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Biomedical subjects

N Alexander

Publications and source records attributed to N Alexander.

At least 55 records · Page 3Linked to original sources
PubMed1991

Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients--a comparison of two oral formulations.

The single-dose and steady state kinetics of morphine given as controlled-release tablets (30 mg every 12 h) and as a solution (15 mg every 6 h) have been compared in 11 cancer patients with chronic pain. The concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were analyzed by HPLC. There were no significant differences between the tablets and solution in the mean steady state concentrations of morphine, M3G or M6G. The tmax was 3.3 h for the tablets compared to 1.1 h for the solution. After giving the controlled-release tablets every 12 h there was a significantly higher fluctuation index of the morphine concentrations than after the solution. Urinary recovery at steady state was comparable between the two preparations, with averages of 57% and 47%, respectively. Thus, no major differences were found in the pharmacokinetics of morphine and its glucuronidated metabolites after 30 mg morphine as controlled-release tablets every 12 h or 15 mg of morphine solution every 6 h, except for a significantly longer tmax and greater fluctuation in morphine concentrations after the controlled-release tablets.

Adenocarcinoma↗
PubMed1991

Effect of environmental stress on release of norepinephrine in posterior nucleus of the hypothalamus in awake rats: role of sinoaortic nerves.

Norepinephrine(NE) release in posterior nucleus(PH) of the hypothalamus was examined before and during acute shaker (oscillation) stress in sinoaortic denervated(SAD) and sham-operated(SO) rats. NE in PH extracellular fluid of freely moving rats was collected by microdialysis and measured by sensitive radioenzymatic assay. Three days after SAD or SO operation, mean arterial pressure(MAP) and heart rate(HR) were significantly higher in SAD rats than SO rats. Baseline levels of NE in PH dialysate were also significantly elevated in SAD rats. Although five minutes of shaker stress elicited pressor and tachycardic responses coupled with increased NE release in PH of both groups, the increases in MAP and dialysate NE were larger in SAD than SO rats. These findings indicate that noradrenergic neurons in the PH respond to stress-induced stimuli and receive tonic input from baroreflex pathways.

Animals↗
PubMed1991

Hypothalamic NE release and cardiovascular response to NaCl in sinoaortic-denervated rats.

We determined the activity of noradrenergic neurons in the nucleus of the posterior hypothalamus (PH) of sinoaortic-denervated (SAD) and sham-operated (SO) rats during cardiovascular responses to intravenous (iv) or local brain dialysis of NaCl. PH extracellular norepinephrine (NE) was collected by microdialysis from freely moving rats, and dialysate NE was measured by radioenzymatic assay. Three days after SAD or SO, mean arterial pressure (MAP) and heart rate (HR) were significantly higher in SAD rats than SO rats. Basal levels of PH dialysate were also significantly elevated in SAD rats. Local dialysis of PH with hypertonic NaCl produced pressor and tachycardiac responses coupled with increased NE release in PH in both groups, but the increases in MAP and dialysate NE were larger in SAD than SO rats. Ganglionic blockade with iv hexamethonium elicited significantly larger depressor and bradycardiac responses in SAD rats, whereas the percent increase of dialysate NE was smaller than that of SO rats. The iv infusion of hypertonic NaCl produced larger pressor responses in SAD than SO rats and a significant increase in dialysate NE from PH of SAD but not SO rats. These findings indicate that 1) PH is an important site of NaCl action and 2) noradrenergic input in PH receives tonic inhibitory input from baroreflex pathways and contributes to cardiovascular hyperactivity and hypertension in SAD rats.

Animals↗
PubMed1991

Acute effect of norfenefrine on the urethral pressure profile in females with genuine stress incontinence.

To study the acute effect of norfenefrine, given orally in aqueous solution, on the urethral closure function, profilometry was performed before and after administration of placebo and increasing doses of norfenefrine in 6 females with genuine stress incontinence. A weak increase in urethral pressure was observed after administration of 90 mg of norfenefrine. No changes in heart rate and blood pressure occurred. The results indicate that the direct sympathomimetic effect of norfenefrine is weak. It is suggested that norfenefrine mainly acts via indirect mechanisms.

Female↗
PubMed1990

Right-left asymmetry of tyrosine hydroxylase in rat median eminence: influence of arterial baroreflex nerves.

Arterial baroreceptor nerves consist of 2 pairs of nerves, carotid sinus and aortic. The latter nerves differ bilaterally as to size and origin suggesting that central baroreceptor activity could be asymmetrical. This was tested by studying activity of tyrosine hydroxylase (TH), the rate limiting enzyme for catecholamine synthesis, on right and left sides of the brain in median eminence (ME), arcuate nucleus (ARCN), paraventricular nucleus (PVN) and supraoptic nucleus (SON). Seven days after right or left sinoaortic denervation (SAD), bilateral SAD or sham-operation (SO), in situ TH activity was determined by the rate of dihydroxyphenylalanine (DOPA) accumulation following administration of a dopa decarboxylase inhibitor. Unexpectedly, the intact, SO rats had significantly lower DOPA concentrations on the left than right sides of ME in two separate studies; right-left differences averaged 24% and 38%. Evidence supporting asymmetry of TH activity was the lower concentrations of catecholamines on left than right sides of the brain in intact SO rats, namely, dopamine in ME and ARCN and norepinephrine and epinephrine in ARCN. Unilateral and bilateral SAD further suppressed TH activity on the left side of the ME; the maximum right-left difference was 58% in rats with right SAD. Their ARCN also showed asymmetry of TH activity. Asymmetry of TH activity was attributable to asymmetry of TH protein which was significantly lower on the left sides of ME and ARCN. This is the first demonstration of bilateral asymmetry of TH in mediobasal hypothalamus and its enhancement by interruption of left or right afferents from the arterial vascular system.

Animals↗
PubMed1990

Progesterone and 17 alpha-hydroxyprogesterone. Novel stimulators of calcium influx in human sperm.

Progesterone and 17 alpha-hydroxyprogesterone (but not other steroids such as testosterone, corticosterone, beta-estradiol, estrone, dehydroepiandrosterone, 20 alpha-hydroxypregnen-3-one, androstenedione, and pregnenolone) were shown to cause an immediate increase, in free cytosolic calcium ([Ca2+]i) in both capacitated and noncapacitated human sperm, using the fluorescent indicator fura 2. Significant increases in [Ca2+]i were observed with 10 ng/ml progesterone, while maximum effects were seen with 1 microgram/ml progesterone. Two other steroids 11 beta-hydroxyprogesterone and 5 alpha-pregnane-3,20-dione exhibited significant activity to increase [Ca2+]i. This increase in [Ca2+]i elicited by progesterone was entirely due to Ca2+ influx from the extracellular medium since the increase in [Ca2+]i was blocked by the Ca2+ chelator EGTA (2.5 mM) and the Ca2+ channel antagonist La3+ (0.25 mM) when added to the medium containing 2.5 mM Ca2+. Progesterone also stimulated the uptake of Mn2+ into sperm as measured by the quenching of fura 2 fluorescence. Progesterone has been found in human follicular fluid at levels capable of stimulating increases in [Ca2+]i. The similarities in responses induced by human follicular fluid and progesterone an increase in [Ca2+]i, and hence the acrosome reaction, is progesterone and/or 17 alpha-hydroxyprogesterone. Progesterone (1 microgram/ml) did not increase [Ca2+]i in somatic cells such as adipocytes, hepatocytes, Balb/c 3T3 cells, normal rat kidney, or DDT1 MF-2 cells. The effects of these progestins to increase [Ca2+]i, by activating a receptor-operated calcium channel, is the first report of such an activity in sperm. This phenomena possibly opens up a new field of steroid action in the area of sterility, fertility, and contraception at the level of the sperm.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Extracellular oxytocin in the paraventricular nucleus: hyperosmotic stimulation by in vivo microdialysis.

The effect of central osmotic stimulation on oxytocin (OT) secretion from the paraventricular nucleus (PVN) was examined using a newly developed in vivo microdialysis technique. A dialysis probe was inserted into the PVN region and microdialysis was performed in conscious animals. Hyperosmotic solutions were delivered via the dialysis probe, and perfusate and blood samples were collected. OT was consistently detected in the PVN dialysate. Hyperosmotic sodium chloride (1 M) produced a significant increase in dialysate and plasma OT, whereas D-mannitol (2 M) had no effect. These results suggest that (1) in vivo microdialysis may provide a useful technique for the evaluation of neuropeptide secretion from specific brain regions and (2) there are sodium-sensitive cells in the PVN region which respond to increases in extracellular sodium, resulting in an increase in central and peripheral oxytocin secretion.

Animals↗
PubMed1990

Microdialysis in the posterior hypothalamus: sodium chloride affects norepinephrine release, mean arterial pressure, heart rate and behavior in awake rats.

A microdialysis probe, implanted in the posterior hypothalamus (PH) was used to examine changes of extracellular norepinephrine (NE) in freely moving rats from which mean arterial pressure (mAP) and heart rate (HR) were continuously monitored. Artificial cerebrospinal fluid (aCSF) was pumped through the probe and 10-microliters dialysate samples were collected at 5-minute intervals and analyzed for NE by radioenzymatic assay. High sodium chloride (NaCl)-aCSF solution elicited pressor and tachycardiac responses and locomotor activity coupled with significant increases in levels of dialysate NE. The latter and the associated cardiovascular effects were significantly attenuated by perfusate lidocaine (0.5%). When alpha-adrenergic receptors in PH were blocked by phenoxybenzamine (0.165 M), high NaCl-aCSF released NE but the associated cardiovascular effects were attenuated. In addition, intravenous ganglionic blockade with hexamethonium (25 mg/kg) also attenuated cardiovascular responses during the high NaCl-aCSF perfusion of PH. These results indicate that PH is one of the important areas for central actions of NaCl and that the cardiovascular and locomotor responses produced by central NaCl, in part, depend on neuroadrenergic activity in PH.

Animals↗
PubMed1990

Gastric dysplasia: inter-observer variation, sulphomucin staining and nucleolar organizer region counting.

Gastric dysplasia is regarded as a pre-neoplastic lesion and is generally believed to have higher potential for malignant transformation with increasing grade. To obtain consistency in diagnosis and management, reproducible diagnostic criteria are needed. We have used the classification system of the International Study Group on Gastric Cancer--ISGGC and investigated the interobserver variation in histological diagnosis. A Kappa statistic of 0.579, which reflects moderate agreement, was obtained for variation between two experienced pathologists. The prevalence of type III intestinal metaplasia was studied and found to occur in 55% of dysplastic areas, but in only 9% of hyperplastic areas (P less than 0.01). In addition, the correlation of mean nucleolar organizer region (AgNOR) counts with diagnostic categorization was investigated. A significant inter-observer variation was found between an experienced pathologist and a postgraduate student and only one of the observers obtained statistically significant separation of mean AgNOR counts between the categories of high-grade dysplasia, low-grade dysplasia, atypical hyperplasia, simple hyperplasia and normal.

Adult↗
PubMed1990

Long-term outcome after photocoagulation for proliferative diabetic retinopathy.

One-hundred and forty patients with 182 treated eyes were followed for up to 10 years after photocoagulation for proliferative diabetic retinopathy. Sixty-eight patients were still alive and under review after 10 years. Mortality was 33% at 10 years and the survivors were younger when treated and had lower systolic and diastolic blood pressures, a lower urea and creatinine and a lower prevalence of proteinuria and ECG evidence of ischaemia at baseline. Sixty-nine percent of all patients and 82% of those followed up for 10 years maintained good vision (6/12 or better) in their better eye at the last follow-up. Visual deterioration occurred mostly in the first 2 years after treatment and risk factors for poor final vision were poor vision at baseline, severity of disc new vessels, and age at presentation. It is concluded that the short-term beneficial effect of photocoagulation is maintained over long periods of follow-up.

Adult↗
PubMed1990

Cross sectional echocardiographic identification of hypoplastic left heart syndrome and differentiation from other causes of right ventricular overload.

To identify the echocardiographic features that can be used to distinguish between hypoplastic left heart syndrome and other causes of right ventricular overload in the sick neonate cross sectional echocardiographic studies of 10 neonates with hypoplastic left heart syndrome were analysed and compared with those in 15 neonates with other causes of right ventricular overload and 15 normal controls. Left ventricular and right ventricular cavity dimensions and the shape and size of the mitral valve annulus and aortic root were recorded and presented both as absolute values (mm) and corrected for body surface area (mm/m2). Logistic regression was used to produce a classification rule to estimate the probability of a neonate having hypoplastic left heart syndrome. The diameter of the mitral valve annulus was the single most discriminative variable. There was, however, considerable overlap of all the calculated features between neonates with hypoplastic left heart syndrome and those with other causes of right ventricular overload. The diagnosis of hypoplastic left heart syndrome should not be based on any one single echocardiographic feature but the general appearance of abnormal left heart valves, small cavity dimensions, and the size of the mitral valve annulus.

Anthropometry↗
PubMed1990

Outcome of radical surgery in hilar cholangiocarcinoma.

In a prospective study performed between 1977 and 1985, 27 patients with cholangiocarcinoma at the confluence of the hepatic ducts underwent resection aiming at cure. Eleven patients underwent local excision and 16 underwent partial liver resection (extended right hepatic lobectomy in 12, left hepatic lobectomy in 3, and extended left hepatic lobectomy in 1). The 60-day hospital mortality rate was 7.4% (2 patients). None of 11 patients who underwent local excision and only 1 (5.5%) of 18 patients who had not undergone previous surgery, or preoperative biliary drainage, died in the hospital. The overall median and mean survival times for the 24 patients who left the hospital were 25 and 29 months, respectively (range, 5 to 80 months). Twenty patients died after a median survival of 22 months (mean, 25 months; range, 5 to 80 months). Four patients are alive and well at 45, 48, 51, and 54 months. Estimated (Kaplan-Meier) survival rates for all 27 patients at 1, 3, and 5 years were 70%, 26%, and 22%, respectively, with almost all patients dying of persistent or recurrent local disease. Survival time after hepatic resection was not statistically different from that after local excision of the lesion (p greater than 0.1). The difference in survival times between patients with histologic clearance and those with microscopically positive or close (less than 1 mm) resection margins was marginally significant statistically (p = 0.037). The quality of life was good. These results are in agreement with those of other studies employing treatment by excision and emphasize the need to assess all patients with hilar cholangiocarcinoma with a view to resection before the adoption of surgical bypass or palliative intubational procedures. However, further progress is unlikely to be made without significant advances in adjuvant therapy.

Adenoma, Bile Duct↗
PubMed1989

Norfenefrine in the treatment of female urinary stress incontinence assessed by one-hour pad weighing test.

Thirty-three women with urinary stress incontinence were treated with the alpha-adrenoceptor-stimulating agent, norfenefrine (Nevadral Retard). Treatment was administered during 3-24 weeks at a daily dosage of 90 mg. Judged by a 1-hour pad weighing test, a significant effect could be demonstrated. With the exception of 1 case of allergic reaction and 1 case of recurrent vomiting, a simultaneously performed tolerability test revealed only minor side effects.

2-Hydroxyphenethylamine↗
PubMed1989

Baroreceptor influences on oxytocin and vasopressin secretion.

The objective of these studies was to investigate the role of arterial baroreceptors in the control of neurohypophyseal secretion. The effect of sinoaortic denervation on basal and osmotic-induced release of oxytocin and vasopressin and on blood pressure was determined. Hypertonic or isotonic saline was infused intravenously into sham-operated or denervated rats 3 days after surgery. Plasma oxytocin and vasopressin were measured at 5 and 15 minutes after the infusion. The control levels of oxytocin were increased in the denervated rats, but vasopressin levels were not significantly altered. The vasopressin and oxytocin responses to hypertonic saline were greater after baroreceptor denervation. Plasma oxytocin was increased from 4.7 +/- 0.9 to 72.2 +/- 8.7 pg/ml in the denervated rats and from 1.8 +/- 0.3 to 39.9 +/- 6.7 pg/ml in the sham-operated control group at 5 minutes after the infusion (p less than 0.01). The plasma vasopressin response to hypertonic saline was 7.1 +/- 0.6 pg/ml in the sham-operated versus 11.1 +/- 1.6 pg/ml in the denervated rats (p less than 0.05). There was no difference between sham-operated and denervated rats in the effect of hypertonic saline on plasma sodium and hematocrit. Mean arterial blood pressure was increased after sinoaortic denervation (116.3 +/- 4.2 mm Hg in the sham-operated vs. 138.2 +/- 8.3 mm Hg in the denervated rats, p less than 0.05); however, there was no difference in the pressor response to hypertonic saline. These results show that the baroreceptor system influences the secretion of both oxytocin and vasopressin, with effects on basal secretion as well as the response to an osmotic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Issues of aging in preventive medicine and the example of osteoporosis.

Aging introduces a unique dimension into the theory and practice of preventive medicine. Preserving functional status and quality of life assume particular importance in old age. Effective preventive care can serve these goals by compressing the morbidity of old age into a shorter period prior to death and by increasing longevity towards its biological potential. The prevalence of osteoporosis and many other chronic diseases increases steadily with age, as does the clinical significance of these conditions. The pathophysiology of osteoporosis, options for its early detection and treatment and the importance of falls as a precipitant of osteoporotic fractures among the elderly are discussed in detail.

Accidental Falls↗
PubMed1988

Sinoaortic denervation changes catecholamines in caudate-putamen of rats.

The 3-day sinoaortic-denervated (SAD) rat has a reduced concentration of dopamine (DA) in caudate-putamen (CP) (Brain Research, 299 (1984) 380-383). This suggested that the nigrostriatal system processes input from the cardiovascular system via arterial baroreceptor pathways. In this study we compared regional DA levels in CP of SAD and sham-operated (SO) rats 3 and 7 days after surgery. Bilateral CP samples were obtained by micropunch from consecutive frozen brain sections. Samples were taken throughout the entire length of CP from dorsal, lateral and ventral areas. Punches of two consecutive sections were pooled and assayed for DA and norepinephrine (NE). SO rats showed a rostro-caudal gradient of DA in all 3 areas. Three-day SAD rats had significantly lower cumulative DA concentrations in each of the 3 CP areas. The concentrations in each region of the 3 areas were also reduced and about half of them achieved statistical significance. SO rats did not show a gradient of NE. Cumulative NE was significantly lower in dorsal and ventral areas of SAD rats. In 7 days SAD rats, DA values were no longer reduced, but were significantly elevated in dorsal but unchanged in ventral areas. These data support evidence of nigrostriatal interaction with baroreceptor pathways.

Animals↗
PubMed1988

Striatal dopamine release and metabolism in sinoaortic-denervated rats by in vivo microdialysis.

The purpose of this study was to provide new evidence favoring the hypothesis that cardiovascular information from arterial baroreceptors is integrated with the nigrostriatal system that contributes to regulation of motor activity. Samples of extracellular striatal dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were collected by the technique of in vivo microdialysis and analyzed by high-performance liquid chromatography-electron capture detection. Rats were prepared with a guide tube placed in the caudate-putamen for subsequent insertion of microdialysis probes. During the 1st wk after sinoaortic denervation (SAD) or sham operation (SO), a microdialysis probe was inserted and perfused with Ringer solution at the rate of 2 microliter/min in the freely moving rats. Samples were collected every 20 min before and after injection of pargyline, 100 mg/kg ip. The results showed that SAD rats have approximately 50% less extracellular striatal DA, DOPAC, and HVA than SO rats (P less than 0.01). After blockade of monoamine oxidase activity with pargyline, striatal DA accumulated three times faster in SO than SAD rats suggesting DA synthesis is reduced in SAD rats. These data provide further evidence that the arterial baroreceptor system affects dopaminergic metabolism in the nigrostriatal system possibly as a means for integration of cardiovascular and motor activity.

3,4-Dihydroxyphenylacetic Acid↗