Non-Compartment and compartmental pharmacokinetics, efficacy, and safety of Kedrion FIX concentrate.

BACKGROUND: An open-label phase II, multicenter clinical trial was conducted at 11  Haemophilia Centres in  Italy, Romania, and Turkey, to evaluate the pharmacokinetics (PK), efficacy, and safety of high purity, plasma-derived, double virus inactivated and double nano-filtered factor IX (pd-FIX) concentrate (Kedrion FIX), EudraCT Number: 2005-006186-14. MATERIAL AND METHODS: 16 previously treated patients (PTPs) with severe or moderately severe haemophilia B were enrolled in the study. At enrolment, 14 underwent the first PK assessment (PK I), and the second PK (PK II) assessment was performed after six months of treatment (5 on-demand and nine prophylaxis) at the end of the study. PK parameters were evaluated by Non-Compartmental Analysis (NCA), One-Compartment model (OCM), and Two-Compartment Model (TCM). Efficacy of Kedrion FIX in all 16 patients was evaluated by the number of bleeding events, and clinical response following the infusions. Periodic FIX inhibitor assays and thrombogenicity tests were scheduled throughout the study to assess the safety of the drug. RESULTS: As compared to the published data on PK of pdFIX, Kedrion FIX displayed a longer half-life (22.37-55.73 hrs), reduced clearance, and regular volume of distribution at PK I by both NCA and OCM. The comparison of outcomes of PK II with those of PK I by OCM,  also showed significant changes, particularly in patients on prophylaxis, who showed some improved parameters of PK. Due to two outlier values at the end of the trial, the NCA parameters of PK I were not compared to those of PK II. Breakthrough bleeds were successfully treated with 1 or 2 infusions. No significant adverse events were observed during the study. DISCUSSION: During the six-month clinical study period, the use of Kedrion FIX resulted in a safe and effective pd-FIX concentrate with excellent PK characteristics.

High grade adenocarcinoma of prostate in smokers of ethnic minority groups and Caribbean Island immigrants.

The degree of differentiation of 670 blacks and white patients treated from 1980-1990 for curative and palliative external beam radiation therapy and surgery at State University of New York Health Science Center at Brooklyn and Kings County Hospital were analyzed retrospectively, stratified according to race, age, smoking, and grade. In addition stage, birth place and median survival were also analyzed. Overall mean age was 69 years (Std. Dev. 8.97). 69% were blacks and 27.8% were whites. 65.4% were smokers and 34.6% were non-smokers. Smokers had high incidence of more invasive and high grade adenocarcinoma of prostate (p < or = 0.00005) compared to control group (non-smokers with prostate carcinoma). Statistically significant difference was found in the degree of differentiation of carcinoma of prostate in smokers compared to non-smokers. Smokers had 15.04% well, 27.07% moderate, and 57.89% poorly differentiated adenocarcinoma compared to non-smokers in which 37.1% were well, 45.16% moderate, and 17.74% poorly differentiated cancer of prostate (p < or = 0.00005). Sixty-three percent blacks and 40.16% whites had Stage D cancer (p < or = 0.00005). 68.3% smokers and 53.3% non-smokers had Stage D cancer (p = 0.01). Overall median survival for blacks was 74.04 months compared to whites of 115.73 months (p < or = 0.00005).

Treatment of advanced transitional cell carcinoma of the bladder with irradiation and concomitant 5-fluorouracil infusion.

Twenty patients with advanced transitional cell carcinoma of the bladder were treated with radiation and concomitant continuous infusion of 5-fluorouracil with or without Mitomycin. Nineteen of 20 patients were assessed for response. Fourteen of 19 patients (74%) obtained a complete response within 3 to 6 months. An additional three patients (15%) acquired and maintained a complete response after local transurethral resection of the tumor and intravesical chemotherapy, raising the overall complete response (CR) rate to 17/19 (89%). Of the two patients with persistent disease, one is alive and well after salvage cystectomy. Eighteen of 20 patients were evaluated for survival with a median follow-up of 38 months. Seven patients remain alive and well 51 to 78 months, whereas three patients died from intercurrent disease. Eight patients died of either distant metastatic disease (7 patients) or regional disease (1 patient). An adjusted survival calculated by the Life Table Method was 53.6% at 5 years, whereas the overall survival was 39%. The combined modality therapy was well tolerated with no need for treatment interruption or reduction in dose. Late bladder complications include one patient with hemorrhagic cystitis, two patients with dysuria, and two with symptoms of irritable bladder. One patient required a colostomy for a chronic hemorrhagic proctitis. Bladder preservation was achieved in 19/20 patients.

Histochemical analyses of steroid hormone receptors in breast and prostatic carcinoma.

Histochemical analyses estrogen (ER) and progesterone (PgR) receptors in breast cancer were statistically correlated with results of dextran-coated charcoal (DDC) and sucrose gradient assays. Correlated for ER was 91% of 363 cases, and for PgR 88% of 255 specimens. Breast cancer ER/PgR positivity by histochemistry correlated with a favorable clinical response to endocrine therapies in 72% of 25 cases, while ER/PgR negativity correlated with a lack of response in 96% of 22 cases with Stage IV disease. Nuclear ER/PgR correlated with a poor response to therapy in 8 of 12 patients. An in vitro technique to detect nuclear translocation of ER revealed two groups of ER positive cases, with 11 of 17 exhibiting translocation and 6 not displaying translocation. In prostatic carcinoma, 72% of 65 men were positive for ER and/or androgen receptor. Comparison of specimens obtained without and with electrocautery revealed a preponderance of nuclear binding in the latter, suggesting heat-induced nuclear translocation of receptor. coumestrol, a naturally fluorescent, entirely unaltered estrogen was also used for histochemical detection of ER. Results correlated with ER by DCC in 87% of 61 breast cancers. Coumestrol was additionally used to visually observe receptor and nuclear translocation of ER in intact whole cells in culture.

Penile scintigraphy for priapism in sickle cell disease.

UNLABELLED: Penile scintigraphy with [99mTc]pertechnetate/99mTc-RBCs was performed in patients with sickle cell disease patients who had priapism to assess the role of this imaging procedure in directing the clinical management of these patients. METHODS: Fifteen studies were performed in 13 patients who were treated according to a protocol not dependent on the imaging results. The scintigraphic findings of penile vascular perfusion (stagnant or nonstagnant patterns) were collated retrospectively with the form of treatment needed for relief of the condition. RESULTS: Four of five patients with the nonstagnant perfusion pattern responded to analgesics and intravenous hydration. Four of eight patients with the stagnant pattern did not require any aggressive interventions such as corporeal aspiration/irrigation, intracorporeal epinephrine or glans-cavernosa shunt. CONCLUSION: Whereas the nonstagnant scintigraphic finding appeared to be a favorable indicator for conservative treatment, the stagnant finding was apparently noncontributory. In addition, no correlation was found between these two types of scintigraphic patterns and the subsequent sexual potency of these patients.

Growth factors in urologic tissues: detection, characterization, and clinical applications.

During the last two decades, enormous strides have been made in understanding cellular and molecular biology. The direction of treatment of many neoplasms and other diseases are starting at the microscopic level. Growth factors are polypeptides that play a part in the development and maintenance of living tissues. We, as well as others, have investigated the role that growth factors play particularly in urologic tissues, both benign and malignant. We review several well-known growth factors and their function in prostate, kidney, and bladder tissues, as well as their functions in other regulating processes of the human body, and also the use of growth factors as tumor markers, and antibodies to growth factors as possible treatment of disease.

Urethrography and cavernosography imaging in a small series of penile fractures: a comparison with surgical findings.

OBJECTIVES: To compare our results of preoperative corporal cavernosography and retrograde urethrography in penile fractures with the clinical and intraoperative findings. METHODS: From January to October 1996, 7 cases of penile fracture were diagnosed at our inner city trauma center. All cases were associated with sexual activity and patients underwent preoperative retrograde urethrography and corpus cavernosography with immediate surgical intervention. RESULTS: We found that 2 patients who presented with blood at the meatus had intact urethras, whereas 2 of the 3 patients who had urethral lacerations did not have a bloody meatus. In 2 cases the urethrogram and cavernosogram revealed lacerations that were not initially detected surgically. However, in another 2 cases, the urethrogram and cavernosogram were falsely negative. Two of the seven corporal fractures were bilateral and five were unilateral. CONCLUSIONS: On the basis of this small sample, it appears that preoperative cavernosography and retrograde urethrography may show additional sites of tears in the corpora and urethra because hematoma formation may mask some ruptures. However, the presence or absence of a bloody meatus may not necessarily correlate with the status of the urethra, and the urologist also should be wary of a false-negative imaging study. We suggest that all cases of penile fracture be explored surgically, but preferably by a subcoronal degloving incision that allows careful examination of the urethra and corpora. Results of a larger series may determine if the routine use of these imaging modalities is justified intraoperatively.

Atypical leiomyoma of prostate.

A prostatic leiomyoma with nuclear atypia, similar in appearance to atypia sometimes seen in uterine leiomyomas, was an incidental finding in a fifty-three-year-old man who underwent prostatectomy for hyperplasia. The smooth muscle nature of the lesion was confirmed by electron microscopic examination. This is the third lesion of this type to be reported.

Bilateral kidney herniation: complication of cutaneous pyelostomy.

A case of bilateral kidney herniation through cutaneous pyelostomy stomas is reported. The child is doing well after successful closure of the pyelostomies and repair of both ureteropelvic junctions obstructions.

Differences in prostate and adipose tissue basic fibroblast growth factor: analysis of preliminary results.

OBJECTIVES: Basic fibroblast growth factor (bFGF or FGF-2) is mitogenic to human prostate epithelial and stromal cells, and it is reported to be elevated in the serum and urine of patients with various cancers, including prostate cancer. Obesity, with increased body fat, is a risk factor for prostate cancer through unknown mechanisms. Because adipose tissue is a source of FGF-2, we determined the quantity and quality of activity of FGF-2 in omental adipose tissue and compared it with normal and cancerous prostate tissues. METHODS: Using heparin-Sepharose chromatography, we extracted proteins from human omental adipose tissue, adenocarcinoma of the prostate, and benign prostatic hypertrophic (BPH) tissues. Each of the mitogenic proteins eluted with NaCl concentrations between 1.4 M and 1.8 M, similar to control FGF-2. Using FGF-2 antisera (which inhibited the mitogenic activity of the proteins), we performed Western blot analysis to confirm their homology to FGF-2. We also assessed recovery, mitogenicity, and angiogenicity of each of the proteins using thymidine incorporation into human umbilical vein endothelial cells and the chorioallantoic membrane assay. RESULTS: There was greater recovery of FGF-2 from omental adipose tissue compared with cancerous or BPH homogenates (40 micrograms [2.0 micrograms/g] versus 25 micrograms [1.25 micrograms/g] and 20 micrograms [1.0 microgram/g], respectively). Moreover. FGF-2 from adipose tissue had greater mitogenic activity (96.2% versus 74.8% and 54%; P < 0.05) and a greater angiogenic activity (5.1 vessels versus 2.9 and 1.8 vessels; P < 0.05) on the chorioallantoic assay. CONCLUSIONS: We suggest that human omental adipose tissue FGF-2 may demonstrate greater mitogenic and angiogenic activity than either BPH or prostate cancer tissue FGF-2. It is not known whether FGF-2 from adipose tissue qualitatively or quantitatively may underlie the relationship between obesity and prostate cancer.

Testicular torsion and usefulness of radionuclide scanning.

The usage of the testicular scan to differentiate torsion from epididymo-orchitis in 33 patients is reported. Our results yielded a surgically confirmed accuracy rate of 77 per cent, and a clinical accuracy rate of 100 per cent. The entity of missed torsion has a characteristic appearance, which we have termed the "halo sign."

Argon laser-assisted vasovasostomy.

Laser-assisted vasovasostomy recently has become a popular procedure in the United States. Only the microsurgical carbon dioxide laser is approved by the Food and Drug Administration for vasovasostomies. Using the HGM argon laser, the procedure was performed on 3 laboratory dogs with a patency rate of 100 percent (6/6) and anastomotic leak 17 percent (1/6). This procedure requires little microsurgical expertise, can be performed without the use of a microscope, and does not require a perfectly dry field. The argon laser is a superior technique to previously described laser-assisted vasovasostomies and further clinical correlation is recommended.

Initial experience with therasonic lithotriptor.

Piezoelectric shock wave lithotripsy has been shown to offer a low-cost, safe, anesthesia-free yet effective means of disintegrating urinary calculi. The Therasonic lithotriptor combines proprietary piezoelectric shock wave technology for effective stone fragmentation with a multi-purpose urologic table and both fluoroscopic and ultrasound imaging for accurate stone localization and real-time treatment monitoring. From December 1, 1988 to November 15, 1989, 138 patients with 172 calculi were treated (94.2% were intrarenal, 5.8% were in ureter). All stones greater than or equal to 4 mm were considered suitable for treatment. Lithotripsy was performed under intravenous sedation except when ancillary procedures were necessary. For evaluation of device effectiveness, 94 patients were available with follow-up greater than or equal to thirty days. Successful fragmentation (stone free or residual debris less than or equal to 4 mm) was achieved in 97 percent of patients. The retreatment rate for stones 0.5-2.0 cm was 11 percent, and the overall retreatment rate was 21.2 percent regardless of stone size. Complications were minimal, transient, and resolved spontaneously.

Percutaneous management of retroperitoneal abscesses.

Retroperitoneal abscesses have been a difficult diagnostic and therapeutic challenge in the past. With the advent of precise noninvasive imaging modalities, they now are defined more easily. Percutaneous guided catheter drainage has changed our therapeutic approach to this disease and enabled rapid and complete drainage to be performed in the majority of cases. Although the literature is replete with documentation of the percutaneous management of intra-abdominal abscesses, series dealing with retroperitoneal abscesses exclusively are surprisingly infrequent. We report on the percutaneous treatment of 31 retroperitoneal abscesses and the combined percutaneous and surgical management of 4 additional cases.

Is intravenous urography indicated in a young adult with hematuria?

OBJECTIVES: Published reports are devoid of U.S. studies investigating the role of the intravenous urogram (IVU) in adult patients of differing ages with hematuria. To evaluate the efficacy of the IVU in patients less than 55 years old, a retrospective analysis was performed. METHODS: The records of all patients (n = 800) undergoing IVU in an inner city hospital from January 1991 through October 1994 were reviewed for age, gender, race, urinalysis data, and cystoscopic and biopsy findings. Age greater than 55 years, recent trauma, and known malignancy were exclusion criteria. Hematuria was the indication for IVU in 128 of 800 patients. Eight (6.2%) of 128 patients had inadequate chart information, leaving a total of 120 evaluable charts. RESULTS: We stratified the 120 patients by age, degree of hematuria (gross versus microscopic), and gender. The younger group (17 to 40 years old) included 64 patients (53%) and the older group (41 to 55 years old) 56 patients (47%). Gross hematuria was reported in 65 patients (54%), whereas 55 (46%) had microscopic hematuria. Men accounted for 78 patients (65%) and women for 42 (35%). The majority of patients were African-Americans (100 [83%] of 120). Abnormal findings were seen in 17 (14%) of 120 patients. The IVU alone provided no diagnosis of immediate consequence. There was no significant difference in findings between the age groups (P = 0.61), gross and microscopic hematuria (P = 0.28), and men and women (P = 0.59). Contrast reactions occurred in 3 (2.5%) of 120 patients. CONCLUSIONS: In this inner city population younger than 55 years of age, the usefulness of the IVU for the evaluation of hematuria is questionable. It did not establish a diagnosis, modify the subsequent evaluation, or change the therapy in any of our patients.

Diminished survival of young blacks with adenocarcinoma of the prostate.

The survival rates of 117 black and white patients treated by primary radiation for carcinoma of the prostate at the State University of New York Health Science Center at Brooklyn and Kings County Hospital Center were analyzed according to age and race. In addition, stage, grade, and delay time in seeking medical attention were analyzed. Survival was similar in both young (less than 60 years) and old (greater than or equal to 60 years) patients, with 45% and 41% 5-year-survival rates, respectively. Survival was better in white patients, 48% 5-year survival, than in blacks, 35% 5-year survival. Black patients presented with higher stage disease than whites (p less than 0.01). This trend was even greater in young black males, who had higher grade (64% versus 11%; p less than 0.04) and higher stage tumors (p less than 0.05). In addition, young blacks delayed seeking medical attention greater than 3 months 72% of the time, as compared to 0% in white young males (p less than 0.005). A survival difference was also seen in young blacks as compared with young whites: 3.9-year median survival versus 6.0-year median survival, respectively.

Radiation-treated carcinoma of prostate. Comparison of survival of black and white patients by Gleason's grading system.

The survival of 117 black and white patients treated by radiation for carcinoma of the prostate at SUNY Health Science Center at Brooklyn (SUNY/HSCB) and Kings County Hospital Center (KCHC) was analyzed according to Gleason's grading system. The effect of total pattern score and its relationship to stage and survival and to race were intercompared. In both black and white racial groups, there was strong correlation between high pattern score and high stage p = less than 001. The percentage of black patients presenting with high pattern score (7-10) was significantly greater, 43 versus 27%; this adversely affected stage and survival. The median survival for white and black patients was 4.8 and 3.2 years, respectively; p = 0.007. Stage for stage and grade for grade, survival was similar in both racial groups.

Radical transurethral resection in the management of muscle-invasive bladder cancer.

The morbidity of radical cystectomy and early reports of good results have stimulated interest in radical transurethral resection of bladder tumors (TURBT) for muscle-invasive transitional-cell carcinoma of the bladder. Various investigators have used surgery alone or with adjuvant or neoadjuvant chemotherapy or radiation. Further research is necessary to define the indications, but at present, radical TURBT for muscle-invasive cancer appears to be appropriate for patients too ill to undergo radical cystectomy, those who decline the open operation, and those enrolled in clinical trials of this approach to bladder cancer.

Multiphasic helical CT criteria for differentiation of recurrent neoplasm and desmoplastic reaction after laparoscopic resection of renal mass lesions.

BACKGROUND AND PURPOSE: Differentiation of recurrent neoplasm and desmoplastic reaction following laparoscopic resection of renal mass lesions poses a problem. The usefulness of multiphasic helical CT-generated criteria based on enhancement and morphologic characteristics was investigated. PATIENTS AND METHODS: The findings in 5 female and 12 male patients aged 29 to 68 years having renal-cell carcinoma (11-38 mm; N = 15) or solitary angiomyolipomas (N = 2) treated by laparoscopic resection (N = 15) or open segmental surgery (N = 2) were analyzed. Multiphasic helical CT was performed in the preenhancement, arterial corticomedullary, parenchymal, and excretory phases generating 2.5- to 7-mm slices. RESULTS: Both recurrent neoplasms showed median postcontrast enhancement of 119 HU in the arterial corticomedullary phase; the median enhancement of desmoplastic masses was 48 HU. In the parenchymal and excretory phase, recurrent neoplasms showed progressive loss of enhancement, whereas desmoplastic lesions sustained enhancement at about the same level. Recurrent neoplasms presented a defined mass with characteristic spiculation, whereas desmoplastic reaction was characterized by an ill-defined mass with spidery projections extending to abutting fat and residual fascial planes. On 2- to 3-month follow-up scans, recurrent neoplasms showed progressive increases in size and desmoplastic reaction a sharp decrease. CONCLUSION: Enhancement of the mass at the operative site on arterial corticomedullary-phase CT to >90 HU strongly suggests recurrent renal-cell carcinoma, while progressive decrease in size on 1- to 3-month follow-up CT suggests a desmoplastic reaction.

Multiphasic helical CT diagnosis of early medullary and papillary necrosis.

PURPOSE: The feasibility of identifying early manifestations of renal papillary necrosis (RPN) and medullary necrosis (RMN) on multiphasic helical CT, leading to prompt treatment for the causative conditions, and its impact on reducing the incidence of late-stage RML and RPN, was investigated. PATIENTS AND METHODS: Sixty-eight patients (35 male, 33 female) aged 19 to 88 years were examined by multiphasic helical CT for complaints of microscopic hematuria (N=49), macroscopic hematuria (N=2), bacteriuria (N=45), pyuria (N=10), fever (N=15), and flank pain (N=27). Preenhancement, arterial corticomedullary, parenchymal, and excretory phase scans generated 1.25 to 7-mm-thick slices. Follow-up CTs were performed at 1 month (N=62) and 3 months (N=58). RESULTS: While the attenuation coefficients of areas suspect for RMN and RPN were similar on preenhancement CT, they differed substantially on the arterial corticomedullary phase (lesions 55 HU mean; normal medulla 120 HU mean) and parenchymal phase (lesions 58 HU mean, normal medulla 210 HU mean). Investigation for predisposing conditions identified diabetes in 18 patients, upper urinary-tract infections in 48, sickle-cell disease or trait in 17, urinary obstruction in 7, and cirrhosis of the liver in 1. On follow-up examinations, enhancement had normalized in 26 compromised areas of 14 patients at 1 month, and 47 areas (23 patients) at 3 months, remained stationary in 28 patients at 1 month and 9 at 3 months, and progressed in 20 at 1 and 26 at 3 months (P<0.001; Fisher's exact test). Patients (N=35) treated for underlying conditions causing ischemia showed reperfusion in 12 cases at 1 month and 20 at 3 months, while of the untreated patients (N=10), none showed reperfusion, and all lesions increased in size. CONCLUSIONS: Multiphasic helical CT is recommended for identification of RMN and RPN at a stage when effective treatment of underlying causative conditions can arrest or reverse the process of devascularization and prevent loss of medullary tissue.