Biomedical subjects

S Howe

Publications and source records attributed to S Howe.

At least 19 recordsLinked to original sources

PubMed2001

An element in intron 1 of the CFTR gene augments intestinal expression in vivo.

The elements controlling the complex developmental and tissue-specific expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene lie outside the basal promoter region and have not been characterized. We previously identified a tissue-specific DNase I hypersensitive site (DHS) in intron 1 (185 + 10 kb) of the CFTR gene. Here we show that removal of the core element abolishes the activity of this DHS in transient transfection assays of reporter/enhancer gene constructs. We then compared expression from a 310 kb yeast artificial chromosome (YAC) that contains the entire CFTR gene with expression from the same YAC from which the DHS element had been deleted. Stable transfection of a human colon carcinoma cell line showed that transcription from the deleted YAC was reduced by approximately 60%. In transgenic mice, deletion of the intron 1 DHS had no effect on expression in the lung, but reduced expression in the intestine by approximately 60%. Thus, the regulatory element associated with the intron 1 DHS is tissue-specific and is required for normal CFTR expression levels in the intestinal epithelium in vivo.

Animals↗

PubMed2001

A comparison of the performance of bacitracin-incorporated chocolate blood agar with chocolate blood agar plus a bacitracin disk in the isolation of Haemophilus influenzae from sputum.

The lack of selectivity of chocolated blood agar (CBA), routinely used for the isolation of Haemophilus influenzae, may lead to masking of the growth of H. influenzae due to overgrowth of competing flora. Bacitracin can be used as a selective agent, either incorporated into the medium or applied to the medium in a filter paper. However, neither method has been evaluated or compared in a large study. Sputum samples (1990) were examined in four laboratories and the isolation rates of H. influenzae on chocolated blood agar with bacitracin added to the medium (BCA) and chocolated blood agar (CBA) with a bacitracin disk were compared. A plain blood agar plate was also inoculated to facilitate the isolation of Streptococcus pneumoniae so that its effects on the isolation of H. influenzae could be assessed. No significant difference was found between the isolation rates of H. influenzae on BCA and CBA with a bacitracin disk, although competing flora was greatly reduced and quantity of growth of H. influenzae increased on BCA. The presence of S. pneumoniae did not affect the isolation of H. influenzae in this study.

Anti-Bacterial Agents↗

PubMed2000

Modular bacterial artificial chromosome vectors for transfer of large inserts into mammalian cells.

To facilitate the use of large-insert bacterial clones for functional analysis, we have constructed new bacterial artificial chromosome vectors, pPAC4 and pBACe4. These vectors contain two genetic elements that enable stable maintenance of the clones in mammalian cells: (1) The Epstein-Barr virus replicon, oriP, is included to ensure stable episomal propagation of the large insert clones upon transfection into mammalian cells. (2) The blasticidin deaminase gene is placed in a eukaryotic expression cassette to enable selection for the desired mammalian clones by using the nucleoside antibiotic blasticidin. Sequences important to select for loxP-specific genome targeting in mammalian chromosomes are also present. In addition, we demonstrate that the attTn7 sequence present on the vectors permits specific addition of selected features to the library clones. Unique sites have also been included in the vector to enable linearization of the large-insert clones, e. g., for optical mapping studies. The pPAC4 vector has been used to generate libraries from the human, mouse, and rat genomes. We believe that clones from these libraries would serve as an important reagent in functional experiments, including the identification or validation of candidate disease genes, by transferring a particular clone containing the relevant wildtype gene into mutant cells or transgenic or knock-out animals.

Animals↗

PubMed2000

Expression of the human CFTR gene from episomal oriP-EBNA1-YACs in mouse cells.

Plasmids carrying the origin of plasmid replication ( oriP ) and expressing the EBNA-1 protein from the Epstein-Barr virus replicate and segregate in human cells and are thus potentially useful vectors for gene therapy. As very large circular molecules, up to 660 kb in size, can be maintained episomally using this system, it is possible to include intact human genes with all their long-range controlling elements which might give high levels of tissue-specific and controlled gene expression. We have shown previously that a 320 kb yeast artificial chromosome (YAC) carrying the intact human CFTR gene can complement the Cambridge null cystic fibrosis mice as a transgene. We have now modified this YAC to a circular molecule carrying both oriP and the EBNA-1 gene. We show that this oriP-EBNA1-YAC can be stably maintained as unrearranged episomes in mouse LA-9 cells, which do not express endogenous cftr, and in mouse CMT-93 cells, which do express endogenous cftr. The human CFTR gene is expressed in some of the cell lines, but the level of expression is very variable between cell lines and is not related to the copy number of the elements.

Alanine↗

PubMed2000

Ondansetron versus placebo for prophylaxis of nausea and vomiting in patients undergoing ambulatory laparoscopic cholecystectomy.

BACKGROUND: Postoperative nausea and vomiting is a common problem in patients undergoing laparoscopic cholecystectomy (LC). The purpose of this study was to evaluate the efficacy of ondansetron given at the induction of anesthesia in patients scheduled for ambulatory LC. METHODS: A total of 84 patients undergoing ambulatory LC were enrolled in a randomized, prospective, double-blinded study in which the subjects received either placebo or 4 mg ondansetron intravenously at induction of anesthesia. A nausea scoring system was employed utilizing a 5-point linear scale, with 1 point given for no nausea and a maximum of 5 points for an episode of emesis. Each patient received a total of four scores postoperatively. RESULTS: The patients receiving placebo had significantly more episodes of nausea (53 versus 32; P <0.009) and emesis (11 versus 2; P <0.02), higher mean total nausea scores (7.2 versus 5.4; P <0.006), and need for additional postoperative antiemetics (23 versus 14; P <0.05) than those receiving ondansetron. CONCLUSIONS: In patients undergoing ambulatory laparoscopic cholecystectomy, ondansetron at induction was highly effective in decreasing postoperative nausea and vomiting and should become the standard.

Adult↗

PubMed2000

Carboxyhemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure.

STUDY OBJECTIVES: There are large reported differences for the carboxyhemoglobin (COHb) half-life (COHb t(1/2)) in humans breathing 100% atmospheric O(2) following CO inhalation in tightly controlled experiments compared to the COHb t(1/2) observed in clinical CO poisoning (range, 36 to 131 min, respectively). Other reports have suggested that the COHb t(1/2) may be affected by gender differences, age, and lung function. We wished to test the hypothesis that the COHb t(1/2) might also be influenced by CO poisoning vs experimental CO exposure, by a history of loss of consciousness (LOC), concurrent tobacco smoking, and by PaO(2). The purpose of the present study was to measure the COHb t(1/2) in a cohort of CO-poisoned patients and to determine if those listed factors influenced the COHb t(1/2). DESIGN: Retrospective chart review from 1985 to 1995. We calculated the COHb t(1/2) of CO-poisoned patients who were treated with high-flow supplemental atmospheric pressure O(2) delivered by nonrebreather face mask or endotracheal tube. SETTING: Hyperbaric medicine department of a tertiary-care teaching hospital. PATIENTS: Of 240 CO-poisoned patients, 93 had at least two COHb measurements > 2% (upper limit of normal) with recorded times of the measurements, permitting calculation of the COHb t(1/2). RESULTS: The COHb t(1/2) was 74 +/- 25 min (mean +/- 1 SD) with a range from 26 to 148 min. By stepwise multiple linear regression analysis, the PaO(2) influenced the COHb t(1/2) (R(2) = 0.19; p < 0.001), whereas the COHb t(1/2) was not influenced by gender, age, smoke inhalation, history of LOC, concurrent tobacco smoking, degree of initial metabolic acidosis (base excess), or initial COHb level. CONCLUSIONS: The COHb t(1/2) of 93 CO-poisoned patients treated with 100% O(2) at atmospheric pressure was 74 +/- 25 min, considerably shorter than the COHb t(1/2) reported in prior clinical reports (approximately 130 +/- 130 min) and was influenced only by the patient's PaO(2).

Adolescent↗

PubMed1998

Family rigidity, adolescent problem-solving deficits, and suicidal ideation: a mediational model.

Family rigidity and adolescent problem-solving deficits have each been linked to adolescent suicidal behaviors. The objective of the present study was to evaluate the hypothesis that family rigidity has primarily an indirect effect on adolescent suicidal ideation through its effect on adolescent problem-solving deficits. College students and their parents completed the Family Adaptability and Cohesion Evaluation Scale II. Students also completed the Problem-Solving Inventory and the Adult Suicidal ideation Questionnaire. Structural equation models confirmed that family rigidity has an indirect effect on adolescent suicidal ideation through its effect on adolescent problem-solving deficits. Directions for treatment efforts are discussed.

Adaptation, Psychological↗

PubMed1998

Demographic differences in prostate cancer incidence and stage: an examination of population diversity in California.

INTRODUCTION: Geographic and racial/ethnic variability in prostate cancer incidence rates and stage distribution may be partly attributed to differences in screening and early detection. METHODS: Using California Cancer Registry data we aimed to characterize variability in prostate cancer rates statewide and to examine differences in the stage at diagnosis of prostate cancer by racial/ethnic group statewide and by census tract per capita income in San Diego County. We calculated annual average (1988-1991) age-adjusted incidence rates per 100,000 (AAIR) of prostate cancer for 49,880 men over age 34 years. Racial/ethnic groups were compared using incidence rate ratios (IRR) (AAIR localized plus regional stages divided by AAIR distant stage). RESULTS: Statewide, Caucasians showed a higher IRR [6.16, 95% confidence interval (CI), 6.00-6.30] than did African Americans (2.34, 95% CI, 1.89-2.89), Hispanics (3.84, 95% CI, 3.63-4.05), or Asian/others (3.61, 95% CI, 1.80-7.22). Within San Diego County, Caucasians living in higher per capita income census tracts (> or = 65th percentile) had a significantly higher IRR (8.80, 95% CI 7.84-9.89) than did lower-income tracts (5.68, 95% CI, 5.13-6.30). CONCLUSION: Findings from the present and similar studies suggest that outcomes research is needed to determine the impact of these demographic differences on prostate cancer mortality and quality of life. This is particularly important given the current controversy regarding the treatment of clinically localized prostate cancers, increasingly found through early detection, which often involve difficult choices between aggressive therapies including prostatectomy or watchful waiting.

Adult↗

PubMed1998

Differences in breast cancer stage at diagnosis between non-Hispanic white and Hispanic populations, San Diego County 1988-1993.

The incidence of breast cancer in the U.S. is lower among Hispanic women than non-Hispanic white women. However, population-based studies show that Hispanic women are more likely to be diagnosed at a later stage than non-Hispanic whites. We aimed to determine whether: 1) a lower proportion of breast cancer was diagnosed at early vs. late stages in Hispanic compared to non-Hispanic white women from 1988-93 in San Diego County, and 2) lower income is related to later stage at diagnosis for both groups. All incident cases of breast cancer in San Diego County from the California Cancer Registry (10,161 cases) were stratified by 'early' (in situ or localized) or 'late' (regional or distant) stage, and by race/ethnicity. Annual average age-adjusted incidence rates/100,000 (AAIR) were calculated. Incidence rate ratios (IRR) (AAIR for early stages divided by AAIR for late stages) were used as a surrogate of early detection. AAIRs for early and late stage disease were significantly higher for non-Hispanic whites (89.3, 42.3) than Hispanic women (46.7, 27.2). The IRR was significantly higher for non-Hispanic whites than Hispanics, (2.11 vs 1.72, p = 0.01). This difference was greatest among women under 50 years old (IRR difference 0.63), and not apparent for women 65 or older (IRR difference 0.06). There was also an association between increasing census tract per capita income and higher rates of early stage disease among non-Hispanic whites but not Hispanics. Results suggest that Hispanic women and lower income women should be targeted for early detection.

Adolescent↗

PubMed1997

Clinical utility of hygroscopic heat and moisture exchangers in intensive care patients.

OBJECTIVE: To compare the degree of bacterial circuit colonization, frequency of ventilator-associated pneumonia (VAP), character of respiratory secretions, rewarming of hypothermic patients, disposable costs, and air flow resistance in intensive care patients ventilated using either a heat and moisture exchanger (HME) or hot water (HW) humidifier circuit. DESIGN: A prospective, randomized blinded trial of patients in the intensive care unit undergoing mechanical ventilation. SETTING: A metropolitan teaching hospital. PATIENTS: One hundred sixteen patients undergoing mechanical ventilation for a minimum period of 48 hrs were enrolled. INTERVENTIONS: Patients were randomized to three ventilation groups using a) an HW circuit with a 2-day circuit change (n = 41); or b) a bacterial-viral filtering HME in the circuit, with either a 2-day (n = 42); or c) a 4-day circuit change (n = 33). MEASUREMENTS AND MAIN RESULTS: Circuit colonization was assessed using quantitative culture of washings taken from the circuit tubing and semiquantitative culture of swabs from the Y connectors. Sixty-seven percent of HW circuits became contaminated compared with 12% in the two HME groups (p < .0001). Median colony counts were lower in the HME groups (p < .0001). If circuits at first circuit change were contaminated in the HW group, 89% of subsequent circuit changes became contaminated compared with 0% and 25% for the 2- and 4-day HME groups, respectively. The frequency of VAP, the time to resolution of admission hypothermia, and the volume and fluidity of secretions were similar for all groups. The resistance of the HME after 24 hrs of use was < 0.025 cm H2O/L at gas flows of 40 L/min. HME use resulted in a cost reduction of $1.48 (Australian)/day. CONCLUSIONS: Circuits with a bacterial-viral filtering HME are less readily colonized by bacteria. Contamination is a random event. Humidification technique has no influence on the frequency rate of VAP, the effectiveness of rewarming, nor the character of the respiratory secretions. Breathing resistance is generally low and disposable costs are reduced when an HME is used.

APACHE↗

PubMed1996

Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators.

Uterine leiomyoma is the most frequent gynecologic neoplasm in women. By using a panel of cell lines derived from spontaneous Eker rat leiomyomas, we examined the estrogen-responsive phenotype of these tumor cells. Leiomyoma-derived ELT cell lines proliferated in response to estrogen, and estrogen-induced cell proliferation could be inhibited by the estrogen antagonist ICI 182780 and the selective estrogen-receptor modulators (SERMs) raloxifene and tamoxifen. In addition to inhibiting cell growth, these antagonists also inhibited estrogen-induced increases in progesterone-receptor expression. These data indicate that SERMs such as raloxifene and tamoxifen act as estrogen antagonists in uterine myometrial cells and suggest that this class of compounds may be effective for treatment of this important gynecologic neoplasm.

Animals↗

PubMed1996

Treatment of recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty.

We report our experience with successful treatment of 2 cases of severe recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty. Both patients had multiple failures of conventional treatments but have been free of stricture recurrence after endourethroplasty with 11 and 25 months follow-up, respectively. Follow-up urethroscopy showed open anastomotic segments with epithelialization after endourethroplasty in both patients. The patient who was continent prior to endourethroplasty remained continent afterward.

Aged↗

PubMed1994

Evaluation of the Roche Cobas Argos 5Diff automated haematology analyser with comparison to a Coulter STKS.

The performance of the Roche Cobas Argos 5Diff (Argos) automated haematology analyser was evaluated by comparison to manual blood film examination and a Coulter STKS (STKS) analyser. The Argos demonstrated excellent between and inter-batch imprecision for all parameters, except the MCHC, and good linearity for Hb, WBC and platelet count (PLT). After an initial fall the PLT, results were stable for up to six h at 18 degrees C in EDTA(K3) after which an increasing proportion of cells were classified as lymphocytes. Results of 239 patient samples analysed on both instruments, compared by linear regression, gave excellent correlation (r2 > 0.90) for most parameters with the exceptions of the MCHC (0.317), eosinophils% (0.756), monocytes% (0.48) and basophils% (0.002). 'Flagging' of cellular abnormalities by the Argos resulted in excellent sensitivity (97.5%), specificity (93.2%) and efficiency/agreement (93.2%), with fewer false positive and negative results than the STKS, although these differences were not statistically significant. The performance characteristics of the Argos were comparable to those of the STKS with a possible improvement in its flagging abilities.

Autoanalysis↗

PubMed1994

Antimyenteric neuronal antibodies in scleroderma.

The pathogenesis of gastrointestinal (GI) dysmotility in scleroderma is incompletely understood, although previous studies have proposed a neuropathic mechanism. We studied patients with scleroderma as compared with other connective tissue disease patients and normal controls for the presence of circulating antibodies to myenteric neurons. Serial dilutions of sera were overlaid on rat intestine, double-labeled with antineurofilament antibody as a myenteric plexus marker, and imaged using indirect immunofluorescence techniques. High titer sera (> or = 1:50) from 19 out of 41 scleroderma patients stained myenteric neurons, whereas none of 22 normals or 5 patients with idiopathic GI dysmotility were positive. Although 6 out of 20 SLE and 6 out of 10 mixed connective tissue disease patients' sera stained myenteric plexus neurons, when positive sera were absorbed with calf thymus extract to remove antinuclear antibody, 15 scleroderma sera, 0 SLE, and 2 mixed connective tissue disease patients retained positive staining of myenteric neurons. Western blotting using actin and neuronal intermediate filament preparations failed to show immunoreactivity with scleroderma sera containing antimyenteric neuronal antibodies. Paraneoplastic sera associated with GI dysmotility stained myenteric neurons in a different pattern than seen with scleroderma sera. A positive correlation between the presence of Raynaud's phenomenon and antimyenteric neuronal antibodies was observed in scleroderma patients. Our results indicate that IgG antibodies reacting with myenteric neurons are present in many patients with scleroderma. Although the neuronal antigen has not yet been identified, the presence of myenteric neuronal antibodies in patients with GI dysmotility and scleroderma suggests a neuropathic process.

Adolescent↗

PubMed1994

Arterial oxygen tension of patients with abnormal lungs treated with hyperbaric oxygen is greater than predicted.

The arterial oxygen (O2) tension (PaO2) of patients with normal gas exchange treated with hyperbaric oxygen (HBO2) can be predicted from their pre-HBO2 arterial to alveolar O2 tension ratio (a/A) which remains constant up to a PaO2 of 2,000 mm Hg. We observed that the a/A could not be used to predict the PaO2 of patients with impaired gas exchange (reduced pre-HBO2 a/As) treated with HBO2. Our study provides information about the PaO2 of patients with abnormal lungs treated with HBO2. For clinical reasons, we measured the PaO2 of 24 patients treated with HBO2. We obtained arterial blood gas values from patients with lung dysfunction (a/A < 0.75) prior to, during, and after HBO2. The pre-HBO2 a/A = 0.45 +/- 0.17 (mean +/- 1 SD). During HBO2 the a/A ranged from 0.7 to 0.8 depending on chamber pressure and returned to the pre-HBO2 baseline after HBO2. We conclude the following: (1) The hyperbaric PaO2s of patients with a/A < 0.75 is greater than expected. (2) However, the PaO2 is lower than in patients with normal lung function (a/A > 0.75). Possible explanations include improvement in ventilation/perfusion matching, reduction of venous admixture, and/or extra-alveolar uptake of O2. (3) Exposures to HBO2 treatment pressures greater than recommended by existing protocols may be required in patients with impaired transfer of O2 across the lung to achieve PaO2s similar to patients with normal lung function treated with HBO2.

Adult↗

PubMed1992

Normobaric measurement of arterial oxygen tension in subjects exposed to hyperbaric oxygen.

This study demonstrates the ability of an automated blood gas analyzer (Radiometer ABL 330) operated at atmospheric pressure to measure the arterial oxygen tension (PaO2) of ten healthy volunteers exposed to hyperbaric oxygen (HBO2) up to 3.0 atmospheres absolute. Arterial blood samples were aspirated from subjects compressed in a single-person hyperbaric chamber and were analyzed immediately in the blood gas analyzer. The subjects' values for PaO2 correlated with the calculated alveolar O2 tension (PAO2) (measured PaO2 = 0.827 x PAO2-15.1) (r2 = 0.97). Tonometric experiments indicated a difference between saline and blood PO2 measurements. We therefore derived a correction factor for blood measurements (corrected PaO2 = 0.908 x PAO2-52.4) (r2 = 0.98). These results compared favorably with PaO2 measurements made with blood gas analyzers calibrated inside walk-in hyperbaric chambers. We conclude that the PaO2 of normal subjects exposed to HBO2 can be measured accurately at atmospheric pressure with this automated blood gas analyzer. Prior to this study, hyperbaric PaO2 measurements could only be performed within walk-in chambers. Our observations generalize the normobaric measurement of hyperbaric PaO2 to patients treated in single-person and walk-in chambers.

Adult↗

PubMed1991

Development of a disability measurement tool for juvenile rheumatoid arthritis. The Juvenile Arthritis Functional Assessment Report for Children and their Parents.

Two questionnaires were developed for measuring disability due to juvenile rheumatoid arthritis (JRA), one based on patient reports and one on parent reports. These questionnaires were termed the Juvenile Arthritis Functional Assessment Report for Children (JAFAR-C) and for Parents (JAFAR-P). The questionnaires were administered to 72 JRA patients ages 7-18 years and to their parents. Respondents rated the patient's recent ability to perform 23 activities. Patient reports and parent reports were found to correlate highly with each other and with an objective assessment performed by therapists. Questionnaire scores did not correlate significantly with the age of the patient. The JAFAR appears to be a convenient, reliable, and valid measure of disability in patients with JRA.

Adolescent↗

PubMed1991

Noninvasive Doppler blood pressure monitoring in the monoplace hyperbaric chamber.

We describe a noninvasive method of monitoring blood pressure in the monoplace hyperbaric chamber. A standard blood pressure cuff was placed on the patient's arm. A Doppler probe, linked to an ultrasonic Doppler flow detector outside the chamber, was secured over the patient's radial artery. Cuff inflation tubing and the Doppler probe wires were passed into the chamber by modifying a standard disposable hyperbaric intravenous pass-through. Blood pressure readings were determined by inflating and slowly deflating the cuff from outside the chamber while observing the sphygmomanometer within the chamber and listening for the first audible flow signal from the Doppler detector, corresponding to the systolic blood pressure. To minimize the risk of fire in the oxygen-filled monoplace hyperbaric chamber, the patient, Doppler detector, and chamber were grounded. Doppler readings obtained from nine normal subjects whose arterial pressures were being measured with indwelling radial arterial catheters (approved as part of another study by the hospital's Investigational Review Board) compare closely with the subject's blood pressures measured with this noninvasive method: 114 +/- 7.6 mm Hg (mean +/- 1 SD) compared to 112 +/- 8.1 mm Hg, respectively (n = 92 measurements in 8 subjects). We conclude that this noninvasive method of monitoring blood pressure within the monoplace hyperbaric chamber is accurate and suitable for monoplace clinical purposes.

Blood Pressure↗