased O2- production in neutrophils was associated with impaired Ca2+ mobilization. In vivo administration of G-CSF increased f-Met-Leu-Phe-triggered Ca2+ mobilization by neutrophils to 43% of control by mo 1 of G-CSF therapy and to 93% of control by mo 4, thus paralleling the improvements in O2- generation. In contrast, G-CSF therapy had no effect on the defective neutrophil chemotaxis. In summary, G-CSF therapy produced a rapid increase in circulating neutrophils and a gradual correction of O2- production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Oral physostigmine and impaired memory in adults with brain injury.

The purpose of this study was to examine the effects of physostigmine, a cholinergic agonist, on memory loss after traumatic brain injury (TBI), as compared to placebo or scopolamine, a cholinergic antagonist, using a double-blind, placebo-controlled design. Each subject received each active drug and placebo. Neuropsychological measures (Wechsler Memory Scale I and II, Selective Reminding Test, Trail-Making Test, Parts A and B, Digit Symbol, and Memory Questionnaire) and measures of clinical balance were completed at baseline, after each drug phase, and at 1 month follow-up. Thirty-six subjects completed the study with results showing an improvement in memory scores in 44% of subjects (responders) while taking oral physostigmine. The most sensitive measure was the Selective Reminding Test, specifically Long-term Storage. The impact of drugs on standing balance as compared to placebo was improved standing time in the responders: (1) with physostigmine when standing tandem with eyes closed (p < 0.05), and (2) with scopolamine when standing on one foot with eyes closed (p < 0.05). Results support the potential benefit of cholinergic agonists on memory after TBI and the need for further research of possible clinical markers for the drug.

Administration, Cutaneous↗
PubMed1994

Antimalarial measures--type, sources of advice and compliance among tourists to Natal/KwaZulu.

Typical advice on antimalarial measures provided by pharmacies as well as actual behaviour in this regard and sources of advice accessed by tourists to northern Natal/KwaZulu were canvassed by telephonic interviews with 70 pharmacies and 53 'care providers' (members of travel parties). Doctors (26%) and pharmacists (40%) were the most commonly approached sources of antimalarial advice. Professional recommendations frequently involved chloroquine-based drugs (80% of recommended drugs), despite the chloroquine-resistant status of the study area. Drug choice reflected the limited availability of new alternatives to chloroquine at the time the study was conducted, as well as ignorance of drug resistance in the area. Possible reasons for the inappropriate nature of many of the reported recommendations, as well as an approach to the dissemination of future prophylactic policy documents, are discussed.

Adult↗
PubMed1993

Characterization of the peripheral-type benzodiazepine receptors in cultured astrocytes: evidence for multiplicity.

In mammalian brain peripheral benzodiazepine (PBZD) receptors are predominantly localized on astroglial cells. Previous studies utilizing whole membrane preparations from brain and peripheral organs of various species have indicated several distinctions between the drug-receptor interactions of the two prototypic PBZD receptor ligands, PK 11195 and Ro5-4864. The present study was undertaken to determine whether putative differences in the binding of PBZD receptor ligands in homogenates of primary astrocyte cultures can be interpreted as the labeling of PBZD receptor subtypes. Equilibrium competition and saturation binding experiments in homogenate preparations of primary astrocytes from cerebral cortex of new born rats revealed that [3H]PK 11195 labels twice the number of [3H]Ro5-4864 binding sites. Unlabeled Ro5-4864 competes for [3H]PK 11195 binding in a manner suggesting the existence of multiple PK 11195 binding sites. The competition binding experiments, using various benzodiazepines, indicate that one binding component of PK 11195 corresponds to Ro5-4864 binding sites, whereas the second is different. The latter binding site does not correspond to the central BZD receptor but displays the pharmacological properties of the PBZD receptor. Further differences between the binding of PK 11195 and Ro5-4864 in astrocytes were detected in the presence of ethanol which was more effective in inhibiting the binding of the latter. Subcellular distribution studies indicated, however, that the binding of both [3H]PK 11195 and [3H]Ro5-4864 is associated primarily with the mitochondrial fraction of astrocytes. Taken together, the present study indicates the existence of non-overlapping PBZD binding sites in astrocytes and thus suggests the existence of PBZD receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Types and complications of femoral neck fractures in children.

This multicenter collaborative study was undertaken to review the types and complications of femoral neck fractures in children. It is a retrospective clinical and radiological review of 108 femoral neck fractures. Cases originated from four different pediatric hospitals. All the patients had plain radiographs. Fractures occurred at all ages (one day to 18 years), and 63% of the patients were boys. Forty-nine fractures were traumatic; 37 were pathologic, 19 were insufficiency fractures; and three were fatigue fractures. Unless the underlying bone was abnormal, significant high velocity trauma, fall from a height or other severe violence was required to fracture the femoral neck. A unicameral bone cyst was the underlying lesion in 40% of pathologic femoral neck fractures and malignancy in 35%. Osteoporosis as in myelodysplasia, osteogenesis imperfecta and from other causes was responsible for 52% of insufficiency fractures. Because of the unique osseous and vascular anatomy of the femoral head and neck in the growing child, these fractures have a high incidence of complications. Complications included avascular necrosis 13%, premature closure of the epiphyseal plate 12%, varus deformity 8.3%, and nonunion 3.7%. Unless there is a clear history of significant violence, a cause for a femoral neck fracture should be sought, e.g. an underlying bone lesion or a metabolic bone disease. These fractures are rare, but are serious injuries since their complications may lead to a life-long disability.

Adolescent↗
PubMed1993

Impairment of calcium mobilization in phagocytic cells in glycogen storage disease type 1b.

Patients with glycogen storage disease (GSD) type 1b, in contrast to patients with GSD 1a, are susceptible to recurrent bacterial infections suggesting defective phagocytic function. We have demonstrated a selective defect in respiratory burst activity but not in degranulation by phagocytic cells in GSD 1b but not in GSD 1a. The respiratory burst abnormality in phagocytic cells from GSD 1b patients was associated with impaired calcium mobilization, whereas these processes were normal in GSD 1a patients. Therefore, the alteration in calcium mobilization was an indication of a signalling defect in phagocytic cells from GSD 1b. However, calcium mobilization was normal in lymphocytes, indicating that defective calcium mobilization was not a global finding in circulating leukocytes, but was specific to phagocytic cells. Calcium mobilization in response to ionomycin was reduced suggesting decreased calcium stores in GSD 1b neutrophils. Therefore, altered phagocytic cell function in GSD 1b patients appears to be associated with diminished calcium mobilization and defective calcium stores. This defective calcium signalling was associated with a selective defect in respiratory burst activity but not degranulation.

Calcium↗
PubMed1993

Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism.

Octreotide, a long-acting analog of somatostatin that inhibits insulin release, has the potential to control hypoglycemia in infants with congenital hyperinsulinism. To examine the efficacy and side effects of octreotide, we evaluated therapy between 1988 and 1993 in 16 infants who did not respond to diazoxide. In nine patients with onset of severe hypoglycemia in the first days of life, octreotide was helpful in stabilizing plasma glucose levels and allowed reductions in the rates of glucose infusion; however, glucose control was inadequate to avoid subtotal pancreatectomy. In two of these nine patients postoperatively and in seven other infants, a trial of long-term treatment with octreotide was undertaken. Four were treated successfully for up to 4.3 years. Octreotide therapy was not associated with thyroid deficiency and caused only transient malabsorption. All patients receiving long-term therapy had some decrease in linear growth and two had subnormal plasma concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 3 compatible with suppression of growth hormone by octreotide. Resistance to octreotide therapy, even with increasing doses, occurred in all patients. These results suggest that octreotide may aid in the acute or long-term treatment of congenital hyperinsulinism in a limited number of selected cases.

Diazoxide↗
PubMed1993

Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease.

Renal stones containing calcium can occur in patients with type 1 glycogen storage disease. We studied 11 patients with glycogen storage disease. Five patients had renal calculi, nephrocalcinosis, or both, and five had hypercalciuria. Serum levels of calcium, phosphorus, parathyroid hormone, and urate were normal. Serum levels of 1,25-dihydroxyvitamin D were elevated in each patient. None of the patients had a metabolic acidosis, but all nine who were tested had evidence of impaired acid excretion. In response to an acid load, eight of the nine patients had subnormal titratable acid excretion, and nine had subnormal ammonia excretion; six of nine patients were unable to secrete hydrogen ions in response to bicarbonate administration. These data indicate that patients with type 1 glycogen storage disease have an incomplete form of distal renal tubular acidosis. This may be the cause of hypercalciuria and nephrocalcinosis in these patients.

Acidosis, Renal Tubular↗
PubMed1993

Isolation, characterization and evolution of ovine major histocompatibility complex class II DRA and DQA genes.

Four full-length ovine major histocompatibility complex (MHC) class II A cDNA clones coding for new alleles of DRA, DQA1 and DQA2 genes were isolated from two ovine lambda gt10 cDNA libraries. The derived amino acid sequences of these clones resemble class II A molecules from other species in both size and structure. Restriction fragment length polymorphism analysis, using an Ovar-DRA probe on DNA from Merino and Romney sheep revealed only limited polymorphism in contrast to the high levels of polymorphism revealed by Ovar-DQA probes. Comparison of the predicted amino acid sequences for the three ovine A genes with class II A genes from five other species revealed that the most variable region of the molecule is the signal peptide. Although virtually every amino acid site shows variation, within or between species, there are some blocks of highly conserved residues. Within gene comparisons of nucleotide differences reveal that the greatest number of changes is found between the alleles of Ovar-DQA1 and -DQA2 genes and the least between Ovar-DRA1 alleles. Phylogenetic analysis of class II A sequences from several species place DRA and DQA genes on two distinct branches, with Ovar-DRA1 and BOLA-DRA, and Ovar-DQA1 and BOLA-DQA being most similar on their respective branches.

Alleles↗
PubMed1993

Transcranial Doppler ultrasound and magnetoencephalography in migraine.

Eighty subjects--30 migraineurs during the attack, 30 patients in the interictal period, and 20 healthy volunteers--were studied using two technologies for functional assessment: transcranial Doppler ultrasound and magnetoencephalography. Transcranial Doppler studies showed an increased mean flow velocity at rest (p less than 0.05) in the middle cerebral artery on the side of the headache and a decreased vasomotor response to CO 2 (p less than 0.001) on the same side compared to control subjects. Biomagnetic measurements of somatosensory evoked fields of 11 patients and 11 control subjects in this study did not demonstrate differences between migraineurs and the control group in current flow or latency measures. The data from this study tend to support the hypothesis of vascular disease as a primary underlying deficit in migraine.

Adult↗
PubMed1993

Interferon-gamma corrects the respiratory burst defect in vitro in monocyte-derived macrophages from glycogen storage disease type 1b patients.

Glycogen storage disease (GSD) type 1b is accompanied by decreased respiratory burst activity in peripheral blood phagocytic cells (i.e. monocytes and neutrophils). To elucidate whether this depressed respiratory burst was due to an intrinsic defect of phagocytic cells or due in part to in vivo host factors, we examined superoxide anion (O2-) production in monocytes from five GSD 1b patients cultured 9 d in vitro to allow for differentiation into macrophages (MDM). O2- production in MDM was measured in response to concanavalin A, fMet-Leu-Phe, and phorbol myristate acetate (PMA) stimulation. GSD 1b MDM had significantly depressed O2- generation with fMet-Leu-Phe and concanavalin A stimulation; however, unlike peripheral blood monocytes, GSD 1b MDM responded to PMA stimulation with O2- production comparable to healthy control donors. The cytokine interferon-gamma (IFN-gamma) has been shown to enhance O2- production in MDM. When GSD 1b MDM were cultured in the presence of IFN-gamma (1 x 10(5) U/L), O2- production in response to fMet-Leu-Phe, concanavalin A, and PMA was enhanced to rates similar to those of control MDM cultured in the presence of IFN-gamma. Thus, the respiratory burst defect observed in circulating phagocytic cells is also present in vitro in cultured GSD 1b MDM. However, in contrast to circulating phagocytic cells, depressed O2- production in GSD 1b MDM is selective to receptor-mediated activation, but not to PMA stimulation. This defect is correctable after short-term treatment with IFN-gamma, suggesting a role for IFN-gamma in treating the phagocytic defect in this disease.

Adolescent↗