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Biomedical subjects

D Neal

Publications and source records attributed to D Neal.

At least 19 recordsLinked to original sources
PubMed2003

Benign prostatic hyperplasia.

In both ageing men and women, there is an increasing incidence of lower urinary tract symptoms (LUTS) which are increasing. These infections have many possible causes, including smooth muscle dysfunction, neurological factors and benign prostatic hyperplasia. Up to 15% to 25% of men aged 50-65 years have LUTS of sufficient severity to interfere with their quality of life. Although benign prostatic hyperplasia is an important cause of these symptoms, and can have serious consequences, clinicians should be aware of these other causes so that the appropriate diagnosis is made before invasive treatments are started. New medical treatments, including alpha-adrenergic blocking agents and 5 alpha-reductase inhibitors mean that many men without complications such as infection, bleeding, or chronic retention, and with mild to moderate symptoms, should be managed in primary care. Combined local protocols between primary and secondary care will help to establish which men with persistent symptoms or complications need referral for a urological opinion to determine the need for further investigation and more invasive forms of management. We review the pathophysiology of the disease, and current approaches to investigation and management of this common problem.

Cross-Sectional Studies↗
PubMed2001

Social and demographic factors predictive of change over seven years in CHD-related behaviours in men aged 18-49 years.

It is possible that the relationship of social status to coronary heart disease is partly mediated through health-related behaviours that have been found to relate to both social status and CHD. Changes in certain health-related behaviours are known to lead to changes in CHD incidence. What are the characteristics of men who change or do not change these behaviours and their subsequent chances of CHD? This study aims to relate changes in men's CHD-related behaviours over a seven-year period to their social and demographic characteristics.A survey was carried out on a random sample of adults in Great Britain in 1984-85 and the equivalent information was obtained again on those participants who were re-interviewed seven years later in 1991-92. Results are presented for the 582 men aged 18-34 and the 584 men aged 35-49 at the first interview who were re-interviewed seven years later. Changes over the seven years in smoking, saturated fat intake, alcohol consumption and exercise were related to social and demographic factors. The two age groups showed broadly similar patterns of behaviour. In both age groups, those who continued with or took up a low fat diet and/or exercise were more likely to be in a higher social class, in employment, to live in private housing and to have more educational qualifications. For the younger men only, those in private housing were more likely to reduce the amount they smoked. Other findings are also reported. The findings suggest that those people who are in less advantageous social and economic situations are less likely to change to a more healthy lifestyle and so should be a focus for health education.

Adolescent↗
PubMed2001

Small increases in insulin inhibit hepatic glucose production solely caused by an effect on glycogen metabolism.

Based on our earlier work, a 2.5-fold increase in insulin secretion should completely inhibit hepatic glucose production through the hormone's direct effect on hepatic glycogen metabolism. The aim of the present study was to test the accuracy of this prediction and to confirm that gluconeogenic flux, as measured by three independent techniques, was unaffected by the increase in insulin. A 40-min basal period was followed by a 180-min experimental period in which an increase in insulin was induced, with euglycemia maintained by peripheral glucose infusion. Arterial and hepatic sinusoidal insulin levels increased from 10 +/- 2 to 19 +/- 3 and 20 +/- 4 to 45 +/- 5 microU/ml, respectively. Net hepatic glucose output decreased rapidly from 1.90 +/- 0.13 to 0.23 +/- 0.16 mg. kg(-1). min(-1). Three methods of measuring gluconeogenesis and glycogenolysis were used: 1) the hepatic arteriovenous difference technique (n = 8), 2) the [(14)C]phosphoenolpyruvate technique (n = 4), and 3) the (2)H(2)O technique (n = 4). The net hepatic glycogenolytic rate decreased from 1.72 +/- 0.20 to -0.28 +/- 0.15 mg. kg(-1). min(-1) (P < 0.05), whereas none of the above methods showed a significant change in hepatic gluconeogenic flux (rate of conversion of phosphoenolpyruvate to glucose-6-phosphate). These results indicate that liver glycogenolysis is acutely sensitive to small changes in plasma insulin, whereas gluconeogenic flux is not.

Animals↗
PubMed2001

Cell relationship in a Wistar rat model of spontaneous prostatitis.

PURPOSE: Prostatitis in men is a painful, noninfectious inflammatory condition. It is similar to interstitial cystitis which is associated with increased bladder mast cell and sensory nerve fiber density as well as suprapubic pain. Certain strains of rats may provide a useful model for studies of the development of spontaneous prostatitis. We evaluated the time course, and involvement of mast cells and sensory nerve fibers in this process using Wistar rats. MATERIALS AND METHODS: The prostates of 4, 6, 8, 10 and 13-week-old male Wistar rats were examined for the degree of inflammation, innervation, mast cell density and nerve mast cell relationship using histochemical and immunocytochemical studies. Bacterial cultures of tissue were performed at 13 weeks. RESULTS: The inflammatory cell index increased progressively with age. Inflammation was moderate and consisted mostly of lymphocytes and macrophages associated with occasional glandular epithelial necrosis and edema. The density of nerve fibers immunoreacting with the neuronal marker protein gene produce 9.5 increased gradually with age and fibers immuno-positive for the sensory neuropeptide calcitonin gene-related peptide more than doubled by 13 weeks compared with by 4 weeks. The density of visible mast cells declined after 4 weeks in a pattern that corresponded with the increased percent of mast cells undergoing degranulation. For the mast cells with calcitonin gene-related peptide immuno-positive nerve fibers within a distance of 40 microm. distance correlated significantly with the degree of degranulation. Bacterial cultures were negative at 13 weeks. CONCLUSIONS: Our results confirm previous reports of spontaneous prostatitis in Wistar rats and indicate that moderate inflammation may occur in 80% of rats at as early as age 13 weeks. While the correlation of the nerve mast cell axis with mast cell degranulation does not prove our hypothesis of mast cell mediated inflammatory mediator release in the development of nonbacterial prostatitis, it suggests that such a relationship is possible.

Age Factors↗
PubMed2000

Development of sensitive colorimetric capture elisas for Clostridium botulinum neurotoxin serotypes A and B.

Sensitive and specific enzyme-linked immunosorbent assays were developed to detect Clostridium botulinum neurotoxin serotypes A (BoNT A) and B (BoNT B) in assay buffer and human serum. The assay is based upon affinity-purified horse polyclonal antibodies directed against the approximately 50 kDa C-fragments of each toxin. Standard curves were linear over the range of 0.1-10 ng mL. Detection was possible at 0.2 ng mL (20 pg/well) and accurate quantitation at 0.5 ng/mL (50 pg well) in assay buffer and 10% human serum. Variations between triplicates was typically 5-10%. Less than 1% cross reactivity occurred between other serotypes when each assay was performed against serotypes A, B and E. When tested against toxins complexed to their associated nontoxic proteins, interference was absent (BoNT B) or < 25% (BoNT A). These assays demonstrate sensitivity close to that of the mouse bioassay without the use of animals and in a much simpler format than other reported assays of similar sensitivity.

Animals↗
PubMed2000

Urinary cytologic findings in patients with benign and malignant adenomatous polyps of the prostatic urethra.

CONTEXT: Urethral adenomatous polyps with prostatic epithelium (also known as benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria, dysuria, and hematospermia, conditions that may prompt cytologic evaluation of urine. DESIGN: The urine cytologic test findings in 5 cases of biopsy-proven BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a urethral polyp were retrospectively evaluated. Immunocytochemical stain for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high-molecular-weight cytokeratin (34betaE12) were used in evaluation of the lesions. RESULTS: In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform, oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the prostatic origin of the clusters in 2 cases. One urine sample contained abundant goblet cells and extracellular mucin, consistent with intestinal metaplasia coexisting in the bladder biopsy specimen. The urine sample in the fifth case of BPEPs contained no columnar cells. The last case had multiple urine cytologic evaluations that demonstrated PSA-positive, malignant-appearing clusters of columnar cells. A biopsy specimen of the polyps was described as a high-grade prostatic intraepithelial neoplasm in adenomatous polyp. However, in this patient, PDA was diagnosed on transurethral resection of the prostate specimen 4 years after the initial urine cytologic test. CONCLUSION: Benign prostatic epithelial polyps should be considered in the differential diagnosis of clusters of columnar cells in urine cytologic testing. Cells with malignant nuclear features should instigate a careful search for a (prostatic) neoplasm, which may present as urethral polyps (e.g., PDA). Stains for PSA or PAP are useful adjuncts in differential diagnosis of this condition.

Acid Phosphatase↗
PubMed1999

A bladder-neck support prosthesis for women with stress and mixed incontinence.

OBJECTIVE: To evaluate the safety and efficacy of a bladder-neck support prosthesis, a vaginal device designed to support the bladder neck, in women with genuine stress and mixed incontinence. METHODS: For enrollment, incontinent women underwent a history, physical examination including cotton-swab test, urinalysis, postvoid residual urine, and multichannel urodynamic testing. Those with genuine stress incontinence or mixed incontinence and urethral hypermobility completed 7-day bladder diaries, the Incontinence Impact Questionnaire, and underwent standardized pad tests. They were fitted with a prosthesis and seen weekly to optimize fit and efficacy. At week 5, they underwent repeat evaluations with the best-fitting prosthesis in place. RESULTS: Seventy women were enrolled and 53 completed the 1-month study (29 genuine stress incontinence, 24 mixed incontinence). The mean ages were 50.4 years for genuine stress incontinence (range 24-76) and 55.7 years for mixed incontinence (range 30-88). A statistically significant reduction in incontinence was noted on pad testing (genuine stress incontinence, mean 46.6-16.6 g; mixed incontinence, mean 31.9-6.8 g) and in the bladder diary (genuine stress incontinence, mean 28.6-7.8 losses per week; mixed incontinence, mean 30.2-15 losses per week). Quality-of-life scores improved in both groups. With the device in place, urodynamic testing indicated normalization of urethral function without evidence of outflow obstruction. Subjects found the device comfortable, easy to use, and convenient. Side effects included five urinary tract infections and 23 cases of vaginal mucosal soreness or mild irritation. CONCLUSION: The bladder-neck support prosthesis significantly reduced involuntary urine loss in women with stress and mixed incontinence.

Adult↗
PubMed1999

The pathophysiology of pulmonary diffusion impairment in human immunodeficiency virus infection.

Numerous reports have demonstrated that prior to the development of acquired immunodeficiency syndrome (AIDS)-related pulmonary complications, human immunodeficiency virus-positive (HIV+) individuals commonly develop unexplained reductions in pulmonary diffusing capacity (DLCO). The potential relevance of this observation is underscored by recent data demonstrating that reductions in DLCO independently predict the subsequent development of opportunistic pneumonia. To delineate the alterations in gas exchange associated with HIV, we investigated a group of HIV+ subjects with unexplained reductions in DLCO, using high-resolution computed tomography (HRCT) of the chest and a separation of diffusing capacity into its membrane (Dm) and capillary blood volume (Vc) components. We compared this abnormal group with HIV+ subjects with more normal gas exchange and also with a group of HIV- volunteers matched for age and smoking history. Compared with other groups, the HIV+ group with diffusion impairment demonstrated prominent reductions in Vc, despite a well-preserved total lung capacity (TLC). HRCT demonstrated virtually no evidence of interstitial fibrosis in any HIV+ subject, but evidence of early emphysema that significantly correlated with DLCO. Our results suggest that the previously reported impairment in pulmonary gas exchange in the HIV+ population involves loss of Vc and likely represents the development of early emphysema.

AIDS-Related Opportunistic Infections↗
PubMed1999

Prostatitis unplugged? Prostatic massage revisited.

Repetitive prostatic massage is not a new tool in the urologists' armatarium. Once the most popular therapeutic maneuver used to treat prostatitis, it was abandoned as primary therapy almost 3 decades ago. Based on experience reported outside North America and anecdotal experiences of some patients and their physicians, it may be making a comeback. Unfortunately, there are almost no prospective data that would substantiate a claim as to its effectiveness. This article discusses the historic aspects of prostatic massage, suggests possible mechanisms of action, and describes the opinions of North American urologists who are associated with academic clinical research centers and are universally acknowledged as experts in the diagnosis and treatment of prostatitis. At this time, the science of prostatic massage must rely on anecdotal experiences, small, uncontrolled studies, and perhaps somewhat biased opinions of the major thought leaders in the field of chronic prostatitis/chronic pelvic pain syndrome.

Chronic Disease↗
PubMed1998

Cancer cell necrosis by autoschizis: synergism of antitumor activity of vitamin C: vitamin K3 on human bladder carcinoma T24 cells.

Scanning and transmission electron microscopy and fluorescence light microscopy were employed to characterize the cytotoxic effects of vitamin C (VitC), vitamin K3 (VitK3) or a VitC:VK3 combination on a human bladder carcinoma cell line (T24) following 1-h and 2-h vitamin treatment. T24 cells exposed to VitC alone exhibited membranous damage (blebs and endoplasmic extrusions, elongated microvilli). VitK3-treated cells displayed greater membrane damage and enucleation than those treated with VitC as well as cytoplasmic defects characteristic of cytoskeletal damage. VitC:VitK3-treated cells showed exaggerated membrane damage and an enucleation process in which the perikarya separate from the main cytoplasmic cell body by self-excision. Self-excisions continued for perikarya which contained an intact nucleus surrounded by damaged organelles. After further excisions of cytoplasm, the nuclei exhibited nucleolar segregation and chromatin decondensation followed by nuclear karryorhexis and karyolysis. This process of cell death induced by oxidative stress was named autoschizis because it showed both apoptotic and necrotic morphologic characteristics.

Adenocarcinoma↗
PubMed1998

Rates of glucagon activation and deactivation of hepatic glucose production in conscious dogs.

To determine the time course of glucagon activation and deactivation of hepatic glucose production (HGP), studies were conducted in 18-hour fasted, conscious dogs. Somatostatin was infused with insulin replaced intraportally at 1.8 pmol x kg(-1) x min(-1) and glucagon replaced peripherally at 1.0 ng x kg(-1) x min(-1). After a 2-hour control period, glucagon infusion was either (1) increased fourfold for 4 hours (GGN 4X), (2) increased fourfold for 30 minutes and returned to a basal rate for 3.5 hours (GGN 4X/1X), or (3) fixed at the basal rate for 4 hours (GGN 1X). In the latter two protocols, glucose was infused peripherally to match glucose concentrations observed during GGN 4X. Glucose turnover was determined by deconvolution with the impulse response of the glucose system described by a two-compartment, time-varying model identified from high-performance liquid chromatography (HPLC)-purified [3-3H]glucose tracer data. In GGN 4X, HGP was stimulated from 15.2 +/- 0.9 micromol x kg(-1) x min(-1) to 52.7 +/- 6.5 micromol x kg(-1) x min(-1) after just 15 minutes, but it decreased over the subsequent 3 hours to a rate 25% above basal. In GGN 4X/1X, the increase in HGP during the first 30 minutes equaled that observed in GGN 4X, but when glucagon infusion was returned to basal, HGP decreased in 15 minutes to rates equal to those observed in GGN 1X. The times for half-maximal activation and deactivation of glucagon action were equal (4.5 +/- 1.0 and 4.0 +/- 1.1 minutes, respectively). The very rapid and sensitive hepatic response to glucagon makes pancreatic glucagon release a key component of minute-to-minute glucose homeostasis.

Animals↗
PubMed1997

Brain of the conscious dog is sensitive to physiological changes in circulating insulin.

The aim of this study was to determine whether a selective, physiologically relevant increase in blood-borne insulin perfusing the brain has an impact on the counterregulatory response to hypoglycemia. Experiments were carried out on 12 conscious 18-h-fasted dogs. Insulin was infused (1 mU x kg(-1) x min(-1)) in separate, randomized studies into a peripheral vein (n = 6) or both carotid and vertebral arteries (n = 6). This resulted in equivalent systemic insulinemia (38 +/- 2 vs. 35 +/- 5 microU/ml) but differing head insulin levels (38 +/- 2 microU/ml during peripheral infusion and an estimated 90 microU/ml during head insulin infusion). Glucose was infused during peripheral insulin infusion to equate the level of hypoglycemia (58 +/- 2 mg/dl) to that obtained during head insulin infusion (57 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and hypoglycemia, incremental area under the curve responses for epinephrine, glucagon and cortisol were increased during head insulin infusion (P < 0.05). Net hepatic glucose output, gluconeogenesis, and lipolysis were increased 50-100% (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog 1) physiologically relevant increases of blood-borne insulin to the head can amplify neuroendocrine and metabolic counterregulatory responses and 2) glucagon secretion can be regulated, in part, by neural efferent activity.

Alanine↗
PubMed1996

Neural and pancreatic influences on net hepatic glucose uptake and glycogen synthesis.

The role of the liver nerves in the disposition of peripherally administered glucose was examined in seven hepatic innervated (HI) and nine hepatic denervated (HD) 42-h-fasted conscious dogs. After a 40-min basal period, there was a 4-h experimental period during which the hepatic glucose load was increased twofold via peripheral glucose infusion. Somatostatin was infused to suppress pancreatic endocrine secretion, and insulin and glucagon were infused intraportally to produce a fourfold increase in insulin and a gradual decrease (approximately 25%) in glucagon. The area under the curve of net hepatic glucose uptake (NHGU) during the glucose infusion period totaled 483 +/- 82 and 335 +/- 32 mg/kg in HD and HI, respectively (P < 0.05). The area under the curve of the hepatic fractional extraction of glucose was 27% greater in HD (P < 0.05). Net hepatic lactate output was similar in the two groups, and net hepatic glycogen synthesis was 3.8 +/- 0.8 vs. 2.7 +/- 0.5 mg.kg dog wt-1.min-1 in HD and HI, respectively (P = 0.13). The direct pathway of glycogen synthesis was responsible for 54-58% of net hepatic glycogen synthesis in both HI and HD (n = 6 for both). In summary 1) NHGU in response to peripheral glucose infusion was approximately 44% greater in HD than in HI, 2) net hepatic glycogen synthesis was enhanced by 41% in HD although the probability of this change was 0.13, and 3) the contribution of the direct pathway to glycogen synthesis was the same in HD and HI. These data are consistent with a role for the liver nerves in regulating the magnitude of NHGU in response to glucose administration. They also indicate that the absence of liver nerves may reduce glycogen turnover during glucose infusion.

Alanine↗
PubMed1996

Intraoperative endoscopy as an adjunct to surgical ligation of multiple arteriovenous malformations.

We present a case report of a 69-year-old man with multiple medical problems who presented to the Veterans Hospital in Tucson, Arizona, with recurrent upper gastrointestinal bleeding following multiple upper endoscopic attempts at chemical injection and thermal coagulation of several vascular malformations of the duodenum. Intraoperative endoscopy was employed to identify the location of three small mucosal lesions. By employing transmural endoscopic illumination and direct endoscopic visualization we identified all arteriovenous malformations and then ligated them with silk ligatures from the bowel wall exterior during surgical exploration, avoiding duodenotomy and duodenectomy. The patient has had an uneventful recovery with no evidence of recurrent bleeding at a 1-year follow-up.

Abnormalities, Multiple↗
PubMed1995

Paradoxical insulin-induced increase in gluconeogenesis in response to prolonged hypoglycemia in conscious dogs.

The aim of this study was to determine the effects of differing insulin concentrations on the gluconeogenic response to equivalent prolonged hypoglycemia. Insulin was infused intraportally, for 3 h, into normal 18-h fasted conscious dogs at 2 (lower, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during high dose to maintain the hypoglycemic plateau (50 +/- 1 mg/dl) equivalent to lower. Epinephrine (806 +/- 180 vs. 2,589 +/- 260 pg/ml), norepinephrine (303 +/- 55 vs. 535 +/- 60 pg/ml), cortisol (5.8 +/- 1.2 vs. 12.1 +/- 1.5 micrograms/dl), and pancreatic polypeptide (598 +/- 250 vs. 1,198 +/- 150 pg/ml) were all increased (P < 0.05) in the presence of high-dose insulin. Net hepatic glucose production increased significantly from 2.2 +/- 0.3 to 3.8 +/- 0.5 mg.kg-1.min-1 (P < 0.05) during high-dose infusion but remained at basal levels (2.3 +/- 0.4 mg.kg-1.min-1) during lower-dose insulin. During the 3rd h of hypoglycemia, gluconeogenesis accounted for between 42 and 100% of glucose production during high-dose infusion but only 22-52% during lower-dose insulin. Intrahepatic gluconeogenic efficiency, however, increased similarly during both protocols. Lipolysis, as indicated by arterial blood glycerol levels, increased by a greater amount during high- compared with lower-dose insulin infusion. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. Gluconeogenesis remained similar to basal levels, but lipolysis was significantly suppressed during both series of hyperinsulinemic euglycemic studies. In summary, these data suggest that 1) the important counterregulatory processes of gluconeogenesis and lipolysis can be significantly increased during prolonged hypoglycemia despite an eightfold increase in circulating insulin levels and 2) the amplified gluconeogenic rate present during the hypoglycemic high-dose insulin infusions was caused by enhanced substrate delivery to the liver rather than an increase in intrahepatic gluconeogenic efficiency.

Animals↗