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Biomedical subjects

G Nyberg

Publications and source records attributed to G Nyberg.

At least 181 records · Page 10Linked to original sources
PubMed1984

Determination of free fractions of tricyclic antidepressants.

The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment. The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible. Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to alpha 1-acid glycoprotein and for total binding in serum. For alpha 1-acid glycoprotein, the k-values ranged from 1 X 10(5) to 8 X 10(5) M-1, and for pooled serum from 0.4 X 10(5) to 8 X 10(5) M-1. The determined number of binding sites on the alpha 1-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2-14 times the concentration of alpha 1-acid glycoprotein.

Antidepressive Agents, Tricyclic↗
PubMed1984

Guanfacine in essential hypertension: effects during rest and isometric exercise.

The antihypertensive effects of guanfacine (0.5 to 4 mg daily) were investigated for 1 yr in 13 patients with essential hypertension. Blood pressure (BP) and heart rate (HR) response was measured during isometric exercise (handgrip) before starting the therapy, after 1 yr of treatment, and 2 wk after withdrawal. Guanfacine in once-daily dosage reduced BP during rest (supine BP: control, 175 +/- 6/103 +/- 4 mm Hg; 1 yr guanfacine, 161 +/- 5/91 +/- 3 mm Hg). Steady-state plasma concentrations after 1 yr were 4.1 +/- 0.59 ng/ml. Resting plasma norepinephrine (NE) and epinephrine (E) levels were lower during active therapy than 2 wk after withdrawal (guanfacine and control: plasma NE, 0.27 +/- 0.03/0.64 +/- 0.13 ng/ml; plasma E, 0.09 +/- 0.02/0.17 +/- 0.05 ng/ml). The relative reduction of plasma catecholamines (guanfacine and withdrawal) was of the same order during handgrip exercise as during supine rest. During isometric handgrip exercise, BP was lower during guanfacine therapy than before treatment and 2 wk after withdrawal, but the increment in BP during handgrip exercise was not affected by the drug despite the lower BP values on therapy. Our data indicate that the central alpha 2-agonist action of guanfacine reduces sympathoadrenal function equally during rest and isometric exercise.

Blood Pressure↗
PubMed1984

Smoking and diabetic nephropathy.

Forty-seven patients with insulin-dependent diabetes (IDDM) and diabetic nephropathy and 47 controls with IDDM without diabetic nephropathy were interviewed about their previous and current smoking habits. The patients in the two groups were matched according to sex, age, age at onset, and duration of diabetes. All patients in the nephropathy group had proteinuria and decreased glomerular filtration. None in the control group had ever had proteinuria as tested by dip stick. The total amount of smoking until date of interview was estimated for each individual and presented as an index. The patients with nephropathy had a significantly higher smoking index than the controls. In the nephropathy group there were also more numerous current smokers, more heavy smokers and fewer individuals who had never smoked than in the control group. The link between diabetic renal microangiopathy and smoking may be through mechanisms such as increased platelet aggregation, accentuated tissue hypoxia and hemodynamic or metabolic effects of repeated noradrenaline release.

Adult↗
PubMed1984

Oral mucosal lesions in systemic lupus erythematosus--a clinical, histopathological and immunopathological study.

The oral mucosa was investigated in 51 patients with systemic lupus erythematosus (SLE). Lesions were seen in 23 patients (45%). Most lesions were of discoid type or erythemas; only 3 were seen in 23 patients (45%). Most lesions were of discoid type or erythemas; only 3 were ulcerations. The hard palate, buccal mucosa and vermilion border were the most frequent sites of involvement. The overall prevalence was not related to disease activity, but discoid lesions and ulcerations were only seen in patients with active disease. Histopathological investigation showed liquefactive degeneration in 6 biopsies of 10 lesions. Immunofluorescence examination was positive in all cases.

Adult↗
PubMed1984

Circulatory effects of nitroglycerin ointment (Nitrong) with special reference to venous distensibility.

Nitroglycerin ointment (Nitrong 2%, 5 cm) and an identical placebo ointment were tested in a double-blind crossover study in five healthy volunteers to determine its influence on heart rate, blood pressure, and venous distensibility during supine rest and at 45 degrees tilt. Two hours after administration, a significantly higher venous distensibility was observed with the active ointment than with placebo. There were insignificant changes in heart rate and blood pressure. Three of the five subjects experienced headache for 6 h or more after active ointment.

Adolescent↗
PubMed1984

Quantitative studies of glomerular ultrastructure in human and experimental diabetes.

A brief review is given of glomerular structural changes in diabetes mellitus and in rats with induced diabetes. The stereological methods for obtaining quantitative structural data are mentioned, and references are given to the underlying theories as well as to more detailed descriptions of the practical performance. In short-term diabetes a glomerular hypertrophy is found with increase in the surface area of the capillaries, in parallel with an increase in glomerular filtration. In long-term diabetes mellitus the picture is dominated by accumulations of basement membrane: thickening of the peripheral basement membrane and expansion of the mesangial regions which hold large amounts of basement membrane material. Rats with a moderate diabetes show the early hypertrophy as well as long-term basement membrane thickening. Severely diabetic rats develop basement membrane thickening but do not show the early hypertrophy, which is therefore not a necessary condition for basement membrane thickening to occur.

Adult↗
PubMed1984

A platelet aggregation inhibitor--ticlopidine--in diabetic nephropathy: a randomized double blind study.

A randomized double blind trial was performed to investigate the effect of the platelet aggregation inhibitor ticlopidine on the rate of decline in renal function in diabetic nephropathy. Twenty-two patients with insulin dependent diabetes complicated by nephropathy completed the trial--11 on ticlopidine, and 11 on placebo for one year. Ticlopidine effectively reduced platelet aggregation in vitro. Renal clearance of 51Cr-EDTA declined from 39 +/- 10 to 30 +/- 13 ml/min per 1.73 m2 body surface in the ticlopidine group and from 42 +/- 9 to 39 +/- 13 in the placebo group. The difference in decline between the two groups was not significant. In the ticlopidine group renal function expressed as the slope coefficient for 1/S-creatinine per month remained the same as before the trial. It is concluded that although there is much evidence to suggest a role of platelets in the development or progression of diabetic nephropathy treatment with ticlopidine could not prevent this process.

Adult↗
PubMed1983

Immune response to bacterial dextrans. II. T cell control of antibody isotypes.

The isotype distribution of Dextran B 512 (Dex)-specific plaque-forming cells (PFC) and serum antibodies was studied after in vivo immunization in C57BL/6 mice. Although IgG2b and IgG3 could also be detected in most individuals, the majority of non-IgM PFC were of the IgA isotype. All classes other than IgM were T cell-dependent, as shown by their complete absence in athymic "nude" mice. This unusual isotype pattern was further investigated by studying the antibody responses to the same Dex epitope coupled to a protein carrier, and to a different hapten coupled to the carrier Dex or to a protein. The results show that IgA responses are epitope-related and selectively associated with anti-Dex antibodies: no IgA PFC are detected against a hapten coupled to Dex or proteins, while the enhanced levels of helper cell reactivity provided by protein carrier to Dex result in the appearance of IgG1 antibodies in addition to IgA. These results indicate that T cells that modulate isotype patterns in these responses can discriminate between Dex- and DNP-specific B cells in the response to the same carrier. Since the same idiotype is detected on a large fraction of the IgM and IgA anti-Dex response and antiidiotypic helper cells have previously been detected in normal C57BL/6 mice, we suggest that idiotype-specific T cells control the production of IgA antibodies upon immunization with Dex.

Animals↗
PubMed1983

Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction.

In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta 1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 +/- 0.5 mukat X liter-1) when the patient was treated within 12 hours of the onset of pain (13.3 +/- 0.6 mukat X liter-1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol less than or equal to 12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started less than or equal to 12 hours and greater than 12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve long-term prognosis.

Aged↗
PubMed1983

Temporomandibular joint involvement in systemic lupus erythematosus.

Temporomandibular joint involvement was studied in 37 systemic lupus erythematosus patients not selected with regard to this involvement. One-third had current complaints and two-thirds had a history of severe symptoms. Objective findings indicating systemic lupus erythematosus arthritis were locking or dislocation, tenderness to palpation, and pain on movement of the mandible. Such changes were found in 8 patients (22%) but in none of the healthy controls. Radiographic changes of the condyles, including flattenings, erosions, osteophytes, and sclerosis, were seen in 11 patients (30%), 4 of whom had deformity of other joints as well.

Adult↗
PubMed1983

Effect of nitroglycerin ointment (Nitrong) on exercise tolerance and several circulatory parameters in patients with angina pectoris.

Nine patients with coronary heart disease, 8 of whom were taking adrenergic beta-blockers, were tested by dynamic (bicycle) and isometric (sitting handgrip) exercise before and 2 and 6 h after application of nitroglycerin 30 mg in an ointment, or a matching placebo ointment, over 225 cm2 surface on the chest, in a double-blind, cross-over, single dose study. Exercise time until stopping from chest pain was significantly increased (by about 20%) by active ointment, and electrocardiographic ST-depression and chest pain intensity were significantly less pronounced during exercise both 2 and 6 h after application. During seated rest, active ointment also produced a significantly lower systolic blood pressure and a significantly higher heart rate at both 2 and 6 h, whereas during handgrip, significant differences from placebo were seen only at 2 h. All patients experienced headache for at least the 6 h of the study. At a given heart rate, ST-depression was less pronounced with active ointment than with placebo.

Aged↗
PubMed1983

Lupus band test in uninvolved oral mucosa in systemic lupus erythematosus.

In 42 patients with systemic lupus erythematosus, clinically normal oral mucosa was investigated with direct immunofluorescence technique for the presence of immunoglobulins G, A and M and complement factor C3 in the mucosal basement membrane zone (the lupus band test, LBT). Punch biopsies were performed in the posterior part of the hard palate (n = 39) or the lower labial mucosa (n = 3). The immunopathological observations were compared with clinical and serological data. The LBT was positive for IgM in 45% of the patients and trace amounts of IgM were found in another 19%. In 7 cases (17%) either IgG, IgA or C3 were found in addition to IgM and these patients all had a severe form of the disease, while the presence of IgM only was not correlated to clinical parameters.

Adult↗
PubMed1983

Diabetic glomerulopathy. Structural characteristics of the early and advanced stages.

Studies of the glomerular structure in diabetes mellitus have helped to elucidate the basis for some functional abnormalities. The decline in glomerular filtration occurring in many long-term diabetics is a functional disorder of great clinical importance. Quantitative structural studies of the glomeruli in diabetics at different stages of disease are necessary to learn about the development of structural changes leading to the end-stage kidney disease. Preliminary results of a study of glomeruli from long-term diabetics with clinical nephropathy are compared with those obtained in control subjects and in diabetics within the first 5 yr of disease. In the long-term diabetics the peripheral basement membrane thickness was doubled. On the average, mesangial regions occupied nearly 60% of the total tuft volume as compared with 33% in the early stages. A marked accumulation of basement membrane material in the mesengial regions had taken place so that 85% of the total basement membrane material of the tufts (i.e., peripheral basement membrane in the capillary walls plus mesangial basement membrane-like material) was localized within the mesangial regions. In the early stages equal amounts were found at these two different sites. The distribution of the lesions within the kidney is under investigation in a light microscopic study of autopsy material from long-term diabetics with varying degrees of glomerulopathy. The severity of the diabetic glomerulopathy was quantitated separately within the superficial and the deep cortical zones. The results showed that there was no tendency toward increased severity in the deep glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

The termination of forelimb nerves in the feline cuneate nucleus demonstrated by the transganglionic transport method.

The projection of forelimb nerves to the cuneate nucleus was studied in the cat by the transganglionic transport method. The cut ends of the median, ulnar, musculocutaneous, medial cutaneous, lateral brachial and antebrachial cutaneous nerves and of the superficial and deep branches of the radial nerve were exposed to horseradish peroxidase (HRP) or to HRP conjugated to wheat germ agglutinin. Nerves innervating the skin terminated in a somatotopical pattern on the cell clusters in the middle region of the cuneate nucleus. Afferents from the paw occupied the largest area and were situated dorsally, with the ulnar part represented medially and the radial part laterally. The palmar side of the digits seemed to be represented superficial to the dorsal side. The projection from the arm was split into a ventromedial and a ventrolateral area. Superimposed on this somatotopy, a reversed termination pattern was also present. Thus medially projecting nerves also had a small separate projection to the lateral part of the nucleus and vice versa. The rostral region of the nucleus was organized in a similar way except for the rostral pole where the somatotopy was lost. The caudal region differed from the middle one in that it appeared to lack representation of the upper and lower arm. The deep branch of the radial nerve terminated in the middle-ventral, 'reticular' region of the cuneate nucleus, with a sparse projection also to the ventral parts of the rostral and caudal regions, including the base of the dorsal horn. Also the musculocutaneous, median and ulnar nerves, but not the pure cutaneous nerves, had projections to these areas, indicating a modality segregation in the cuneate nucleus. The rostral pole of the nucleus, however, appeared to constitute an area of overlap between projections from deep and superficial receptors.

Afferent Pathways↗
PubMed1982

New design for clinical trial of antihypertensive drugs applied to pindolol, clopamide, and combinations thereof.

A beta-blocker (pindolol) and a diuretic (clopamide) were given in different dosages, singly and in two different combinations, to 71 patients with mild to moderate essential hypertension. The trial design was such that patients took both drugs singly and in combination, and in different doses, according to a set plan. The best regimen for each patient was determined by taking into account not only blood pressure but also resting heart-rate, body-weight, serum potassium, and serum urate. For 19 patients (27%) monotherapy was best--pindolol for 16 and clopamide for 3. For the remaining patients, a combination of pindolol 10 mg and clopamide 5 mg was best for 39, and in 35 of these one tablet daily was sufficient. All patients reached the preset target blood-pressure. The differences in proportions responding best to the following pairs of regimens compared--monotherapy vs combination, and combination of clopamide 5 mg and pindolol 5 mg vs combination of clopamide 5 mg and pindolol 10 mg--were significant (2p less than 0.01). The process by which the best treatment is chosen according to this study design resembles much more closely that followed in general medical practice, than does the process in the conventional hypertension trial, in which only average effects are reported and compared.

Adult↗
PubMed1982

Binding of thioridazine and thioridazine metabolites to serum proteins. An in vitro study.

The binding constants of the binding between thioridazine and its metabolites, side-chain sulfoxide, side-chain sulfone and ring sulfoxide, on the one hand, and the plasma proteins, alpha 1-acid glycoprotein, albumin and total serum proteins, on the other, were determined. The binding constants between the drug substances and alpha 1-acid glycoprotein were found to be about a thousand times higher than the binding constants between the drug substances and albumin. The binding constants of whole serum were close to those of alpha 1-acid glycoprotein. Analysis of the binding data indicated competition between thioridazine and its metabolites. A number of drug substances were screened for possible binding interaction with thioridazine and its metabolites. Tricyclic antidepressants and propranolol significantly increased the free concentration of thioridazine. Also salicyclic acid and the plasticizing agent, TBEP, had this effect.

Binding Sites↗
PubMed1982

Cardiovascular effect of nicotine chewing gum in healthy non-smokers.

Nicotine chewing gum (Nicorette 4 mg) and an identical placebo gum were administered on different days, in a double-blind cross over fashion, to 4 men, aged 25-52 years, and 4 women, aged 21-49 years, all healthy non-smokers. The subjects chewed the gum for 30 min and heart rate, blood pressure, electrocardiogram, finger tip temperature, calf and hand blood flow and whole blood nicotine levels were measured for 240 min in the supine position, under indirect body heating. 72% -96% of the nicotine was absorbed. Only heart rate showed a significant increase (10%-12%) during the study as compared to placebo. The mean peak nicotine level was 6.5 ng/ml, which occurred at 15-60 min and roughly coincided with the peak heart rate, and then levelled off to around 3 ng/l at 120-240 min. All subjects complained of nausea, dizziness or anxiety to varying degrees. It is concluded that if healthy non-smokers chew Nicorette gum 4 mg by mistake, they would probably suffer more from generally unpleasant symptoms than from any cardiovascular upset.

Adult↗