Biomedical subjects
F E Johnson
Publications and source records attributed to F E Johnson.
Appendicitis in patients with previous spinal cord injury.
BACKGROUND: Acute abdominal emergencies are particularly dangerous in patients with impaired sensation. METHODS: Thirty patients with spinal cord injury who later developed appendicitis were identified in Department of Veterans Affairs computer files over a 5-year period; 26 were evaluable. RESULTS: The mean age was 55 years (range 27 to 79); all were males. Abdominal distention or discomfort was present in 16 of 26 (62%), while 2 of 26 (8%) presented in shock. A palpable right lower quadrant mass was present in 6 of 26 (23%). The mean initial white blood cell count was 18,000/mm3. Only 9 of 26 (35%) had the diagnosis of appendicitis made on admission. In 12 of 26, computed tomography was done; all correctly diagnosed appendicitis. The mean delay in diagnosis after hospitalization was 2 days (range 0 to 5). Perforated appendicitis was found at surgery in 24 of 26 (92%). Twenty-three of 26 (88%) underwent appendectomy; 3 of 26 (12%) underwent right colectomy. The 30-day mortality rate was 4%. Six of 26 (23%) developed a postoperative complication. The mean length of stay was 16 days. CONCLUSIONS: Acute appendicitis in spinal-cord-injured patients frequently presents late and complications are common. Computed tomography appears to be an excellent diagnostic modality. Some of the adverse outcomes which are related to preexisting spinal cord injury may be preventable with early intervention.
Current followup strategies after radical prostatectomy: a survey of American Urological Association urologists.
PURPOSE: Followup care of men who have undergone potentially curative surgical treatment for prostate cancer varies widely among clinicians. To determine current practice patterns we mailed a custom designed questionnaire to American and nonAmerican urologists who were American Urological Association (AUA) members. MATERIALS AND METHODS: Surveys were mailed to a random sample of the approximately 12,000 AUA members, comprising 3,205 Americans and 1,262 nonAmericans. Evaluable surveys were returned by 760 American (24%) and 290 nonAmerican (23%) urologists. Our analysis is based on these 1,050 responses. RESULTS: In generally healthy patients after radical prostatectomy for stages T1 to 2NOMO and T3a to cNOMO prostate cancer the most frequently recommended followup diagnostic tests included office visit with digital rectal examination, serum prostate specific antigen (PSA) and urinalysis. Although there is appreciable variation in the frequency of use of these methods, respondents generally recommended office visit with digital rectal examination, serum PSA and urinalysis every 3 months in year 1, every 6 months in years 2 to 5 and annually thereafter. Other tests, such as serum prostatic acid phosphatase, bone scan, and abdominal and pelvic computerized tomography and magnetic resonance imaging, are rarely recommended. CONCLUSIONS: Our survey provides information regarding current followup strategies recommended by AUA urologists after radical prostatectomy for stages T1 to 2NOMO and T3a to cNOMO disease. Office visits and digital rectal examination, urinalysis and PSA measurement are the main tools that urologists currently use. Although optimal strategy remains unknown, these data permit the rational design of clinical trials of alternate followup strategies based on actual current practice to answer this important question.
Role of chronic catheterization in the development of bladder cancer in patients with spinal cord injury.
OBJECTIVES: Patients with spinal cord injury (SCI) and chronic indwelling catheters are known to be at increased risk of bladder malignancy. "Decatheterization" by clean intermittent catheterization, external condom catheterization, or spontaneous voiding is thought to reduce the risk by decreasing the chronic mucosal irritation and rate of infection. We examined two Department of Veterans Affairs (DVA) data bases to test this theory. METHODS: A population-based retrospective analysis of invasive treatments for carcinoma of the bladder in all DVA hospitals was conducted using computerized inpatient files from fiscal years 1988 to 1992. RESULTS: One hundred thirty patients with bladder malignancy were identified from a pool of 33,565 patients with SCI (0.39%). All 130 patients underwent either radical cystectomy (n = 63, 48%) or transurethral resection of bladder tumor (n = 67, 52%). The 30-day perioperative mortality and overall 5-year survival rates were 2 (1.5%) and 49 (38%) of 130, respectively. Of the 130 patients analyzed, 42 (32%) had adequate data available regarding tumor pathologic findings and method of bladder management for analysis. The average age at diagnosis was 57.3 years. The histologic finding was transitional cell carcinoma in 23 (55%), squamous cell carcinoma in 14 (33%), and adenocarcinoma in 4 (10%) of 42. Bladder management was an indwelling urethral catheter in 18 (43%), suprapubic catheter in 8 (19%), clean intermittent catheterization in 8 (19%), and condom catheter in 6 (14%) of 42 patients. Squamous cell carcinoma was more common in patients with indwelling urethral catheters and suprapubic tubes (11 of 26, 42%) than in those using clean intermittent catheterization, condom catheterization, or spontaneous voiding (3 of 16, 19%). CONCLUSIONS: Bladder cancer was diagnosed in approximately 0.39% of this large SCI population during a 5-year period. Most cancers (55%) were transitional cell carcinomas. Squamous cell carcinoma was more common in patients with SCI and indwelling catheters than those without chronic catheterization. These data continue to suggest that avoidance of indwelling catheters, when feasible, is the preferred method of bladder management in patients with SCI.
Follow-up of patients with thoracic malignancies.
The optimal approach to the post-treatment management of patients with thoracic malignancies is a controversial topic. This is primarily because of the lack of widely accepted practice guidelines. Several guidelines have been promulgated for the follow-up of thoracic malignancies, but none have been tested in randomized controlled trials. The problem is an especially interesting one because little is known about how outcomes vary when the follow-up strategy is altered.
Kappa-opioid receptor binding varies inversely with tumor grade in human gliomas.
BACKGROUND: Opioid agonists can inhibit cell proliferation in various neural tumor cell lines, including rat gliomas. Because opioid antimitogenic effects are mediated by opioid receptors, it was of interest to the authors to determine opioid receptor levels in human brain tumors. METHODS: Specimens obtained at craniotomy from 30 patients with glioma and nonneoplastic brain disorders were evaluated for their kappa-opioid receptor binding. Kd and Bmax values were estimated from homologous competition binding curves with the kappa1-selective radioligand [3H]U69,593. RESULTS: Receptor binding density was greatest in nonneoplastic brain tissue, less in Grade 2 and 3 astrocytoma, and least in glioblastoma multiforme. CONCLUSIONS: These results suggest that opioid receptor-based stratification of grade may have clinical utility in distinguishing glioblastoma multiforme from lower grade astrocytomas, and thereby may facilitate diagnosis and treatment.
Brain opioid receptor adaptation and expression after prenatal exposure to buprenorphine.
Previous in vivo studies revealed that buprenorphine can down-regulate mu and up-regulate delta2 and kappa1 opioid receptors in adult and neonatal rat brain. To assess gestational effects of buprenorphine on offspring, pregnant rats were also administered this drug and opioid receptor binding parameters (Kd and Bmax values) were measured by homologous binding assays of postnatal day 1 (P1) brain membranes. Buprenorphine concentrations of 2.5 mg/kg injected into dams elicited an up-regulation of kappa1 opioid receptors as detected with the kappa1-selective agonist 3H-U69593. Parallel studies with the mu-selective agonist [D-ala2, mephe4,gly-ol5] enkephalin revealed a buprenorphine-induced down-regulation in receptor density at 0.3, 0.6 or 2.5 mg/kg drug treatment. A greater down-regulation of mu receptors for P1 males than for their female counterparts was observed. Buprenorphine did not cause a reduction in binding affinity in these experiments. Changes in opioid receptor adaptation induced by buprenorphine were further supported by data from cross-linking of 125I-beta-endorphin to brain membrane preparations. RT-PCR analysis of opioid receptor expression was also estimated in P1 brains. However, significant changes in neither mu nor kappa receptor message were detected in P1 brains as a result of prenatal buprenorphine treatment under the conditions of these experiments. Since buprenorphine is being evaluated in clinical trials for the treatment of heroin abuse, the in utero actions of the drug have ramifications for its use in the treatment of maternal drug abuse.
How tumor stage affects surgeons' surveillance strategies after surgery for carcinoma of the upper aerodigestive tract.
BACKGROUND: The factors that influence decision-making among surgeons are not well understood. The authors evaluated how tumor stage in otherwise healthy patients subjected to potentially curative surgery for upper aerodigestive tract (UADT) epidermoid carcinoma affects the self-reported follow-up strategies employed by practicing surgeons. METHODS: Hypothetical patient profiles and a detailed questionnaire based on these profiles were mailed to the 824 members of the Society of Head and Neck Surgeons (SHNS) and the 522 members of the American Society for Head and Neck Surgery who were not members of SHNS. The effect of TNM stage on the surveillance strategies chosen by the respondents was analyzed. RESULTS: Ten of the 14 most commonly employed surveillance modalities were ordered significantly more frequently with increasing TNM stage. This effect persisted through 5 years of follow-up, but the differences across stages were small. Only 30% of respondents modified their strategies according to the patient's TNM stage. CONCLUSIONS: Most surgeons performing surveillance after potentially curative surgery in otherwise healthy patients with UADT carcinoma use the same follow-up strategy irrespective of TNM stage. These data permit rational design of a randomized clinical trial of two alternate follow-up plans.
Costs of posttreatment surveillance for patients with upper aerodigestive tract cancer.
OBJECTIVES: To determine the range of recommended follow-up strategies for patients with upper aerodigestive tract cancer treated with curative intent and to estimate the cost of follow-up. DESIGN: Economic analyses of the costs associated with 31 follow-up strategies (12 generic and 19 site specific) identified from a MEDLINE search of the literature for 1978 to 1997 and a search of major textbooks. Generic strategies are not specific for site or histology and are exclusive of strategies designed for the rare patient, ie, patients who would not be considered average in terms of clinical characteristics. Charge data obtained from the Part B Medicare Annual Data File and the Hospital Outpatient Bill File were used as a proxy for cost. SETTING: Ambulatory care. MAIN OUTCOME MEASURES: Nationwide Medicare-allowed charges and an actual-charge proxy for 5 years of surveillance after treatment for upper aerodigestive tract cancer. RESULTS: Medicare-allowed charges for 5-year follow-up ranged from a low of $739 to a high of $14,079 for the generic and site-specific strategies combined and from $739 to $4646 for the 12 generic strategies alone. When Medicare-allowed charges were converted to a proxy for actual charges using a conversion ratio of 1.62, the range was $1198 to $22,807 for all strategies combined (a 19-fold difference in charges) and $1198 to $7597 for the generic strategies alone (a 5-fold difference in charges). CONCLUSIONS: Charges vary extensively across surveillance strategies, particularly if site-specific strategies are considered, although the potential benefit of more intensive, higher-cost strategies on survival or quality of life has yet to be demonstrated.
A comparison of adrenalectomy with other resections for metastatic cancers.
BACKGROUND: Although adrenal metastases were once considered incurable, recent anecdotal reports recommend adrenalectomy for isolated metastases. METHODS: Computerized files of all US Department of Veterans Affairs (DVA) hospital admissions and deaths from 1988 to 1994 identified patients undergoing isolated adrenal resections, and hospitalization records were obtained. Patients without a death record were assumed to be alive. RESULTS: In 47 patients with adrenalectomy for metastases, only 5 patients did not die within 3 years: 2 each had metachronous renal or colorectal metastases, and 1 had a pulmonary primary. Thirteen patients with other primary sites all expired within 3 years. Operative mortality was 4% in these 47 patients and also in 706 other adrenalectomies without metastases. CONCLUSIONS: Adrenalectomy for metastatic carcinoma in the DVA was safe, with a projected 5-year survival rate (13%) that is significantly inferior (P < or = 0.05) to resections for colorectal metastases to lung (36%) or liver (26%), but superior to brain (none).
Evaluation and management of men whose radical prostatectomies failed: results of an international survey.
OBJECTIVES: To determine how urologists evaluate and treat men who develop recurrent prostate cancer after radical prostatectomy. METHODS: Surveys were mailed to 4467 American Urological Association members comprising 3205 U.S. and 1262 non-U.S. urologists randomly selected from a total membership of approximately 12,000. One thousand four hundred sixteen were returned and 1050 (760 U.S. and 290 non-U.S.) surveys were evaluable. RESULTS: To evaluate men with an elevated or rising prostate-specific antigen (PSA) level more than 1 year after radical prostatectomy, 98% of respondents use digital rectal examination, 68% use bone scan, 54% use transrectal ultrasound with biopsy, 36% use abdominal or pelvic computed tomography scan, 31% use transrectal ultrasound without biopsy, 25% use prostatic acid phosphatase, 11% use monoclonal antibody scan, and 5% use abdominal or pelvic magnetic resonance imaging. Respondents evaluate men with an elevated or rising PSA within 1 year of radical prostatectomy similarly. To treat documented local recurrence, 81% of respondents recommend radiation therapy, 7% recommend orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists, 6% recommend observation only, and 5% recommend combined androgen ablation. To treat documented distant recurrence, 50% recommend combined androgen ablation, 42% recommend orchiectomy or LHRH agonists, and 7% recommend observation only. To treat PSA-only recurrence, 54% recommend observation only, 16% recommend combined androgen ablation, 15% recommend orchiectomy or LHRH agonists, and 13% recommend radiation therapy. CONCLUSIONS: The evaluation of men whose radical prostatectomy failed varies among urologists and does not depend on time of recurrence. Radiation therapy is used by most urologists to treat local recurrence. Hormonal manipulation is used by more than 90% of urologists to treat distant recurrence. More than 50% of urologists recommend observation for men with biochemical-only recurrence.
Outcome after proctectomy for rectal cancer in Department of Veterans Affairs Hospitals: a report from the National Surgical Quality Improvement Program.
OBJECTIVE: To define risk factors that predict adverse outcomes after proctectomy for cancer in Department of Veterans Affairs Medical Centers. SUMMARY BACKGROUND DATA: Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy. METHODS: The National VA Surgical Quality Improvement Program contains prospectively collected and extensively validated data on >287,000 patients. All patients undergoing proctectomy for rectal cancer from 1991 to 1995 who were registered in this data base were selected for study. Independent variables examined included 68 presurgical and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rates for each of the 10 most common complications and the 30-day mortality rate. RESULTS: Five hundred ninety-one patients were identified; 467 (79%) underwent abdominoperineal resection and 124 (21%) were treated with sphincter-saving procedures. Thirty percent of patients had one or more complications after proctectomy. Prolonged ileus, urinary tract infection, pneumonia, and deep wound infection were the most frequently reported complications. The 30-day mortality rate was 3.2% (19 deaths). For most complications, 30-day mortality rates were significantly higher for patients with complications than for those without. Thirty-day mortality rates for several complications exceeded 50%: cardiac arrest requiring cardiopulmonary resuscitation, deep venous thrombosis or thrombophlebitis, coma lasting >24 hours, acute renal failure, cerebrovascular accident, and pulmonary embolism. Four presurgical factors predicted a high risk of 30-day mortality in the logistic regression analysis: elevated blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds. CONCLUSIONS: Mortality rates after proctectomy in VA hospitals are comparable to those reported in other large series. Most postsurgical complications are associated with an increased 30-day mortality rate. Elevated presurgical blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds predict a high risk of 30-day mortality.
Lung cancer patient follow-up: motivation of thoracic surgeons.
STUDY OBJECTIVES: To analyze variation in beliefs that potentially motivate thoracic surgeons in the design of posttreatment surveillance strategies for lung cancer patients and to examine the relationship between motivation and follow-up intensity. DESIGN: International survey. SETTING: Ambulatory care. PARTICIPANTS: All 3,700 members of the Society of Thoracic Surgeons were surveyed to measure their follow-up practices during the 5-year period after treatment, physician beliefs, and variation in these beliefs. The relationship between beliefs, as potentially motivating factors, and follow-up intensity was also analyzed. MEASUREMENTS AND RESULTS: Age, General Thoracic Surgery Club membership, percentage of practice that was noncardiac, South Central United States practice location, and overseas practice location were most frequently related to beliefs that potentially motivate physicians in the design of surveillance strategies. When viewed independently of follow-up practice patterns, thoracic surgeons appear to be motivated by the desire to please patients, avoid malpractice suits, and improve patient quality of life. When viewed in relation to self-reported follow-up, none of these motivating factors were consistently associated with follow-up intensity. Belief in curative treatment of recurrence and enhanced likelihood of immediate palliative treatment leading to improved survival were the factors most frequently associated with variation in follow-up. Although the ability of the logistic and stepwise regression models to predict test use and follow-up intensity was less than optimal for TNM stage I patients, predictive ability was substantially improved for TNM stage II and III patients by including earlier-stage practice patterns as an independent variable. CONCLUSIONS: Physician characteristics and beliefs predicted a less than expected amount of the variation in self-reported follow-up intensity by TNM stage when modelled without knowledge of follow-up practice for any other TNM stage. Discrepancies between self-reported and actual follow-up may be partially responsible, although lack of surveillance guidelines is more likely. The inclusion of barriers to follow-up may improve future models.
Quality of life measurements do not support palliative pancreatic cancer treatments.
Although resection for pancreatic cancer is occasionally curative, its major value lies in restoring patients to a more normal life. The objective of this study was to evaluate the functional quality of life (QoL) of patients undergoing various treatments for pancreatic cancer using a nationwide, multi-institutional, non-referral patient population. From 822 pancreatic cancer patients treated from 1989 to 1995, and listed in the Department of Defense (DoD) hospital central computerized tumor registry, we selected 781 with evaluable survival information. Local tumor registrars had contacted patients at least yearly and prospectively compiled a QoL index using a self-reported Karnofsky performance status (KPS); values were obtained for patients alive in March of 1995 and/or 1996. Survival duration and KPS scores were then compared by stage and treatment using analysis of variance (F-test). Resection significantly increased KPS and mean survival time with stage I-II cancers and improved mean survival time, but not KPS, in patients with node positive (stage III) disease. The projected five-year survival rate after resection in stages I-II was 24% but zero for stage III. Patients receiving combined chemo- and radiation therapies, whether given as adjuvant or primary treatment, had significantly longer mean survival duration. However, KPS scores were not higher in treated patients. These data indicate that patients live longer and better lives after resection of localized pancreatic cancers, but QoL measurements do not support resection for pancreatic cancer involving lymph nodes. Unresected patients selected for combined chemo- and radiation therapy live longer, but not better, lives.
A phase II evaluation of pentoxifylline combined with radiation in the treatment of brain metastases.
Pentoxifylline (PTX) has pharmacological properties that suggest potential utility as a radiation sensitizer, and preclinical animal studies have been promising. In a non-randomized phase II trial, we used PTX plus standard-dose external-beam whole-brain radiation treatment (WBRT) in patients with brain metastases. Seventeen patients were entered; 14 received both WBRT and PTX and were considered evaluable. Nine of the 14 completed treatment. Analyzing data on all 14 evaluable patients according to intent to treat, median survival time was 33 days, comparable to published data from historical controls. PTX toxicity was not a common cause of patient dropout, supporting higher PTX doses in future trials.
Transforming growth factor beta peptide antagonists and their conversion to partial agonists.
Transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of various human diseases. Synthetic TGF-beta antagonists therefore could have therapeutic utility. Here we show the development of such compounds. Three synthetic pentacosapeptides designated beta125-(41-65), beta225-(41-65), and beta325-(41-65), whose amino acid sequences correspond to the 41st to 65th amino acid residues of TGF-beta1, TGF-beta2, and TGF-beta3, respectively, inhibit the binding of 125I-labeled TGF-beta isoforms to TGF-beta receptors in mink lung epithelial cells with IC50 of approximately 0.06-2 microM. beta125-(41-65) blocks TGF-beta1-induced growth inhibition and TGF-beta1-induced plasminogen activator inhibitor-1 expression in these cells. The variants designated beta125-(41-65)W52A/D55A and beta325-(41-65)R52A/D55A, in which both Trp52/Arg52 and Asp55 are replaced by alanine residues, do not have TGF-beta antagonist activity. Multiple conjugation of beta125-(41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as measured by DNA synthesis inhibition. These results suggest that the (W/R)XXD motif is important for the activities of these TGF-beta peptide antagonists and that this motif may be the active site sequence of TGF-beta.
Major hepatic resection. Indications and results in a national hospital system from 1988 to 1992.
OBJECTIVE: To determine the indications for and outcomes of hepatic resection in a US hospital system. DESIGN: A retrospective study of 444 consecutive hepatic resections (i.e., 286 wedge or segmental resections and 158 lobectomies) using computerized medical records. SETTING: All US Department of Veterans Affairs hospitals. PATIENTS: US veterans (99% men). INTERVENTION: Major hepatic resection. MAIN OUTCOME MEASURE: Survival, as determined by the absence of a death record. RESULTS: One hundred fifty-eight lobectomies or larger resections were recorded (36% of the total); the 30-day operative mortality was 12% for lobectomies and 5% for wedge resections. However, the diagnosis had a greater influence on the operative mortality: 11 (4%) of 275 patients with colorectal metastases, 15 (21%) of 71 patients with hepatomas, 2 (9%) of 23 patients without cancer (but 0 [0%] of 7 patients with hemangiomas), 3 (12%) of 25 patients with cholangiocarcinomas, and 4 (8%) of 50 patients with metastases from other primary cancers. Approximately one third (i.e., 92) of the patients who underwent a resection of their colorectal metastases underwent a resection of their colorectal metastases underwent a concurrent colectomy, while the rest of the patients underwent these surgical procedures metachronously. The operative mortality was equal (i.e., 4%) for the resection of synchronous vs metachronous colorectal metastases. The mean survival time after the resection of metachronous vs synchronous colorectal metastases was 34 months vs 30 months, respectively, and the projected 5-year survival after either procedure was 26%. The projected 5-year survival was 20% for patients with hepatoma and 8% for patients with cholangiocarcinoma. With uncommon pathologic types, the mean survival time after metastatic resection was longest for those with renal primary tumors (3 patients, 55 months). CONCLUSIONS: Hepatic resection is a safe and effective therapy for colorectal metastases (5-year survival, 26%) and hemangioma; hepatoma resection is dangerous (operative mortality, 21%) but effective (5-year survival, 20%).
Experience with distal bile duct cancers in U.S. Veterans Affairs hospitals: 1987-1991.
BACKGROUND: Treatment selection and results were reviewed in a population with distal bile duct cancers. METHOD: Cases of bile duct cancer were retrieved from computerized U.S. Department of Veterans Affairs records from 1987-1991. RESULT: A total of 156 patients with distal bile duct cancers were recovered (34 resections, 37 operative bypasses, and 85 nonoperative biliary intubations). Mean survival after resection was 22 months, which was significantly higher than after biliary bypass (14 months) or intubation (11 months). Death rate within 30 days of resection, bypass, or intubation was 11%. Distal bile duct cancer had a much higher resectability rate (48%) than did pancreatic cancer (22%) and significantly longer mean survival by stage. Projected 5-year survival rate after resection was 21% for localized cancers, but no 3-year survivors were seen with nodal metastases regardless of treatment. CONCLUSIONS: Resection increases survival in patients with distal bile duct cancer. Five-year survival was achieved only when patients when nodal or other metastases were absent; most resections do not result in cure and prolonged survival also can occur without resection.