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Biomedical subjects

R A Santucci

Publications and source records attributed to R A Santucci.

At least 19 recordsLinked to original sources

Grade IV renal injuries: evaluation, treatment, and outcome.

Of our last 2483 renal trauma patients, 113 had grade IV injuries. In most the mechanism was a penetrating injury (60%: 30% gunshot, 30% stab wounds). Associated injuries were common (80%) and hospital stays prolonged, averaging 16 days. Most of the patients (70%) required transfusion, some massively (average volume 4.4 liters, range 0-30 liters). Surprisingly, not all patients with grade IV renal injuries had gross hematuria: 25% had microhematuria, and 4% had neither microscopic nor gross hematuria. Computed tomography (CT) diagnosed the injury correctly in 100% of the patients in whom it was performed; when CT was not available, "one-shot" intraoperative intravenous pyelography (IVP) demonstrated grossly abnormal findings in 90%. Renal exploration was performed in 78%, resulting in 69% renorrhaphy and 9% nephrectomy rates in our 113 patients. Almost all those with penetrating trauma required exploration (97%), whereas only 50% of those with blunt trauma did so. The overall complication rate and kidney-specific complication rate did not differ significantly between patients who were observed and those who underwent surgery. Complications rates were similar in grade IV renal laceration patients and grade III patients. Delayed complications after hospital discharge were not seen, although follow-up was rare in this inner-city trauma population. Among the 21% of patients in whom postoperative nucleotide renal function scans were available, function was generally good (average 36%). Only patients who underwent concomitant vascular repair had poor function (below 20%).

Abdominal Injuries↗

Validation of the American Association for the Surgery of Trauma organ injury severity scale for the kidney.

BACKGROUND: We queried an observational database of renal trauma patients to validate the organ injury severity scale (kidney) of the American Association for the Surgery of Trauma (AAST). METHODS: In a retrospective review of our renal trauma database (2,467 patients) with 58 clinical and radiographic patient variables, statistical "classification trees" were used to determine factors predicting need for surgical repair. RESULTS: Scales correlated with the need for surgery (grade I = 0%, grade II = 15%, grade III = 76%, grade IV = 78%, and grade V = 93%) and for nephrectomy (grade I = 0%, grade II = 0%, grade III = 3%, grade IV = 9%, and grade V = 86%). Classification tree analysis (confirmed in 83 additional patients) identified the AAST organ injury severity scale as the most important variable predicting the need for renal repair. CONCLUSION: In a retrospective review of more than 2,500 patients, we determined that the AAST organ injury severity scale correlates with the need for kidney repair or removal. Classification tree analysis confirmed the scale as the prime variable predicting need for surgical repair.

Algorithms↗

Petroleum jelly lipogranuloma of the penis treated with excision and native skin coverage.

Penile augmentation by injection of petroleum jelly is still performed by nonmedical practitioners abroad and causes foreign body reactions with resultant scarring, deformity, and ulceration. Surgical treatment involves removal of the foreign material and granuloma, followed by scrotal flaps, inguinal flaps, free flaps, or split-thickness skin grafts. We present the use of native penile skin for coverage after resection of oleogranuloma in the first case of which we are aware. Local penile skin coverage allows for an excellent surgical result, with many potential advantages over flaps or skin grafts.

Adult↗

Intermittent androgen suppression in the LuCaP 23.12 prostate cancer xenograft model.

BACKGROUND: Intermittent androgen suppression (IAS) has been proposed as a method of delaying the onset of androgen-independent growth in prostate cancer. While several pilot studies have demonstrated the feasibility of such a treatment, no study to date has defined the effect of IAS on survival. METHODS: We developed an IAS protocol for mice bearing the LuCaP 23.12 human prostate cancer xenograft, with each cycle consisting of 1 week of androgen replacement with a testosterone pellet followed by 3 weeks of androgen withdrawal. Mice that responded to castration with a 40% or greater decrease in serum prostate-specific antigen (PSA) were randomized to treatment with either continuous androgen suppression (CAS) or IAS. Serum PSA, tumor volume, and overall survival were monitored. RESULTS: A total of 75 mice met the randomization criteria. There was no significant difference of survival between animals treated with CAS or IAS (185 vs. 239 days, P = 0.1835). Serum PSA showed evidence of cycling with hormonal manipulation. No cycling was noted in tumor volume. CONCLUSIONS: IAS is not associated with a decrease in survival compared to CAS, yet in patients may offer quality-of-life improvements. Further studies of IAS in the setting of Institutional Review Board (IRB) approved clinical trials should be encouraged. Prostate 43:63-70, 2000. Published 2000 Wiley-Liss, Inc.

Animals↗

Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation.

Functional inhibition of tissue factor (TF) has been shown to improve coronary blood flow after myocardial ischemia/reperfusion (I/R) injury. TF initiates the coagulation protease cascade, resulting in the generation of the serine protease thrombin and fibrin deposition. Thrombin can also contribute to an inflammatory response by activating various cell types, including vascular endothelial cells. We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I/R injury. At-risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes, which was associated with a low level of extravascular fibrin deposition. Functional inhibition of TF activity with an anti-rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61% (P = 0.004) and 44% (P = 0.014), respectively. Similarly, we found that inhibition of thrombin with hirudin reduced infarct size by 59% (P = 0.014). In contrast, defibrinogenating the rabbits with ancrod had no effect on infarct size, suggesting that fibrin deposition does not significantly contribute to infarct size. Functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration. We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R.

Animals↗

Gentamicin for the practicing urologist: review of efficacy, single daily dosing and "switch" therapy.

PURPOSE: We review the literature on gentamicin, including single daily dosing and "switch" therapy. MATERIALS AND METHODS: We used MEDLINE to search the literature from 1966 to June 1997, and then manually searched bibliographies to identify studies that our initial search might have missed. RESULTS: Gentamicin has attractive characteristics, including wide spectrum, infrequent resistance, economy and familiarity. Although limited by well known toxicities, gentamicin remains a drug of choice for serious Gram-negative infections. Dosing strategies, such as single daily dosing and switch therapy, have renewed enthusiasm for this time-honored drug. CONCLUSIONS: Gentamicin remains a valuable drug in urology. Once daily dosing and switch therapy offer the potential to increase effectiveness and convenience while decreasing toxicity and costs.

Aminoglycosides↗

Measurement of tissue factor activity in whole blood.

High circulating levels of the procoagulant molecule tissue factor (TF) are associated with thrombosis in a variety of diseases including unstable angina, cancer, and sepsis. Currently, there are no clinical assays to measure the level of TF activity in whole blood. We present an assay called Tissue Factor Clotting Time ("TiFaCT") that detects fibrin formation in human blood. The mean baseline clotting time in a healthy population was 472 +/- 94 s (mean +/- SD, n = 150). Bacterial lipopolysaccharide (LPS or endotoxin) shortened the clotting time in a time-dependent manner. Inhibitory anti-TF antibodies prolonged the clotting time of LPS-stimulated blood, indicating that the shortened clotting time was due to induction of TF expression. Patients with unstable angina had shortened mean baseline clotting time (284 +/- 86, n = 13) compared with healthy volunteers (474 +/- 98, n = 30), suggesting that these patients had elevated levels of circulating TF. The TiFaCT assay should prove clinically useful in quantifying the levels of circulating TF in patients at risk of thrombosis.

Adult↗

Urodynamic evaluation and long-term results of the orthotopic gastric neobladder in men.

PURPOSE: Orthotopic neobladders are most commonly formed from colon and/or small bowel segments. However, after excellent results were reported in children, we constructed gastric neobladders in select men who had undergone cystectomy. Although gastric neobladders in adults have been reported to have decreased capacity, to our knowledge neither long-term followup nor urodynamic parameters have been reported in these patients. MATERIALS AND METHODS: Gastric neobladder was performed in 8 patients following cystectomy for malignancy in 7 and undiversion in 1. Average followup was 43 months and all patients underwent urodynamic evaluations an average of 9.1 months after surgery. Patients also completed an incontinence questionnaire. The gastric neobladder group was compared to a similar group of patients who underwent neobladder construction from either small bowel (Kock/Hautmann/Studer) or ileocecal segments (Mainz). RESULTS: The gastric neobladder group had significantly reduced mean bladder capacity compared to the ileal or ileocecal neobladder group (309 versus 551 cc, respectively, t = 0.001), while compliance was similarly decreased (27 versus 59 cc/cm. H2O, respectively, t = 0.04). Incontinence rates were greater in the gastric neobladder group (63%) compared to the ileal or ileocecal neobladder group (8% to 23%, t = 0.02). Complication rates were comparable. Revision or removal was required in 3 (38%) patients for severe incontinence, intractable dysuria and ureterogastric anastomotic stricture, respectively. CONCLUSIONS: Adult gastric neobladders as currently constructed are associated with poor urodynamic parameters and high incontinence rates. Routine use of gastric neobladders in adults is not recommended. They may be appropriate, especially as composites, in select cases such as renal failure or inadequate bowel length. The reasons for success in some patients and not in others are unknown.

Adult↗

Continence and urodynamic parameters of continent urinary reservoirs: comparison of gastric, ileal, ileocolic, right colon, and sigmoid segments.

OBJECTIVES: To compare the urodynamic parameters and continence rates among five different continent urinary reservoirs. METHODS: Continent urinary reservoirs were constructed in 40 patients with an average age of 60 years (range 23 to 81). Twenty-three had orthotopic neobladders ("neobladders"), and in 17 the reservoirs exited by way of an abdominal wall stoma as "stomal urinary reservoirs." In the neobladders, the detubularized segment was ileum (Hautmann) in 5, ileocecal (Mainz) in 8, sigmoid in 4, and gastric in 6. In the stomal urinary reservoirs, the segment was ileocecal in 11 (Mainz) and right colon in 6 (Indiana). Urodynamic studies were performed at a mean of 9.1 months. RESULTS: Stomal urinary reservoirs had the best continence rates (Indiana pouch 100%, Mainz pouch 91%). Neobladder continence rates were as follows: Hautmann, 80%; Mainz, 75%; sigmoid, 50%; and gastric, 33%. Day and night incontinence rates were nearly identical. Compared with the other pouches, gastric and sigmoid reconstructions had the smallest capacity, were the least compliant, and were the most contractile. CONCLUSIONS: Stomal urinary reservoirs using ileocecal valve and right colon, with or without an overlying patch of ileum, provide similar excellent results. Continence approached 100% in compliant patients without the need for revision. Patients with neobladders were less continent, although those with ileal or ileocecal configurations still had very good continence rates. Neobladders of sigmoid or stomach can be used when necessary, but with greater incontinence rates. This poorer continence can be explained by the decreased capacity, decreased compliance, and a tendency toward high pressure spikes despite detubularization.

Adult↗

Effects of phenylbutyrate on proliferation and apoptosis in human prostate cancer cells in vitro and in vivo.

Phenylbutyrate (PB) is a potent differentiating agent and currently under investigation for the treatment of prostate cancer (CaP) and other malignancies. We have studied the impact of PB in vitro and in vivo on differentiation, proliferation and apoptosis in the LNCaP and LuCaP 23.1 prostate cancer xenograft models. In vitro we found that i) PB increased PSA secretion/cell, ii) inhibited cell proliferation in a time- and dose-dependent manner resulting in a cell cycle arrest in G1-phase and iii) induced apoptosis at concentrations of 2.5 mM after 3 days of treatment. In PB treated animals tumor growth stabilized or regressed. Combination of castration and PB treatment had a synergistic antiproliferative effect. The growth-inhibitory and differentiating properties and a low toxicity profile of PB provide rationale for further clinical studies in patients with CaP.

Androgens↗

Is partial cystectomy the treatment of choice for mucinous adenocarcinoma of the urachus?

OBJECTIVES: To determine if well-differentiated colonic-type adenocarcinoma of the urachus behaves in a benign fashion, and thus might be treated by segmental rather than radical cystectomy. METHODS: A retrospective review of the literature since 1863 with one added case review is presented here. Only cases with photomicrograph confirmation were accepted. RESULTS: Sixteen previously reported patients with well differentiated colonic-type adenocarcinoma of the urachus were treated by partial cystectomy. None were treated by radical cystectomy. Most (88%) of these patients were cured, whereas all patients (100%) treated in the last 45 years were cured. CONCLUSIONS: These data support a more limited approach to the surgical excision of these benign-appearing tumors. The influence of this histologic type on the prognosis of patients with urachal tumors has not been previously reported.

Adenocarcinoma, Mucinous↗

Some small prostate cancers are nondiploid by nuclear image analysis: correlation of deoxyribonucleic acid ploidy status and pathological features.

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p < 0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.

Cell Nucleus↗