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Biomedical subjects

D Kirk

Publications and source records attributed to D Kirk.

At least 19 recordsLinked to original sources

The changing role of surgery in metastatic non-seminomatous germ cell tumour.

In the last 2 years (1989-1990) we have treated a total of 53 patients with metastatic nonseminomatous germ cell tumours (teratoma). In ten cases surgery to remove residual abdominal masses was required on completion of chemotherapy and normalisation of tumour markers (HCG and AFP). In a further three patients with large intra-abdominal masses and little or no other sites of disease surgery was performed as a therapeutic intervention, in the context of plateauing or rising tumour markers despite intensive chemotherapy. In all three, this approach resulted in a rapid fall in tumour markers, and following further chemotherapy all three remain disease free at 7, 12 and 25 months. For this small sub-group of patient failing to respond to chemotherapy who have resectable lesions, interventional surgery should be considered as part of a combined approach to treatment.

Adult

Effect of percutaneous nephrolithotomy on thermoregulation.

Hypothermia is a well recognised complication of open surgery. We had observed hypothermia, occasionally followed by rebound hyperthermia in the early post-operative period, in patients undergoing percutaneous nephrolithotomy, and therefore decided to monitor patients undergoing this procedure more closely. During a 12-month period, 32 patients were monitored during 38 percutaneous nephrolithotomies; 12 procedures were performed using irrigation fluid at room temperature (22 degrees C) and 26 with fluid warmed to 37 degrees C. Although no statistically significant differences between temperature changes were seen, the most profound temperature falls occurred in patients who received fluid at room temperature. The recovery ward staff observed improved post-operative recovery in patients who had received warmed fluid. Three of the 5 patients who underwent more than 1 percutaneous procedure received fluid at 22 degrees C and fluid at 37 degrees C on separate occasions. In each patient a more profound temperature fall occurred when the cold fluid was used. Only 1 patient, who received cold fluid, developed rebound hyperthermia in the early post-operative period. Warming of irrigation fluid and close monitoring of core temperature may prevent unnecessary morbidity in patients undergoing percutaneous nephrolithotomy.

Adult

Chronic testicular pain following vasectomy.

The incidence of chronic testicular pain following vasectomy has not been previously assessed. We have carried out a survey by postal questionnaire and telephone interview of 172 patients 4 years after vasectomy to assess the incidence of chronic testicular pain. Significant early post-operative complications occurred in 6 patients (3.5%): 2 infection, 3 haematoma and 1 orchitis. Chronic testicular discomfort was present in 56 patients (33%), considered by 26 (15%) to be troublesome but not by the other 30 (17%). Testicular discomfort related to sexual intercourse occurred in 9 cases (5%). Of the 9 patients who had sought further medical help only 2 had had further surgery (1 an epididymectomy and 1 excision of a hydrocele). Only 3 patients regretted having had the vasectomy because of chronic pain. On ultrasound examination, epididymal cysts were a common finding on both asymptomatic and symptomatic patients following vasectomy. Prior to vasectomy, all patients should be counselled with regard to the risk of chronic testicular pain.

Adult

Is there still a place for prolonged bladder distension?

Over a 2-year period, 31 patients underwent prolonged hydrostatic bladder distension for benign and malignant bladder disease in this unit. Of these, 29 patients had benign functional disorders or bladder contracture, and in 2 patients hydrodistension was performed for complications of treatment for bladder neoplasia. Of the 29 patients with benign disease, 6 observed marked improvement and 8 some improvement in their symptoms, and 12 received no benefit. Patients with detrusor hypersensitivity fared better than those with detrusor instability or interstitial cystitis. A patient with malignant bladder disease died soon after the procedure as a result of a myocardial infarction. Problems attributed to the hydrostatic balloon catheter were responsible for 2 failures. The regional anaesthetic technique failed to provide adequate anaesthesia for hydrodistension in 9 procedures and limited the duration to 2 h in 13 others. Following recall of the perished balloon catheters by the manufacturer, and the introduction of continuous spinal anaesthesia, the number of technical failures has been reduced. This technique still has an important role to play in the relief of severe symptoms unresponsive to medical treatment, but it is important that ideal conditions are provided for hydrodistension in order to ensure maximum success, particularly when the alternative is major surgery.

Adolescent

Is indoramin an effective alternative to prostatectomy?

Alpha-1-adrenergic antagonists are recommended for symptomatic treatment of patients awaiting prostatic surgery. Their efficacy has been confirmed in placebo controlled clinical trials, but to date no comparison of their effects with the results of subsequent prostatectomy has been made. Fifty-five patients awaiting prostatectomy were assessed (by symptom scores and peak urinary flow rates) prior to treatment, on indoramin 20 mg bd, and 2 months following prostatectomy. Side effects while taking indoramin were experienced by 36% of patients. Despite an overall improvement in mean symptom scores, 26% of patients with obstructive and 30% of those with irritative symptoms who were assessed while taking indoramin failed to experience any improvement. Of the 31 patients assessed while on indoramin and again following surgery, prostatectomy produced a greater symptomatic relief than indoramin. The increase in peak flow rate following prostatectomy was 11.7 ml/s compared with 3.2 ml/s on indoramin. However, 5 patients preferred to continue taking indoramin rather than proceeding to surgery. Indoramin is no substitute for prostatectomy. Although some patients might benefit from treatment while awaiting surgery, significant side effects may severely restrict its use for this purpose. The response to indoramin cannot be used as an accurate predictor of response to prostatectomy.

Humans

Terazosin in the treatment of benign prostatic hyperplasia: a multicentre, placebo-controlled trial.

The dynamic component of bladder outflow obstruction due to benign prostatic hyperplasia (BPH) has been shown to be modified by alpha 1 adrenergic receptors. Terazosin is an alpha 1 receptor-blocking agent with a long half-life permitting once-daily dosing. This drug was administered in a multicentre, randomised, placebo-controlled trial involving patients with symptomatic bladder outflow obstruction. Of 132 patients recruited for the study, 86 were randomised to receive placebo or terazosin, 81 completed the study, and 80 were considered eligible for efficacy analysis. All terazosin treatment groups showed dramatic improvement in obstructive symptoms when compared with the placebo group, but these differences were not statistically significant because of the small numbers of patients in each group. There were improvements in peak urinary flow rates, mean urinary flow rates, and residual urine volumes for the placebo and terazosin groups, but there were no statistically significant differences in the changes between the groups. Terazosin was well tolerated by patients in this study and may provide symptomatic relief in patients with BPH.

Adrenergic alpha-Antagonists

Local hyperthermia for prostatic disease: in vitro studies on human prostatic cancer cell lines.

Local hyperthermia for benign and malignant prostatic disease remains largely empirical. In an attempt to understand the biological action of hyperthermia, and its potentiation by antiandrogen seen in clinical practice, the interaction of the two has been studied in prostatic cancer cell lines. Human prostatic cancer cell lines LNCaP and DU 145 were studied to examine the effects of heat shock treatment (HST), androgen (5 alpha-dihydrotestosterone: 5 alpha DHT) and antiandrogen (hydroxyflutamide: OH-Flut) on cell growth and survival. Response (measured as increased DNA content) to 5 alpha DHT demonstrated that LNCaP was androgen sensitive, whereas DU 145 was androgen insensitive; OH-Flut stimulated LNCaP growth but had no effect on DU 145 growth. Thermotolerance was exhibited by DU 145 cells but not by LNCaP cells. The combination of HST followed by OH-Flut markedly reduced survival of LNCaP cells compared with HST alone. This effect was not observed in DU 145 cells. The enhanced cytotoxic effect of antiandrogen and hyperthermia could minimise the effect of thermotolerance in malignant cells surviving initial hyperthermia treatment and might suggest real clinical value for the combination or sequence.

Cell Division

Nucleolar organizer regions in benign and malignant prostatic disease.

A modified silver stain technique for visualizing nucleolar organizer regions (AgNOR counting) was applied to 24 benign and 23 malignant prostatic biopsies. Marked inter-observer variation was found, particularly in sections with high AgNOR counts. After averaging the AgNOR counts of both observers, there was no significant difference in counts between the benign and the malignant biopsies. The AgNOR count appeared to be increased in tumours up to Gleason histological grade 6, but not in tumours of Gleason histological grade 7 or more.

Humans

Who should have a prostatectomy? A survey of the management of patients presenting with bladder outflow obstruction.

A postal questionnaire was sent to 33 urologists and to 15 general surgeons who perform prostatic surgery in Scotland. Forty-six out of 48 surgeons replied. The waiting time for outpatient consultations and waiting list statistics of the respondents were compared. Differences in access to and use of imaging, laboratory and urodynamic facilities are reported. Waiting times were affected by the individual surgeon's policy. In busy units, the desire to achieve acceptable waiting times may lead to rationing of treatment to only the most severe cases. Better provision and use of modern investigational facilities might better select those patients who will benefit most from surgical management, leading to more effective use of resources. Medical audit of surgical patients must start from the time of their referral and not confine itself to patients undergoing treatment.

Attitude of Health Personnel

Marked antiinflammatory effects of decentralization of the superior cervical ganglia.

Intravenous challenge with parasite antigens in Nippostrongylus brasiliensis-sensitized rats resulted in anaphylactic shock and, in some animals, death. Surviving animals showed significant drop in mean arterial blood pressure, cardiac output, and blood flow to the trachea, bronchioles, and mesentery. After anaphylaxis, changes in the cellular and protein composition in bronchoalveolar lavage fluids (BALF) were assessed. 8 h after antigen challenge, there was significant influx of inflammatory cells and an increase in the levels of histamine and serum-derived immunoglobulins (IgG and IgM) in BALF. Chemotactic activity for neutrophils was also present in BALF. Once we established this anaphylaxis-induced model of pulmonary inflammation, we sought to determine whether or not the superior cervical ganglia (SCG) modulate this inflammation. We performed bilateral superior cervical ganglionectomy or decentralization of the SCG. Our results show that decentralization significantly reduced mortality (by 68%) after anaphylaxis. Furthermore, the increases in levels of serum-derived proteins, histamine, and influx of cells (especially neutrophils) observed in BALF after anaphylaxis were attenuated by both decentralization and ganglionectomy. By contrast, hemodynamic parameters in the respiratory tract and the presence of neutrophil chemotactic activity in BALF were not influenced by decentralization. Thus, the severity of pulmonary inflammation initiated by systemic anaphylaxis is depressed by bilateral ganglionectomy or decentralization of SCG.

Animals

Low dose methotrexate and doxorubicin in hormone-resistant prostatic cancer. Scottish Urological Oncology Group.

A group of 24 patients, all of whom had progressive disease following initial hormone therapy for advanced prostatic carcinoma, were given intravenous methotrexate (30 mg/m2) and doxorubicin (15 mg/m2) at 2-week intervals for a planned 6-treatment course. Seventeen patients completed the full course. Assessment included "quality of life" criteria, using the subjective assessment of performance status, severity of pain and analgesic consumption. Over half of the patients improved in each of these modalities and 8 (33%) improved in all 3. As toxicity was acceptable, low dose chemotherapy may have a part to play in these patients who present a difficult management problem.

Aged

A multi-centre phase two study of intravesical epirubicin in the treatment of superficial bladder tumour.

Epirubicin (4'-epi-adriamycin) was used in the treatment of widespread superficial carcinoma of the bladder. Thirty-seven patients received 50 mg in 50 ml of saline retained for 60 min. There was an overall response rate of 59% but this was of short duration. Thirty percent of patients progressed despite therapy. Therapy was associated with an incidence of side effects which necessitated therapy withdrawal in 12 (32.4%) patients. It is concluded that epirubicin, in the dose used in this study, cannot be recommended for routine intravesical chemotherapy and that further studies, at a reduced dosage, are necessary to evaluate this agent.

Administration, Intravesical

Androgen receptors--a method to measure functional behaviour in human prostatic cancer.

Androgen receptors were measured in soluble and nuclear fractions of tissues obtained from 25 patients. A method using mibolerone, a synthetic androgen, as a ligand is described. This method, which includes the presence of excess ORG 2058 to eliminate interaction with progesterone receptors, gives a reliable determination of androgen receptor content and has been used to predict response to hormonal treatment. However, the results suggest that the presence of functional receptor is not, in itself, a sufficient index of hormonal dependence of the tumour.

Aged

Epidermal growth factor receptor, nuclear proliferation antigen and interleukin-2 receptor expression in prostatic cancer.

Immunohistochemical methods have been used to study the relationship between epidermal growth factor receptor (EGF-R), T-lymphocyte infiltrate, interleukin-2 receptor (IL-2R) expression and the degree of cellular proliferation using the monoclonal antibody Ki-67. EGF-R was detected in only 2 out of the 19 malignant biopsies, but was present in the benign elements of all twelve of the heterogeneous biopsies examined. The level of immune response, as indicated by the percentage of T cells expressing the IL-2R, did not correlate with the expression of the nuclear proliferation antigen determined by Ki-67 monoclonal antibody staining intensity. This study fails to show a statistically significant correlation between the expression of EGF-R or nuclear proliferation antigen and the degree of the cell mediated immune response to the tumour.

Adenocarcinoma

Hormonal regulation of human endometrial stromal cells in culture: an in vitro model for decidualization.

Stromal cells derived from proliferative or secretory human endometria, cultured in the absence of steroid hormones, grew as monolayers that showed only occasional areas of immunoreactive fibronectin and did not produce detectable levels of prolactin (PRL) or laminin. Treatment with physiological doses of estradiol and progesterone induced PRL production and stimulated cell proliferation, resulting in multilayering with an increase of the saturation density. Electron microscopy showed the development of gap junctions, whereas immunofluorescence revealed a dense pericellular matrix containing fibronectin and laminin. These findings show that human endometrial stromal cells in culture respond to physiological doses of ovarian hormones with ultrastructural, proliferative, and biochemical changes that are characteristic of decidualization in vivo. This culture system thus provides an in vitro model for human decidualization.

Cell Division