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Biomedical subjects

J Vale

Publications and source records attributed to J Vale.

At least 19 recordsLinked to original sources
PubMed2000

Erectile dysfunction following radical therapy for prostate cancer.

With the earlier detection of prostate cancer and the increasing demand for treatment of organ-confined dizease, quality of life issues are becoming more important. Development of erectile dysfunction (ED) following radical therapy is a particular concern, and occurs in perhaps a third of patients treated by radiotherapy and 30-70% of patients treated by radical prostatectomy. Although it is assumed that the ED relates to damage to the nerves subserving erection, this view has been questioned recently and in at least a proportion of patients the cause appears to be vascular. Despite the likely cause of their ED, all patients presenting with ED after treatment for prostate cancer should undergo assessment by history and examination to ensure that there are no other correctable risk factors. Patients can then be considered for a number of treatment options, and currently sildenafil (Viagra, Pfizer) is usually used as first-line therapy assuming there are no contraindications, such as severe ischaemic heart disease or nitrate therapy. Sildenafil improves erectile function in 70% of patients with ED post-radiotherapy, but appears less effective in men after radical prostate surgery with a response rate of 40-50%. Other treatment options include self-injection or intra-urethral administration of alprostadil, and some patients are happy to use a vacuum erection device. Finally, if all else fails, patients may be suitable for penile implant surgery.

Erectile Dysfunction↗
PubMed2000

Symptomatic paroxysmal hemidystonia due to a demyelinating subthalamic lesion.

We present a case of paroxysmal hemidystonia in a patient with an isolated demyelinating lesion in the subthalamic region, involving the posterior arm of the internal capsule and extending to the subthalamic nucleus and mesencephalon, possibly due to multiple sclerosis. Compared with similar reports in the literature, in our case there was a paucity of lesions, permitting a more direct clinico-anatomical correlation. The role of the subthalamic region and basal ganglia circuitry in the genesis of symptomatic dystonia is discussed.

Adult↗
PubMed1998

Inhibitors of glutathione reductase as potential antimalarial drugs. Kinetic cooperativity and effect of dimethyl sulphoxide on inhibition kinetics.

We have developed inhibitors of glutathione reductase that improve on the inhibition of literature lead compounds by up to three orders of magnitude. Thus, analogues of Safranine O and menadione were found to be strong, reversible inhibitors of yeast glutathione reductase. Safranine O exhibited partial, uncompetitive inhibition with Ki and alpha values of 0.5 mM and 0.15, respectively. Thionine O was a partial (hyperbolic) uncompetitive inhibitor with Ki and alpha values of 0.4 microM and 0.15, respectively. LY83583 and 2-anilino-1,4-naphthoquinone also showed (hyperbolic) partial, uncompetitive inhibition with micromolar Ki values. For Nile Blue A a model for two-site binding with (parabolic) uncompetitive inhibition fitted the data with a Ki value of 11 microM and a kinetic cooperativity between the sites of 0.12, increased to 0.46 by preincubation of the enzyme and Nile Blue A in the presence of glutathione disulphide. Analysis of the effects of preincubation on the kinetics and cooperativity indicated the possibility of a slow conformational change in the homodimeric enzyme, the first such indication of kinetic cooperativity in the native enzyme to our knowledge. Further evidence of conformational changes for this enzyme came from studies of the effects of dimethyl sulphoxide which indicated that this co-solvent, which at low concentrations has no apparent effect on initial velocities under normal assay conditions, induced a slow conformational change in the enzyme. Thionine O, Nile Blue A and LY83583 were redox-cycling substrates producing superoxide ion, detectable by means of cytochrome c reduction, but leading to no loss of glutathione reductase activity, under aerobic or anaerobic conditions. The water-soluble Safranine analogues Methylene Blue, Methylene Green, Nile Blue A and Thionine O (5 mg/kg i.p. x 5) were effective antimalarial agents in vivo against P. berghei, but their effect was small and a higher dose (50 mg/kg i.p. x 1) was toxic in mice. Comparison was made with human glutathione reductase and its literature-reported interactions with several tricyclic inhibitors as studied by X-ray diffraction. It is possible that the conformational changes detected in the present study from alterations in detailed kinetic inhibition mechanisms may shed light on information transfer through the glutathione reductase molecule from the dimer interface ligand pocket to the active-site.

Animals↗
PubMed1998

The pharmacological basis of anterior segment therapy.

The main concerns in anterior segment therapy are allergy, inflammation and infection. Allergic reactions can be divided into four types with differing etiologies. Although all types may be manifested in ocular inflammatory states, Type I, involving the release of histamine is probably the most common, being involved in responses to pollen, drugs and in GPC and VKC. Inflammation is a complex, multicomponent, protective response involving the synthesis, release and actions of many chemical mediators, including prostaglandins which are synthesised from cell membrane components. Drugs used act through a number of mechanisms: decongestants act directly on dilated vessels to cause constriction and decreased permeability; antihistamines block the access of histamine to its receptors in the target tissues and mast cell stabilisers prevent the release of mediators including histamine in response to the antigen/antibody interaction. Both the non-steroidal anti-inflammatory drugs and steroids decrease the production of the prostaglandins by inhibiting the action of cyclo-oxygenase and phospholipase respectively. Most infections are bacterial and the majority of drugs used are antibacterial. However, many of the principles of antibacterial therapy can be applied to the other classes of drugs. The basic principle in the treatment of any infection is that of selective toxicity, which is the ability to effect harm to the infecting cells (e.g. bacteria) without a similar effect being exerted on the host cells. This selectivity may be qualitative, at no drug concentration is the host cell affected in the same way as the invading cell, or quantitative where the separation of effect is dose dependent. The selectivity may have a biochemical or distributional basis, and the effects may be, in the case of bacteria, bactericidal or bacteriostatic. Most antibiotics used in anterior segment therapy show quantitative biochemical selectivity and are bacteriostatic in action. The antiviral compound (aciclovir) shows quantitative biochemical selectivity because it is a pro-drug activated in infected cells.

Anterior Eye Segment↗
PubMed1996

Myxoid renal cell carcinoma: histological, immunocytochemical and ultrastructural study.

Renal cell carcinomas show a variety of histological features. A case of a renal tumour arising in a 44 year old African man is reported. The tumour was composed of a cobweb-like pattern of narrow anastomising tubules lined by cuboidal cells separated by a hypocellular myxoid stroma. Immunohistochemical stains were consistent with a renal cell origin. The differential diagnosis in these cases includes sarcoma.

Adult↗
PubMed1996

Radiation-induced changes in neuropeptides in the rat urinary bladder.

PURPOSE: To determine whether there was a change in innervation in the rat urinary bladder following x-ray irradiation. MATERIALS AND METHODS: The urinary bladders were obtained from rats irradiated 6 months previously with single doses of 15 Gy and 25 Gy x-radiation, and from nonirradiated (control) animals. They were examined immunohistochemically to localize neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), met-enkephalin (m-ENK), leu-enkephalin (l-ENK), somatostatin (SOM) and the enzyme, tyrosine-hydroxylase (TH). Computer assisted image analysis was used to assess the density of immunoreactive nerve fibres. RESULTS: The greatest density of nerves observed in the bladder from control animals contained NPY, followed (in decreasing order) by CGRP, VIP, SP and TH. The nerves appeared to run predominantly along the longitudinal axis of the circular and longitudinal muscle fibres. SP-, CGRP-, TH- and occasionally VIP-immunoreactive nerves were observed in the lamina propria, at the base of the urothelium. Perivascular nerves containing neuropeptides and TH were observed throughout the bladder wall. There was an absence of m-ENK-, l-ENK- and SOM-immunoreactive nerves in the control and irradiated rat urinary bladders. In the rat urinary bladder irradiated with 25 Gy x-radiation, there was a significant increase (P < 0.05) in the density of NPY-, TH- and SP- but not CGRP- and VIP-immunoreactive nerves. There were regional differences within the bladder, that is, there was an increase in VIP-, CGRP- and SP-immunoreactive nerves around and within the urothelium. NPY-immunoreactive nerves were seen in the connective tissue and elastic fibres of the lamina propria for the first time. An increase in the density or fluorescence intensity of perivascular TH- but not neuropeptide-containing nerves was observed. CONCLUSIONS: The increase in the density of NPY-, SP- and TH-immunoreactive nerves in the irradiated bladders may be due to axonal sprouting which contributes to the symptoms of radiation injury.

Animals↗
PubMed1994

Parathyroid cancer: clinical variations and relationship to autotransplantation.

OBJECTIVE: To identify the clinical and pathological characteristics of parathyroid cancer to determine the best method of treatment and to prevent the use of malignant tissue for autotransplantation. DESIGN: A chart review over a 20-year period (1973 to 1993). SETTING: Two tertiary-care referral centres in Ontario with specialty interest in disease of the thyroid and parathyroid glands. PATIENTS: Sixteen patients, identified as has having parathyroid cancer (equivocal diagnosis in 9 and definitive diagnosis in 7). MAIN OUTCOME MEASURES: The clinical and histologic features, treatment, morbidity and mortality of parathyroid cancer. RESULTS: Some patients with an equivocal diagnosis had postoperative recurrent hyperparathyroidism characterized by multiple soft-tissue implants of parathyroid that persisted after reoperation. The others had infiltrative attachment of parathyroid lesions to the thyroid gland and were eucalcemic and disease free up to 12 years after treatment. Three of the seven patients with a definitive diagnosis of parathyroid cancer were treated for a neck mass; the others were treated for hypercalcemia and multiple lytic bone lesions, hypercalcemia and renal disease and secondary hyperparathyroidism. En-bloc resection, carried out in all but one case, was curative in five cases. The patient with secondary hyperparathyroidism underwent total parathyroidectomy and autotransplantation but died of metastatic parathyroid cancer 1 year later. CONCLUSIONS: Because of the difficulty in making a histologic diagnosis of parathyroid cancer, en-bloc resection of the thyroid and parathyroid glands and locally invaded structures is the appropriate treatment to avoid tumour spillage. Caution should be exercised in the use of donor parathyroid tissue for autotransplantation.

Adenoma↗
PubMed1993

Colour flow and spectral Doppler imaging after papaverine-induced penile erection in 220 impotent men: study of temporal patterns and the importance of repeated sampling, velocity asymmetry and vascular anomalies.

Of 220 impotent men studied, 52 demonstrated venous leakage, 85 had arterial insufficiency and 65 showed normal vascular response. Persistent diastolic velocity > 7 cm/s diagnosed venous leakage with a sensitivity of 94% and a specificity of 69%, using cavernosography as the reference standard. Using clinical response as the reference standard maximal systolic velocity of 30 cm/s identified normal penile arterial response with a sensitivity of 96% and specificity of 82%. There was a good correlation between penile arterial insufficiency and a strong history of arteriopathy. Time to peak systole > 0.1 s was a reliable predictor of arteriogenic impotence and Pulsatility Index (PI) < 300 was discovered only in patients with either venous leakage or arteriogenic impotence. Peak systolic velocity (Tmax) occurred between 5.2 and 6.5 min after injection, and diastolic velocity was minimal at 9 min with only the normal responders showing reversed diastolic flow. However, 22% had a delayed response (Tmax range 1-18 min). Velocity asymmetry was equally common in the three groups and unilateral sampling would have misdiagnosed 6% of patients studied. Vascular anomalies were seen in 13%, particularly a single feeding artery, dorsal vein flow or collateral arterial flow.

Adult↗
PubMed1993

Long-term urodynamic effects of finasteride in benign prostatic hyperplasia: a pilot study.

A group of 69 men with bladder outflow obstruction due to benign prostatic hyperplasia (BPH) were treated in a double-blind placebo-controlled study with finasteride (Proscar), a 5 alpha-reductase inhibitor, 5 mg or 10 mg/day, or an identical placebo for 3 months; subsequently, 20 patients received finasteride 5 mg/day in an open extension study. Ten of these patients have now completed 3 years of therapy and have been reevaluated with pressure/flow urodynamics. In finasteride-treated patients dihydrotestosterone (DHT) declined by over 60%, remaining unchanged with placebo. Symptom scores fell in both groups of patients, maximum flow rate values decreased on placebo but improved by a mean of 1.5 ml/s in the 10-mg group and 3.3 ml/s in the 5-mg group. After 1 year of therapy, the reduction in symptom score was well maintained and the flow rate had increased by a mean of 2.7 ml/s; the mean prostate volume was reduced by 14% and prostate-specific antigen (PSA) had declined by 28%. In the 10 patients treated for 3 years who consented to further urodynamic study, the maximum urinary flow rate had improved from a mean baseline value of 8.7 ml/s to a mean of 13.8 ml/s, while maximum subtracted voiding pressure had decreased from a mean baseline value of 72 cm H2O to an unobstructed mean value of 44 cm H2O. Side effects were minimal and reversible on stopping the medication.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1992

Use of the ASI titanium stent in the management of bladder outflow obstruction due to benign prostatic hyperplasia.

An expandable titanium intraprostatic stent was inserted into 30 patients with infravesical obstruction due to benign prostatic hyperplasia (BPH). All of the men were considered unsuitable for transurethral resection of the prostate as a result of comorbid conditions. In 25 patients effective micturition was reestablished with this technique. In 21 of these men, who have been followed for longer than 1 year, the mean maximum flow rate at 1 year was 10.8 ml. per second and the mean residual urine was 56 ml. Although urinary tract infections occurred subsequent to stent insertion in 10 individuals, these resolved after appropriate antibiotic treatment and no stents have had to be removed for this reason. Followup cystoscopy or examination by electron microscopy of those stents that have been removed has shown partial epithelialization of the stent surface in a proportion of patients, and a minor degree of incrustation occurred in 1 case. We conclude that an expandable intraprostatic titanium stent is an acceptable alternative to transurethral resection of the prostate or long-term catheterization in this particular group of high risk patients.

Aged↗
PubMed1990

Pharmacocavernometry in the assessment of erectile impotence.

Thirty-three impotent men underwent pharmacocavernometry and cavernography. Ten patients had a good clinical response to 60 mg papaverine, nine had a moderate clinical response and in 14, the response was judged to be a poor one. Twelve patients had evidence of abnormal venous leakage from the corpora. Subsequent investigation with isotope phallography showed six patients to have arterial insufficiency and in three of these patients this was amenable to reconstructive vascular surgery. We conclude that pharmacocavernometry provides a useful, cheap and reliable method for the investigation of impotent men which may be performed on an outpatient basis.

Adult↗
PubMed1986

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy.

A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.

Adenoma↗
PubMed1985

Feeding, growth, and biochemical studies in very low birthweight infants.

Fifty infants of gestational age 28 to 32 weeks and birthweight less than 1501 g were reviewed on the expected date of delivery and at conceptional ages of 4, 8, and 12 months. All infants were at home by the expected delivery date, were fed on demand, and weighed regularly. On the expected delivery date and at 4 months, the amounts of formula milk and weaning food accepted were recorded; energy and protein intakes were calculated; and serum sodium, potassium, urea, protein, and osmolality were measured. The birthweight of these infants ranged between the 3rd and 75th centiles (on average about the 20th) but at the expected delivery date was, on average, below the 3rd centile. Infants who had been weaned in the first 4 months after the expected delivery date (n = 26) had similar energy and protein intakes and similar biochemical indices to those weaned later (n = 24). They achieved catch up growth (below 3rd to 10-25th centile) by 1 year, irrespective of the time of weaning and without any differences in metabolic 'stress'.

Blood Proteins↗