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Biomedical subjects

G Nyberg

Publications and source records attributed to G Nyberg.

At least 91 records · Page 5Linked to original sources
PubMed1993

Glomerular structure and function in proteinuric type 2 (non-insulin-dependent) diabetic patients.

Glomerular ultrastructure was examined in a series of 20 Type 2 (non-insulin-dependent) diabetic patients with proteinuria. Reference was made to data previously obtained in non-diabetic kidney donors and in Type 1 (insulin-dependent) diabetic patients with similar degrees of proteinuria. The Type 2 diabetic patients demonstrated the changes which characterize the diabetic glomerulopathy seen in Type 1 diabetic patients: basement membrane thickening, and increase in the mesangium and mesangial matrix expressed as fraction of the glomerular volume. Among the Type 2 diabetic patients there was more variation than among the Type 1 diabetic patients, as this group included subjects with normal parameters. The group means and coefficients of variation (= SD/mean) of the glomerulopathy parameters combined in the glomerulopathy index = basement membrane thickness/10+ Vv(matrix/glom).100 were 81 (0.30) and 92 (0.15) in the two diabetic groups, clearly different from the non-diabetic index, 42 (0.16). All Type 2 diabetic patients who also had retinopathy had a glomerulopathy index above the normal range. Similar changes in glomerular composition were seen in the two diabetic groups: with increasing glomerulopathy the volume of matrix dominated over the peripheral basement membrane, and a shift in the ratio of interfaces was seen: mesangial surface towards capillary lumen increased relative to the urinary surface, and peripheral capillary surface comprised less of the total capillary surface. Data indicated marked glomerular hypertrophy, which correlated with the mesangial volume fraction, thus encompassing preserved filtration surface per glomerulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Early glomerulopathy is present in young, type 1 (insulin-dependent) diabetic patients with microalbuminuria.

Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18-29) years, duration of diabetes 12 (8-15) years, mean blood pressure 93 (87-115) mm Hg, glomerular filtration rate 132 (101-209) ml.min-1.1.73 m2 -2, albumin excretion rate (mean over 1 year) 32 (15-194) micrograms/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549-641 nm) vs 305 nm (287-325 nm), p = 0.0001; mesangial volume fraction 0.22 (0.21-0.23) vs 0.19 (0.18-0.21), p = 0.04, and matrix volume fraction 0.13 (0.12-0.13 vs 0.09 (0.08-0.10), p = 0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Aiming for steady 24-hour plasma concentrations: a comparison of two calcium antagonist and beta-blocker combinations.

This was an open randomised, steady-state, two-way crossover study to evaluate and compare the variability of the plasma profiles of two fixed combinations of a dihydropyridine calcium antagonist and a beta 1-selective adrenoceptor blocker with different pharmaceutical formulations. Six young (mean age 27 years) healthy men received either an extended-release tablet formulation combining felodipine (5 mg) plus metoprolol (50 mg) or a capsule containing a nifedipine sustained-release tablet (20 mg) plus atenolol powder (50 mg) once daily for 7 days each, in random order with a wash-out period of at least 7 days between active treatments. On the last day of each study period, plasma drug concentrations were monitored at regular time intervals up to 24 h after dosing. The variability in plasma concentrations over the dosing interval was found to be markedly less with the felodipine-metoprolol combination than with the combination of nifedipine and atenolol. This was documented by statistically significant differences between felodipine and nifedipine as well as between metoprolol and atenolol in the ratio between peak (Cmax) and trough (Cmin) plasma concentrations and also in the fluctuation index (Cmax-Cmin divided by the average plasma concentration). The mean Cmax:Cmin ratio for felodipine and metoprolol was 3.3 and 2.7, respectively, and 11.5 and 11.8 for nifedipine and atenolol, respectively. On the basis of these analyses, the extended-release tablet combination of felodipine and metoprolol produced smoother plasma profiles than the capsule combination of nifedipine and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Renal retransplantation in patients with HLA-antibodies.

The results of 92 consecutive renal retransplantations, performed during a 5-year period in recipients with HLA-antibodies, were retrospectively analysed. The actuarial 1-year graft survival (1-y GS) was 65% for all retransplantations, as compared with 63% for first grafts in sensitized recipients. For the second (n = 56), third (n = 24) and fourth-fifth (n = 12) grafts 1-y GS was 64%, 71% and 58%, respectively. Acute rejection was the major cause of graft loss (45%). Recipients with > 3 years GS of the preceding transplant had significantly better GS at retransplantation. Also, grafts with no HLA mismatches had significantly prolonged GS. One-y GS was 78% when PRA (panel reacting antibody) was less than 50%, and 60% when PRA was more than 50%. A benefit of repeated mismatches was demonstrated in the subgroup with PRA < 50%, in contrast to recipients with PRA > 50%, suggesting that, in some patients, an absence of antibody response against certain antigens might be used as a basis for future deliberate mismatching.

Female↗
PubMed1992

Dyslipoproteinemia in diabetic renal failure.

Plasma concentrations of lipids and apolipoproteins (Apo) were determined in 34 patients with long-standing type I (insulin-dependent) diabetes mellitus. Twenty-four patients had renal insufficiency (GFR 4 to 55 ml/min) due to diabetic nephropathy, while 10 patients had no clinical signs of nephropathy. Results were compared with those in 42 non-diabetic patients with comparable degree of renal insufficiency and with asymptomatic control subjects. Diabetic patients without nephropathy had plasma lipid and apolipoprotein concentrations similar to those of the control subjects. Diabetic patients with renal insufficiency had a significant increase in triglycerides (TG) and, to a lesser extent, in total cholesterol (TC). The patients also had reduced levels of ApoA-I and ApoA-II, increased levels of ApoC-II and ApoC-III, while increases in levels of ApoB and ApoE were statistically significant in patients with GFR < 20 ml/min. These lipids and apolipoprotein abnormalities were accentuated with decreasing renal function. The reduction in the ApoA-I/ApoC-III ratio characteristic of renal insufficiency was found in normo- and hyper-TG diabetic patients with nephropathy; this ratio was correlated with the GFR levels. Patients with higher HbA1C values had higher levels of ApoC-II and ApoC-III. The findings in the diabetic patients corresponded with those in non-diabetic patients with renal insufficiency. However, diabetic patients had higher ApoC-III and ApoE levels. The abnormalities of lipid metabolism in diabetic renal insufficiency seem to reflect primarily metabolic impairments characteristic of renal insufficiency, but may be further accentuated by the diabetic state and the metabolic control.

Adult↗
PubMed1992

Absence of pre-dose rebound phenomena with once daily 5-ISMN in a controlled-release formulation.

To avoid the development of nitrate tolerance secondary to relatively constant elevated plasma nitrate concentrations, intermittent nitrate dosing has been advocated. However, a nitrate-free interval may induce a rebound increase in myocardial ischaemia, and thus increase anginal symptoms during the latter portion of the dosing interval. This was suggested by the results of recent studies in which nitroglycerin patches were administered intermittently with a 12 h nitrate-free interval. The present investigation was carried out to determine whether a controlled-release formulation of 60 mg isosorbide-5-mononitrate (5-ISMN) would produce such a rebound phenomenon. Seventy-nine patients, who had participated in four crossover, placebo-controlled studies in which the treatment arms lasted for between 1 and 2 weeks, were reviewed. These studies had assessed the efficacy of this nitrate preparation by exercise testing and each had included exercise testing at the end of each treatment phase, 24 h after the last medication had been administered. There were no differences noted in the time to onset of angina, the time to onset of 1 mm ST segment depression or the total exercise duration between the two treatment phases, indicating an absence of rebound phenomena at the end of the dosing interval. The reason for the absence of a detectable pre-dose rebound is unclear, but the plasma concentration profile of 5-ISMN produced by the presently used preparation, resulting in a nitrate-low instead of nitrate-free interval, may have contributed.

Adult↗
PubMed1992

Glomerular volume in kidneys transplanted into diabetic and non-diabetic patients.

Biopsies taken at the time of renal transplantation in 12 non-diabetic and 23 diabetic patients were studied by quantitative light- and electron-microscopy. Repeat biopsies were taken at 6 months and/or after 2-3 years in patients who had acceptable graft function. All patients except two received cyclosporin as part of the immunosuppression. Glomerular volume was significantly increased, + 36(95% CI +6 to +65) % (p = 0.03), in the diabetic patients at 6 months which differed from the change of -20 (-50 to +10) % in the non-diabetic patients (p = 0.03). After 2-3 years glomerular volume was equal to the baseline value in the diabetic patients, while the change from baseline in the non-diabetic patients was -21 (-42 to -1) %. Substantial glomerular occlusion was seen in only three diabetic patients after 2-3 years. Total structural volumes per glomerulus in the 2-3-year biopsies showed an increase in basement membrane material of 0.09 x 10(6) microns 3 in the diabetic patients, significantly different from the change in non-diabetic patients (-0.10 x 10(6) microns 3, p = 0.003). No correlation was obtained between the 6-month increase in glomerular volume and the development of diabetic glomerulopathy at 2-3 years. The fact that glomerular hypertrophy was not present in the entire series may be due to the cyclosporin and to rejection. Nevertheless the diabetic group did show an early hypertrophy which did not seem to play a major role in the ensuing development of diabetic glomerulopathy.

Adult↗
PubMed1992

Differentiation of pituitary adenoma and meningioma: visualization with positron emission tomography and [11C]-L-deprenyl.

Seven patients with clinically nonsecreting pituitary adenoma and 5 patients with meningioma were examined with positron emission tomography using [11C]-LL-deprenyl and [11C]-LL-methionine. The dynamics of the uptake of [11C]-L-deprenyl in the pituitary adenomas demonstrated a rapid and high uptake immediately after the injection, and, later, an almost constant level was observed that was equal to or higher than that observed in normal brain tissue. In the meningiomas, however, the initially high uptake was followed by a marked decrease with time, reaching a level that was approximately half that observed in brain tissue. The study demonstrated high binding of [11C]-L-deprenyl to monoamine oxidase B in pituitary adenomas, whereas the binding in meningiomas was very low. This fact can be used in the differential diagnosis of pituitary adenoma and parasellar meningioma. Operative samples from 10 patients with meningioma and from 5 patients with pituitary adenoma were analyzed biochemically for activity of monoamine oxidase B, using [14C]-phenyl-ethylamine as substrate. The nonsecreting pituitary adenomas demonstrated high enzyme activity, the secreting adenomas about one-tenth of that of the nonsecreting, and the meningiomas one-thirtieth of that of nonsecreting adenomas.

Adenoma↗
PubMed1992

Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics.

The clinical features and toxicokinetics of amitriptyline were studied in nine patients with severe amitriptyline poisoning. Amitriptyline and amitriptyline metabolites were studied in plasma, red blood cells, and cerebral spinal fluid. Eight patients were intubated and six required assisted ventilation. Two patients had ventricular arrhythmias, three patients convulsions and two were hypotensive. All complications developed within four hours of admission. Early in the course of the intoxication the QRS duration correlated with plasma, unbound and red blood cell nortriptyline concentration. The QRS duration also correlated with unbound but not the plasma amitriptyline concentration. The level of consciousness correlated with the plasma and unbound amitriptyline both in alpha and beta phase and with red blood cell amitriptyline in alpha phase. There was no correlation between nortriptyline concentration and level of consciousness. No correlation between coma grade or QRS duration and cerebral spinal fluid concentration of amitriptyline was found. There was no correlation between any hydroxymetabolite in blood or cerebral spinal fluid and QRS duration or coma grade. The beta half-life for amitriptyline was shorter for two patients with high concentrations of hydroxymetabolites. Although intubated, neither patient required assisted ventilation or developed complications. Because of the wide range of concentrations of amitriptyline and amitriptyline metabolites observed between individuals, it is not possible to predict outcome based on a single tricyclic antidepressant concentration.

Amitriptyline↗
PubMed1992

Amitriptyline and amitriptyline metabolites in blood and cerebrospinal fluid following human overdose.

The toxicokinetics of amitriptyline were studied in nine patients admitted to hospital in Matthew-Lawson Coma Scale grade III-IV after an estimated ingestion of 1-5 g amitriptyline. Gastric lavage was performed and 50 g activated charcoal were given orally. Venous blood samples were taken on admission and at 1, 2, 4, 8, and 24 h, and in some patients at 36 and 48 h after admission. Arterial blood samples were taken at 1, 4, 8, and 24 h after admission. Lumbar punctures were performed 1 h after admission in 8 patients and again 4 h later in 5 patients. A urine sample was screened for other drugs. The bound and unbound fraction of amitriptyline and its metabolites nortriptyline, E and Z forms of 10-OH-amitriptyline and nortriptyline were analyzed in plasma, whole blood, red blood cells, and cerebrospinal fluid using an HPLC technique. The T1/2 alpha and T1/2 beta for amitriptyline were 1.5 - 3.1 and 15 - 43 h respectively. The rate of elimination of amitriptyline was not dose-dependent. The arteriovenous differences in the total amitriptyline+nortriptyline concentration were maximal in patients admitted soon after intake of drugs. Amitriptyline concentrations in cerebrospinal fluid were quantitatively similar to the unbound amitriptyline concentration in blood. The highest cerebrospinal fluid amitriptyline concentration was 506 nmol/L. There were large individual differences in plasma, blood and cerebrospinal fluid concentrations between different individuals. Repeated quantitative analysis of amitriptyline and its metabolites is unlikely to contribute to the clinical management of most patients with amitriptyline overdose.

Adult↗
PubMed1992

Recurrence of SLE in transplanted kidneys: a follow-up transplant biopsy study.

Renal transplant biopsies were obtained from 16 patients with systemic lupus erythematosus 6 months to 11 years post-transplant. Eight biopsies were taken on clinical grounds while eight were elective. Histopathological findings suggesting recurrent lupus nephritis were found in seven biopsies, five of which were taken on clinical indication. By light-microscopy, five graft biopsies showed proliferative glomerulopathy and two glomerulosclerosis. Immunofluorescence was positive for IgM and C3 in a finely granular pattern in all biopsies, for C1q in three, but for IgG in only two. Electron-dense deposits were found in all seven biopsies with predominantly subendothelial location. All but one patient had clinical signs of renal involvement, but only three had extrarenal symptoms and three had serological signs of active SLE. Upon increased immunosuppressive therapy, renal and serological signs improved but one graft was later lost due to recurrent SLE nephritis.

Adolescent↗