Dalteparin in combination with abciximab during percutaneous coronary intervention.

BACKGROUND: Despite proved efficacy for either dalteparin or platelet glycoprotein IIb/IIIa blockade in improving clinical outcomes of patients with non-ST-segment elevation acute coronary syndromes, algorithms guiding concomitant therapy with these agents have not been devised. The purpose of this study was to assess anticoagulant effect and clinical safety for several dose regimens of dalteparin administered in combination with abciximab during percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing PCI with standard dose abciximab received dalteparin as follows: 120 IU/kg subcutaneously (SQ) to a maximum of 10,000 U if < or =8 hours before PCI (n = 3); for PCI 8-12 hours after the SQ dose, an additional 40 IU/kg intravenously (IV) was administered (n = 1); for PCI >12 hours after SQ dalteparin or with no prior dalteparin therapy, random allocation to 40 (n = 27) or 60 (n = 28) IU/kg IV during PCI was performed. Those patients who received 60 IU/kg of dalteparin IV had a lower incidence of procedural thrombosis (0% vs 11.1%, P <.01), more consistent antithrombotic effect (anti-factor Xa activity) and a similar incidence of major bleeding (3.7% vs 2.6%) compared with patients who received 40 IU/kg of intravenous dalteparin. CONCLUSIONS: Dalteparin 60 IU/kg IV appears to be safe and effective when administered in conjunction with abciximab for percutaneous coronary intervention.

High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. METHODS: Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. RESULTS: High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and the status of 10 dogs (40%) dogs was unknown. Gleason scores ranged from 6 to 10, with a mean of 8.4 and a median of 8. CONCLUSIONS: High grade PIN is present in a small but substantial number (3%) of military working dogs. Of military working dogs with prostatic adenocarcinoma, 72% had high grade PIN. The true prevalence in each of these cohorts is likely to be higher given the sampling variation inherent in evaluating a single random histologic section. Aged male dogs seem to have substantial clinical utility as an animal model for prostatic carcinogenesis. We recommend that serial sectioning and total embedding of the prostate should be used to more thoroughly characterize premalignant and malignant diseases in aged military working dogs. This method will provide important data to determine whether a model of spontaneous PIN in elderly dogs may have clinical utility in developing strategies directed toward preventing and treating prostate.

Urinary tract infections and pregnancy in women who underwent antireflux surgery in childhood.

PURPOSE: For several decades ureteroneocystostomy has been performed in children to correct primary vesicoureteral reflux. A purported indication for antireflux surgery is to prevent significant upper urinary tract infection during pregnancy. We performed a long-term followup of women who underwent antireflux surgery during childhood to determine outcome in regard to urinary tract infection history and pregnancy. MATERIALS AND METHODS: We identified 227 women of childbearing age who underwent ureteral reimplantation for primary vesicoureteral reflux from 1964 through 1981. Of the 122 women contacted 41 had been pregnant (77 total pregnancies). Cystitis or asymptomatic bacteriuria and pyelonephritis developed during 18 and 5 pregnancies, respectively. The 77 pregnancies resulted in 57 term births, 7 voluntary pregnancy interruptions and 13 spontaneous abortions. RESULTS: Patients who previously underwent successful antireflux surgery continued to have a significant number of urinary tract infections through the intervening years. Despite a higher than expected incidence of pyelonephritis, they had relatively little hypertension and renal insufficiency. During pregnancy the incidence of pyelonephritis was only slightly higher than that of the general population. However, severe complications of pregnancy, such as preeclampsia, premature birth and acute renal failure, occurred more frequently in women with a history of renal scarring or hypertension (7 of 12) than in those with a history of recurrent infection alone (3 of 10). CONCLUSIONS: When renal scarring is present, reflux should be corrected before pregnancy to minimize maternal and fetal morbidity. When scarring is not present, the literature suggests that women with a history of reflux are at increased risk for pyelonephritis during pregnancy whether or not ureterocystostomy was performed. Pregnant women with a history of reflux may benefit from prophylactic antibiotics and women with reflux nephropathy should be followed throughout life.

Prostatic intraepithelial neoplasia (PIN) and other prostatic lesions as risk factors and surrogate endpoints for cancer chemoprevention trials.

The most efficient strategy for chemoprevention clinical trials are short-term studies which focus on surrogate endpoint biomarkers (SEBs) in high-risk target populations. High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer, and is found in a significant number of routine contemporary needle biopsies without cancer. The frequency and extent of PIN are decreased with androgen deprivation therapy, suggesting that it is a suitable endpoint biomarker for modulation. Potential SEBs for screening chemopreventive agents for prostate cancer in short-term Phase II trials include (1) histologic premalignant lesions, such as high-grade PIN; (2) biochemical markers, including prostate-specific antigen (PSA) serum concentration; and (3) morphometric markers, including nuclear texture, shape, and roundness; size and number of nucleoli; and number of apoptotic bodies; (4) proliferation markers, including MIB-1 and PCNA; (5) genetic markers, including nuclear DNA content (ploidy), oncogene c-erbB-2 (HER-2/neu) expression, fluorescence in situ hybridization for chromosome 8; and PSA-producing cells in the blood detected by reverse transcriptase polymerase chain reaction; and (6) differentiation markers, such as microvessel density as a determinant of angiogenesis. Each of these endpoint biomarkers is measured easily and accurately in serum or in tissue specimens such as formalin-fixed, paraffin-embedded needle biopsies, and may be modifiable by intervention. The clinical utility of these biomarkers as modulatable endpoints in prostate cancer chemoprevention needs to be demonstrated in future clinical trials.

Color flow imaging in children with clinically suspected testicular torsion.

32 boys with symptoms of an acute scrotum had testicular sonography with color flow imaging (CFI). Patients ranged in age from 4-15 years (avg = 11 yrs). Symptoms were present from 12 h to 5 days (avg = 42 hrs). CFI correctly predicted presence or absence of testicular perfusion in 11 boys who had surgical exploration of the scrotum. 8 of these 11 patients had hemorrhagic infarction of the testicle, 1 had torsion of the appendix epididymis, 1 had epididymitis, and 1 had bilateral incomplete torsions with normal testicular perfusion. The remaining 21 patients did not have an operation. At least a 1 year follow-up of all patients has shown no clinical evidence of testicular atrophy to suggest a missed diagnosis of torsion. Absence or markedly decreased testicular flow was easily identified and indicates testicular ischemia/infarction. Conversely, hyperemia of the testis and/or epididymis is usually associated with trauma or infection. However, incomplete torsion or spontaneous detorsion may demonstrate normal testicular flow on CFI. Only close correlation of clinical symptomatology and gray scale findings with CFI can identify these patients, who remain at high risk for subsequent complete torsion and infarction.

Arteriovenous malformation of scrotum: a case report.

Arteriovenous malformations of the scrotum are rare. We report a case of arteriovenous malformation involving the scrotal vessels. The patient presented with painful scrotal swelling, which was mainly in the skin and the Dartos layers. Vascular lesions of the scrotum are rare. By far the most common condition is varicocele. Our patient was examined by 2 other urologists before us and no one made the diagnosis of arteriovenous malformation on clinical examination. Diagnosis was made by auscultation with the Doppler stethoscope. We suggest that the possibility of a scrotal arteriovenous malformation and hemangiomas should be entertained in patients with unilateral scrotal swelling.

The rapid induction of liver glycerophosphate acyltransferase in mice by clofibrate, a hypolipidemic agent.

Administration of clofibrate to adult mice (20-25 mg of clofibrate/day) increased liver glycerophosphate acyltransferase (EC 2.3.1.15) activity by 2.3-fold within 24 h. This increased glycerophosphate acyltransferase activity was mainly localized in the liver microsomal fraction. Three other hypolipidemic drugs, i.e. Bezafibrate (Boehringer Mannheim Co.), Gemfibrozil (Warner-Lambert Co.) and Wy-14,643 (Wyeth Laboratories), when fed to mice, also increased the liver glycerophosphate acyltransferase activity by 2-3-fold in 24 h. Simultaneous administration of inhibitors of protein biosynthesis, such as cycloheximide or actinomycin D completely abolished such stimulation of liver glycerophosphate acyltransferase by clofibrate.