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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 73 records · Page 4Linked to original sources
PubMed2001

Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world.

SBMA (spinal and bulbar muscular atrophy), also called Kennedy disease, is an X-chromosomal recessive adult-onset neurodegenerative disorder caused by death of the spinal and bulbar motor neurones and dorsal root ganglia. Patients may also show signs of partial androgen insensitivity. SBMA is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene on the X-chromosome. Our previous study suggested that all the Nordic patients with SBMA originated from an ancient Nordic founder mutation, but the new intragenic SNP marker ARd12 revealed that the Danish patients derive their disease chromosome from another ancestor. In search of relationships between patients from different countries, we haplotyped altogether 123 SBMA families from different parts of the world for two intragenic markers and 16 microsatellites spanning 25 cM around the AR gene. The fact that different SBMA founder haplotypes were found in patients from around the world implies that the CAG repeat expansion mutation has not been a unique event. No expansion-prone haplotype could be detected. Trinucleotide diseases often show correlation between the repeat length and the severity and earlier onset of the disease. The longer the repeat, the more severe the symptoms are and the onset of the disease is earlier. A negative correlation between the CAG repeat length and the age of onset was found in the 95 SBMA patients with defined ages at onset.

Exons↗
PubMed2001

The amygdala: vigilance and emotion.

Here we provide a review of the animal and human literature concerning the role of the amygdala in fear conditioning, considering its potential influence over autonomic and hormonal changes, motor behavior and attentional processes. A stimulus that predicts an aversive outcome will change neural transmission in the amygdala to produce the somatic, autonomic and endocrine signs of fear, as well as increased attention to that stimulus. It is now clear that the amygdala is also involved in learning about positively valenced stimuli as well as spatial and motor learning and this review strives to integrate this additional information. A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies. Where appropriate, we attempt to integrate basic information on normal amygdala function with our current understanding of psychiatric disorders, including pathological anxiety.

Amygdala↗
PubMed2001

The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: a pediatric intergroup trial (POG 9049/CCG 8882).

PURPOSE: This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors of the sacrococcygeal region (SCT). METHODS: Seventy-four of 317 children presenting to Pediatric Oncology Group (POG)/Children's Cancer Group (CCG) institutions from 1990 through 1996 with malignant germ cell tumors had malignant SCT. There were 62 girls and 12 boys with a median age of 21 months (range, 3 days to 37 months) and median serum alpha-fetoprotein of 35,500 ng/mL. Twelve had undergone resection of a benign SCT as a newborn. Forty-four (59%) had evidence of metastatic disease at time of diagnosis. Presentation by type (Altman classification) was I, 0; II, 2; III, 30; and IV, 42. The initial procedure was biopsy in 45 and resection in 29. Patients were assigned randomly to receive 4 cycles of chemotherapy with etoposide (E) and bleomycin (B) and either high-dose cisplatin (200 mg/m(2) per cycle; HDP) or standard dose cisplatin (100 mg/m(2) per cycle; P). After completion of chemotherapy, 42 of 45 initially treated with biopsy underwent resection. RESULTS: Overall 4-year survival rate is 90% (SE = 4%) and 4-year event-free survival (EFS) is 84% (SE = 6%). Event-free survival data for subgroups of interest are as follows: 4-yr EFS% (SE) P Values Mets (44) 88 (6).48 No Mets (30) 80 (8) HDP EB (37) 89 (6).21 P EB (37) 78 (7) Initial Resection (29) 90 (7).50 Delayed Resection (42) 83 (7) Complete Resection (49) 90 (5).19 CR/PR Partial Resection (22) 77 (10) Biopsy Only (3) 33 (27).005 (3 way) CONCLUSIONS: (1) The current survival rate of malignant sacrococcygeal tumors is excellent even with metastases. (2) Delayed surgical resection is not associated with an adverse outcome. (3) In this subset the treatment comparison was inconclusive however, followed the trend in the overall study of more than 300 children in which the high-dose cisplatin group had superior EFS (P<.05).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Inflammatory pseudotumor of the alimentary tract: clinical and surgical experience.

BACKGROUND/PURPOSE: Initially described in 1937, inflammatory pseudotumor (IPT) inflammatory myofibroblastic tumor (IMT) or plasma cell granulomas are synonymous for an inflammatory solid tumor that contains spindle cells, myofibroblasts, plasma cells, and histocytes. Common sites of presentation include lung, mesentary, liver, and spleen; intestinal presentations are rare, and the etiology remains obscure. This report details the clinical and surgical experiences in 4 children with alimentary tract IPT at a single institution. METHODS: A retrospective chart review was conducted of pediatric patients with the pathologic diagnosis of IPT. RESULTS: Between 1990 and 1999, 4 patients (4 girls, ages 5 to 15 years) were identified with gastrointestinal tract origins of IPT. Symptoms at presentation included anemia (n = 4), intermittent abdominal pain (n = 3), fever (n = 3), weight loss (n = 2), diarrhea (n = 2), dysphagia (n = 1). Two patients had comorbid conditions of juvenile rheumatoid arthritis and mature B cell lymphoma. Three of 4 patients had elevated sedimentation rates. The sites of origin were the gastroesophageal junction, the colon, the rectum, and the appendix, with the referral diagnosis achalasia, perforated appendix, inflammatory bowel disease, and recurrent lymphoma, respectively. All were treated with aggressive surgical resection, and 3 girls have had no recurrences since the initial surgery. One patient had 3 recurrences within 8 months of presentation; she remains disease free 8 years later. CONCLUSIONS: IPT, although rare in the gastrointestinal tract, mimics more common problems. Successful surgical management is possible even in cases of multiple recurrences.

Child↗
PubMed2001

Confirmatory serologic testing for acute toxoplasmosis and rate of induced abortions among women reported to have positive Toxoplasma immunoglobulin M antibody titers.

OBJECTIVE: Results obtained with commercial testing kits for immunoglobulin M Toxoplasma antibodies may be inaccurate or may be inaccurately interpreted, which may influence whether a woman decides to terminate the pregnancy. This study was undertaken to determine whether confirmatory testing at a reference laboratory and communication of the results and an expert interpretation to the patient's physician would affect the rate of induced abortions among pregnant women with positive results of testing for immunoglobulin M Toxoplasma antibodies in outside laboratories. STUDY DESIGN: This was a retrospective cohort study of 811 consecutive pregnant women for whom the toxoplasma serologic profile was performed at a reference laboratory. Almost all the patients had been informed by their physicians that a result of a test for immunoglobulin M Toxoplasma antibodies performed in an outside laboratory was positive. Women were separated into those with a toxoplasma serologic profile result suggestive of a recently acquired infection (group 1) and those with a result suggestive of an infection acquired in the more distant past (group 2). Physician reports of induced abortions were used to determine rates of induced abortion in groups 1 and 2. RESULTS: Of the 811 women 321 (39.6%) were considered likely to have a recent infection (group 1) and 490 (60.4%) were considered likely to have a past infection (group 2). Physicians reported pregnancy outcomes for 433 (53.4%) of 811 women (65.1% and 45.7% in groups 1 and 2, respectively). Whereas 36 of 209 women in group 1 (17.2%) terminated the pregnancy, only 1 of 224 women in group 2 (0.4%) chose abortion (P <.001). CONCLUSION: Confirmatory serologic testing in a reference laboratory and communication of the results and their correct interpretation by an expert to the patient's physician decreased the rate of unnecessary abortions by approximately 50% among women for whom positive immunoglobulin M Toxoplasma test results had been reported by outside laboratories.

Abortion, Induced↗
PubMed2001

Histology-specific expression of a DNA repair protein in pediatric rhabdomyosarcomas.

PURPOSE: DNA repair enzymes have a critical role in cellular maintenance and survival. The enzyme apurinic/apyrimidinic endonuclease/redox factor 1 (APE/ref1), a key protein in the base excision repair pathway, displays both repair and redox control. We examined the role of APE/ref1 in pediatric embryonal and alveolar rhabdomyosarcomas (ARMS). MATERIALS AND METHODS: Using an immunohistochemical method, fixed tissue from 31 newly diagnosed pediatric rhabdomyosarcomas were evaluated for expression of APE/ref1. Tissue was obtained from Indiana University and the Cooperative Human Tissue Network. RESULTS: We demonstrated high levels of expression within the localized and metastatic embryonal rhabdomyosarcomas. This contrasted with both localized and metastatic ARMS, which had low levels of APE/ref1 expression. This histology-specific difference proved to be significant (P = 0.003). Furthermore, the expression within all tumors examined was localized to the nucleus and did not differ between localized and metastatic tumors. CONCLUSIONS: We propose several hypotheses to explain this histology-specific expression of APE/ref1 in pediatric rhabdomyosarcomas. Because the majority of ARMS expressed either the PAX3/FKHR or PAX7/FKHR fusion transcript, the low level of expression may be related to the redox activity of APE/ref1. The low levels may also be related to the bioreductive activity of APE/ref 1.

Adolescent↗
PubMed2001

Inhibition of ganciclovir-susceptible and -resistant human cytomegalovirus clinical isolates by the benzimidazole L-riboside 1263W94.

The average 50% inhibitory concentration (IC(50)) values for AD169 were 0.22 +/- 0.09 microM 1263W94 and 5.36 +/- 0.12 microM ganciclovir. For 35 human cytomegalovirus (HCMV) clinical isolates the average IC(50) was 0.42 +/- 0.09 microM 1263W94, and for 26 ganciclovir-susceptible HCMV clinical isolates the average IC(50) was 3.78 +/- 1.62 microM ganciclovir. Nine HCMV clinical isolates that were resistant to ganciclovir were completely susceptible to 1263W94.

Anti-HIV Agents↗
PubMed2001

Alveolar macrophage activity and the pulmonary complications of haematopoietic stem cell transplantation.

BACKGROUND: The success of haematopoietic (bone marrow or peripheral blood) stem cell transplantation (SCT) is compromised by pulmonary complications. We hypothesised that a proinflammatory alveolar microenvironment, reflected in alveolar macrophage (AM) cytokine production, would predispose to such complications. METHODS: AM were isolated from adult SCT recipients by bronchoalveolar lavage before SCT (n=32) and during post-transplant pancytopenia (n=23). Concentrations of tumour necrosis factor (TNF)alpha, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-1 beta, IL-6, and IL-8 in 24 hour AM culture medium were measured by enzyme linked immunosorbent assay and compared with both the occurrence of post-SCT lung disease and with subjects' previous respiratory histories. RESULTS: Eleven subjects developed lung disease within 6 months of SCT. These subjects had higher median pre-transplant AM TNFalpha (8 (IQR 1-8) v 2 (1-5) ng/10(6)AM, p=0.01, median difference (D) = 3, 95% CI 0.1 to 7), GM-CSF (5 (0.7-8) v 0.2 (0.1-0.8), p=0.006, D = 4, 95% CI 0.5 to 7), and IL-6 (0.5 (0.1-1) v 0.1 (0.02-0.3), p=0.049, D = 0.3, 95% CI 0.0002 to 1) production than remaining subjects; IL-1 beta and IL-8 did not differ. During pancytopenia high AM GM-CSF production again predicted later lung disease (1 (0.7-9) v 0.1 (0.06-0.3), p=0.01, D = 1, 95% CI 0.1 to 6). A history of recent chest disease was associated with high AM TNFalpha and GM-CSF production and with post-SCT lung disease. Pre-SCT lung function was unrelated to post-SCT lung disease. CONCLUSIONS: Recent respiratory disease and persistent proinflammatory AM behaviour detectable before transplantation are associated with lung disease following SCT. These associations may prove useful in pre-transplant risk assessment.

Adolescent↗
PubMed2001

Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients.

Thirty patients with cancer pain completed a double-blind crossover study comparing controlled-release (CR) and immediate-release (IR) oxycodone. In open-label titration (2 to 21 days), these patients were stabilized on IR oxycodone qid. They were then randomized to double-blind treatment with CR oxycodone q12h or IR oxycodone qid for 3 to 7 days followed by crossover at the same daily dose. Mean (+/- SD) pain intensity (0 = none to 10 = severe) decreased from a baseline of 6.0 +/- 2.2 to 2.7 +/- 1.1 after titration with IR oxycodone dosed qid. Pain intensity remained stable throughout double-blind treatment: 2.7 +/- 1.9 with CR oxycodone and 2.8 +/- 1.9 with IR oxycodone. Acceptability of therapy and pain scores correlated with plasma oxycodone concentrations for each interval and were similar for both medications (IR and CR oxycodone). Adverse events were similar for both formulations. Following repeat dosing under double-blind conditions, oral CR oxycodone administered q12h provided analgesia comparable to IR oxycodone given qid.

Administration, Oral↗
PubMed2001

Multimodal assessment of dissociation in adolescents: inpatients and juvenile sex offenders.

Two samples of adolescents were studied to assess the validity of several measures of dissociation. The first sample included 70 males from a residential treatment program for adolescent sex offenders (ASO). The second were 47 psychiatric inpatients. The measures included the DSM-IV field trial questionnaire for Dissociative Disorders of Childhood, Child Dissociative Checklist, Adolescent-Dissociative Experiences Schedule, Trauma Symptom Checklist for Children, and the Dissociation Research scale. Ten of the 70 adolescent sex offender subjects (14.3%) were identified as meeting DSM-IV criteria for a Dissociation-spectrum disorder diagnosis and two (4.2%) of the psychiatric patients. Between-groups analyses with the ASO revealed significant differences on the Child Dissociative Checklist and the Dissociation Research Scale. Cumulative trauma did not differ significantly between the dissociative and nondissociative groups of ASO, but physical abuse was related to a diagnosis of dissociation in this sample. The dissociation measures were highly intercorrelated for both groups, and suggest that they measure a similar construct.

Adolescent↗
PubMed2001

Cyclooxygenase-2 expression and prostaglandin E(2) synthesis are up-regulated in carcinomas of the cervix: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors.

The prevalence of cervical cancer in South African women is reported as being the highest in the world, occurring, on the average, in 60 of every 100,000 women. Cervical cancer is thus considered an important clinical problem in sub-Saharan AFRICA: Recent studies have suggested that epithelial tumors may be regulated by cyclooxygenase (COX) enzyme products. The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis are up-regulated in cervical cancers. Real-time quantitative RT-PCR and Western blot analysis confirmed COX-2 ribonucleic acid and protein expression in all cases of squamous cell carcinoma (n = 8) and adenocarcinoma (n = 2) investigated. In contrast, minimal expression of COX-2 was detected in histologically normal cervix (n = 5). Immunohistochemical analyses localized COX-2 expression and PGE(2) synthesis to neoplastic epithelial cells of all squamous cell (n = 10) and adenocarcinomas (n = 10) studied. Immunoreactive COX-2 and PGE(2) were also colocalized to endothelial cells lining the microvasculature. Minimal COX-2 and PGE(2) immunoreactivity were detected in normal cervix (n = 5). To establish whether PGE(2) has an autocrine/paracrine effect in cervical carcinomas, we investigated the expression of two subtypes of PGE(2) receptors, namely EP2 and EP4, by real-time quantitative RT-PCR. Expression of EP2 and EP4 receptors was significantly higher in carcinoma tissue (n = 8) than in histologically normal cervix (n = 5; P < 0.01). Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation after in vitro culture of cervical cancer biopsies and normal cervix in the presence or absence of 300 nmol/L PGE(2). cAMP production was detected in all carcinoma tissue after treatment with exogenous PGE(2) and was significantly higher in carcinoma tissue (n = 7) than in normal cervix (n = 5; P < 0.05). The fold induction of cAMP in response to PGE(2) was 51.1 +/- 12.3 in cervical carcinoma tissue compared with 5.8 +/- 2.74 in normal cervix. These results confirm that COX-2, EP2, and EP4 expression and PGE(2) synthesis are up-regulated in cervical cancer tissue and suggest that PGE(2) may regulate neoplastic cell function in cervical carcinoma in an autocrine/paracrine manner via the EP2/EP4 receptors.

Adenocarcinoma↗
PubMed2001

An evaluation of the physicochemical risk for renal stone disease during pregnancy.

Seventeen subjects were studied during the third trimester of pregnancy (PG) and post partum (NPG) to evaluate the effect of pregnancy on the physicochemical risk of renal stone disease. Levels of urinary saturation for calcium oxalate (CaOx), brushite (Br), uric acid (UA), and monosodium urate (NaU) were determined as well as urinary excretions of stone-forming elements. In addition to urinary calcium excretion, assessment of calcium metabolism included serum calcium and parathyroid hormone. Urinary calcium excretion was 251 +/- 127 mg/day during pregnancy and 121 +/- 67 mg/day post partum (p < 0.001). This was associated with a higher intake of dietary calcium and altered renal handling of calcium with an increase in the filtered load and a decrease in renal tubular reabsorption. The increase in urinary calcium resulted in a higher level of saturation of the urine for calcium oxalate (NPG 2.1 +/- 1.0 vs PG 3.0 +/- 1.1, p < 0.02) and brushite (NPG 1.2 +/- 0.9 vs PG 1.9 +/- 1.1, p < 0.05) compatible with an increased risk of stone formation.

Adult↗
PubMed2001

Implantation of dual chamber pacemaker defibrillator and placement of endocardial leads via the axillary vein.

OBJECTIVES: To assess the preliminary clinical results of implantation of dual chamber pacemaker defibrillator and to evaluate the safety and effectiveness of placement of endocardial leads in the axillary vein. METHODS: Seven patients with ventricular tachycardia and/or ventricular fibrillation (VT/VF), associated with bradyanhythmia received implantation of a dual chamber pacemaker defibrillator, including 5 patients with coronary artery disease and 2 patients with dilated cardiomyopathy. The atrial and ventricular leads were introduced via the axillary vein under venographic guidance. RESULTS: Dual chamber pacemaker defibrillators were successfully implanted in the left chest subcutaneous pocket in 5 patients and the left pectoral muscular pocket in 2 patients. All the VT/VF occurring either inducibly during the procedure or spontaneuously during follow-up were detected promptly and treated successfully. Both the pacing and sensing functions were satisfactory. The endocardial leads required were successfully introduced via the axillary vein without major complications. CONCLUSIONS: Dual chamber pacemaker defibrillators can provide reliable therapy for VT/VF and the dual chamber pacing function. Placement of endocardial leads via the axillary vein under venographic guidance is safe and effective.

Aged↗
PubMed2000

Enhancement of the acoustic startle response by dopamine agonists after 6-hydroxydopamine lesions of the substantia nigra pars compacta: corresponding changes in c-Fos expression in the caudate-putamen.

Rats with 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway show enhanced locomotor and stereotyped behaviors when challenged with direct and indirect dopamine (DA) agonists due to the development of postsynaptic supersensitivity. To determine if this phenomenon generalizes to other motor behaviors, we have used this rat model of Parkinson's disease to examine the effects of the direct dopamine D(1) receptor agonist SKF 82958 and the indirect DA agonist L-3,4-dihydroxyphenylalanine (L-DOPA) on the acoustic startle response. In addition, we used the expression of c-Fos protein as a marker of neuronal activity to assess any corresponding drug-induced changes in the caudate-putamen (CPu) after L-DOPA administration. Male Sprague-Dawley rats received bilateral injections of 6-OHDA into the substantia nigra pars compacta and 1 week later were tested for startle after systemic administration of SKF 82958 (0.05 mg/kg) or L-DOPA (1, 5, 10 mg/kg). SKF 82958 produced a marked enhancement of startle with a rapid onset in 6-OHDA-lesioned but not SHAM animals. L-DOPA produced a dose- and time-dependent enhancement of startle in 6-OHDA-lesioned rats that had no effect in SHAM animals even at the highest dose (10 mg/kg). Furthermore, L-DOPA produced a dramatic induction of c-Fos in the CPu in 6-OHDA-lesioned animals. Consistent with other literature, these data suggest that neurons in the CPu become supersensitive to the effects of DA agonists after 6-OHDA-induced denervation of the nigrostriatal pathway and that supersensitive dopamine D(1) receptors may mediate the enhancement of startle seen in the present study.

Acoustic Stimulation↗
PubMed2000

Processing of cdk5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells.

Recently, it was shown that conversion of cdk5 activator protein p35 to a C-terminal fragment p25 promotes a deregulation of cdk5 activity, which may contribute to neurodegeneration in Alzheimer's disease. In this study, we present evidence that calpain is a protease involved in the conversion of p35 to p25. To activate calpain, rat cerebellar granule neurons were treated with maitotoxin (MTX). A C-terminus-directed anti-p35 antibody detected that p35 conversion to p25 paralleled the formation of calpain-generated alpha-spectrin (alpha-fodrin) breakdown products (SBDP's) in a maitotoxin-dose-dependent manner. Two calpain inhibitors (MDl28170 and SJA6017) reduced p35 processing but were unchanged when exposed to the caspase inhibitor carbobenzoxy-Asp-CH(2)OC(=O)-2, 6-dichlorobenzene or the proteasome inhibitors (lactacystin and Z-Ile-Glu(OtBu)Ala-Leu-CHO). p35 protein was also degraded to p25 when rat brain lysate was subjected to in vitro digestion with purified mu- and m-calpains. Additionally, in a rat temporary middle cerebral artery occlusion model, p35 processing to p25 again paralleled SBDP formation in the ischemic core. Lastly, in malonate-injured rat brains, the ipsilateral side showed a striking correlation of SBDP formation with p35 to p25 conversion and tau phosphorylation (at Ser202 and Thr205) increase. These data suggest that calpain is a major neuronal protease capable of converting p35 to p25 and might play a pathological role of activating cdk5 and its phosphorylation of tau in Alzheimer's disease.

Animals↗
PubMed2000

GABA in the deep layers of the superior Colliculus/Mesencephalic reticular formation mediates the enhancement of startle by the dopamine D1 receptor agonist SKF 82958 in rats.

GABA transmission in the deep layers of the superior colliculus/deep mesencephalic reticular formation (deep SC/Me) mediates several motor responses, including those expressed after systemic administration of dopamine agonists. In the present study we examined the role of the deep SC/Me in the modulation of the acoustic startle reflex and its enhancement by the dopamine D(1) agonist SKF 82958. Rats were implanted with bilateral cannulas into the deep SC/Me or superficial layers of the SC (super SC) and 1 week later were infused with various compounds. The GABA(A) antagonist bicuculline (0, 5, and 10 ng) produced a dose- and time-dependent enhancement of startle after infusion into the deep SC/Me, but not the super SC. Infusion of the GABA(A) agonist muscimol (0.1 microg) into the deep SC/Me, but not the super SC, blocked the enhancement of startle by systemic SKF 82958 (1 mg/kg) but had no effect on baseline startle by itself. This effect was not produced by infusion of the D(1) antagonist SCH 23390(1 microg) or the glutamate antagonist NBQX (0.1 microg). Deposits of FluoroGold into the deep SC/Me, combined with immunohistochemistry for glutamic acid decarboxylase (GAD), confirmed a direct GABAergic input from the substantia nigra pars reticulata (SNr) to the deep SC/Me. These results suggest that GABA tone in the deep SC/Me modulates the expression of startle as well as the enhancement of startle by dopamine D(1) agonists. On the basis of these data and previous work, we have proposed a striatonigral-tectal-reticular neural pathway mediating the effects of dopamine D(1) agonists on startle.

Acoustic Stimulation↗