Patient characteristics and treatment patterns for patients with benign prostatic hyperplasia, erectile dysfunction or co-occurring benign prostatic hyperplasia and erectile dysfunction in general practices in the UK: a retrospective observational study.

AIMS: The aim of this study was to assess patient characteristics, medication treatment patterns and healthcare resource utilization among men with existing erectile dysfunction (ED) or benign prostatic hyperplasia (BPH), who are newly diagnosed with the second condition (BPH or ED) compared with those with only one condition. METHODS: This retrospective cohort study utilized the Clinical Practice Research Datalink. Males, aged 40 years or older, newly diagnosed with ED or symptomatic BPH between 1 June 2010 and 31 May 2011, were selected. Patient demographics, existing comorbidities and baseline medication use were analysed. Treatments initiated for the incident condition and treatment patterns were reported at 6, 12, 18 and 24-months postdiagnosis. Referrals to urologists and visits to general practitioners were reported around diagnosis and during follow-up. RESULTS: This study included 11,501 incident patients with BPH, of which 23% had a prior ED diagnosis and 9,734 incident patients with ED, of which 17% had a prior BPH diagnosis. The average age at diagnosis of BPH was similar across both cohorts. Among incident patients with ED, those with prior diagnosis of BPH were diagnosed at an older average age (65 ± 9.2 years) compared to those without BPH (57 ± 9.1 years). The majority of patients in both incident BPH cohorts (62.9-65.5%) were prescribed alpha-blockers as initial treatment. The majority of patients in both incident ED cohorts (49.6-51.6%) were prescribed sildenafil as initial treatment followed by tadalafil (24.3-26.0%). At 12 months, 50% of incident patients with BPH and 80% of patients with ED had discontinued the therapy initiated. CONCLUSION: This study found that in the UK, patients with co-occurring BPH and ED when newly diagnosed with the second condition initiated the same treatments as those without prior ED or BPH. During the first year, treatment patterns including discontinuation were comparable in the groups with one of the conditions and co-occurring BPH and ED.

Reversal of multidrug resistance in HL-60 cells by verapamil and liposome-encapsulated doxorubicin.

The means of circumventing multidrug resistance was investigated in HL-60 and HL-60R (a drug resistance variant) cell lines. The HL-60R cell line was developed from the parent line by serial exposure to increasing concentrations of doxorubicin over a 4-month period. This drug resistant cell line expressed P-glycoprotein in its cell surface and is 80-fold more resistant than the parent cell line. Multidrug resistance, as evaluated by a cell cytotoxicity assay using doxorubicin, can be overcome by use of verapamil. Multidrug resistance can also be circumvented when doxorubicin is encapsulated in liposomes. The combination of verapamil and doxorubicin-encapsulated liposomes does enhance circumvention of multidrug resistance beyond the effect of each agent alone, implying a synergistic effect. The lipid composition of the liposomes does affect the rate of drug uptake but not the overall cytotoxic effect of doxorubicin. The synergistic reversal of multidrug resistance by doxorubicin-encapsulated liposomes and verapamil suggests a multifactorial basis for drug resistance in this cell line.

Case report: congenital adrenal hyperplasia and malignant Leydig cell tumor.

Leydig cell tumors are very rarely seen testicular tumors and can be difficult to distinguish from testicular tumors of the adrenogenital syndrome. Testicular tumors of the adrenogenital syndrome are confined to patients with congenital adrenal hyperplasia. The authors report a case of a patient with malignant Leydig cell tumor and a history of congenital adrenal hyperplasia (adrenogenital syndrome). To the authors' knowledge, this has not been reported previously.

Case report: cholangiocarcinoma and hypercalcemia.

Hypercalcemia is a relatively common problem seen in the presence of malignancy, and is the most common life-threatening metabolic disorder in patients with cancer. In the hospitalized patient, malignancy is the most common cause of hypercalcemia. It is estimated that hypercalcemia occurs in 10% to 20% of patients with cancer. Usually, it is a sign of advanced disease. Approximately 85% of patients with cancer and hypercalcemia will have disease metastatic to bone. The remaining 15%, however, will have some other etiology for their hypercalcemia, typically squamous carcinomas of the head and neck, esophagus, and lung. This type of hypercalcemia has been termed humoral hypercalcemia of malignancy and has been associated with the secretion of various cytokines, including parathyroid hormone-related protein. In this case report, the authors document the production of parathyroid hormone-related protein by an adenocarcinoma-cholangiocarcinoma. This is documented both by measurement of the protein in the patient's serum and staining of the protein within the tumor by a monoclonal antibody. A general discussion of hypercalcemia and malignancy also is provided.

Urokinase-type plasminogen activator expression in human prostate carcinomas.

The prostate gland is the most common site of cancer in men in the United States. The biologic behavior of an individual tumor, however, varies widely, with some cancers taking a relatively indolent course and other progressing rapidly to disseminated disease. Prognostic factors that might help predict a tumor's aggressiveness and invasiveness are limited. The expression of urokinase plasminogen activator was evaluated in 36 human prostate cancer specimens. Using an immunohistochemical method with monoclonal antibody #394, 70.6% (12 of 17) of cancer specimens with extracapsular extension showed increased expression of urokinase plasminogen activator, compared with 26.6% (4 of 15) of specimens without capsular invasion. Increased expression was localized to the glandular cytoplasm, with tumor stroma yielding predominantly negative results. These findings provide additional evidence of the role of urokinase in determining the biologic behavior and metastatic potential of prostate cancer.

p53 expression in incidental prostatic cancer.

Incidental prostate cancer is an indolent disease typically characterized by a benign clinical course. This is not clearly established, however, as recent reports suggest that up to 27% of cases progress with long-term follow-up. The indolent history of this disease led initially to the hypothesis that mutations of the p53 gene would be an infrequent event in this patient population. Archival specimens from 24 patients with Stage A1 carcinomas were evaluated for abnormal p53 expression. In 23 patients the disease was diagnosed after transurethral resection for bladder outlet obstructive symptoms, and in one patient after a radical prostatectomy. Using a monoclonal antibody (PAb 240) and an immunohistochemical technique, a total of 36 microfoci of tumor were evaluated. Thirteen (36%) microfoci were positive with an intense nuclear staining pattern (2+), and eight (22%) microfoci had an intermediate staining pattern. Four areas of prostatic intraepithelial neoplasia also stained positively with a 2+ staining pattern. These results suggest that abnormal p53 expression is a feature of a significant number of incidental prostatic carcinomas and that this occurrence is an early event in the development of the malignant phenotype.

A pilot study of the physician acceptance of tele-oncology.

During the winter of 1993, medical oncologists from an urban, university-based hospital provided oncology care to rural patients using interactive video clinics (tele-oncology). In order to assess physician satisfaction with this form of outreach, surveys were performed after the video encounters, as well as after a limited number of subsequent clinical encounters on site. Various aspects of satisfaction were evaluated. Although the sample was small (a total of 41 clinical encounters and 3 oncologists), the results suggested that there was a reasonable level of physician satisfaction with, and confidence in, the use of video to replace some on-site oncology consultations. A definitive study of tele-oncology for providing care to rural cancer patients therefore appears to be warranted.

Biochemical signal transmitted by Fc gamma receptors: phospholipase A2 activity of Fc gamma 2b receptor of murine macrophage cell line P388D1.

The detergent lysate of the P388D1 macrophage cell line was subjected to affinity chromatography on two different media, Sepharose coupled to heat-aggregated human IgG (IgG-Sepharose) and Sepharose coupled to the phosphatidylcholine analog rac-1-(9-carboxyl)nonyl-2-hexadecylglycero-3-phosphocholine (PC-Sepharose). Both IgG- and phosphatidylcholine-binding proteins were further purified by Sephadex G-100 gel filtration and isoelectric focusing in the presence of 6 M urea. The isolated IgG-binding proteins specifically bound to IgG2a, but not to IgG2b, whereas the isolated phosphatidylcholine-binding proteins specifically bound to IgG2b but not to IgG2a. Phosphatidylcholine-binding proteins possessed a typical phospholipase A2 activity (phosphatide 2-acylhydrolase, EC 3.1.1.4), which was maximal (10 mumol/min per mg of protein) at pH 9.5, depended on Ca2+, and was specific for cleavage of fatty acid from the C-2 position of the glycerol backbone of phosphatidylcholine. The noted enzymatic activity was augmented 4-fold by preincubating phosphatidylcholine-binding proteins with heat-aggregated murine IgG2b but not with IgG2a. IgG-binding proteins, on the other hand, are devoid of any detectable phospholipase A2 activity. Thus, the functional significance of Fc gamma 2b receptor of P388D1 macrophage cell line would be the generation of phospholipase A2 activity at the cell surface upon specific binding to Fc gamma 2b fragment.

Mutant p53 expression in prostate carcinoma.

The expression of the mutant p53 tumor suppressor gene was evaluated in 33 human prostate carcinomas. Using an immunohistochemical method with monoclonal antibodies PAb 1801 and PAb 240, 26 (79%) tumors demonstrated positive immunostaining for mutant p53. Only areas of glandular tumor were positive, with adjacent stromal elements and areas of glandular hyperplasia being negative. The predominant staining pattern was cytoplasmic. This pattern may be related to p53 binding to certain heat shock proteins (HSP 72/73), as a monoclonal antibody to these proteins demonstrated a cytoplasmic location as well. These results demonstrate that abnormal p53 expression is a frequent event in prostate cancer.

Studies of Fc gamma receptors of human B lymphocytes: phospholipase A2 activity of Fc gamma receptors.

The presence of phospholipase A2 activity within human B cell Fc gamma receptors was investigated. Lysate produced by detergent treatment of chronic lymphocytic leukemia cells that had 1% of the cells surface radioiodinated was subjected to affinity chromatography by using either rac-1-(9-carboxynonyl)-2-hexadecylglycero-3-phosphorylcholine-Sepharose (PC-Sepharose) or heat-aggregated human IgG-Sepharose 4B conjugate (IgG-Sepharose). The materials eluted from both adsorbants by ethylenediaminetetraacetate- or urea-containing buffer were further purified by gel filtration and isoelectric focusing in the presence of 6 M urea. Both isolated PC- and IgG-binding materials were homogeneous, when judged by gel filtration and isoelectric focusing, and had identical isoelectric points (pI = 6.5), peptide maps, and amino acid compositions. Furthermore, both preparations catalyzed equally the hydrolysis of phosphatidylcholine to release fatty acid from the 2 position. Optimal enzymatic activity depended on the presence of Ca2+, was maximal at pH 9.5, and was augmented by Fc gamma fragments. Both preparations specifically bound to the Fc portion of IgG and inhibited human antibody-coated erythrocyte rosette formation by peripheral mononuclear cells. Our data thus demonstrate the identity of PC- and IgG-binding materials and suggest that a functional activity of the human B cell Fc gamma receptor is the generation of phospholipase A2 activity within the plasma membrane.

Overexpression of Her-2/neu may be an indicator of poor prognosis in prostate cancer.

Previous reports have shown that Her-2/neu oncogene expression in human breast cancer and ovarian cancer may be associated with poorer prognosis. We report the expression of Her-2/neu on fresh samples of known prostatic adenocarcinoma but not on those of benign prostatic hypertrophy. Using a monoclonal antibody (TA1) directed against human Her-2/neu oncogene product and an immunohistochemical staining method, no Her-2/neu expression was noted with benign prostatic hypertrophy (15 samples). With prostatic adenocarcinoma samples, a subset (9 of 25) showed overexpression of Her-2/neu. Such overexpression is correlated with higher histological grade, higher stage of disease, and high S phase and aneuploidy on flow cytometric analysis. These findings suggest that Her-2/neu may be a prognostic marker in prostate cancer as well.