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T Davidson

Publications and source records attributed to T Davidson.

At least 19 recordsLinked to original sources
PubMed1998

Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities.

Sex-typed cognitive abilities were assessed in 33 hypogonadal men receiving testosterone replacement therapy, 10 eugonadal men receiving testosterone in a male contraceptive clinical trial, and 19 eugonadal men not administered testosterone. Prior to and following hormone administration, men completed four tests measuring visuospatial ability, three tests measuring verbal fluency, two tests measuring perceptual speed, and a measure of verbal memory. Group differences in testosterone levels were unrelated to performance on most cognitive measures, including visuospatial ability. Relative to other men, hypogonadal men were impaired in their verbal fluency and showed improved verbal fluency following treatment with testosterone. These data suggest that testosterone may enhance verbal fluency in hypogonadal men and support the general hypothesis that current levels of testosterone may influence some aspects of cognitive function.

Adult↗
PubMed1998

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

Adult↗
PubMed1997

Prevention of immunotoxin-induced immunogenicity by coadministration with CTLA4Ig enhances antitumor efficacy.

Immunotoxins have shown promise as antitumor agents in clinical trials. However, they have not become part of standard cancer therapy because of factors that include their inherent immunogenicity, which limits the duration of therapy. To address this issue, we evaluated in preclinical models the concomitant use of the immunosuppressive agent CTLA4Ig and BR96 sFv-PE40, a single-chain immunotoxin that binds to carcinoma cells expressing Le(y). Cotreatment with CTLA4Ig, an inhibitor of the CD28/CTLA4-CD80/CD86 costimulation pathway, blocked the production of Abs against BR96 sFv-PE40 in immunocompetent rodents and dogs. It also blocked hypersensitivity reactions in rats carrying colon carcinoma allografts during a second course of BR96 sFv-PE40 therapy, and the cotreatment with CTLA4Ig resulted in enhanced antitumor activity. Cotreatment with CTLA4Ig also prevented hypersensitivity reactions induced by repeat dosing of BR96 sFv-PE40 (q3dx5) in dogs. The production of anti-BR96-sFv-PE40 Abs was decreased in CTLA4Ig-cotreated rodents and dogs resulting in increased plasma levels of BR96 sFv-PE40 relative to non-CTLA4Ig-cotreated animals. These data show that cotreatment of immunotoxins with CTLA4Ig, by inhibiting the production of anti-immunotoxin Abs, can extend the duration of BR96 sFv-PE40 therapy to give greater exposure, reduced toxicities, and increased efficacy.

Abatacept↗
PubMed1997

Implantable cardioverter-defibrillators and pregnancy: a safe combination?

BACKGROUND: The purpose of this investigation was to evaluate the outcome of pregnancy in women with implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: A multicenter retrospective analysis was performed on women with an ICD who became pregnant. Data were collected on 44 patients. The mean age and ejection fraction at the time of the initial ICD implant were 25.6+/-4.9 years and 49.8+/-9.7%, respectively. The mean follow-up after the ICD implant was 4.8+/-2.8 years. Forty-two women had abdominally implanted generators, and 2 had a prepectoral device. Thirty had epicardial lead sensing systems, and 14 had transvenous. Thirty-six (82%) experienced no complications, and 8 (18%) had a medical or device-related complication. The ICD-related problems included tenderness at the ICD pocket scar (2 patients), generator migration (1), and pericarditis secondary to the epicardial patches (1). Medical complications were pulmonary embolism (1), therapeutic abortion (1), worsening hyperthyroidism (1), congestive heart failure (1), and weight loss (1). Thirty-seven women delivered vaginally, and 7 underwent cesarean section. Thirty-nine babies were born healthy, 1 was stillborn, 2 were small for gestational age, 1 had transient hypoglycemia, and 1 woman had a therapeutic abortion unrelated to the ICD. During pregnancy, 33 women received no ICD therapy, 8 had 1 shock, 1 had 5 discharges, 1 had 11 shocks, and 1 had 5 shocks. The total number of shocks during pregnancy ranged from 0 to 11, with an average of 0.66+/-1.9 discharges. Five women had 7 additional pregnancies without an ICD shock. CONCLUSIONS: The mere presence of an ICD should not defer a women from becoming pregnant unless she has an underlying structural cardiac disease that is considered a contraindication. Pregnancy does not increase the risk of major ICD-related complications or result in a high number of ICD discharges.

Adolescent↗
PubMed1997

Probability of successful defibrillation at multiples of the defibrillation energy requirement in patients with an implantable defibrillator.

BACKGROUND: The probability of successful defibrillation has been determined in normal animals but not in patients undergoing defibrillator implantation. Therefore, the purpose of this prospective study was to determine the probability of successful defibrillation in humans on the basis of a step-down defibrillation energy requirement. METHODS AND RESULTS: Fifty-three consecutive patients underwent five separate inductions of ventricular fibrillation after the defibrillation energy requirement was determined with the use of small decrements and a step-down protocol (20, 15, 12, 10, 8, 6, 5, 4, 3, 2, 1, and 0.8 J). The first shock energy for defibrillation was either 1.0, 1.3, 1.5, 1.7, or 2.0 times the defibrillation energy requirement, and the likelihoods of successful defibrillation were 70+/-27%, 84+/-12%, 86+/-25%, 80+/-29%, and 88+/-32%, respectively (P=.03). The frequencies of uniformly successful defibrillation (5 of 5 defibrillation attempts) were 30%, 27%, 60%, 64%, and 73%, respectively (P=.01). Seven patients in whom the defibrillation energy requirement was <4 J had an overall rate of successful defibrillation of 54+/-20% compared with 86+/-20% in the remaining 47 patients (P=.002). The likelihood of successful defibrillation at twice the defibrillation energy requirement was 98% in the 46 patients with a defibrillation energy requirement of >4 J and 67% in the 7 patients with a defibrillation energy requirement of <4 J (P=.17). An absolute safety margin of 7 J was associated with a 96% probability of successful defibrillation. CONCLUSIONS: The probability of successful defibrillation is 70% at the defibrillation energy requirement. The probability plateaus at 88%, at twice the defibrillation energy requirement. A 96% probability of successful defibrillation is achieved at an absolute safety margin of 7 J, and a 98% success rate is achieved at energies that are twice the defibrillation energy requirement if the defibrillation energy requirement is >4 J. If the defibrillation energy requirement is <4 J, larger multiples of the defibrillation energy requirement are needed to achieve a high probability of successful defibrillation.

Arrhythmias, Cardiac↗
PubMed1997

Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli.

Mood and response to auditory sexual stimuli were assessed in 33 hypogonadal men receiving testosterone (T) replacement therapy, 10 eugonadal men receiving T in a male contraceptive clinical trial, and 19 eugonadal men not administered T. Prior to and after 6 weeks of hormone administration, men completed a mood questionnaire, rated sexual arousal to and sexual enjoyment of auditory sexual stimuli, and performed a dichotic listening task measuring selective attention for sexual stimuli. Mood questionnaire results suggest that T has positive effects on mood in hypogonadal men when hormone levels are well below the normal male range of values, but does not have any effects on mood when hormone levels are within or above the normal range. However, increased sexual arousal and sexual enjoyment were associated with T administration regardless of gonadal status. Eugonadal men administered T also increased in the bias to attend to sexual stimuli. In contrast, the comparison group of eugonadal men not administered T showed no mood or sexual behavior changes across the two test sessions. These data support a positive relationship between T and sexual interest, sexual arousal, and sexual enjoyment in men.

Administration, Sublingual↗
PubMed1997

Staging of symptomatic primary breast cancer with MR imaging.

OBJECTIVE: This study was designed to investigate the accuracy of contrast-enhanced MR imaging in the locoregional staging of symptomatic primary breast cancer and to determine the impact of contrast-enhanced MR imaging in planning surgical management. MATERIALS AND METHODS: Ninety patients with primary breast cancer (including two bilateral cancers) diagnosed and treated on the basis of conventional triple assessment (clinical, cytologic, and mammographic examination) underwent MR imaging at 1.0 T using a three-dimensional fast low-angle shot T1-weighted pulse sequence before and after contrast enhancement. A short inversion time inversion recovery sequence was also obtained to evaluate the axilla of each patient. After resection, tumors were histopathologically mapped in detail and correlated with the extent of contrast enhancement on MR imaging. RESULTS: On the basis of triple assessment, 53 cancers were treated by wide local excision, of which 17 (32%) had positive margins at excision. Residual disease at reexcision was detected in eight of these 17 patients, a finding that correlated accurately with the extent of contrast enhancement on MR imaging. MR imaging was more accurate than mammography in determining invasive tumor size (r2 = .93 versus r2 = .59), in depicting multifocality and extensive intraductal component (sensitivity, 81% versus 62%), and in assessing nipple-retroareolar complex. MR imaging-histopathologic correlation was possible in 75 axillae. Sensitivity and specificity for axillary node metastases were 90% and 82%, respectively. CONCLUSION: MR imaging of the breast has value in the preoperative locoregional staging of symptomatic primary breast cancer and is useful in planning a single definitive surgical resection in patients with breast cancer.

Adult↗
PubMed1997

Comparison of magnetic resonance imaging and conventional triple assessment in locally recurrent breast cancer.

BACKGROUND: Magnetic resonance imaging (MRI) was compared with triple assessment (clinical examination, cytology and mammography) in the differentiation of post-treatment changes from local recurrence of breast carcinoma. METHODS: Thirty patients treated previously by breast conservation surgery and radiotherapy with clinical suspicion of local recurrence were evaluated prospectively by triple assessment and MRI. Breast MRI was performed on a 1-tesla scanner using a T1-weighted three-dimensional fast low angle shot pulse sequence before and after contrast enhancement. RESULTS: Local recurrence was confirmed histologically in 14 patients. Of these, mammography identified seven (sensitivity 50 per cent), cytology 11 (sensitivity 79 per cent) and breast MRI 13 (sensitivity 93 per cent). Compared with histological measurement, breast MRI allowed an accurate estimation of the extent of local recurrence (r2 = 0.98). Morphologically abnormal areas without contrast enhancement correlated with postradiation changes. False-positive contrast enhancement was seen in two patients (specificity 88 per cent) in whom histology confirmed inflammatory changes only. CONCLUSION: Breast MRI is useful in the evaluation of patients with a high clinical suspicion of local recurrence within the irradiated conserved breast.

Adult↗
PubMed1997

Characterization of vascular leak syndrome induced by the toxin component of Pseudomonas exotoxin-based immunotoxins and its potential inhibition with nonsteroidal anti-inflammatory drugs.

Clinical trials of immunotoxins in cancer patients have been limited in many cases by vascular leak syndrome (VLS). Recently, rats were identified as a model for VLS induced by BR96 sFv-PE40, a carcinoma-reactive single-chain immunotoxin. In this study, the toxin component of this immunotoxin, PE40, was found to be responsible for inducing hydrothorax in rats, thereby demonstrating that direct binding to the BR96 antigen was not essential to the onset of VLS. Mutational analysis of PE40 determined that both ADP ribosylation and proteolytic processing functions innate to Pseudomonas exotoxin A (PE) were necessary for PE40 to induce hydrothorax in rats; however, neither function by itself was sufficient for VLS induction. Additionally, nonsteroidal anti-inflammatory agents were found to block VLS in rats receiving BR96 sFv-PE40. These results demonstrate that the toxin component of PE-based immunotoxins induce VLS and suggest agents for clinical management of the toxicity.

ADP Ribose Transferases↗
PubMed1996

Evaluation and extraction of the Accufix atrial J lead.

The Accufix (Telectronics Pacing Systems, Englewood, Colo.) atrial active fixation pacemaker lead has a preformed J stiff retention wire that can fracture and erode through the atrium. We screened 85 patients with digital fluoroscopy and detected 18 (21%) lead fractures. Fourteen (16%) leads were successfully extracted by percutaneous techniques. The mean time for extraction and placement of a new atrial lead was 109 +/- 53 min, and a lead > 1 year old but not in the presence of a fracture was associated with a significantly longer extraction time. There were two extraction complications. One patient had a fever following the extraction, and one patient had a focal sensory deficit 1 week after the extraction probably caused by a paradoxical embolus. Standard percutaneous extraction tools can be used for successful and safe removal of a fractured Accufix lead.

Aged↗
PubMed1996

Breast surgery after neoadjuvant treatment. Is it necessary?

The optimum management of women with advanced loco-regional breast cancer (T3-4, N1-2) is controversial. Neoadjuvant therapy in the form of chemotherapy and or radiotherapy is popular and results in an encouraging local response in over 70% of patients. However, should subsequent surgery (either mastectomy or breast conservation treatment) be undertaken in women who respond? We present a prospective evaluation of 15 patients with T3-4, N1-2 tumours (including 1 bilateral cancer) who underwent mastectomy after achieving a complete clinical response to neoadjuvant treatment. All patients had 6 cycles of chemotherapy and 10 also received 50 Gy radiotherapy. In addition to clinical examination, the response to neoadjuvant treatment was assessed by mammography (in all cases) and by magnetic resonance imaging (MR) (in eight patients). Careful histopathological assessment of the breast was undertaken to determine the extent of residual disease. In all patients histological malignancy was recognized within the breast. The size varied from 0.6 to 6.5 cm in maximum diameter with three grade I, eight grade II and five grade III tumours. Axillary lymph nodes were positive in seven patients. In conclusion, surgery is indicated for control of residual disease in locally advanced breast cancer regardless of the response to neoadjuvant treatment. Our preliminary observations suggest a potential role for breast MR in defining the extent of residual disease which may aid in the planning of surgery.

Adult↗
PubMed1996

Pharmacokinetics and pharmacodynamics of CTLA4lg (BMS-188667), a novel immunosuppressive agent, in monkeys following multiple doses.

The dose proportionality and multiple dose pharmacokinetics of CTLA4Ig, an immunosuppressive drug under development, were investigated in 12 cynomolgus monkeys in a parallel study. The activity of CTLA4Ig in suppressing the immunoresponses to sheep red blood cell (SRBC) was also assessed. Two monkeys per gender were randomly assigned to one of the three dose levels, 1.0, 2.9, and 8.7 mg/kg of CTLA4Ig. The monkeys in each dose level received the assigned intravenous dose of CTLA4Ig by a bolus injection into a saphenous vein on days 1, 4, 8, 11, 15, and 18. Immediately after the administration of CTLA4Ig on day 1, each monkey was challenged with SRBC. Serial blood samples were collected up to 720 h following administration of CTLA4Ig on day 18 (last dose). In addition, predose blood samples were obtained on days 1, 4, 8, 11, 15, and 18. Serum samples were analyzed for the concentrations of CTLA4Ig using a validated ELISA method. The data obtained were subjected to noncompartmental pharmacokinetic analyses. The serum concentrations of CTLA4Ig attained steady state by day 11 regardless of the dose levels. The mean AUC0-720 values of CTLA4Ig increased in a dose proportional manner. The mean values of Cmax increased in a ratio of 1:3:3:8:5 while the dose administered increased in a ratio of 1:3:9. Predose serum concentrations (Cmin) of CTLA4Ig increased in a dose proportional manner. The mean T1/2 values were not significantly different among the dose groups, suggesting that the elimination characteristics of CTLA4Ig were not altered as the dose increased. Dose-related immunosuppressive activity of CTLA4Ig (78-98% inhibition) was observed in monkeys immunized intravenously with SRBC. In conclusion, CTLA4Ig exhibits linear kinetics and demonstrates significant immunosuppressive activity over a dose range of 1.0-8.7 mg/kg in monkeys.

Abatacept↗
PubMed1996

Confidentiality and managed care: ethical and legal concerns.

As managed care companies take over the allocation of funds, the monitoring of treatment, and the measurement of outcomes, social workers encounter an ethical and legal dilemma with the demise of confidentiality in the professional-client relationship. Given that the profession has long heralded the protection of client confidentiality, it is timely that social workers re-examine traditional ethical and legal responsibilities to clients and challenge managed care personnel to protect clients' right to confidentiality. This article highlights problems concerning confidentiality that often arise for social workers working with managed care systems. It focuses also on ethical and legal standards related to confidentiality and social work responsibilities regarding informed consent.

Confidentiality↗
PubMed1996

Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study.

The effect of testosterone (T) replacement on changes in mood was studied for 60 days in 51 hypogonadal men. All patients were withdrawn from their prior T replacement for at least 6 weeks before enrollment. Of these patients, 18 received T enanthate 200 mg im every 20 days, 16 received sublingual T cyclodextrin (SLT) at a dose of 2.5 mg three times daily, and 17 received SLT at a dose of 5.0 mg three times daily. The total treatment period was 60 days. The patients were asked to respond to a questionnaire on 7 consecutive days before the start of treatment and on 7 consecutive days before their visits to the clinic on days 21, 41, and 60 of treatment. The following mood parameters were assessed using a 7-point Likert rating scale: angry, alert, irritable, full of pep (energy), sad/blue, tired, friendly, nervous, and well/good. When compared with the baseline period, T replacement led to significant decreases in anger (P = 0.0045), irritability (P = 0.0009), sadness (P = 0.0033), tiredness (P = 0.0035), and nervousness (P = 0.0291), and significant improvement in energy level (P = 0.0020), friendliness (P = 0.0072), and sense of well-being (P = 0.024) in all subjects as a group. Analyses of the area under the curve (AUC) of baseline serum T levels before T replacement showed significant positive correlations between serum T (AUC) and friendliness (r = 0.29, P < 0.05) and sense of well-being (r = 0.27, P < 0.05), and significant negative correlations with nervousness (r = -0.27, P < 0.05), irritability (r = -0.29, P < 0.05) and tiredness (r = -0.28, P < 0.05). Similar correlations were found between serum dihydrotestosterone (DHT) and some of the mood parameters. After T replacement in the hypogonadal men, these correlations between AUC of serum T levels and the positive and negative mood scores disappeared. These results were corroborated in a subsequent study in which 30 hypogonadal men were supplemented with SLT 5 mg three times daily for 6 months. The patients were less nervous (P = 0.0025) and more alert (P = 0.0004), friendly (P = 0.042), and energetic (P = 0.0001) during the 6-month treatment period compared with baseline. We conclude that T replacement therapy in hypogonadal men improved their positive mood parameters, such as energy, well/good feelings, and friendliness and decreased negative mood parameters including anger, nervousness, and irritability, and direct correlations between serum T and DHT with mood scores were only observed in the baseline period when serum androgen levels were below the normal range. The latter observation suggests that once a minimally adequate serum T/DHT level was achieved by T replacement therapy, further increases in serum T/DHT levels did not further contribute to the improvement in mood variables.

Administration, Sublingual↗
PubMed1996

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

Administration, Sublingual↗