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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 199 records · Page 11Linked to original sources
PubMed1995

Predictive factors for peripheral-blood progenitor-cell collections using a single large-volume leukapheresis after cyclophosphamide and granulocyte-macrophage colony-stimulating factor mobilization.

PURPOSE: (1) To study the ability of mobilized peripheral-blood progenitor cells (PBPC) collected in a single large-volume leukapheresis performed on a predetermined date to accelerate engraftment after high-dose cyclophosphamide and thiotepa; (2) to establish the minimum dose of PBPC associated with early engraftment; and (3) to identify parameters predictive of collection of large numbers of PBPC. PATIENTS AND METHODS: Twenty-three patients with breast cancer received cyclophosphamide (4 g/m2) and granulocyte-macrophage colony-stimulating factor ([GM-CSF] 5 micrograms/kg/d x 15 days) for PBPC mobilization. A single leukapheresis was performed 15 days after cyclophosphamide administration. Then, patients received high-dose cyclophosphamide and thiotepa followed by reinfusion of PBPC and 4-hydroperoxycyclophosphamide (4HC)-purged bone marrow. PBPC concentration was measured in serial peripheral-blood samples and in the leukapheresis product. Correlation analysis between PBPC dose and engraftment and between leukapheresis yield and patient characteristics was attempted. RESULTS: A single leukapheresis processed a median 36 L (range, 24 to 46) blood and collected 5 x 10(6) CD34+ cells/kg (< 0.3 to 24) and 6.2 x 10(5) colony-forming units granulocyte-macrophage (CFU-GM)/kg (< 0.001 to 29). All sixteen patients (70%) reinfused with > or = 2.9 x 10(6) CD34+ cells/kg reached a level of greater than 1,000 leukocytes/microL by day 13 and greater than 50,000 platelets/microL by day 15. All of these patients had a percentage of peripheral-blood CD34+ cells > or = 0.5%, and all but one, a level of greater than 100,000 platelets/microL, on the day of leukapheresis. The bone marrow CD34+ cell percentage at study entry predicted the number of CD34+ cells collected after PBPC mobilization (R2 = .42, P = .002). All patients with > or = 2.5% bone marrow CD34+ cells experienced early engraftment. CONCLUSION: Reinfusion of PBPC collected in a single leukapheresis accelerates engraftment in the majority of patients. Pretreatment bone marrow CD34+ cell content determines PBPC mobilization capacity and may help select hematopoietic rescue strategies.

Adult↗
PubMed1995

Assessment of psychological distress in Persian Gulf troops: ethnicity and gender comparisons.

This study reports results of psychological assessment among military participants in Operation Desert Storm, a more diverse ethnic and gender mix of American troops than has been mobilized for previous military operations. Symptoms of current psychological distress, including negative mood states, somatic complaints, and posttraumatic stress disorder, in addition to personal and trauma characteristics, were measured in 653 Persian Gulf war-zone-exposed and 259 stateside-duty troops to test the hypothesis that ethnic minority status and female gender are associated with greater levels of psychological distress following war-zone duty. Findings point to potentially negative sequelae to war-zone stress in a portion of troops and suggest that ethnic minorities, but not necessarily women, may be more vulnerable to psychological risk.

Adult↗
PubMed1995

Dose response effects of hypertonic saline and dextran on cardiovascular responses and plasma volume expansion in sheep.

Despite the established efficacy of 7.5% NaCl/6% dextran-70 in the treatment of hypovolemia, the optimal formulation of a hyperosmotic/hyperoncotic small volume resuscitation solution has yet to be defined. The present study investigates the cardiovascular effects of hypertonic saline ranging from 3.75%-25% NaCl (HS) and dextran-70 (D-70) ranging from 3 to 24%. HS and D-70 were studied alone or in specific combinations at a dose of 4 mL/kg, in euvolemic sheep. Blood samples were collected before, during and up to 60 min after infusion of the test solutions. Dose-dependent effects of HS were immediate increases in cardiac output (CO) of 30-85%, falling to 10-35% over baseline after 60 min. HS concentrations over 3.75% significantly reduced systemic vascular resistance, but HS had no significant effect on mean arterial pressure (MAP). Plasma volume (PV) expansion with HS was an immediate, but transient increase of 12-35%. Infusion of D-70 induced sustained 10-20% increases in CO and 10-30% increases in PV, peaking 10 min post-infusion. D-70 also resulted in small (5-12 mmHg) increases in MAP. Cardiovascular effects of D-70 correlated with a dose-dependent increase in plasma dextran concentrations. All HS solutions significantly increased plasma Na, which peaked at > or = 200 mEq/L in the 25% group. The effects of D-70 and HS combined were additive on PV expansion and CO. These data indicate that concentrations of HS and D-70 which are higher than those currently used have a greater capability for expanding PV, but use of HS > 7.5% may be limited by resulting hypernatremia.

Animals↗
PubMed1995

Isolation of thyroid peroxidase and lack of autoantibodies to the enzyme in dogs with autoimmune thyroid disease.

Fifty serum samples from dogs with clinical signs of hypothyroidism and autoantibodies (AA) to thyroglobulin (Tg), thyroxine, or triiodothyronine were screened for AA to thyroid peroxidase (TPO). Thyroid peroxidase is the antigen against which microsomal AA are formed in human beings with lymphocytic thyroiditis. The TPO was isolated from canine thyroid tissue, using a modification of the procedure for purifying porcine TPO. The enzyme was solubilized from the membrane, using a deoxycholate-trypsin solution, followed by ammonium sulfate precipitation and diethylaminoethyl Sephadex chromatography. Activity of TPO was determined, using an iodide oxidation assay and a guaiacol assay. A monoclonal antibody to canine Tg, coupled to an immunoaffinity column, was used to eliminate the contaminating Tg from the TPO preparation. Using the TPO preparation as an antigen, an ELISA was performed on 10 serum samples and immunoblot assays were performed on 50 canine sera. Autoantibodies to TPO were not found in any of the sera. Assays also were performed, using purified porcine and human TPO and evidence of cross-reactivity with canine TPO was not identified. The absence of AA to TPO in dogs suggests a different pathogenesis for autoimmune thyroid disease in dogs than that hypothesized for lymphocytic thyroiditis in human beings.

Animals↗
PubMed1995

Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.

Alcoholism↗
PubMed1994

The Clinician-Administered Rating Scale for Mania (CARS-M): development, reliability, and validity.

There are currently seven rating scales available to assess manic symptomatology. All, however, have some limitations that could restrict their clinical and research utility. To resolve these deficiencies the Clinician-Administered Rating Scale for Mania (CARS-M) was developed and normed on 96 patients with mixed diagnoses during baseline and following treatment. Interrater reliability was established across multiple raters viewing 14 videotaped interviews and comparing agreement among individual items and total scores. Test-retest reliability was assessed on 36 patients twice during baseline. The mean intraclass correlation coefficient among five raters across items for each of the 14 patients was 0.81, and for total scores 0.93. Principal components analysis of items revealed two factors: mania, and psychosis. Test-retest reliability was significant for both factors (range = 0.78 to 0.95). Internal validity, comparing each item with its respective total factor score, revealed significant correlations for all items. Correlation of CARS-M total scores with mania rating scale (MRS) total scores was 0.94. Results indicate the CARS-M is both a reliable and valid measure of the severity of manic symptomatology, which incorporates a number of methodological improvements leading to greater precision and clinical utility.

Adolescent↗
PubMed1994

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

Adult↗
PubMed1994

Bone marrow micrometastases in chemotherapy-responsive advanced breast cancer: effect of ex vivo purging with 4-hydroperoxycyclophosphamide.

Tumor contamination of hematopoietic stem cell grafts may influence the outcome of breast cancer patients treated with high-dose chemotherapy. The goals of this study were: (a) to evaluate the prevalence of tumor contamination of bone marrow (BM) harvests in patients responding to systemic chemotherapy; (b) to evaluate reduction of BM tumor contamination by ex vivo purging with 4-hydroperoxycyclophosphamide (4HC); and (c) to compare the tumor contamination of peripheral blood progenitor cell collections and BM in advanced-stage breast cancer patients designated for peripheral blood progenitor cell infusion. We evaluated pre- and post-4HC purge BM specimens from 20 patients for tumor contamination using immunocytochemistry and for in vitro growth potential of tumor cells using a tumor cell clonogenic assay. Pre-4HC purge BM specimens from 15 of 20 (75%) patients were immunocytochemistry and tumor cell clonogenic assay negative. The remaining 5 BM specimens were immunocytochemistry positive, but only 3 of 5 specimens were tumor cell clonogenic assay positive. In vitro tumor colony growth was not observed in any post-4HC purge BM specimens. We also evaluated nine patients with bone or BM metastases from the start of induction chemotherapy. We found less tumor involvement of peripheral blood progenitor cell collections than of simultaneously obtained bone marrow aspirates. We conclude that bone marrow micrometastases occur with low frequency in women with chemotherapy-sensitive breast cancer and that ex vivo purging with 4HC may render tumor cells nonviable.

Adult↗
PubMed1994

Operative treatment of the degenerated segment adjacent to a lumbar fusion.

Fourteen patients with a previous lumbosacral fusion underwent neural decompression and fusion of degenerated adjacent motion segment. The most common level was L3-L4, and there was an average of 3.2 (range 1-7) previous lumbosacral surgical procedures. The average interval from the first fusion until operative intervention on the degenerated adjacent segment was 11.5 years (range 3-29 years). Five patients had an uninstrumented fusion, of which only one progressed to arthrodesis. Three of these five patients with pseudarthrosis after uninstrumented fusion--and the remaining nine patients--had fusions with instrumentation. Ten of twelve instrumented fusions progressed to solid arthrodesis. The pseudoarthrosis rate of 80% was decreased to 17% with the use of supplemental instrumentation. There was a significant number of complications and poor results, especially in patients with advanced osteoporosis and those with a short interval between adjacent segment degeneration, respectively. Eleven of 14 patients reported some postoperative pain relief.

Female↗
PubMed1994

Inhibition of neutrophil leukotriene generation by the 21-aminosteroid, U-74389F.

The 21-aminosteroids are potent inhibitors of iron-dependent lipid peroxidation and more protective than methylprednisolone in models of trauma and reperfusion, but without glucocorticosteroid side effects. Histologically, animals treated with 21-aminosteroids have decreased neutrophil (PMN) infiltrates and diminished tissue destruction associated with trauma or reperfusion. Since PMN contribute to organ failure following ischemia-reperfusion, we assessed the effect of U-74389F (U7), on normal PMN function. Neutrophils from normal volunteers were incubated for 90 min with either vehicle, 15 microM U7 or 80 microM methylprednisolone (MP), in DMSO. Lactoferrin released and generation of leukotrienes to calcium ionophore A23187, also oxygen consumed to PMA and leukotriene B4 (LTB4) and chemotaxis to FMLP and LTB4, were determined for each group of PMN. Lactoferrin released to A23187 was significantly decreased in both steroid groups (7.29 +/- 0.82 micrograms vs 3.06 +/- 0.57 micrograms U7 and 2.88 +/- 0.62 micrograms MP, P < 0.01). PMN incubated with U7 or MP generated significantly less LTB4 (60.6 +/- 4.3 ng vs 47.7 +/- 2.4 ng U7 and 43.3 +/- 5.6 ng MP, P < 0.05). There were no differences noted in the ability of PMN incubated with either compound to consume oxygen or to respond to chemotactic stimuli. We conclude that the proven protective action of the 21-aminosteroids in models of ischemia-reperfusion is related to the ability of "steroids" to inhibit leukotriene generation and degranulation and may be related to the prevention of tissue lipid peroxidation by scavenging oxygen radicals.

Antioxidants↗
PubMed1994

Wound-induced and developmental activation of a poplar tree chitinase gene promoter in transgenic tobacco.

Wounding hybrid poplar (Populus trichocarpa x P. deltoides) trees results in the expression of novel wound-inducible (win) mRNAs thought to encode proteins involved in defense against pests and pathogens. Members of the win6 gene family encode acidic multi-domain chitinases, with combined structure and charge characteristics that differ from previously described chitinases. Win6 expression has been shown to occur in pooled unwounded leaves of a wounded (on multiple leaves) poplar plant. Here we demonstrate that wounding a single leaf induces win6 expression locally, in the wounded leaf, and remotely, in specific unwounded leaves with strong vascular connections to the wounded leaf. We also demonstrate that a win6 promoter-beta-glucuronidase (GUS) gene fusion (win6-GUS) responds to wounding locally and remotely in transgenic tobacco. These data indicate that the poplar win6 promoter has regulatory elements that are responsive to 'wound signals' in the heterologous host. In addition, win6-GUS is developmentally activated in unwounded young leaves and floral tissues of transgenic tobacco. Similar developmental expression patterns are found to occur for win6 in poplar trees, demonstrating that a herbaceous plant can serve as a host for woody tree transgene analysis and can accurately predict expression patterns in tree tissues (e.g. flowers) that would be difficult to study in free-living trees.

Adaptation, Biological↗
PubMed1994

The effects of in vivo cocaine on norepinephrine-stimulated phosphoinositide hydrolysis in rat brain.

We examined the effects of a cocaine challenge on behavioral stimulation and NE-stimulated [3H]inositol-1-phosphate (IP1) formation in rat cerebral cortex after single (high dose) or repeated (low dose) cocaine administration. As previously reported, single high dose (40 mg/kg, IP) and repeated low dose (10 mg/kg, 8 IP injections) administrations of cocaine resulted in behavioral sensitization to a challenge injection of cocaine (10 mg/kg). In saline-pretreated animals, the acute cocaine challenge significantly potentiated the NE-stimulated [3H]IP1 formation as compared with the saline challenge, while in cocaine-pretreated animals, NE-stimulated phosphoinositide (PI) turnover was not significantly altered. These results suggest that although some of the acute effects of cocaine may be mediated by enhanced alpha 1-adrenergic receptor-linked PI hydrolysis, behavioral sensitization does not involve the alpha 1-adrenergic receptor-linked PI signal transduction system.

Animals↗
PubMed1994

The pattern of physical symptom changes in major depressive disorder following treatment with amitriptyline or imipramine.

The study describes a sequential analysis of depression-related physical symptoms and their relationship to imipramine and amitriptyline plasma levels over 4 weeks of treatment in 79 unipolar and bipolar patients hospitalized for major depressive disorder. Insomnia diminished in all patients after 2 weeks of drug administration. After 4 weeks, the sleep of patients whose depressive disorder has significantly improved was nearly normal, whereas patients who remained depressed showed continued sleep impairment. Reductions in loss of appetite, weight and sexual interest paralleled mood improvement. Tricyclic plasma levels significantly correlated with improved sleep. The findings suggest a close link between depressed mood and physical symptoms during recovery from major depressive disorder.

Adult↗
PubMed1994

CSF and plasma MHPG, and CSF MHPG index: pretreatment levels in diagnostic groups and response to somatic treatments.

The authors report a significant positive correlation between levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in cerebrospinal fluid (CSF) and plasma in drug-free affective disorder patients (major depression, mania, and schizoaffective disorder), but not in schizophrenia. Recent kinetic studies on the relationship between plasma and CSF MHPG discourage the interpretation of independent CSF MHPG levels without correction for the diffusion of MHPG across the blood-brain barrier. The authors therefore examine pretreatment CSF and plasma MHPG levels, and the CSF MHPG index (CSF MHPG corrected for by using simultaneously obtained plasma MHPG according to the method of Kopin et al. [1983]). No significant differences were found in these pretreatment MHPG measures among the four diagnostic groups. Changes in these MHPG indices, and their correlations with behavioral rating scores, are also examined with respect to response to the four major somatic therapies (neuroleptics, lithium, antidepressants, and electroconvulsive therapy).

Adult↗
PubMed1994

Cerebrospinal fluid somatostatin concentrations in schizophrenia and schizoaffective disorder: the effects of antipsychotic treatment.

The authors examined the effects of antipsychotic treatment on cerebrospinal fluid somatostatin like immunoreactivity (CSF SLI) in 14 schizophrenic and 3 schizoaffective patients. There was a modest but significant increase in CSF SLI in 13 out of the 14 schizophrenic patients. In addition, there was a significant positive correlation between duration of treatment and post-treatment CSF SLI concentrations. No differential response was noted in patients also treated with the anticholinergic benztropine.

Adult↗
PubMed1994

Oral communication skills of children who are hard of hearing.

Forty children with mild to severe hearing losses were administered a battery of speech and language tasks. The children's speech was characterized by misarticulation of affricates and fricatives, mild-moderate hoarseness, mild resonance problems, and good intelligibility. Their language samples included syntactic errors, primarily involving the use of bound morphemes and complex sentence structures. The children's pragmatic errors consisted primarily of providing inadequate or ambiguous information to the listener. These results indicate a consistent pattern of oral communication behavior that reflects the reduction of acoustic input that they experience.

Articulation Disorders↗