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Biomedical subjects

J A Gonzalez

Publications and source records attributed to J A Gonzalez.

At least 19 recordsLinked to original sources
PubMed2003

Production and use of replication-deficient adenovirus for transgene expression in neurons.

Adenoviruses infect a wide range of cell types, do not require integration into the host cell genome, and can be produced as replication-deficient viruses capable of expressing transgenes behind any desired promoter. Thus, they are ideal for use in expressing transgenes in the postmitotic neuron. This chapter describes simplifications in the protocols for making recombinant adenoviruses and their use in expressing transgenes in primary neurons of several different types.

Adenoviridae↗
PubMed2001

Knockdown of PSD-95/SAP90 delays the development of neuropathic pain in rats.

Our previous work has shown that PSD-95/SAP90 is required for NMDA receptor-mediated thermal hyperalgesia. To address the role of PSD-95/SAP90 in chronic pain, the present study investigated the effect of the deficiency of PSD-95/SAP90 on nerve injury-induced neuropathic pain. Following unilateral L5 spinal nerve injury, mechanical and thermal hyperalgesia developed within 3 days and persisted for 9 days or longer on the injured side. The intrathecal administration of antisense oligodeoxynucleotide specifically against PSD-95/SAP90, but not sense or missense oligodeoxynucleotide, dose-dependently delayed the onset of tactile allodynia and thermal hyperalgesia. These results suggest that PSD-95/SAP90 might be involved in the central mechanisms of the development of chronic neuropathic pain.

Animals↗
PubMed2001

Outpatient second trimester pregnancy termination.

We evaluated the efficacy of initiating a second trimester medical abortion outside of a health care facility using patient self-administered serial intravaginal misoprostol. Patients scheduled for second trimester medical termination of pregnancy were randomized to an inpatient or outpatient group. Both groups received a single 200-microg vaginal misoprostol tablet every 6 h. No other abortifacients were used. The home group self-administered the misoprostol and returned to the hospital for clinical reasons or after 24 h and again at 48 h. Forty-two women were assigned to the inpatient and 45 to the outpatient groups. There was no difference between the groups in demographics or indications for terminations. The median hours from first misoprostol to delivery of the fetus was 12 and 14 (inpatient versus outpatient, respectively; p = 0.28). The total median hours in hospital were 24 versus 11 (inpatient versus outpatient, respectively; p <0.05). Two patients (4%) in the outpatient group delivered the fetus outside of the hospital. There were no cases of hemorrhage in either group. Outpatient initiation of second trimester medical termination with self-administered misoprostol is effective and decreases time of hospitalization.

Abortion, Induced↗
PubMed2000

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial.

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.

Aged↗
PubMed2000

A comparison of external beam radiation therapy versus radical prostatectomy for patients with low risk prostate carcinoma diagnosed, staged, and treated at a single institution.

BACKGROUND: The authors retrospectively reviewed their institution's long term experience treating a group of comparably staged low risk prostate carcinoma patients with either radical prostatectomy or external beam radiation therapy (RT) to determine whether the method of treatment resulted in significant differences in biochemical control and/or survival. METHODS: From January of 1987 through December of 1994, 382 patients (157 who underwent radical prostatectomy and 225 who received external beam RT) were treated with curative intent for localized prostate carcinoma at William Beaumont Hospital. All patients had a pretreatment serum prostate specific antigen (PSA) level < or =10.0 ng/mL and a biopsy Gleason score </=6. Patients treated with RT received a median dose of 66.6 gray (Gy) (range, 59.2-70.2 Gy) to the prostate. Patients treated surgically underwent radical retropubic prostatectomy with a pelvic lymph node dissection. For surgical patients, biochemical failure was defined as a detectable PSA level > or =0.2 ng/mL at any time after prostatectomy. For RT patients, biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Pretreatment PSA levels and Gleason scores were not significantly different between patients treated with radical prostatectomy or RT. The median follow-up in each treatment group was 5.5 years. RESULTS: The 7-year actuarial rates of biochemical control and cause specific survival were not significantly different between patients treated either with radical prostatectomy or RT (67% vs. 69% for biochemical control and 99% vs. 97% for cause specific survival, respectively). A number of clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical failure (i.e., age, pretreatment PSA, Gleason score, and treatment modality). Only pretreatment PSA and Gleason score were significantly related to outcome in both univariate and multivariate analyses. CONCLUSIONS: Low risk prostate carcinoma patients with similar pretreatment PSA levels and biopsy Gleason scores treated at the same institution with either radical prostatectomy or RT achieved similar 7-year rates of biochemical control and cause specific survival, regardless of treatment technique. These findings suggest that for patients with pretreatment PSA levels </=10 ng/mL and Gleason scores </=6, conventional doses of external beam RT and radical retropubic prostatectomy can be expected to produce comparable treatment results unaffected by age at diagnosis.

Age of Onset↗
PubMed2000

The use of antihypertensive therapy in Spain (1986-1994).

We aimed to analyze the trends in antihypertensive therapy in Spain during the period 1986 to 1994, as well as the change in the pattern of different drugs, in relation to different national/international recommendations for hypertension treatment. Antihypertensive consumption was studied using the defined daily dose (DDD) and the DHD (DDD/1000 inhabitants/day) of each drug, as defined by the Drug Utilization Research Group of the European Office of the World Health Organization. The anatomical classification of hypotensive drugs has been made according to EPhMRA (European Pharmaceutical Market Association) guidelines. A significant increase of 117.4% (41.39/90 DHD) in antihypertensive drug consumption was observed in the period 1986 to 1994. In 1986 diuretics were the most consumed (30.27 DHD), followed by calcium antagonists (5.37), beta-blockers (3.93), and the angiotensin-converting enzyme (ACE) inhibitor (1.37). In 1994 ACE inhibitors, calcium antagonists, and beta-blockers increased significantly (P < .0001), whereas diuretics were still the most commonly prescribed. Nifedipine and captopril were the most used among calcium antagonists and ACE inhibitors. National and international recommendations had no effect on prescription patterns. Antihypertensive therapy of all types is increasing in Spain. Diuretics remain the most popular, beta-blockers stay stable, whereas the newer types are rising rapidly. National and international recommendations had no effect on prescription patterns.

Adrenergic beta-Antagonists↗
PubMed1999

Treatment outcome with adjuvant and salvage irradiation after radical prostatectomy for prostate cancer.

OBJECTIVES: To determine the factors associated with outcome by reviewing our institution's experience treating patients with external beam radiation therapy (RT) after radical prostatectomy. METHODS: Sixty-one patients received RT to the prostatic fossa after radical prostatectomy for prostate cancer (median dose 59.4 Gy). Thirty-eight patients received adjuvant RT within 6 months of surgery for adverse pathologic findings only. Therapeutic RT was administered to 23 patients either for a persistently elevated postoperative prostate-specific antigen (PSA) level (n = 2), a rising PSA level more than 6 months after surgery (n = 9), or a biopsy-proven local recurrence (n = 12). Preoperative and preradiation PSA values, Gleason score, pathologic findings, patient age, total RT dose, and indication for RT were analyzed for their impact on biochemical control. The median follow-up was 48 months. RESULTS: Patients treated with adjuvant RT achieved 3 and 5-year biochemical control rates of 84% and 67%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. No variable was associated with 5-year outcome. The 5-year actuarial rate of biochemical control for patients treated with therapeutic RT was 16%. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. Only a pre-RT PSA level of 2 ng/mL or less was associated with an improved rate of biochemical control at 3 years (80% versus 27%, P = 0.001). However, at 5 years, this difference was not statistically significant. A separate analysis was performed to determine the prognostic factors associated with outcome for the entire group of patients. Only the indication for RT (adjuvant versus therapeutic) was associated with 5-year outcome. Patients treated with adjuvant RT had a statistically significant improvement in 5-year actuarial rates of biochemical control (67% versus 16%, P <0.001) and disease-free survival (66% versus 46%, P = 0.037) but not in overall survival. There were no statistically significant differences between patient groups with respect to age, preoperative PSA, Gleason score, pathologic T stage, median follow-up, and total RT dose. CONCLUSIONS: At our institution, patients treated with adjuvant RT after prostatectomy for adverse pathologic findings achieved excellent rates of biochemical control that were significantly better than that of similar patients treated therapeutically for persistent or rising PSA or clinical local recurrence.

Adenocarcinoma↗
PubMed1998

The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup.

PURPOSE: Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG. MATERIALS AND METHODS: Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data. RESULTS: Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted. CONCLUSIONS: Intravesical Tice BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months.

Adjuvants, Immunologic↗
PubMed1996

Anomalous left coronary artery originating from the pulmonary artery in an adult.

We report the case of a 63-year-old man who presented at our hospital with paroxysmal atrial fibrillation. He was found to have an anomalous left coronary artery originating from the pulmonary artery. The patient underwent successful revascularization with the use of a left internal mammary artery bypass graft.

Atrial Fibrillation↗
PubMed1995

Are pelvic computed tomography, bone scan and pelvic lymphadenectomy necessary in the staging of prostatic cancer?

OBJECTIVE: To investigate the effectiveness and economy of pelvic computed tomography (CT), bone scan and pelvic lymphadenectomy as staging modalities in patients undergoing radical prostatectomy. The use of prostate specific antigen (PSA) and Gleason's score as adjuncts to predict extracapsular disease were also evaluated and their economic implications examined. PATIENTS AND METHODS: Between January 1990 and June 1993, 861 men were newly diagnosed with prostate cancer, of whom 409 underwent surgery. All patients underwent pelvic CT scans and PSA analysis. Patients undergoing surgery had pre-operative bone scans and Gleason's scoring of their pathological tissue. RESULTS: Only 13 (1.5%) of 861 men had positive pelvic CT scans. Of the 409 patients who underwent surgery, all had negative pelvic CT and bone scans, and all underwent a modified pelvic lymphadenectomy; 192 (47%) had extracapsular disease. Only 15 (3.7%) patients who underwent surgery were found to have positive nodes. CONCLUSIONS: The use of pelvic CT and bone scans for clinical staging in patients with a PSA level of < or = 20 ng/mL should not be advocated because they have a very low yield and are not cost effective. We question the role of a modified pelvic lymphadenectomy for staging purposes, either by an open or laparoscopic procedure, because the yield of positive diagnoses is very low.

Bone Neoplasms↗
PubMed1995

Peripartum seizure and HIV infection.

Two patients with new-onset seizure within hours of parturition subsequently tested positive for human immunodeficiency virus (HIV). The peripartum period appears to predispose asymptomatic HIV-infected individuals to seizure. Such patients, especially with suggestive risk factors, should be screened for HIV-antibody.

Adult↗
PubMed1994

Revascularization by the retropharyngeal route for extensive disease of the extracranial arteries.

PURPOSE: This is a retrospective study of 16 patients who had an average of 3.25 arteries supplying the brain that were occluded or severely diseased. In all of them severe disease or occlusion of the left carotid and subclavian arteries precluded an ipsilateral repair. METHODS: These patients with extensive extracranial arterial disease underwent revascularization from the opposite side of the neck through a retropharyngeal tunnel. Twelve patients had contraindications for a transthoracic repair. RESULTS: There were no early deaths. Postoperative complications included one graft occlusion, one anastomotic disruption with hemorrhage, and one stroke, all resulting from management errors. Follow-up was 100%. Primary patency rate was 94%, and survival was 87.5%. Two patients died in the interval: one from a myocardial infarction and one from cause unknown. CONCLUSIONS: The retropharyngeal route is a shorter and more direct path across the neck and occasionally permits direct carotid-to-carotid transposition without the use of prosthetic bypasses. Even in the presence of extensive extracranial disease, these reconstructions have an excellent patency rate, and these patients have a survival 87.5% after a mean follow-up of 5.56 +/- 4.0 years.

Adult↗
PubMed1993

Reduction of thrombogenicity with argon laser angioplasty. Comparison with balloon angioplasty.

Direct argon or thermal laser angioplasty (LA) was evaluated for thrombogenicity using angioscopy, and compared with balloon angioplasty (BA). In each of 8 dogs, 4 segments (both proximal and distal iliac arteries) were treated by laser-thermal and/or balloon angioplasty. One segment was treated by balloon angioplasty and 3 other segments were treated with either thermal LA with 7 W using a "Hot-Tip" laser probe (2.0 mm), or BA and thermal LA, or a special optical probe which emits a 3 W argon laser beam. Mean percent area stenosis by thrombus was 44 +/- 23 in balloon-dilated, 23 +/- 21 in thermally-treated and balloon-dilated, 3 +/- 3 in thermally-treated, and 1 +/- 4 in directly-lased segments at 30 min. It was 62 +/- 28 in balloon dilated, 31 +/- 29 in thermally-treated and balloon-dilated, 5 +/- 6 in thermally-treated, and 1 +/- 2 in directly-lased segments at 60 min. Balloon-inflated segments had the highest percent area stenosis which was significantly higher than that of either the direct laser or thermally-treated segments (p < 0.0005). Histology showed thermal necrosis in laser-treated sites, and wall tears in BA sites. Thus, LA can provide a less thrombogenic arterial surface than BA.

Angioplasty, Balloon↗