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Biomedical subjects

A Stevenson

Publications and source records attributed to A Stevenson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis.

Tubular damage is a recognized feature of both overt diabetic nephropathy and glomerulonephritis. However, the pattern and mechanism of tubular damage in the two clinical settings remain unclear. Two groups of patients with macroalbuminuria (albuminuria > 300 mg/day) were studied. Group 1 comprised 41 patients with biopsy proven primary glomerulonephritis and group 2 comprised 28 patients with clinical diabetic nephropathy due to insulin dependent diabetes mellitus. Serum creatinine, creatinine clearance, glomerular proteinuria (albuminuria and transferrinuria), markers of tubular damage such as urinary excretion of lysosomal enzyme (N-acetyl glucosaminidase), brush border enzymes (leucine aminopeptidase and gamma-glutamyl transferase) and retinol binding protein (tubular protein) were measured. Both groups were comparable in serum creatinine, creatinine clearance, glomerular proteinuria and excretion of N-acetyl-glucosaminidase. However, a significantly higher degree of tubular brush border enzymuria and a lower level of tubular proteinuria were seen in group 1 than in group 2. In group 1, albuminuria correlated to tubular enzymuria and tubular proteinuria. However, there was no correlation in diabetic patients between parameters of glomerular and tubular damage or dysfunction. The data presented suggested that the pattern of tubulopathy is different in patients with comparable degree of macroalbuminuria due to diabetic nephropathy and glomerulonephritis. Moreover, in diabetic nephropathy contrary to glomerulonephritis, markers of tubular damage are unrelated to glomerular proteinuria. This may suggest different mechanisms of tubular damage in the two clinical settings. We recommended that in all patients with proteinuria, particularly those with diabetic nephropathy, markers of renal tubular damage may be useful in monitoring the course of their disease.

Acetylglucosaminidase↗
PubMed1994

Evidence of oxidant injury and tubular damage in early diabetic nephropathy.

Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.

Adult↗
PubMed1993

The value of quantitative testicular biopsy and deoxyribonucleic acid flow cytometry in predicting sperm recovery from electrostimulated ejaculates.

Spermatogenic abnormalities have been reported in the majority of men following spinal cord injury, and they contribute to the multifactorial etiology of reproductive dysfunction. Thus far, few have studied the seminiferous epithelium in this group of patients by objective criteria. While quantitative micrometry and flow cytometric analysis are accurate and reproducible methods of quantitating spermatogenesis, the latter is simpler and permits needle aspiration for tissue recovery. The objective of this study is to determine the value of quantitative micrometry and flow cytometric analysis as methods of predicting total sperm yield in electrostimulated ejaculates. Incisional testicular biopsy was performed in 12 anejaculatory men, and the tissue specimens were divided for analysis by quantitative micrometry and flow cytometric analysis. Quantitative micrometry consisted of determining the mean tubular wall thickness, mean tubular concentration of the Sertoli cells and mature spermatids in a minimum of 10 round seminiferous tubules per patient. Specimens were prepared for flow cytometric analysis and the deoxyribonucleic acid histogram was analyzed to determine the percentage of cells in each ploidy compartment. Of the quantitative micrometry parameters analyzed a significant correlation resulted between the total sperm yield per electroejaculate and the mean tubular concentration of late spermatids (p = 0.001) as well as with the mean tubular ratio of late spermatids to Sertoli cells (p = 0.003). The tubular concentration of spermatids resulted in a sensitivity and specificity of 100% and 75%, respectively, to predict adequate sperm yield in semen. Likewise, the mean tubular ratio of spermatids to Sertoli cells resulted in a sensitivity and specificity of 75% and 87.5%, respectively, in its ability to predict normal sperm yield in the recovered ejaculate. Deoxyribonucleic acid flow cytometry analysis showed a normal haploid compartment in all 6 specimens studied, and each was associated with high numbers of sperm in recovered semen. Quantitative histometric parameters correlate significantly with the total sperm yield obtained in electrostimulated ejaculates and may have a role in the selection of candidates for treatment in reproductive rehabilitation programs.

Biopsy↗
PubMed1993

Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus.

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hydrocarbon exposure and tubular damage: additional factors in the progression of renal failure in primary glomerulonephritis.

To investigate the role of hydrocarbon exposure in the progression of glomerulonephritis, 68 patients (12 female) with biopsy-proven primary glomerulonephritis (60 proliferative cases, 8 membranous) were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Serum creatinine, proteinuria, and urinary excretion of markers of renal tubular damage were measured. Patients were assessed for evidence of progressive renal failure (PRF) (defined as persistent rise of serum creatinine > 50 mumol/l above the baseline) during a mean follow up period of 5 years. Patients were divided according to the presence or absence of PRF, (group 1, n = 29, with PRF) and (group 2, n = 39, without PRF). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood pressure control. The derived chronic hydrocarbon exposure scores were significantly higher in group 1 than 2 (p < 0.001). Moreover, hydrocarbon exposure score since the diagnosis of glomerulonephritis was significantly higher in group 1 than 2 (p < 0.001). In group 1, 73% of patients continued to be exposed to hydrocarbons at their work site after the diagnosis of glomerulonephritis, compared to only 13% in group 2 (p < 0.001). At renal biopsy, group 1 had a significantly higher mean serum creatinine than group 2 but the degree of proteinuria and proportion of patients with hypertension were similar. During follow-up serum creatinine rose significantly in group 1 but not in group 2. In group 2, proteinuria fell significantly during follow-up but remained unchanged in group 1. A higher proportion of patients from group 1 developed hypertension requiring antihypertensive drugs (84% vs. 28%; p < 0.001). Urinary marker secretion data indicated a possible association between tubular damage and renal impairment. These results suggest that chronic hydrocarbon exposure and renal tubular damage are important additional risk factors in the progression of primary glomerulonephritis.

Acetylglucosaminidase↗
PubMed1993

Hereditary non-polyposis colorectal cancer (Lynch syndrome I) in a 13 year old male.

A case of adenocarcinoma of the colon is reported. It presented in a family with hereditary non-polyposis colorectal cancer (HNPCC). Colonoscopic screening at a young age is recommended in such families. It also suggests a genetic basis for colorectal carcinogenesis in this family. Three of the members of this family also have peptic ulceration and an association between this syndrome and HNPCC is postulated.

Adolescent↗
PubMed1993

Aging and spontaneous reactivation of human plasma cholinesterase activity after inhibition by organophosphorus pesticides.

The in vitro rates of aging and spontaneous reactivation of human plasma cholinesterase (ChE) after inhibition by several organophosphorus pesticides (OPs) have been studied. After inhibition by OP the enzyme can undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the enzyme. The rates of these two reactions depend on the nature of the phosphoryl group of the OP bound to the active site of ChE. Most OPs registered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom. Reaction rate constants for aging and spontaneous reaction are reported. Dimethoxy OPs cause half-lives of aging in human plasma ChE of approximately 6 hours and 23 hours at 37 degrees C and 22 degrees C respectively; for diethoxy OPs the values are 12 hours and 39 hours. Reappearance of enzyme activity, after removal of OP, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours and 15 hours at 37 degrees C and 22 degrees C. These effects, both in vivo and ex vivo, may have relevance in developing a monitoring strategy for dimethoxy OPs using plasma ChE measurements. Inhibition by diethoxy OPs spontaneously reactivates very slowly, even at 37 degrees C, and would not practically influence the measured inhibition. No spontaneous reactivation was detected in human plasma ChE inhibited by the methoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylamino substituted OP (crufomate) during 45 hours incubation at 37 degrees C.

Cholinesterase Inhibitors↗
PubMed1993

Renal impairment with chronic hydrocarbon exposure.

Occupational hydrocarbon exposure is believed by some investigators to play an important role in the development of several non-neoplastic renal diseases. In view of the continuing debate in this area of nephrology we adopted a cross-sectional approach by investigating the prevalence of clinical or sub-clinical renal dysfunction in subjects chronically exposed to hydrocarbons at their work site. Three groups of healthy men working in different and separate areas of a major car manufacturing plant in the North-west of England participated in the study. Group 1 comprised 112 paint sprayers with exposure to paint-based hydrocarbons, group 2 comprised 101 volunteers working in the transmission area of the plant with exposure to petroleum-based mineral oils, and group 3 comprised 92 automated press operators with minimal background exposure to lubricants who acted as internal controls. Early markers of renal dysfunction such as serum creatinine, urinary total protein, albumin, transferrin, retinol binding protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion were measured. Upper reference values of the parameters measured were derived from 105 comparable laboratory based controls with no occupational exposure to hydrocarbons or heavy metals. Group 1 had a significantly higher prevalence of elevated serum creatinine than the other groups and a higher prevalence of abnormal urinary total protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion than groups 2 and 3. Group 2 had normal serum creatinine but a significantly higher prevalence of abnormal urinary total protein, transferrin, retinol binding protein, N-acetyl-glucosaminidase, and leucine-amino-peptidase excretion than group 3. Serum albumin was similar in all groups. There was some clustering of abnormal findings but the markers of renal dysfunction used in the study identified 37 individuals in group 1 and 31 subjects in group 2 with at least one abnormal parameter, compared to only five individuals in internal controls. This difference between the two target groups and group 3 was highly significant (p < 0.001). Subjects with chronic paint exposure had renal impairment and tubular dysfunction. Tubular dysfunction was also prominent with petroleum oil exposure. We therefore conclude that chronic hydrocarbon exposure may be associated with clinical and sub-clinical renal dysfunction. We advocate careful monitoring of workers exposure to hydrocarbons and for more effective preventive measures.

Adult↗
PubMed1989

Celiprolol in systemic hypertension.

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.

Antihypertensive Agents↗
PubMed1986

The epidemiology of malaria in a population surrounding Madang, Papua New Guinea.

Malaria is prevalent throughout coastal and lowland Papua New Guinea. Recent changes, including a shift from predominance of Plasmodium vivax to Plasmodium falciparum, appearance of chloroquine-resistant P. falciparum and decreased effectiveness of vector control programs have been observed. Epidemiological features of malaria were studied through four six-month surveys of a population of 16,500 in Madang Province from 1981-1983. Baseline data on parasitology, splenic enlargement, serology, hemoglobin levels, prevalence of 4-aminoquinolines, utilization of mosquito nets and incidence of fever were collected for use in future evaluation of malaria control measures including possible field trials of an antimalarial vaccine. Prevalence of parasitemia (all species, all ages) varied from 35.0% to 42.7% over the four surveys each of which covered a random sample of 25% of the population. The ratio of parasite species was: P. falciparum 70:P. vivax 25:P. malariae 5 in the dry seasons, shifting slightly in favor of P. falciparum during the wet seasons. Intense year-round transmission was indicated by decreasing parasite prevalence and splenic enlargement with age, low density asymptomatic parasitemias and high prevalence of antimalarial antibodies (i.e., greater than 80% of the population over five years of age was ELISA-positive). Levels of endemicity varied geographically, presence of 4-aminoquinolines in urine samples was relatively common (12.7% positive) and chloroquine resistance was widespread (81.6% in vitro, 46.6% in vivo).

Adolescent↗
PubMed1975

Serum immunoglobulin levels in patients with breast cancer.

Serum immunoglobulin levels IgA, IgG, and IgM have been estimated in 92 patients with breast cancer and 50 control patients, 40 of whom had benign disease of the breast. In patients with breast cancer, IgA was significantly raised at all stages and IgG was significantly reduced, but the two abnormalities were not necessarily concomitant. These findings may suggest a disturbance in the secretory immune system, and immunologic defect even when the cancer is localized to the breast.

Breast Neoplasms↗
PubMed1975

Fifty-two consecutive aortic valve replacements employing local deep hypothermia.

From August, 1972, to May, 1974, 52 consecutive aortic valves were replaced with the Björk-Shiley tilting-disc prosthesis. The hospital mortality was zero. Patients ranged in age from 14 to 77 years, and 19 patients had simultaneous correction of associated cardiac lesions. Using techniques of low flow and local deep hypothermia, aortic valve replacement can be accomplished with little risk even in patients with associated coronary arteriosclerosis. Coronary artery perfusion is unnecessary and often hazardous. Follow-up periods vary from one to twenty-one months. Forty-nine patients are alive and substantially improved.

Adolescent↗
PubMed1973

Local immunoglobulin production in breast cancer.

Immunoglobulin levels (IgA, IgG, IgM) have been estimated in protein extracts of 55 malignant and 20 benign tumours of the breast, and in 17 normal tissues from a cancer bearing breast. IgA and IgG were significantly reduced in cancer compared with both benign and normal tissues but IgM, detected in only a third of tumours, was significantly increased. Total immunoglobulin levels and IgG in the malignant tumours correlated with plasma cell infiltration.The menstrual status of the patient had no influence on these findings.

Adenofibroma↗