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Biomedical subjects

G Nyberg

Publications and source records attributed to G Nyberg.

At least 19 recordsLinked to original sources

Neovascularization at the vascular pole region in diabetic glomerulopathy.

BACKGROUND: Diabetic nephropathy is associated with renal structural changes involving all of the compartments. Most characteristic is the diabetic glomerulopathy. Studies of the histological changes during the early phases of nephropathy have included the glomerulopathy and also the juxtaglomerular structures. Neovascularization, well-known in diabetic retinopathy, has also been observed in the kidney. The present study concerns estimates of frequency of neovascularization at the vascular pole region in early stages of diabetic nephropathy. METHODS: Extra efferent arterioles at the glomerular vascular pole were detected during measurements of the vascular pole area applying 1-microm serial sections through kidney biopsies. It was observed that more than one efferent arteriole existed occasionally. The present study was carried out with the aim of estimating the frequency of this phenomenon in diabetic patients and in non-diabetic controls, the diabetic patients categorized according to the level of albumin excretion rate. RESULTS: Neovascularization was first observed in IDDM patients with microalbuminuria. Some of the cases presented the phenomenon in all of the glomeruli studied. As the examinations of many kidney biopsies continued the phenomenon was observed also in the non-diabetic control group and in one IDDM patient with normoalbuminuria. However, the frequency was statistically highly significantly increased in patients with elevated albumin-excretion. Within this group a strong correlation between frequency of neovascularization and the severity of diabetic glomerulopathy is seen. CONCLUSIONS: The vascular abnormality localized to the vascular pole region is observed occasionally in the normal kidney, but the frequency is increased in patients with diabetic glomerulopathy. The abnormality may develop as a consequence of a long-standing diabetic glomerulopathy and might lead to less pronounced elevation of albumin excretion.

Adolescent

Breast-feeding during treatment with cyclosporine.

BACKGROUND: Mothers treated with cyclosporine (CsA) have previously not been allowed to breast-feed due to the reported accumulation of the drug in breast milk. The purpose of this study was to evaluate the consequences of allowing breast-feeding. METHODS: Seven infants were breast-fed by mothers who had undergone kidney transplantation alone (n=5) or simultaneous kidney and pancreas transplants (n=2). In addition to CsA, all mothers received prednisolone at 5-7.5 mg/day and six mothers received azathioprine at 50-100 mg. CsA concentration was measured in the whole blood of mothers and babies and in breast milk. Serum creatinine was measured in babies 1 week after birth and after 4-12 months of breast-feeding. RESULTS: Blood CsA levels ranged from 55 to 130 ng/ml in mothers (12-hr trough), 50 to 227 ng/ml in breast milk (mean for each woman), and was below the detection limit of 30 ng/ml in all infants. Breast milk concentration ranged from 87 to 440 ng/ml in 16 samples obtained at various time points from one mother. Infants' serum creatinine ranged from 25 to 54 micromol/L at 1 week after birth and 23-52 micromol/L after breast-feeding. All babies thrived. CONCLUSIONS: Breast-fed infants of mothers treated with CsA received less than 300 microg per day of CsA and absorbed undetectable amounts. There were no demonstrable nephrotoxic effects or other side effects. Thus, women with kidney transplants could be allowed to breast-feed.

Adult

Focal segmental glomerulosclerosis in a kidney transplant population: hereditary and sporadic forms.

Between 1985 and 1993, 16 of 1000 kidney transplant patients in Göteborg had biopsy-verified primary focal segmental glomerulosclerosis (FSGS), and among them they received 23 transplants. Their age range was 19-67 years (median 39 years). Patients were followed for 3-10 years (median 6.5 years). Eight patients were members of seven separate families in which at least one other member had FSGS, while eight cases were sporadic. The patients with hereditary FSGS were younger at onset of symptoms than sporadic cases (median 12.5 vs 26 years, P = 0.041) but not at the time of renal failure. Only one versus five had received immunotherapy. After transplantation, recurrence of FSGS occurred in five grafts, all in sporadic cases, and two of these were lost. In conclusion, it appears that there are at least two forms of FSGS, one hereditary and one sporadic form. The hereditary form does not seem to recur after transplantation, whereas the risk in sporadic cases is very high.

Adult

Enlargement of the juxtaglomerular apparatus in insulin-dependent diabetes mellitus patients with microalbuminuria.

Kidney biopsies from 15 insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria were investigated to obtain quantitative data on the juxtaglomerular apparatus. The IDDM patients were young and normotensive with a mean duration of microalbuminuria of 2 years. Eight healthy kidney donors served as controls. Measurements taken by light microscopy, using 1-microm serial sections of epon blocks, included volumes of the juxtaglomerular apparatus and of glomeruli, areas of the macula densa and luminal area of the juxtaglomerular (afferent and efferent) arterioles at the level of the glomerular vascular pole. The volume of the juxtaglomerular apparatus was significantly larger in the IDDM group than in controls [6.08 (2.96-18.8) 10(4) microm3 vs 3.48 (1.84-5.21) 10(4) microm3, P=0.003, median and (range)], as was the volume of the juxtaglomerular apparatus relative to glomerular volume [1.89(1.28-4.21)% vs 1.48 (1.13-1.71)%, P=0.004]. The area of the macula densa was also larger in the IDDM patients (1370 microm2 vs 937 microm2, P=0.03). Luminal areas of the afferent and efferent arterioles and the ratio between them did not differ significantly between the two groups. In conclusion, the juxtaglomerular apparatus is enlarged more than would be expected from the glomerular hypertrophy in IDDM patients with microalbuminuria.

Adolescent

Renal structural changes in insulin-dependent diabetic patients with albuminuria. Comparison of cases with onset of albuminuria after short or long duration.

The large interindividual variation in diabetes duration until the onset of nephropathy is partly unexplained. This study was performed to compare renal structure in insulin-dependent (IDDM) patients who had developed signs of nephropathy after a short or long duration of diabetes. Renal biopsies were obtained from 17 IDDM patients, with albumin excretion rate 20-300 microg/min and normal blood pressure. Six patients had <25 years duration ("short-term", early onset of microalbuminuria) and eight patients had duration >30 years ("long-term", late onset of microalbuminuria). Biopsies were obtained 18 months after entry into a study testing the effect of low-dose antihypertensives. Parameters characterizing diabetic glomerulopathy were significantly increased in IDDM patients compared with those in 17 living donors: Basement membrane thickness, mean and (CV): 591 nm (0.17) vs 320 nm (0.12), mesangial volume fraction per glomerulus 0.27 (0.19) vs 0.19 (0.10), matrix volume fraction per glomerulus 0.16 (0.20) vs 0.097 (0.22), matrix star volume 38.5 microm3 (0.43) vs 13.9 microm3 (0.31), (p<10(-4) for each). Comparison of short vs long-term patients showed no significant differences in glomerulopathy parameters, glomerular volume or extracellular material per glomerulus, whereas the fraction of occluded glomeruli was significantly increased in long-term patients. A close correlation obtained between fraction of occluded glomeruli and glomerular filtration rate (r=0.72, p= 0.001). Glomerular occlusion occurred unrelated to the severity of diabetic glomerulopathy. It is suggested that diabetic macroangiopathy and arteriolar hyalinization may play an important role in the renal function of patients with slow development of nephropathy.

Adult

Morphologic high-risk factors in IgA nephropathy.

AIM: Morphologic risk factors for developing end-stage renal failure (ESRD) due to IgA nephropathy may be difficult to identify in populations where the course is benign in the vast majority. Ours is a high-risk population. METHODS: Protocols of 67 biopsies from native kidneys of kidney transplant patients with IgA nephropathy were reevaluated with respect to the prevalence of certain structural findings. Time points for onset of symptoms, biopsy procedure, and ESRD were recorded. RESULTS: Features seen with more than expected frequency were: extracapillary proliferation in 49%, cellular infiltrates in the interstitium in 89%, marked tubular atrophy in 54%, and IgA deposits in the peripheral capillary loops in 71%. With extracapillary proliferation the remaining time to ESRD was 3.5 +/- 3.2 versus 7.0 +/- 4.2 years without (p < 0.0004). With marked tubular atrophy the remaining time was 3.5 +/- 2.7 and 8.2 +/- 4.2 years without (p = 0.0002). Cellular infiltrates in the interstitium also signified shorter progression (p = 0.009). Except for the presence of IgA in the periphery, no finding by immune fluorescence was more frequent than expected or correlated with progression. CONCLUSION: Extracapillary proliferation, interstitial cellular infiltrates, marked tubular atrophy, and IgA deposits in the peripheral capillary loops indicate risk of progressive renal failure in IgA nephropathy, but other findings by immune fluorescence do not.

Adult

Coronary aneurysms in patients with autosomal dominant polycystic kidney disease.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of intracranial aneurysms. Reports on arterial aneurysms in other locations have not been conclusive. The present study was initiated to investigate the prevalence of coronary aneurysms. Thirty ADPKD patients who had undergone coronary angiography on clinical indication were identified, 15 after renal transplantation. For each ADPKD patient, a control patient was identified with end-stage renal disease, investigated by coronary angiography, and matched for age, sex, and time relation to transplantation. All angiograms were retrieved and reevaluated with respect to aneurysms, defined as an increase in artery diameter by 50% or more, as well as to pathologic ectasias not fulfilling this criterion. Aneurysms were detected in four ADPKD patients and two control subjects. Five more ADPKD patients, but none of the control subjects, had minor ectasias. One ADPKD patient had a dissecting aortic aneurysm, and another died of aortic dissection during bypass surgery. This study adds to the evidence of an increased risk of extracranial aneurysms in ADPKD patients.

Cardiovascular Diseases

Systemic vasculitis in a kidney transplant population.

BACKGROUND: Systemic vasculitis as original disease might adversely influence the result of kidney transplantation. METHODS: The clinical course after 32 transplantations to 26 patients with microscopic polyangiitis, Wegener's granulomatosis, Henoch-Schonlein purpura, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, or Goodpasture's disease was evaluated. The median follow-up time was 82 months (range, 4-132 months). Frozen sera from 25 transplantations were analyzed for Goodpasture antibodies, myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA), and proteinase 3 ANCA. RESULTS: Survival of patients and grafts did not differ between patients and matched controls. Recurrent vasculitis occurred with seven grafts (four patients with microscopic polyangiitis or Wegener's granulomatosis, two patients with Henoch-Schonlein purpura, and one patient thrombotic thrombocytopenic purpura). New-onset hematuria was the initial renal symptom in five patients. Treatment with corticosteroids, cyclophosphamide, and/or plasma exchange was most often effective, but two grafts were lost. Proteinase 3 ANCA titers were increased to 12-738 U/ml before seven transplants. The patient with the lowest titer lost his graft due to recurrence, two other patients had reversible recurrence after 1 year and 5 years, two patients lost their grafts due to unknown/unrelated causes, and two patients' grafts remain without recurrence. Myeloperoxidase ANCA were increased to 22-39 U/ml before two transplants, which have been uneventful for 4 years. CONCLUSIONS: An awareness of the small but perpetual risk of recurrence facilitates early treatment that may save the transplant. Testing for hematuria and early transplant biopsies, and possibly monitoring of ANCA titers, are essential, but pretransplant ANCA titers have no predictive value in asymptomatic patients. Results of kidney transplantation in patients with vasculitis are as good as in other patients.

Adult

Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers.

OBJECTIVE: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release (ER) felodipine and controlled-release (CR/ZOK) metoprolol compared with the free combination of felodipine ER metoprolol CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine and metoprolol when administered as ER formulation. METHODS: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis in six subjects. RESULTS: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding pharmacodynamics was detected between the fixed combination and the corresponding free combination. CONCLUSION: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination.

Adrenergic beta-Antagonists

Glomerular volume and the glomerular vascular pole area in patients with insulin-dependent diabetes mellitus.

The vascular pole area (VPA) and glomerular volume were measured in renal biopsies from 9 insulin-dependent diabetes mellitus (IDDM) patients with normal albumin excretion rate (IDDM group 1), 38 IDDM patients with albumin excretion rate > 15 micrograms/min (IDDM group 2) and 10 living kidney donors (ND). The volume of individual glomeruli was estimated as the sum of profile areas factored by the measured distance between levels, t approximately 10 microns, and VPA as the sum of chords multiplied by t. Mean glomerular volume was increased in IDDM patients but reached statistical significance only in IDDM group 2 (P = 0.002 vs ND). VPA was significantly different among the groups, mean (CV%) was 2036 (29) microns2 in ND, 3555 (34) micron2 in IDDM group 1, and 3528 (48) microns2 in IDDM group 2, p = 0.004 and 0.001, IDDM versus ND. VPA calculated as a percentage of the surface area of the corresponding glomerulus was 2.4 (23)% in ND, 3.4 (27)% in IDDM group 1, and 3.3 (42)% in IDDM group 2; P = 0.007 and 0.01, IDDM versus ND. The intra-biopsy coefficient of variation was high (20-35%) and of the same order in all groups for all three measurements. Glomerular volume and absolute as well as relative size of VPA showed a positive correlation with estimates of mesangial expansion in IDDM group 2 and the VPA showed a negative correlation with GFR. Thus, part of the enlargement may represent a compensatory phenomenon triggered by the development of structural and functional abnormalities in the diabetic kidney.

Adolescent

Rejection rates in kidney transplant patients with and without IgA nephropathy.

BACKGROUND: Based on graft survival rates it has been claimed that patients with IgA nephropathy have a reduced risk of rejection after kidney transplantation. We wanted to evaluate this hypothesis. METHODS: Certified IgA nephropathy was the original disease in 70 of 874 consecutive kidney transplant patients (8.0%). Eighty per cent of the patients were men. Median age was 37 years, range 9-64. Fifty-three per cent had living donors and 20% of the transplantations were pre-emptive. Non-diabetic patients matched for age, sex, type of donor, and transplant number served as controls. Median follow-up time was 68 months. Duration of treatment for rejection during the first year post-transplant and graft loss due to rejection was recorded. RESULTS: The fraction of patients treated for rejection during the first year was 53% versus 54% of controls and the number of days when any antirejection treatment was given was 5.0 +/- 7.5 versus 5.5 +/- 7.4. Actual 3-year graft survival was 81% versus 80% and the number of grafts lost due to rejection was 9 versus 11. CONCLUSIONS: Rejection rates were not reduced in patients with IgA nephropathy and survival of grafts and patients not better than for matched controls.

Adolescent

Gender differences in a kidney transplant population.

The purpose of this study was to compare female and male kidney transplant recipients. Of 1095 consecutive kidney transplants, 63.7% were to male recipients. Detailed demographic background data and follow-up data were used in the analysis. Female and male recipients were the same age, median 44, range 1-71 years. The male/female ratio was increased in all adult age groups, and most pronounced in the middle-aged. The proportions of first transplants and of preemptive transplants were not different, and 22.0% of men compared with 24.4% of women had living donors. Biopsy-verified chronic glomerulonephritis was found 2.4 times more often in men than in women, unknown diagnosis including non-biopsy-verified chronic glomerulonephritis 2.3 times, and adult dominant polycystic kidney disease 1.8 times. A larger proportion of men than women received antirejection treatment, 59.5% vs 49.5% (P = 0.002). Cumulative survival of patients or grafts was not different, but women > or = 50 years of age tended to have poorer 1-year graft survival than men, 69% vs 78% (P = 0.06). It is concluded that the increased proportion of men in our transplant programme is mainly due to their higher requirement of renal replacement therapy.

Adolescent

Autosomal dominant polycystic kidney disease in a kidney transplant population.

AIM: To define specific manifestations of autosomal dominant polycystic kidney disease in kidney transplant patients. METHODS: Of 874 consecutive first renal transplant patients 1985-1993, 114 (13%) had autosomal dominant polycystic kidney disease (ADPKD). Mean age was 53 +/- 8 years, 62% were men, and 83% received cadaveric kidneys. Control patients were matched for sex, age and donor type. Median follow-up time was 63 months. One patient was lost to follow-up. Medical records before and after transplantation were reviewed. RESULTS: Survival of patients and grafts was similar in ADPKD patients and controls. Twenty-five ADPKD patients died, four of causes not seen in the controls; two aortic aneurysms, one urothelial cancer, one colon perforation. Four more ADPKD patients but no control had diverticulitis (P = 0.03), two with perforation. Cardiovascular morbidity was not increased. Eight patients had subarachnoidal haemorrhage before transplantation and two during follow-up. Nineteen patients had undergone nephrectomy before transplantation, 11 because of voluminous kidneys, five for infection, pain or bleeding, two for suspected malignancy, one for hypertension. After transplantation, seven patients underwent nephrectomy, only one related to kidney size. During the first year, need of phlebotomy occurred in 14% of patients versus 4% of controls, P = 0.02. Urinary tract infection rates were not increased. No morbidity was related to liver cysts. CONCLUSION: The specific features of kidney transplantation to patients with ADPKD were few: enlarged kidneys, relevant only before transplantation, erythrocytosis, and as rare but serious events, diverticulitis with perforation.

Adult

Predictors of renal morphological changes in the early stage of microalbuminuria in adolescents with IDDM.

OBJECTIVE: To evaluate the impact of glycemic control, blood pressure, lipid levels, glomerular filtration rate (GFR), age, and duration of IDDM on the degree of structural glomerular changes in the transitional stage of microalbuminuria. RESEARCH DESIGN AND METHODS: Fifteen adolescents (seven boys and eight girls) with > 5 years of duration of IDDM and with low-grade microalbuminuria (15-30 micrograms/min) participated. Seventeen living kidney donors served as healthy control subjects. Five-year mean HbA1c; 5-year mean systolic and diastolic blood pressure; GFR, cholesterol, and triglycerides 2-5 years before renal biopsy; age; and duration of IDDM were investigated and related to basement membrane thickness (BMT), mesangial and matrix volume fractions, and the overall glomerulopathy index [(BMT/10 + mat/glom, %) + matrix star volume]. RESULTS: BMT and the overall diabetic glomerulopathy were increased in diabetic patients as compared with control subjects (P < 0.001), whereas matrix volume fraction, but not mesangial volume fraction, tended to be increased (P = 0.11). In multivariate analysis, BMT was predicted by 5-year mean HbA1c, diabetes duration, and previous GFR (R2 = 0.71, P = 0.003). With matrix volume fraction as the dependent variable, BMT and diabetes duration were the only significant determinants (R2 = 0.63, P = 0.003). Diabetes duration, 5-year mean HbA1c, and GFR were the variables with an independent influence on the overall diabetic glomerulopathy index (R2 = 0.72, P = 0.003). Preceding blood pressure and lipid levels or age had no significant independent influence on these morphometric measures. CONCLUSIONS: In the very early stage of microalbuminuria in IDDM adolescents, a high percentage of the variation in BMT and overall severity of glomerulopathy is explained by prolonged hyperglycemia and diabetes duration. Previous glomerular hyperfiltration may also add to the prediction of these morphological changes.

Adolescent

PET-methionine of skull base neuromas and meningiomas.

Eighteen patients with intracranial skull base tumours diagnosed at CT or MR as neuromas or meningiomas were studied with positron emission tomography (PET) using L-(methyl-11C) methionine. Compared with normal cerebellar tissue, the uptake of methionine in the tumours increased more rapidly and reached a higher level, and showed a slow decline after a peak occurring about 5 min after the injection. All the meningiomas exhibited considerably higher accumulation of the tracer compared with the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding structures (tumour to cerebellum ratios 2.62-5.37, mean 3.63). The uptake was homogeneous in all meningiomas, which were all of the syncytial type. The neuromas showed lower contrast against the cerebellum (tumour to cerebellum ratios 1.1-1.87, mean 1.48). Some neuromas displayed an irregular pattern with regions of decreased tracer uptake corresponding to small cystic areas within the neuroma. There was no overlap in methionine uptake between the two tumour groups. The results indicate that PET-methionine may contribute to the evaluation, treatment planning and follow-up of patients with skull base meningiomas and neuromas.

Adult