Search PubMed⌕ Search

Biomedical subjects

D W Newling

Publications and source records attributed to D W Newling.

At least 19 recordsLinked to original sources
PubMed2000

Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction.

The case of a 73-year-old man with chronic cystitis due to Corynebacterium urealyticum was complicated by hematuria and urinary stone formation. The diagnosis was based on an amplification product obtained using polymerase chain reaction for mycobacterial species on urine and a bladder biopsy specimen. A specific 212 bp amplification fragment that did not hybridize with a Mycobacterium-specific probe was recognized. Sequence analysis of the fragment revealed Corynebacterium urealyticum. Routine urine cultures were negative, but prolonged culture on sheep blood agar led to the isolation and identification of Corynebacterium urealyticum. Identification was confirmed by polymerase chain reaction on the colonies. The patient was treated successfully with vancomycin. Integration of molecular laboratory diagnostics with conventional microbiology and pathology was synergistic for the diagnosis.

Aged↗
PubMed2000

Use of balloon catheters for ureteral occlusion in urinary leakage.

PURPOSE: Urinary fistula after treatment for cancer constitutes a therapeutic dilemma, especially in patients who have had various other treatments. We report on 7 patients with urinary leakage, treated conservatively with ureteric occlusion by way of percutaneous transrenal balloon catheters. MATERIALS AND METHODS: The indication for ureteral occlusion was persisting urinary leakage despite diversion by nephrostomy and drainage with atransurethral catheter. All patients had had previous treatment because of pelvic malignancy. Small Foley balloon catheters and angioplasty catheters were used. These devices were inserted percutaneously in an antegrade fashion. RESULTS: In all but 2 of the patients the leakage ceased with the aid of these devices. Insufficient ureteral occlusion necessitated unilateral uretero-cutaneostomy in 1 patient. In another patient a vesico vaginal fistula was closed surgically. The maximum duration of occlusion was 169 (mean 94, range 45-169) days, without any evidence of ureteric pressure necrosis. Despite good overall results many adjustments and replacements of catheters were necessary because of recurrent urinary leakage caused by inadequate obstruction and/or leakage of the occluding catheters. CONCLUSIONS: We conclude that long-term ureteral occlusion with percutaneous transrenal balloon catheters appears to be safe and does not result in pressure necrosis. Using this approach, urinary fistula can heal in some patients without the need for open surgery.

Adult↗
PubMed1999

Defining an international research agenda for quality of life in men with prostate cancer.

BACKGROUND: While the traditional goal in the management of patients with prostate cancer has been to maximize survival, the recent advent of the medical outcomes movement has underscored the importance of patient-centered issues, such as health-related quality of life (HRQOL). METHODS: In this paper we present a comprehensive approach to the study of HRQOL in men with prostate cancer. We begin by defining HRQOL in general, discussing its measurement, and placing it in the context of prostate cancer. We then describe the primary goals of HRQOL research and present examples of validated instruments. We finish by proposing a quality of life research agenda for the next two decades. RESULTS: Contemporary perspectives on HRQOL are based on the World Health Organization's definition of health as not merely the absence of disease, but as a state of physical, emotional, and social well-being. HRQOL measurement must adhere to the strict methodological principles of survey psychometrics and is best accomplished with any of several validated instruments. Once collected, HRQOL information is useful for prostate cancer patients facing difficult treatment decisions. CONCLUSIONS: A solid foundation for HRQOL research has been built in early- and late-stage prostate cancer. It includes the development of new instruments and the establishment of descriptive data. This groundwork will allow investigators to address more complex research issues, such as interpreting interactions among HRQOL domains, presenting HRQOL data to future patients, optimally timing HRQOL data collection, uncovering innate and alterable factors that influence HRQOL, and exploring the intercultural nuances of HRQOL assessment.

Health↗
PubMed1999

Combination 186Re-HEDP and cisplatin supra-additive treatment effects in prostate cancer cells.

UNLABELLED: Radionuclide therapy has proven to be an efficacious palliative treatment for metastatic prostate cancer. Its potential therapeutic possibilities may be substantially increased by combining it with effective radiosensitizing drugs. METHODS: This study explores the radiosensitizing properties of cisplatin when combined with 186Re-labeled hydroxyethylidene diphosphonate (HEDP) in the treatment of R3327-MATLyLu prostate cancer cells in vitro. A concomitant incubation during 4 d, combining various concentrations of cisplatin (0, 0.42, 0.83 and 1.67 micromol/L) and 186Re-HEDP (0, 1.84 and 3.69 MBq/mL [0, 50 and 100 microCi/mL, respectively]) was followed by the determination of the cell numbers surviving and the replating of these cells in semisolid agar. RESULTS: The surviving fraction of clonogenic tumor cells after combination treatment clearly showed synergism when analyzed by a panel of three different published analytical methods. In addition, analysis of variance demonstrated a significant interaction between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001). Treatment with 186Re-HEDP and cisplatin by sequential incubation yielded similar, but never superior results. CONCLUSION: It is concluded that radionuclide therapy in combination with cisplatin is able, in principle, to improve therapeutic success rate in metastatic prostate cancer in a more than additive way.

Animals↗
PubMed1998

Sexual dysfunction associated with the management of prostate cancer.

Improvements in the management of prostate cancer have increased the need to consider patients' quality of life, in particular in relation to sexual function. The causes of sexual dysfunction are varied and derive from both the condition and its management. Health professionals must choose their treatment strategies with great care. Patient expectations must be understood, and patients should be offered counselling, as an understanding of what can reasonably be expected contributes to patients' perception of their quality of life. There are few studies on sexual dysfunction in patients with prostate cancer. A first step would be to develop reliable questionnaires for the assessment of the problem. This article describes and discusses the findings of one such recently developed questionnaire. When baseline measures of sexual function have been established and the extent of sexual dysfunction in patients with prostate cancer is reliably quantified, large multicentre trials can be performed to evaluate the impact of different therapies on sexual function and quality of life. Sexual dysfunction is an area which will be of increasing importance to urologists who manage prostate cancer and one that should not be underestimated.

Aged↗
PubMed1997

Second-line treatment of metastatic prostatic carcinoma.

Second-line palliative treatment of patients who have failed hormone therapy for advanced prostate cancer remains an important challenge in this disease. Very few agents have been shown to have a positive impact on survival, and toxicity is often therapy limiting in this elderly group of patients. Improvements in pain and performance status with maintenance of a reasonable functional status are worthwhile goals of any therapy at this stage. The earlier diagnosis of progressive disease from a rising prostate-specific antigen (PSA), and the use of validated quality of life questionnaires, can lead to useful improvements in the quality of the lives of these patients whose quantity we cannot at present lengthen.

Aged↗
PubMed1997

Nerve growth factor stimulates in vitro invasive capacity of DU145 human prostatic cancer cells.

The prevalence of nerve growth factor (NGF) production in different human prostatic tumor cell lines (DU145, PC-3, LNCaP-FGC) was investigated using a specific enzyme-linked immunosorbent assay (ELISA) and compared to that of different human and rat prostatic tissue samples. In addition, the biological effects of NGF beta addition to the human prostatic cancer cell cultures were investigated. The ELISA technique showed the DU145 cell line to secrete measurable levels of NGF in the culture medium. When neurite-outgrowth determination in a pheochromocytoma cell line was used as a bioassay, the NGF synthesized by DU145 cells was confirmed to exhibit functional biological activity. No effect of exogenously added NGF could be established on tumor cell proliferation, on the basis of either colorimetric tetrazolium-based staining assay or bromodeoxyuridine incorporation. Also the expression of prostate specific acid phosphatase was not influenced by NGF addition. However, the in vitro invasive capacity (Matrigel) of DU145 cells was significantly increased by inclusion of 50 ng or 100 ng NGF beta/ml culture medium. In view of the clinically well-known perineural invasion of prostate cancer cells, the possible involvement of NGF as a (paracrine) factor in prostatic cancer metastatic behavior should be investigated further.

Alkaline Phosphatase↗
PubMed1997

Homologous testis transplantation in dogs.

There is growing interest in the possible use of homologous testis transplantation for the treatment of anorchia and male infertility. In order to test the surgical and immunological feasibility of this therapy, three series of experimental studies of homologous testis transplantation were carried out in dogs. In the first pilot study, four beagles from the same litter were transplanted using microsurgical techniques for end-to-end anastomosis of the testicular vessels and the vas deferens. These dogs received cyclosporin A (CyA) for 3 months after transplantation. The longest functional graft survival in this series was 163 days, strongly suggesting that long-term survival of a homologously transplanted testis graft is possible. A second series of operations was performed on ten mongrel dogs. The same surgical technique was employed and the series was divided into three groups. Group 1 received CyA monotherapy, group 2 a combination of CyA and prednisolone, and group 3 received no immunosuppression. The average graft survival time in this series was 28 days, significantly less than the 71 days in the first series. The dogs in group 2, however, had graft survival times that were three times longer than those in the other two groups, suggesting that CyA in combination with prednisolone yields the best graft survival. In the third series, five littermates received a testis graft after castration. Immunosuppression was achieved by administration of CyA and prednisolone for 3 months. In three out of five animals, the graft survived until the immunosuppressive therapy was suspended. Histological biopsies of the graft 3 months after transplantation showed the same maturation of sperm cells as in the control testis of the same dog. The results of the last series suggest that long-term survival of homologously transplanted testis grafts in dogs is, indeed, possible with the aid of CyA and prednisolone.

Animals↗
PubMed1997

Glutathione S-transferase activity and subunit composition in transitional cell cancer and mucosa of the human bladder.

OBJECTIVES: Clinical data indicate that drug resistance to chemotherapy may occur in all stages of transitional cell cancer (TCC). Glutathione S-transferases (GSTs) are a family of detoxification enzymes composed of four different classes, denoted alpha (GSTA), mu (GSTM), pi (GSTP), and theta (GSTT), each containing one or more homo- or heterodimeric isoforms (GSTA1-1, GSTA1-2, and so forth), GSTs play a prominent role in drug detoxification and have been associated with resistance of tumor cells to anticancer agents. GST activity and isoenzyme levels were studied in TCC and normal bladder mucosa. METHODS: Enzyme activity was studied in samples of TCC (n = 37), adjacent normal bladder mucosa (n = 37), and in bladder mucosa of control patients without TCC (n = 46). GST isoenzyme composition was studied in mucosa and TCC of 14 patients and 11 controls. RESULTS: The mucosa of patients with TCC showed GST activity (191 +/- 21 nmol/min/mg cytosolic protein), similar to the mucosa of controls (176 +/- 15 nmol/min/mg). GST activity was significantly increased in TCC (666 +/- 157 nmol/min/mg) in comparison with adjacent mucosa (P < 0.003). In mucosa samples, the levels of GSTA (A1-1, A1-2, and A2-2) were below the detection limit in 92% of the samples. GSTM (GSTM1-1) was found in 9 controls and in 7 patients with TCC but not in the other 7 patients, whereas GSTP (GSTP1-1) could be detected in all samples. The levels of GSTM1-1 and GSTP1-1 were similar in mucosa of patients and controls. The mean relative increase of GSTP1-1 levels in TCC was 4.6-fold (P < 0.002). In the 7 patients with GSTM1-1-detectable expression in adjacent normal mucosa, mean GSTM1-1 levels in TCC were increased 2.8-fold compared with mean levels in normal adjacent mucosa (P < 0.02). GSTA was measured in five samples of TCC at relatively low levels. CONCLUSIONS: Overexpression of GSTP1-1 and GSTM1-1 may suggest that in the process of TCC carcinogenesis, a selection pressure occurs, resulting in a tumor with enhanced detoxification properties, including that of therapeutic drugs.

Aged↗
PubMed1997

Radionuclide therapy for prostate cancer lumbar metastasis prolongs symptom-free survival in a rat model.

OBJECTIVES: The present study was initiated to explore the effects of hydroxyethylidene diphosphonate labeled with rhenium 186(186Re-HEDP) treatment on the progression of lumbar skeletal metastasis in an animal model and to correlate the eventual treatment efficacy with the radioisotope tissue distribution. METHODS: The effect of 186Re-HEDP on the progression of lumbar metastasis from prostate cancer was investigated in the Copenhagen rat model. Metastatic prostate tumor deposits were induced in male rats by tail vein injection of R3327-MATLyLu prostate tumor cells under concomitant clamping of the inferior caval vein. The development of clinical symptoms such as onset of hind leg paralysis and urinary bladder swelling was monitored and related to the presence of tumor cells within histologic sections of L-5 and L-6 vertebrae. RESULTS: The 186Re-HEDP administration, given either 1 day or 8 days after surgical induction of lumbar metastasis, could significantly increase the symptom-free survival of the animals. These results were confirmed by a significant decrease in the presence of histologically detectable tumor tissue. Biodistribution studies demonstrated the uptake of the major part of the radioisotope within bone tissue. Uptake of radioactivity within the lumbar vertebrae on a microscopic scale, as shown by phosphor screen autoradiography, was concentrated in areas of bone formation and turnover. Signs of radiotoxicity, such as bone marrow replacement by fat cells and the absence of megakaryocytes, were observed. CONCLUSIONS: The results show that radionuclide treatment using 186Re-HEDP is a potentially efficacious treatment option in prostate cancer disseminated to the skeleton. The optimal treatment dose should be determined carefully and aimed at acceptable levels of myelotoxicity.

Animals↗
PubMed1997

The palliative therapy of advanced prostate cancer, with particular reference to the results of recent European clinical trials.

The palliative therapy of advanced prostate cancer still remains a perplexing problem. If advanced prostate cancer is defined either as a primary advanced-stage tumour (T3, T4, N0-N1), or a rising PSA level after primary and hopefully curative therapy, or the traditional patient presenting with small- or large-volume metastases with or without symptoms, then some 60% of all patients have advanced disease when first seen. There is still a need for the continuation of large prospective, randomized studies in all stages of this common illness, to define the role of the different therapeutic options at our disposal. The urological and urooncological worlds must be patient and not jump to too many early conclusions over the benefit of the various therapies until a statistical advantage for both individual and combined therapeutic options has been shown.

Androgen Antagonists↗
PubMed1997

Facing progressive localized prostatic cancer.

Patients diagnosed with locally progressive prostate cancer can be divided into three groups according to the stage of their disease. The first group includes patients with locally progressive cancer presenting initially as either T3 or T4; the second group involves individuals treated curatively who then develop local progression in the pelvis; the third group includes patients who present with metastatic disease and who develop recurrence of locally advancing disease in the pelvis despite undergoing hormonal therapy. This article reviews the treatment options currently available for patients in these three groups. The factors involved in deciding which is the most appropriate therapy are discussed, and the effectiveness of each treatment and the complications associated with it are presented.

Combined Modality Therapy↗
PubMed1997

Clinical assessment and management of stage T3 prostate cancer.

The early recurrence of prostate cancer originally staged as locally more than T2 and nonmetastatic, cast doubts over the adequacy of the staging of this form of the disease. Monotherapy with curative intent, either by radical prostatectomy or radiotherapy, results in around half of the patients failing within 5 years. While improvements in staging of the disease are essential, the early results of combined modality therapy, particularly the combination of neo-adjuvant hormones and surgery, have been disappointing. Neo-adjuvant maximal androgen blockade followed by radiotherapy does appear to offer survival benefit for patients with locally advanced disease, and other studies combining radiotherapy adjuvant hormonal therapy and surgery with routine postoperative with radiotherapy are eagerly awaited. Combination therapy might not give the hoped-for additive effects of the two therapies, but almost certainly will give an increased incidence of complications.

Androgen Antagonists↗
PubMed1996

Primary signet-ring cell carcinoma of the urinary bladder.

Signet-ring cell carcinoma of the urinary bladder is a rare tumour, accounting for approximately 0.24% of all bladder malignancies. In this study, the clinicopathological findings in 13 cases are described. This malignancy is far more common in men than in women (ratio 11:2). The distribution by age and clinical symptoms can not distinguish it from transitional cell carcinoma. The tumour behaves like other high grade malignancies, presenting frequently at an advanced stage, and having an unfavourable clinical outcome. No special therapy seems superior to another.

Adult↗
PubMed1996

Transplantation of the testis; from the past to the present.

Since the development of surgery, the possibility of testis transplantation has fascinated man for centuries. Hunter and Berthold are considered to be the most important investigators in this field and, in addition, to be the founders of modern endocrinology. The association of testis transplantation with rejuvenation led to widespread popularity for this treatment in the first three decades of the twentieth century. At the same time, controversies concerning the aim of the treatment have coloured the early years of endocrinology. In the 1960s renewed interest in the subject arose for experimental reasons, leading to the development of microsurgical techniques for autotransplantation of high-lying undescended testes in children. Homologous testis transplantation has never become a subject of great interest, probably for ethical reasons. This possible treatment for hypogonadism, however, has been developed experimentally and has been performed in man only in Russia and China, evidently with success. The details of these studies and their outcomes are discussed.

Animals↗
PubMed1996

The management of hormone refractory prostate cancer.

Prostate cancer patients deemed unsuitable for curative therapy by means of radical prostatectomy or radiation are offered androgen ablation or suppression therapy, which normally results in an inhibition of prostate cellular growth for a period of 12-18 months. Death of patients from prostate cancer is directly related to the development of clones of cells capable of multiplying and metastasising without androgen stimulation, and to date efforts to suppress these cells have been singularly unsuccessful. There are a number of treatment options available, and these include secondary hormone therapy, growth factor inhibition, chemotherapy, combination therapies and interstitial radiotherapy. The merits and disadvantages of these management approaches are discussed.

Androgen Antagonists↗