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Biomedical subjects

G Granerus

Publications and source records attributed to G Granerus.

At least 55 records · Page 3Linked to original sources

Estimation of renal function in diabetic nephropathy. Comparison of five methods.

Plasma as well as renal clearance of 51Cr-EDTA, serum creatinine, plasma beta-2-microglobulin and endogenous creatinine clearance were compared and evaluated in patients with diabetic nephropathy and in control patients with renal disease of other origin. The difference between the plasma clearance and the renal clearance of 51Cr-EDTA, that is the extrarenal clearance, was found to be higher in diabetics than in control patients (7.0 vs. 3.5 ml/min; p less than 0.001). The serum creatinine correlated well with the glomerular filtration rate (GFR), but in the individual case the GFR was not at all predictable from serum creatinine. The plasma beta-2-microglobulin did not correlate better than serum creatinine to 51Cr-EDTA clearance, and did not permit an earlier diagnosis of renal insufficiency. Endogenous creatinine clearance overestimated GFR by 0-180%. Due to residual urine, the coefficient of variation was higher in diabetic patients than in controls, but the effect of this imperfection was reduced by using multiple collection periods. In conclusion, the renal clearance of 51Cr-EDTA was found to be preferable to the other methods.

Adult↗

Long-term follow-up of histamine turnover in mastocytosis.

To study the long-term histamine turnover in patients with mastocytosis, the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid was measured. Eighteen patients, 10 with urticaria pigmentosa and 8 with systemic mastocytosis, were followed for several years (mean 4.2 years). Younger individuals (less than 30 years) had initially normal excretion or tended to normalize their excretion during follow-up, while older patients (greater than 30 years) often had systemic manifestations and higher excretion values, which increased in some cases during the observation period.

Adolescent↗

Drainage of the upper urinary tract as recorded with renography in patients with a continent urostomy (Kock pouch). An experimental study with various degrees of reservoir filling.

The drainage from the upper urinary tract was studied by the use of renography in thirteen patients with well functioning continent ileal reservoirs for urinary diversion (Kock-pouch). Renography was performed with empty reservoir and with submaximal or maximal filling of the reservoir. The reservoir pressure was continuously recorded when renography was performed with a full reservoir. When the reservoir was empty renography showed normal drainage in all patients. When the reservoir was full the renography was normal in eight patients, these having a mean reservoir volume of 715 ml but showed a delay in five patients, these having a mean reservoir volume of 930 ml. When the renography was repeated in the latter group of patients with submaximal filling (mean reservoir volume 544 ml) there was no delay of the drainage phases on the renograms. In these five patients the considerable "over-filling" of the reservoir had resulted in volumes greatly exceeding the previously recorded maximal reservoir capacity and also in pressures exceeding considerably those usually recorded in ileal reservoirs. These results show that the pressure in the bladder substitute is of great significance for the drainage from the upper urinary tract and that the low pressure ileal reservoir under ordinary circumstances does not obstruct the flow from the upper urinary tract.

Adult↗

Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.

The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/1.73 m2 body surface area (p less than 0.05) and the filtration fraction had decreased from 14.3 to 12.8% (p less than 0.025). During two years' treatment with captopril in 14 patients the mean arterial blood pressure had fallen by 5 mm Hg (p less than 0.005) and the deterioration in glomerular filtration rate had decreased from 10.3 to 2.4 ml/min/year (p less than 0.005). There was no correlation between the fall in blood pressure and the reduction in the deterioration of glomerular filtration rate. These findings suggest that the effects of angiotensin converting enzyme inhibition on renal haemodynamics protect renal function. Inhibitors of angiotensin converting enzyme should be considered for lowering blood pressure in patients with diabetic nephropathy.

Adult↗

Treatment of chronic urticaria with PUVA or UVA plus placebo: a double-blind study.

Chronic urticaria is a disease for which the available range of treatment modalities is limited. Ultraviolet radiation has recently been shown to affect histamine release from mast cells. We therefore studied the effects of PUVA and UVA on chronic urticaria. Nineteen patients took part in the study, which was designed as a randomized double-blind study. Eleven patients received PUVA, and 8 received UVA plus a placebo. In the PUVA group, 7 patients showed improvement, 3 noticed no change, and 1 became worse. In the group that received UVA plus placebo, 5 patients experienced an improvement, whereas the other 3 showed no change. The differences between the groups were not statistically significant. However, the probability of achieving this degree of improvement in both groups just by chance is less than 1%. Consequently, the improvement noted could have been due to either UVA alone or a placebo effect. It is concluded that PUVA is not better than UVA in the treatment of chronic urticaria.

Adult↗

125I-hippuran absorption from the human renal pelvis.

The absorption of 125I-hippuran from human renal pelvis was studied peroperatively in 18 patients with obstruction at the pelviureteric junction. Three types of experiment were included: absorption during induced diuresis, absorption at a constant intrapelvic pressure of 30 cm. H2O, and excretion of the indicator by the contralateral kidney. Total and separate glomerular filtration rate were measured using 51Cr-EDTA clearance technique and isotope renography. Distal tubular function was evaluated as maximum concentration ability. During induced diuresis the intrapelvic pressure increased to an average maximum value of 31.6 cm. H2O. The excretion of isotope from the contralateral kidney varied from one to 44% of the given dose. A significant correlation (r = 0.87) between the maximum intrapelvic pressure obtained and the amount of isotope excreted from the contralateral kidney was demonstrated. At a constant intrapelvic pressure of 30 cm. H2O the excretion of isotope from the contralateral kidney varied from two to 26% of the dosage given. The low value probably depended on the impaired function of the obstructed kidney. Our results show the existence of a significant reflux from the renal pelvis of small molecules, which was affected by renal function, intrapelvic pressure and volume.

Adult↗

Intraepithelial migration of nasal mucosal mast cells in hay fever.

Mast cells were studied by light microscopy in mucosal imprints and in biopsies of nasal mucosa of 12 birch pollen allergic individuals before and during the pollen season, using techniques optimized for the demonstration of mucosal mast cells. We also measured the histamine content of nasal mucosa, whole blood and plasma, and counted the numbers of circulating blood basophils. Before the pollen season the nasal mucosa was found to contain many mast cells located in the mucosal connective tissue stroma, and very few cells with basophilic and metachromatic granules were found in mucosal imprints. During the pollen season there was a redistribution of mast cells into the epithelium, many such cells now being recovered in mucosal imprints. The total number of mucosal mast cells counted in tissue sections did not change significantly with the onset of the pollen season, suggesting a redistribution of mucosal mast cells by migration. Judged by morphologic appearance and naphthol-AS-D chloroacetate esterase activity, the intraepithelial mast cells found in tissue sections had rather the properties of tissue mast cells than of blood basophils, and only a few of the basophilic cells of the imprints had a morphology compatible with blood basophils. The histamine content of the mucosa, as well as histamine levels of whole blood and plasma, and circulating blood basophil numbers did not change significantly in relation to the pollen season. These findings suggest that an intraepithelial migration of mucosal mast cells is part of the allergic mucosal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dissociation of renin and noradrenaline release in the renal circulation. Studies on patients with renal hypertension.

Plasma renin activity (PRA) and noradrenaline concentration (NA) were measured in the renal veins (V) and arterial blood (A) in 30 patients investigated for renin-mediated hypertension. Both PRA and NA concentrations in arterial blood were above our reference limits and they were positively correlated. In 18 of the patients renin secretion was unilateral from the diseased side. Their renal vein NA concentration was always higher on that side, compared to the contralateral one, but there were V-A gradients for NA on both sides in all but two cases. In 15 of the patients with such lateralisation of renin secretion the changes of PRA and NA V-A gradients were determined 30-60 min after an i.v. injection of dihydralazine. Both PRA and NA increased more markedly in the renal vein on the affected side where the estimated renal plasma flow was lower than on the contralateral side. The NA gradients increased less than the PRA gradients when changes on the renin secreting side were compared in patients with proven increase of renin secretion. We conclude that patients with renal hypertension have a high sympathetic nervous activity as evidenced by increased plasma NA concentrations and (V-A) gradients for NA on both sides. The release of NA into the renal circulation in renin mediated hypertension is thus not invariably accompanied by renin release. The higher renal vein NA concentration on the involved renin secreting side is explained by reduced RPF on this side.

Adult↗

The bone marrow in urticaria pigmentosa and systemic mastocytosis. Cell composition and mast cell density in relation to urinary excretion of tele-methylimidazoleacetic acid.

The bone marrow sections from five normal subjects and 18 patients with mastocytosis were examined to establish criteria to distinguish urticaria pigmentosa from systemic mastocytosis. Nine patients had increased numbers of mast cells in bone marrow sections stained with a long toluidine blue staining technique specific for mast cells, whereas five patients exhibited increased numbers of mast cells on May-Grünwald-Giemsa-stained smears of bone marrow. A positive correlation between the number of mast cells in sections of the bone marrow and the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid was found. In ten of the examined bone marrow specimens, focal lesions containing mast cells, lymphocytes, and eosinophils appeared. The presence of these focal lesions together with either an increased number of mast cells in bone marrow sections and/or increased urinary excretion of telemethylimidazoleacetic acid is considered diagnostic of systemic mastocytosis. No patient exhibited myeloproliferative condition or other major hematologic abnormality.

Adult↗

Cellular repository for blood histamine in normal and nematode-infected rats.

Infections with the nematode N. brasiliensis is associated with a recruitment of intestinal mucosal mast cells (MMC) which increase greatly in numbers. We have studied histamine levels in the gut, whole blood and plasma in relation to MMC of the gut and blood cell morphology during the course of the infection in an attempt to clarify possible relations between circulating blood basophils and MMC. The results show a parallel increase in MMC numbers and histamine content of the gut, remaining high to day 20 after infection. Blood histamine increased from a control level of 30-40 ng/ml to a maximum of 200 ng/ml on day 12 to 14, but returned towards the control level already on day 16 after infection. There was a corresponding increase in plasma histamine to a maximum of 80 ng/ml. The total number of blood neutrophils increased during the early phase of the infection and there was a pronounced eosinophilia from day 10 to 16. No cells containing metachromatic granules were found in a screening comprised of 10,000 cells per specimen. During day 10 to 16 we found a number of coarsely granuled and vacuolated cells. The granules stained darkly by the Giemsa stain but not metachromatically with Toluidine Blue or with Alcian Blue at a low pH. We interpret this as an equivalent to the so-called toxic granulation occurring in human neutrophils. These cells may have been mistaken for basophils by previous investigators. The cellular repository for the high concentration of histamine in the blood is unknown. We suggest, as a working hypothesis, that it is contained in a circulating progenitor for MMC which has the ability to synthesize and, in a loosely bound state store, histamine, but which has not yet acquired the ability to assemble the specific metachromatic granules.

Animals↗

Treatment of two mastocytosis patients with a histidine decarboxylase inhibitor.

Alpha-fluoromethylhistidine, alpha-FMH (L-641.575, Merck, Sharp and Dohme), a specific irreversible inhibitor of the mammalian histidine decarboxylase, was investigated for its effect on possible histamine symptoms in mastocytosis. Two patients were treated for 28 and 22 weeks respectively. The first patient had systemic mastocytosis and a severe malabsorption causing weight loss, excessive fecal fat losses and electrolyte disturbances, the main symptom being frequent diarrhoea. The second patient had mainly skin manifestations diagnosed as urticaria pigmentosa and the main symptom was pruritus. There were no side effects of the drug. The first patient produced formed stools after one week of treatment, concomitant with a decrease in plasma histamine and in urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid (MeImAA). In the second patient definite benefit of the treatment was observed after two months. However, changes in histamine parameters occurred earlier. Plasma histamine and urinary MeImAA were reduced after one week and in two or three weeks reached a steady-state level of about 25% of pretreatment values. The results indicate an effective inhibition of histamine synthesis in both patients but only the diarrhoea seemed to be causally related to the change in histamine metabolism.

Aged↗

Function of human autologous kidney grafts after extracorporeal preservation with Sacks' II solution.

The function of 18 human kidney grafts was studied before and 3 months after autotransplantation without prior bench surgery on the parenchyma or the vessels. Kidney protection was accomplished by pre-treating the patient with mannitol and low molecular weight dextran solution and flushing the kidney with a Xylocaine-heparin mixture and cold Sacks' II solution. The mean cold ischaemia time was 239 min (range 140-345 min). The glomerular filtration rate (GFR) remained unchanged post-operatively in terms of both total and split kidney GFR. Proximal and distal tubular integrity, as studied by determination of beta2-microglobulin excretion and concentration ability respectively, was also preserved.

Adult↗

Suppression of T lymphocyte mitogen response in patients with mastocytosis.

Immunological functions were studied in 22 patients with mastocytosis. Lymphocyte stimulation with concanavalin A (Con A) and phytohemagglutinin showed that the patients responded with lower mitogenic activity than healthy controls. Furthermore, the lymphocytes of patients with the most extensive mast cell disease had a significantly lower Con A mitogen response than the lymphocytes of the rest of the patients. The effect of histamine and its specific metabolites, tele-methylhistamine and tele-methylimidazoleacetic acid (MeImAA), on the Con A lymphocyte mitogen response was also studied in healthy controls. Histamine had a clear suppressive effect, while the metabolite tele-methylhistamine caused only slight inhibition and MeImAA apparently had no effect. The total T cell, suppressor and helper cell numbers, measured with monoclonal antibodies, and the amount of immunoglobulins in serum were found to be normal.

Adult↗

Urinary excretion of histamine, methylhistamine (1-MeHi) and methylimidazoleacetic acid (MeImAA) in mastocytosis: comparison of new HPLC methods with other present methods.

New HPLC-methods for the determination of histamine, 1- MeHi and MeImAA in human urine were compared with methods presently at use in our laboratory, the enzymatic double-isotope assay for histamine, the DNFB-method for 1- MeHi and the semiquantitative estimation of MeImAA by thin layer chromatography (TLC). A fairly good agreement between the methods was obtained for the measurement of histamine and 1- MeHi , although there was a rather large random error probably due to poor precision of the present methods. The TLC-method for MeImAA used so far overestimated by about 20% the HPLC-values, probably due to inaccurate correction for recovery by the internal standard technique. There was found to be a strong correlation between the urinary excretion of 1- MeHi and MeImAA in mastocytosis patients and the molar ratio MeImAA /1- MeHi appeared significantly higher compared to normal controls and patients with chronic granulocytic leukemia indicating in general a more efficient histamine catabolism in mastocytosis.

Adult↗