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J A Freeman

Publications and source records attributed to J A Freeman.

At least 19 recordsLinked to original sources

Prognostic markers in bladder cancer: a contemporary review of the literature.

PURPOSE: We provide a contemporary review of bladder tumor markers and summarize their role as prognostic indicators. MATERIALS AND METHODS: A comprehensive review of the literature on prognostic markers for transitional cell carcinoma of the bladder was performed. RESULTS: Intense research efforts are being made to identify and characterize better various bladder cancers and their true biological potential. The need to predict which superficial tumors will recur or progress and which invasive tumors will metastasize has led to the identification of a variety of potential prognostic markers. Blood group antigens, tumor associated antigens, proliferating antigens, oncogenes, peptide growth factors and their receptors, cell adhesion molecules, tumor angiogenesis and angiogenesis inhibitors, and cell cycle regulatory proteins have recently been identified. The potential clinical applications of these tumor markers are under active investigation. Recent attention has focused on which tumor markers may predict the responsiveness of a particular bladder cancer to systemic chemotherapy. CONCLUSIONS: At present conventional histopathological evaluation of bladder cancer (tumor grade and stage) cannot predict accurately the behavior of most bladder tumors. With a better understanding of the cell cycle, and cell to cell and cell to extracellular matrix interactions as well as improved diagnostic techniques (immunohistochemistry), progress is being made to identify and characterize other potential prognostic markers for transitional cell carcinoma of the bladder. The ultimate goal is to develop reliable prognostic markers that will accurately predict not only the course but also the response of a tumor to therapy. This information may then be used to dictate more aggressive treatment for tumors that are likely to progress and less aggressive treatment for those that are unlikely to progress. In the future these biological markers may also be used in gene therapy for the treatment of bladder cancer.

Antigens, Neoplasm

Prospective pathologic analysis of female cystectomy specimens: risk factors for orthotopic diversion in women.

OBJECTIVES: To prospectively evaluate our previously established pathologic risk factors in women undergoing cystectomy for bladder cancer and to determine if these criteria identify appropriate female candidates for orthotopic diversion. METHODS: Prospective pathologic evaluation was performed on 71 consecutive female cystectomy specimens removed for primary transitional cell carcinoma of the bladder. The histologic grade, pathologic stage, presence of carcinoma in situ, number, and location of tumors were determined. In addition, final pathologic analysis of the bladder neck and proximal urethra was performed and compared with the intraoperative frozen-section analysis of the distal margin (proximal urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14 (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor involvement was found to be the most significant risk factor for tumor involving the urethra (P <0.001). All patients with urethral tumors demonstrated concomitant bladder neck tumors. However, more than 60% of patients with bladder neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient with a normal bladder neck demonstrated tumor involvement of the urethra. Intraoperative frozen-section analysis of the distal surgical margin was performed on 47 patients: 45 without evidence of tumor and 2 patients with urethral tumor involvement. In all cases, the intraoperative frozen-section analysis was correctly confirmed by final permanent section. CONCLUSIONS: We prospectively demonstrate that bladder neck tumor involvement is a significant risk factor for urethral tumor involvement in women. However, despite bladder neck tumor involvement, a number of women undergoing cystectomy for bladder cancer have a normal urethra and may be candidates for orthotopic diversion. Furthermore, our data demonstrate that intraoperative frozen-section analysis of the distal surgical margin accurately and reliably evaluates the proximal urethra and currently determines which patients undergo orthotopic diversion at our institution.

Adult

Primary malignant melanoma with rhabdoid features: a histologic and immunocytochemical study of three cases.

Malignant rhabdoid tumors are morphologically characterized by the presence of sheets of large polygonal cells with abundant cytoplasm containing eosinophilic inclusions. They have vesicular nuclei, often with prominent central nucleoli. The term rhabdoid tumor was originally coined to describe a group of rare, aggressive renal neoplasms of childhood. Since then, similar lesions, so-called extrarenal malignant rhabdoid tumors have been increasingly reported. The evidence to date suggests that, at least in extrarenal locations, rhabdoid tumors do not constitute a homogeneous entity, but rather represent the shared morphological pattern of a diverse range of malignant neoplasms. Although such rhabdoid features are not uncommon in metastatic malignant melanoma, they have only once been briefly described in a primary lesion. We report three further cases of cutaneous primary malignant melanoma with rhabdoid morphology.

Adult

Tricyclic pyrone analogs: a new class of microtubule-disrupting anticancer drugs effective against murine leukemia cells in vitro.

Novel 1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano [4,3-b][1]benzopyrans were synthesized in Hua's laboratory (code names H5, H10, H14 and H15) and tested for their ability to prevent L1210 leukemic cells from synthesizing macromolecules and growing in vitro. The aryl groups of these tricyclic pyrone (TP) analogs are either 3, 4-dimethoxyphenyl in H5 and H15 or 3-pyridyl in H10 and H14. Since 50 M H5 and H10 both inhibit DNA synthesis and tumor cell growth by 79-100%, concentrations 25 M were used in this study to assess the structure-activity relationships for this class of compounds. At 10-25 M, H5 and H14 are more potent inhibitors of DNA, RNA and protein synthesis than H10. In contrast, at 5-25 M, H10 is much more effective than H5 and H14 at inhibiting the growth of L1210 cells over a 4-day period. Interestingly, H15 inhibits DNA synthesis as much as H10 but fails to alter tumor cell growth. This discrepancy between the ability of TPs to inhibit macromolecule synthesis and leukemic cell growth suggests that other molecular targets may be involved in the antitumor action of these drugs. Their short-term inhibition of nucleic acid synthesis is reversible following drug removal but their long-term inhibition of tumor cell growth is not. Moreover, 25 M H5 and H10 are not cytotoxic at 2 days but equally decrease cell viability at 4 days, suggesting that the potent and irreversible inhibition of cell proliferation observed 1-4 days after H10 treatment is not solely caused by drug cytotoxicity. The effectiveness of H10 as inhibitor of L1210 cell growth is comparable to that of a spectrum of representative anticancer drugs. A critical finding is that 5 M H10 blocks the polymerization of purified tubulin by 90% and, therefore, may be a novel microtubule de-stabilizing drug. Indeed, H10 inhibits tubulin polymerization and L1210 cell growth as much as 5 M of vincristine (VCR). In contrast, 5 M H5 alters neither tubulin polymerization nor tumor cell growth. The ability of H10 to disrupt microtubule dynamics indirectly suggests that TPs may be novel cell cycle-specific anticancer drugs useful for arresting mammalian cells in mitosis.

Animals

The impact of inpatient rehabilitation on progressive multiple sclerosis.

One of the primary aims of rehabilitation for patients with multiple sclerosis (MS) is to reduce their levels of disability and handicap, yet little systematic research into the outcomes of this intervention has been undertaken. This stratified, randomized, wait-list controlled study evaluated the effectiveness of a short period of multidisciplinary inpatient rehabilitation in people with MS. Sixty-six patients in the progressive phase of the disease were assessed at 0 and 6 weeks with validated measures of impairment (Expanded Disability Status Scale and Functional Systems), disability (Functional Independence Measure), and handicap (London Handicap Scale). Both groups were comparable in terms of age, sex, disease duration and severity, disability, and handicap. At the end of 6 weeks, although the level of impairment in both groups remained the same, those who participated in a short period of inpatient rehabilitation (average of 25 days) significantly improved their level of disability and handicap compared with those in the wait-list control group. Despite unchanging impairment, inpatient rehabilitation resulted in reduced disability and handicap in patients with progressive MS.

Adult

Expectant management as an option for men with stage T1c prostate cancer: a preliminary study.

The outcome of patients selecting observation of clinical stage T1c prostate cancer is unknown. A total of 101 men with clinical stage T1c prostate cancer were evaluated, counseled, and monitored in a standard fashion. Altogether, 27 men who elected observation were older and had greater co-morbidity but similar tumor characteristics as compared with 74 men who elected radical prostatectomy. In all, 9 men demonstrated clinical or biochemical evidence of progression after a mean follow-up of 23 months; 4 men who underwent radical prostatectomy had specimen-confined disease and undetectable post-operative levels of PSA. Observation appears to be a viable option for some men with clinical stage T1c prostate cancer.

Aged

New technique of vaginal reconstruction following anterior exenteration.

Vaginal reconstruction is important in sexually active females undergoing anterior exenteration for malignant disease. We describe a technique for vaginal reconstruction used in two women who underwent radical cystectomy that required en bloc removal of the anterior vaginal wall. A polyglycolic acid mesh with a pedicle graft of greater omentum creates the anterior 270 degrees and the apex of the neovagina. The technique is simple and adds to the urologist's armamentarium of reconstructive procedures that improve quality of life following exenterative surgery.

Female

Rigid fixation and strain patterns in the pig zygomatic arch and suture.

PURPOSE: In orthognathic surgery, rigid fixation is routinely used to hold together bone fragments that may experience heavy force from attached masticatory muscles. Internal fixation plates are assumed to hold bony parts rigidly, but the mobility at such sites subjected to normal masticatory function has not been measured. The purpose of this study was to investigate in vivo the degree to which a linear plate immobilizes separated bones, specifically sutures. MATERIALS AND METHODS: Three female miniature pigs (Sus scrofa) had 1.3-mm Synthes titanium plates placed across the suture in the zygomatic arch. Foil strain gauges were used to record load deformation in the zygomatic and squamosal (temporal) bones and across the vertical and horizontal parts of the suture. Strain was recorded in vivo during mastication and in anesthetized pigs with electrical stimulation of masticatory muscles. RESULTS: Strain at the suture was not reduced from normal levels. The plate induced increases in strain within the bones, but the changes were slight. CONCLUSION: The results indicate that linear "rigid fixation" does not immobilize sutures.

Animals

Evaluation of an on-line patient exposure meter in neuroradiology.

PURPOSE: To assess the clinical performance and usefulness of an on-line patient exposure meter installed on a neuroradiologic biplane imaging system. MATERIALS AND METHODS: A commercial on-line patient exposure meter was installed on each plane of a biplane neuroradiologic imaging system. The meter computed skin exposures on the basis of selected technique factors (tube potential and current) and information about patient location relative to the x-ray tube. Simulations were performed to measure the system accuracy with an angiographic anthropomorphic head phantom with the skin exposures measured with an ionization chamber. Skin doses were computed for 114 consecutive patients who underwent diagnostic and interventional neuroradiologic procedures. RESULTS: Agreement between measured and computed skin exposures in fluoroscopy, plain radiography, and digital imaging was generally within 5% of the true skin dose. For all fluoroscopic and radiographic procedures, total median skin doses were 1.20 and 0.64 Gy for the frontal and lateral planes, respectively. In both planes, patient skin doses resulted primarily from digital subtraction angiographic acquisitions. In 29 (25%) patients, the skin dose exceeded 2.00 Gy, but no radiation-induced deterministic effects were observed. CONCLUSION: An on-line patient exposure meter can provide accurate radiation skin dose data in patients undergoing diagnostic and therapeutic neuroradiologic procedures.

Angiography

Anaesthetists' attitudes towards an anaesthesia simulator. A comparative survey: U.S.A. and Australia.

Anaesthesia simulation has been suggested as a method to enhance the training of clinicians without exposing patient to risk. Recently, two anaesthesia simulators have become commercially available in the U.S.A. Attitudes towards anaesthesia simulators have not been previously surveyed. With institutional approval, a survey questionnaire was given to 1. all clinical staff of the Department of Anesthesiology, University of Pittsburgh Medical Center, and 2. all anaesthetists attending the Annual General Meeting of the Australian Society of Anaesthetists. An information sheet containing details about anaesthesia simulation in general and the special capabilities of a particular commercial anaesthesia simulator was included with the survey instrument. The survey was anonymous and contained 15 questions. Attitudinal responses were recorded using an anchored visual analog 100 mm scale. We surveyed anaesthetists during September-October 1993. Completed forms were returned by 183 anaesthetists. Respondents were aged 25-67 years (mean age 41 +/- 10 yr) and were grouped by staff position (78% faculty, 22% trainees), sex (79% male; 21% female), country of practice (44% Aust, 56% U.S.A.) and years in practice. Seventy-three per cent staff were in favour (VAS > 60) of departmental purchase of a simulator (with no significant difference between countries) and 76% expressed willingness (VAS > 60) to undergo testing in their own time (with Australian anaesthetists significantly more willing to do so). However, 65% were not in favour (VAS < 40) of the compulsory use of a simulator for re-certification or re-accreditation of anaesthesia practitioners, with American anaesthetists (anesthesiologists) significantly more opposed to it. The most frequent comment related to the cost. There is majority support for the purchase of an anaesthesia simulator but there is widespread concern for its high cost. In general, anaesthesia simulation is perceived more as an education tool rather than an instrument for (re)certification.

Accreditation

Orthotopic lower urinary tract reconstruction in women using the Kock ileal neobladder: updated experience in 34 patients.

PURPOSE: Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients. MATERIALS AND METHODS: Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70). RESULTS: There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming. CONCLUSIONS: The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

Adult

Early cystectomy for clinical stage T1 transitional cell carcinoma of the bladder.

Early radical cystectomy for a high-grade tumor invading the lamina propria (T1) remains controversial. In 1997, we cannot identify accurately which of these high-risk tumors will progress to muscle-invasive disease and metastases. In the near future, urologists may be able to use the presence of genetic alterations, such as p53 mutations, to help make therapeutic decisions. Previous reports on superficial bladder cancer treated with intravesical bacillus Calmette-Guérin immunotherapy have demonstrated a decrease in recurrence and progression. Unfortunately, there is no reliable method to predict which patients with a high-grade T1 tumor will fail to respond to intravesical therapy. Failure of intravesical therapy to control these aggressive tumors is associated with a significant rate of pathological upstaging and metastases. Radical cystectomy will cure a high percentage of these T1 tumors with acceptable morbidity and low mortality. In an era of nerve-sparing cystectomy and orthotopic neobladder reconstruction, early radical cystectomy is an alternative that should be discussed with the patient before instituting intravesical therapy.

Adjuvants, Immunologic

Orthotopic reconstruction in a woman following cystectomy and cutaneous urinary diversion. The 1st reported case.

Orthotopic lower urinary tract reconstruction has become the procedure of choice in selected male and female patients at our institution following cystectomy with excellent functional results. A natural extension of the orthotopic neobladder is undiversion to the intact native urethra in patients who had previously undergone cystectomy and cutaneous urinary diversion. Undiversion has been successfully performed in selected male patients; however, to our knowledge, undiversion has not been reported in women. Herein, we present the 1st case of undiversion in a female patient who had undergone prior cystectomy and cutaneous urinary diversion.

Anastomosis, Surgical

The use of orthotopic neobladders in women undergoing cystectomy for pelvic malignancy.

Since June 1990, 21 women aged from 31 to 78 years (mean, 62 years) have undergone lower urinary tract reconstruction by means of an orthotopic Kock ileal reservoir following cystectomy. The indication for cystectomy included 15 patients with transitional-cell carcinoma of the bladder, 2 patients with urachal adenocarcinoma, 1 patient with cervical carcinoma, 1 patient with a mesenchymal tumor of endometrial origin, 1 patient with interstitial cystitis, and 1 patient with a fibrotic irradiated bladder. A total of four complications (two early and two late) have occurred in this group of patients. Excellent continence has been achieved during the day and night in 95% and 89% of the patients, respectively. In all, 16 of 20 patients void volitionally per urethra without a residual urine volume, whereas 4 patients require intermittent catheterization to empty the neobladder. All patients are completely satisfied. One patient died of metastatic transitional-cell carcinoma without a pelvic recurrence. Of the remaining 20 patients, 18 are currently alive without evidence of recurrent disease. Tumor recurrence has occurred in two patients: one patient with an extensive mesenchymal tumor developed a sigmoid recurrence necessitating conversion to a continent cutaneous diversion, and one patient developed a right iliac recurrence. This initial experience with lower urinary tract reconstruction in women has yielded extraordinary results, and we feel that the option of orthotopic reconstruction following cystectomy can safely be offered to selected female patients.

Adult

The Kock ileal neobladder: updated experience in 295 male patients.

PURPOSE: Since 1986 orthotopic lower urinary tract reconstruction using the Kock ileal neobladder has been our diversion of choice in patients undergoing cystectomy. We report on the first 295 male patients undergoing this procedure from May 1986 through December 1993. MATERIALS AND METHODS: Complications were assessed, tabulated, subdivided into early (3 months or less postoperatively) and late types, and further categorized with respect to relationship to neobladder construction. Continence was individually evaluated via a detailed patient questionnaire. RESULTS: The pouch related early and late complication rates were 7.2 and 11.6%, respectively, and pouch related abdominal reoperation rates were 0.0 and 1.4%, respectively. Analysis of late pouch related complications revealed 4.1% stone formation and 2.4% afferent nipple stenosis rates, and only 1 case (0.3%) of ileal urethral anastomotic stricture. Of the patients 87 and 86% reported good or satisfactory daytime and nighttime continence, respectively. With regard to age, while overall continence was similar, a significantly greater percentage of patients younger than 70 years experience good daytime and nighttime continence relative to the older counterparts. Of the patients 5% perform regular intermittent catheterization and 2.7% required an artificial urinary sphincter due to unacceptable continence. CONCLUSIONS: The Kock orthotopic ileal neobladder can be constructed with minimal morbidity and extraordinary functional results. We strongly advocate its use when possible.

Adult

Bilateral emphysematous pyelonephritis: a case report and review of the literature.

Emphysematous pyelonephritis is a rare, rapidly progressive, life-threatening infection of the renal parenchyma. It most commonly is unilateral, is found almost exclusively in diabetics, is associated with gas-forming coliform bacteria, and is characterized by the presence of gas within the renal parenchyma. Early aggressive therapy (combined medical and surgical) is the hallmark of successful treatment. A high index of suspicion coupled with radiographic imaging is essential to make a timely diagnosis and guide therapeutic intervention. Bilateral emphysematous pyelonephritis is an even more rare phenomena, with only 14 reported cases in the English literature and is associated with a high patient mortality. We herein present an additional case and review the literature as it pertains to bilateral emphysematous pyelonephritis. Appropriate care requires aggressive combined medical and surgical therapy in an attempt to preserve renal function without increased mortality.

Emphysema

Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation.

We determined the pharmacokinetics and pharmacodynamics of cisatracurium, one of the 10 isomers of atracurium, in 14 patients with end-stage liver disease undergoing liver transplantation and in 11 control patients with normal hepatic and renal function undergoing elective surgery. Blood samples were collected for 8 h after i.v. bolus administration of cisatracurium 0.1 mg kg-1 (2 x ED95). Plasma concentrations of cisatracurium and its metabolites were determined using an HPLC method with fluorescence detection. Pharmacokinetic variables were determined using non-compartmental methods. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve using a Puritan-Bennett Datex (Helsinki, Finland) monitor. Pharmacodynamic modelling was completed using semi-parametric effect-compartment analysis. Volume of distribution at steady state was 195 (SD 38) ml kg-1 in liver transplant patients and 161 (23) ml kg-1 in control patients (P < 0.05), plasma clearance was 6.6 (1.1) ml kg-1 min-1 in liver transplant patients and 5.7 (0.8) ml kg-1 min-1 in control patients (P < 0.05), but elimination half-lives were similar: 24.4 (2.9) min in liver transplant patients vs 23.5 (3.5) min in control patients (ns). The time to maximum block was 2.4 (0.8) min in liver transplant patients compared with 3.3 (1.0) min in control patients (P < 0.05), but the clinical effective duration of action (time to 25% recovery) was similar: 53.5 (11.9) min in liver transplant patients compared with 46.9 (6.9) min in control patients (ns). The recovery index (25-75% recovery) was also similar in both groups: 15.4 (4.2) min in liver transplant patients and 12.8 (1.9) min in control patients (ns). After cisatracurium, peak laudanosine concentrations were 16 (5) and 21 (5) ng ml-1 in liver transplant and control patients, respectively. In summary, minor differences in the pharmacokinetics and pharmacodynamics of cisatracurium in liver transplant and control patients were not associated with any clinically significant differences in recovery profiles after a single dose of cisatracurium.

Adult