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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 91 records · Page 5Linked to original sources
PubMed2000

Intracranial fibromuscular dysplasia in a six-year-old child: a rare cause of childhood stroke.

Intracranial fibromuscular dysplasia is a nonatheromatous angiopathy that most commonly affects adult women and is rarely recognized in children. Symptoms include stroke and headache, although the vasculopathy may be asymptomatic. Diagnosis is based on angiographic appearance, commonly described as a "string of beads." The etiology of intracranial fibromuscular dysplasia is not known, although possible causes include genetic predisposition, trauma, and underlying connective tissue disease. Treatment of intracranial fibromuscular dysplasia is largely supportive once symptoms become manifest. We report a 6-year-old girl who presented to our center for further evaluation of a large left middle cerebral artery distribution infarction. The patient was previously healthy, without known risk factors for stroke. Initial symptoms consisted of a dense global aphasia and a right hemiparesis. On arrival, the patient's aphasia had improved but she continued to have significant deficits in both receptive and expressive language as well as residual right hemiparesis. Magnetic resonance imaging and conventional angiographic studies demonstrated characteristic beading of the distal portion of the left internal carotid artery, as well as the proximal middle cerebral artery. Laboratory evaluation, echocardiogram, and renal ultrasound were normal. The renal vasculature did not demonstrate evidence of intracranial fibromuscular dysplasia. In conclusion, intracranial fibromuscular dysplasia should be considered in the differential diagnosis of childhood stroke. When recognized, other sites of vascular involvement should be sought, and consideration of underlying disorders is important, as connective tissue disorders have been associated with a propensity to develop this vascular abnormality. Careful follow-up is warranted, due to possible progression of disease.

Brain↗
PubMed2000

High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers.

To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.

Aged↗
PubMed2000

Analysis of physician ability in the measurement of pulsus paradoxus by sphygmomanometry.

CONTEXT: Measurement of pulsus paradoxus (PP) is one of several measures previously advocated in the National Heart, Lung, and Blood Institute asthma management guidelines: a pulsus of > 12 mm Hg warranted hospital admission. It is one of only a few measures that is not effort dependent and therefore important in the evaluation of patients with asthma. OBJECTIVE: Determination of physician accuracy in measuring PP. DESIGN: A model of induced PP in a trained healthy subject without respiratory disease was constructed with a fixed inspiratory resistance with measurement of inspiratory air pressure and beat-to-beat BP noninvasively. SETTING: Laboratory. PARTICIPANTS: Attending physicians from emergency medicine and critical care disciplines who served as consecutive examiners of the trained reference subject generating known PP. INTERVENTIONS: A total of 19 attending physicians were assessed for ability in measuring PP by sphygmomanometry and by palpation. The reference subject generated 4 degrees of PP sequentially, with each examiner blinded to the value of negative inspiratory pressure and PP. Examiners first assessed PP qualitatively by palpation, followed by its measurement within 2 min. MAIN OUTCOME MEASURE: Proximity of physician-measured PP (PPm) to true PP (PPt). RESULTS: At inspiratory pressures of - 10, - 15, - 20, and - 25 mm Hg, PPt was 13.7, 16.2, 19.1, and 20.7 mm Hg, respectively (F = 14.8, p < 0. 0001; analysis of variance [ANOVA]). At the same pressures, PPm was 13.1, 17.5, 17.7, and 18.0 mm Hg (p > 0.10; ANOVA). Linear regression of PPm against PPt for each examiner revealed a slope (SE) of 0.53 (0.23), and not a 1:1 relationship. CONCLUSIONS: Past and present guidelines do not account for the challenges in measuring PP, especially in tachypneic patients. Sphygmomanometric determination of PP should be augmented by new aids developed through technological innovation.

Adult↗
PubMed2000

Efficacy of bonded and nonbonded amalgam in the treatment of teeth with incomplete fractures.

BACKGROUND: This clinical study compared the efficacy of adhesive-retained vs. pin-retained complex amalgam restorations in the treatment of molars with incomplete fractures. Both relief of chewing pain and cold sensitivity were evaluated at two weeks, three months and one year. METHODS: The authors treated 38 patients with a chief complaint of chewing sensitivity on vital molar teeth (40 teeth in the study). A random-number generator determined the treatment method for each tooth. Twenty teeth received bonded amalgam restorations. Twenty teeth received amalgapins or threaded pins to retain the amalgam. Teeth were evaluated for postoperative chewing sensitivity. A visual analog pain scale was used to evaluate cold response to a skin-refrigerant-soaked cotton pellet at each visit. After 12 months, all 40 teeth were available for evaluation. RESULTS: Chewing pain was completely eliminated in all but one tooth. A Student's t-test found no significant difference (P > .05) in preoperative cold sensitivity between the bonded and nonbonded groups. A paired t-test comparison indicated that the teeth in the bonded group were significantly less sensitive to cold after three months and 12 months than they were at the time of the baseline measurements (P < .0001). A paired t-test indicated no significant difference between preoperative and postoperative cold sensitivity scores for teeth in the nonbonded group (P > .05). CONCLUSIONS: Both adhesively bonded and mechanically retained complex amalgam restorations were successful in resolving chewing sensitivity in cracked molars. For 39 of 40 teeth, chewing sensitivity did not return during the one-year follow-up period. At three months and 12 months, cold sensitivity was reduced in the bonded restorations. At all three time periods, cold sensitivity remained similar to baseline levels for the mechanically retained restorations. CLINICAL IMPLICATIONS: Incomplete tooth fracture in molars can be successfully treated by covering fractured cusps with amalgam restorations. This study excluded teeth with prolonged sensitivity to a cold stimulus or those with periodontal evidence of root fracture. With these exclusions, elimination of chewing sensitivity was predictable. Teeth restored with bonded restorations experienced a decrease in sensitivity to a cold stimulus at three months and at 12 months, but not at two weeks. The cold sensitivity of teeth restored with nonbonded restorations was similar at baseline, two weeks, three months and one year.

Adult↗
PubMed2000

The association between greater continuity of care and timely measles-mumps-rubella vaccination.

OBJECTIVES: This study assessed whether greater continuity of care is associated with timely administration of measles-mumps-rubella (MMR) vaccination. METHODS: We studied 11,233 patients continuously enrolled in Group Health Cooperative (GHC) from birth to 15 months. We used a preestablished index to quantify continuity of care based on the number of primary care providers in relation to the number of clinic visits. MMR vaccination status at 15 months was assessed with automated immunization data systems at GHC. RESULTS: In a logistic regression model, both medium continuity (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.08, 1.33) and high continuity (OR = 1.36, 95% CI = 1.22, 1.52) were associated with increased likelihood of being immunized by 15 months compared with patients in the lowest tercile of continuity of care. CONCLUSION: Greater continuity of care is associated with more timely immunization.

Child Health Services↗
PubMed2000

Practical value of Ki-67 and p53 labeling indexes in stereotactic biopsies of diffuse and pilocytic astrocytomas.

OBJECTIVE: Stereotactic biopsies are increasingly being used for the diagnosis and grading of astrocytomas, and there is a growing need to obtain maximum information from these tissue samples. In everyday practice, p53 protein and Ki-67 immunohistochemical analyses are the most frequently used ancillary studies to aid in diagnosis and grading, but their exact role is not clearly established. This study was undertaken to evaluate the practical value of these markers in stereotactic biopsy samples from diffuse astrocytomas as well as pilocytic astrocytomas. Methods/Results.-We analyzed the Ki-67 (MIB-1) and p53 labeling indexes in the stereotactic biopsy specimens from 11 pilocytic astrocytomas; 8 grade 2, 15 grade 3, and 16 grade 4 diffuse astrocytomas. Pilocytic astrocytomas and diffuse astrocytomas were evaluated as 2 separate groups. There was a strong correlation with poor outcome when both labeling indexes were higher than 15% in the same tumor for diffuse astrocytomas (P < 0.01). The indexes did not correlate with outcome in pilocytic astrocytomas. CONCLUSION: Combined Ki-67 and p53 labeling indexes higher than 15% indicated a worse outcome than suggested by the histologic grading. The analysis aided or improved histologic evaluation of stereotactic biopsies in our patients. We believe that a realistic prognostic upgrading of diffuse astrocytomas should be made only when labeling indexes for both markers are greater than 15%.

Adolescent↗
PubMed2000

High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers.

PURPOSE: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ability to suppress testosterone secretion in patients. Various studies also indicate that LHRH analogs might have direct inhibitory effects on prostate tumors mediated by specific LHRH receptors. In this study we investigated the presence and characteristics of receptors for LHRH and their messenger (m) ribonucleic acid (RNA) expression in specimens of human prostate adenocarcinomas and benign prostatic tissue. MATERIALS AND METHODS: In vitro ligand competition assays as well as reverse transcriptase polymerase chain reaction (RT-PCR) were performed to investigate the expression of receptors for LHRH in surgical specimens of human prostate cancers and benign prostatic tissue. RESULTS: Sixty-nine of 80 (86%) cancers exhibited specific, medium to high-affinity binding for [D-Trp6]LHRH with a dissociation constant (Kd) of 6.55+/-0.4 nM and a maximal binding capacity (Bmax) of 483.6+/-25.4 fmol./mg. membrane protein. Two prostate cancer patients who were treated with the LHRH agonist goserelin prior to prostatectomy did not show tumor LHRH receptors. The expression of mRNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Benign prostatic tissue also displayed LHRH receptor gene expression, but exhibited lower Bmax value. There was a negative correlation (p <0.001) between LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity but an increased binding affinity. CONCLUSIONS: The expression of specific receptor proteins for LHRH in human prostate cancer provides a rationale for the improvement in methods for therapy of this malignancy based on LHRH analogs.

Aged↗
PubMed2000

Immunization status of children born to human immunodeficiency virus (HIV)-infected mothers in two Texas cities.

BACKGROUND: Because HIV-infected and HIV-exposed children are at risk of acquiring infectious diseases, they should be immunized. METHODS: We abstracted charts at pediatric HIV clinics in Dallas and San Antonio, matched the children to birth certificates and assessed up-to-date immunization status. RESULTS: Of the 178 children, 108 (61%) were up to date for the diphtheria-tetanus-pertussis (DTP), polio, and measles-mumps-rubella (MMR) series. In multivariate analysis, predictors of delayed immunization included maternal high-risk sexual partners and infant antiretroviral therapy. CONCLUSION: In this population of children born to HIV-infected mothers, immunizations were up to date in 61%, a figure that exceeds or equals immunization levels for other Texas children. Texas falls short of the recommended goal of 90% immunization for children of HIV-infected mothers and healthy children.

Child, Preschool↗
PubMed2000

Left main coronary artery rotational atherectomy and stenting.

BACKGROUND: Coronary artery bypass surgery is a difficult option in patients who are not candidates for bypass surgery and high-risk patients with critical left main coronary artery (LMCA) disease. We report outcomes and short-term follow-up of patients who had LMCA rotational atherectomy and/or stenting, assess the role of these interventions in protected and unprotected significant LMCA stenosis, and review the literature. METHODS: We reviewed the cases of seven men with critical LMCA stenosis for whom coronary artery bypass surgery was considered a high risk. Five patients had rotational atherectomy, one had coronary artery stenting, and one had both. RESULTS: In all cases, angiographic success was achieved, and symptoms were relieved. Six patients were discharged from the hospital in 3 to 6 days. One patient who had cardiogenic shock, respiratory failure, and acute renal failure before the procedure died of arrhythmia 4 days afterward. Another patient had elective coronary artery bypass graft surgery 3 weeks later for recurrent angina. Cardiac catheterization was repeated in 1 month for chest pain in three patients at 4 to 7 months follow-up, and none had progression of residual stenosis in the LMCA. CONCLUSIONS: Our study suggests that LMCA rotational atherectomy and stenting are safe and effective revascularization procedures in high-risk patients and patients who are not candidates for bypass surgery.

Aged↗
PubMed1999

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404.

PURPOSE: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. METHODS AND MATERIALS: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. RESULTS: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. CONCLUSIONS: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Site-specific splice variation of the human P2X4 receptor.

P2X4 receptors are expressed in specific brain areas. We now describe site-specific splice variations of the human P2X4 receptor subunit, occurring at residue [YVIG / WVFV(W)] near the end of the first predicted transmembrane domain. p2X4(b) is formed by the insertion of an additional 16 amino acids. p2X4(C) is formed by deleting a cassette of 130 amino acids, including six of the 10 conserved extracellular cysteine residues. Transfection of P2X4(a), but not p2x4(c), formed functional channels in Xenopus oocytes and human 1321N1 cells. After transfection of p2X4(b) small, inconsistent ATP-evoked responses were detected only in the human cells, but when co-expressed, p2x4(b) may alter the function of P2X4(a) in oocytes. The distribution of splice variant RNA within human brain suggests regionally-dependent expression. These data indicate that the functions of the human P2X4 receptor may be altered by alternative splicing.

Adenosine Triphosphate↗
PubMed1999

Aminoisoquinolines: design and synthesis of an orally active benzamidine isostere for the inhibition of factor XA.

The design, synthesis and SAR of sulfonamidopyrrolidinone fXa inhibitors incorporating a new benzamidine isostere, namely aminoisoquinolines, is described. These inhibitors have higher Caco-2 cell permeability than comparable benzamidines and attain higher levels of exposure upon oral dosing. The most potent member 14b (fXa Ki=6 nM) is selective against other serine proteases of interest (>600 fold).

Administration, Oral↗
PubMed1999

Prospective study of HTLV-I infection in an initially asymptomatic cohort.

A prospective clinical study of 20 initially asymptomatic HTLV-I-seropositive carriers was commenced in 1991 to determine the natural history of the infection in relation to HTLV-I proviral load, immune responses, and lymphocyte phenotype. Proviral load varied widely between carriers but was relatively constant within an individual over time. The lymphocyte phenotype and prevalence of activated lymphocytes were not predictive of disease and the magnitude of the cytotoxic T-lymphocyte response to HTLV-I was independent of proviral load. Incident conditions, some related to HTLV-I infection, including a case of HTLV-I-associated myelopathy (HAM), were documented in 9 carriers. Development of myelopathy and uveitis was associated with high peripheral blood HTLV-I proviral load that predated symptoms. Persistently high proviral load appears to predate the development of HTLV-I-associated inflammation in neuro-ophthalmic tissue.

Adult↗
PubMed1999

Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: results of a Phase II study.

PURPOSE: To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas. METHODS AND MATERIALS: Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse. RESULTS: A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site. CONCLUSIONS: Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain.

Adolescent↗