Serum protein binding of phenytoin, diazepam and propranolol in chronic renal diseases.

The effect of chronic renal disease on the serum free fraction of phenytoin, diazepam and propranolol was examined in vitro among 60 conservatively treated patients with renal insufficiency of varying degree and different etiology, and in 10 patients with a nephrotic syndrome. The control group comprised 10 age and sex-matched healthy subjects. The free fractions were separated at 37 degrees C using a pressure ultrafiltration method. The highest free fractions of phenytoin and diazepam in uremic patients were 4 to 5-fold the normal. The free fractions were about twice the normal at a creatinine concentration of 800 mumol/l, and 2 to 4-fold at an urea concentration of 20-40 mmol/l. The creatinine and urea correlated with the free fractions of phenytoin and diazepam in a similar manner. The effect of a decreased serum albumin on the free fractions of these drugs was clear when its concentration was under 30 g/l. The creatinine and urea did not correlate with the free fraction of propranolol. However, after mathematically correcting the free fraction of propranolol to correspond to an alpha 1-acid glycoprotein (alpha 1-AGP) concentration of 0.9 g/l, it correlated significantly with creatinine and urea. The concentration of alpha 1-AGP was the most important determinant for the free fraction of propranolol. For practical purposes, the change in the free fractions of phenytoin and diazepam can be adequately predicted by the serum creatinine or urea and serum albumin levels. For propranolol the only parameter which needs to be analyzed is the serum alpha 1-AGP concentration.

Concentrations of iodothyronines in serum of patients with chronic renal failure and other nonthyroidal illnesses: role of free fatty acids.

The mean concentration of free thyroxin (FT4) in serum, as determined by direct equilibrium dialysis, was decreased in patients with chronic renal failure (CRF) and increased in patients with various other nonthyroidal illnesses (NTI). The mean concentration of dialyzable free triiodothyronine (FT3) in serum was equally low in both groups of patients. Patients with CRF of various etiology but a similar degree of renal failure as estimated from serum creatinine assay had very similar concentrations of FT4 and FT3 in their serum. Mean thyroxin (T4) and triiodothyronine (T3) concentrations in serum were decreased in CRF and NTI, whereas the mean reverse-T3 concentration in serum was normal in CRF and increased in NTI. T4-binding globulin and albumin were markedly decreased in CRF and NTI; T4-binding prealbumin was increased in CRF and decreased in NTI. The mean concentration of nonesterified free fatty acids (FFA) in serum was increased in NTI but not in CRF. The weak, but significant, positive correlation observed between FT4 and FFA in serum (r = 0.34, P less than 0.01) in NTI indicates that the increase in serum FT4 in this group of patients could be an effect, at least in part, of FFA competing with T4 for binding sites on serum proteins. The stronger correlation detected between the serum FT4 concentration and the FFA/albumin molar ratio in serum (r = 0.60, P less than 0.001) demonstrates the importance of a low albumin concentration for expression of the effect of FFA on FT4 in severe systemic illnesses.

The usefulness of micro- and macrochromatographic determinations of glycohemoglobin in diabetic patients with nephropathy.

Determination of glycohemoglobin in blood (HbA1) represents an established measure of glycemic control in diabetic patients. In patients with uremia, however, the determination can be subject to pitfalls which may limit its reliability. In order to evaluate the clinical usefulness of HbA1 determinations in diabetic patients with nephropathy, concentrations of HbA1 and its subfractions HbA1c and HbA1a+b were measured by micro- and macrocolumn chromatography in 58 diabetic and 80 non-diabetic patients with impaired renal function. Fifteen diabetic patients without nephropathy and 15 healthy subjects served as controls. The concentrations of HbA1 and its subfractions were significantly higher in non-diabetic patients with nephropathy than in healthy controls. A positive correlation was seen between HbA1 and plasma glucose concentrations in all subjects, and between HbA1 and serum urea and creatinine concentrations in the non-diabetic subjects. When measured repeatedly in the same patient there was a positive correlation between HbA1 and plasma glucose concentrations in diabetic patients with azotemia. There was no change in HbA1 concentrations measured immediately before and after hemo- or peritoneal dialysis. The increase of chromatographically determined HbA1 concentrations in azotemic patients is most likely due to the joint action of carbamylation of hemoglobin with urea derived cyanate and deterioration of glycemic control induced by azotemia. Despite these problems, chromatographically determined HbA1 is still a clinically useful measure of glycemic control in diabetic patients with nephropathy. This presumes repeated measurements in the same patient and the use of appropriate reference levels which consider the degree of renal impairment.

Relation between serum group II pepsinogen concentration and the degree of Brunner's gland hyperplasia in patients with chronic renal failure.

Serum concentrations of group I and II pepsinogens (PG I and PG II) were determined in 15 patients with chronic renal failure. Gastroduodenoscopy with biopsy and acid secretion tests were also performed. Five patients had histologically confirmed severe Brunner's gland hyperplasia manifesting as multiple polyps in the duodenal bulb. Five patients had a mild form of Brunner's gland hyperplasia which was evident only by histological analysis. Five had no signs of such alterations. The three groups of patients were comparable in age, sex, mean level of serum creatinine, mean duration of dialysis treatment, distribution of non-dialysed and dialysed patients, and gastric histology. In patients with severe Brunner's gland hyperplasia the mean serum PG II concentration was significantly higher than in the other patients. Both the serum PG I and the serum PG II concentrations decreased after receiving a well functioning renal transplant in the two patients who underwent transplantation.

Chronic gastritis and gastric acid secretion in uraemic and renal transplant patients.

Upper gastrointestinal endoscopy with biopsies from the antrum, body and duodenum, as well as tests for acid secretion were performed on 43 uraemic patients, 17 women and 26 men, (mean age 49.7 years) and on 46 patients with well-functioning renal transplant received 10 months earlier (12 women and 34 men, mean age 40.6 years) in order to study the background of peptic lesions in uraemic patients. Eighty-nine age- and sex-matched subjects selected from a random population sample consisting of 434 persons served as a control group. All groups of renal patients were similar with respect to the prevalence and severity of antral or body chronic gastritis. Compared with control subjects their antrum had significantly less advanced chronic gastritis, which was due to the lack of atrophic changes. Furthermore, the gastric body tended to show fewer alterations than that of the controls. The acid secretion capacity in the renal patients decreased with the increasing severity of atrophic changes in the body mucosa. However, definite hypoacidity was found in some of the renal patients with normal body mucosa. Thus, a true "state of hypoacidity" seems to occur in chronic uraemia.

Association of P and other fimbriae with clinical pyelonephritis in children.

196 episodes of urinary tract infection in children were analysed. 74 were classified as pyelonephritic (PN), 61 as cystitis (C), and 61 as asymptomatic bacteriuria (ABU) on the basis of three clinical signs (elevated temperature, erythrocyte sedimentation rate, and/or white blood cell count). The frequency of P-fimbriae was found high in PN (77%), and significantly lower in C (23%), ABU (20%) and among fecal strains (16%). The common, type 1 fimbriae were also more frequent in PN (92%) than in the other groups (84-76%), whereas other, so-called X-fimbriae, were relatively rare in all the patient groups (15-6%). P-fimbriation was not significantly associated with the presence or absence of reflux or obstructive anomalies. By contrast, the frequency of P-fimbriation increased with increasing severity of the clinical symptoms of pyelonephritis (95% in episodes of elevated temperature, erythrocyte sedimentation rate and white blood cell count).

The effect of renal transplantation on gastric acid secretion and on the serum levels of gastrin and group I pepsinogens.

To gain further understanding of the peptic complications encountered in renal transplant surgery, 84 patients (19 with chronic renal failure on dietary treatment, 29 on regular dialysis treatment, 36 with a well-functioning renal transplant) were studied with regard to gastric acid secretion capacity and serum concentrations of gastrin and group I pepsinogens (PG I). The mean duration of preoperative dialysis treatment of the dialysed patients was 13.7 months. The mean length of postoperative follow-up of the transplant patients was 10.1 months. There was no significant difference between the mean gastric acid secretion of the three groups of patients. All the means were within the reported reference interval for healthy controls. However, 26% of the non-dialysed, 17% of the dialysed and 28% of the transplant patients had gastric hyposecretion. The mean serum concentration of gastrin was elevated in all patient groups and unaffected by normalization of renal function through transplantation, unlike PG I, which was normalized by the procedure. Thus, in the present era of treatment of chronic renal failure with a relatively short period of dialysis treatment, the frequent gastric hypoacidity, which is known to be peculiar to non-dialysed uraemic patients, seems also to characterize dialysis and transplant patients.

Multiple duodenal polyps in uraemia: a little known clinical entity.

Multiple duodenal polyps were found by endoscopy in five out of 33 patients with chronic renal failure and in one of 300 controls. In the uraemic cases the polyps were caused by circumscribed nodular hyperplasia of Brunner's glands. One of these five patients later underwent surgery for duodenal obstruction caused by the polyps; the other patients were asymptomatic. One of the controls had multiple duodenal polyps. The recorded incidence of multiple duodenal polyps was significantly higher among patients with chronic renal failure than in patients without renal disease. Patients with chronic renal failure and polyps did not differ significantly from the other renal patients in the comparison of variables such as gastric acid secretion, serum concentrations of gastrin and group I pepsinogens or mean length of dialysis treatment. The mean pH of gastric resting juice was significantly higher, however, in uraemic patients with polyps than in those without. Uraemic patients displayed a gastric acid secretion capacity within normal range, and significantly raised serum gastrin and group I pepsinogen concentrations.

Character of urinary tract infections and pyelonephritic renal scarring after antireflux surgery.

We followed 40 girls who had undergone antireflux surgery (the Politano-Leadbetter technique) at the mean age of 5.2 years until they reached a mean age of 9.5 years. Each girl was matched with a control. The pairs were matched for age at the onset of urinary tract infections and time of operation or selection, number as well as grade (1 to 3) of severity of the preoperative episodes and grade (II to IV) of reflux. Followup time for each member of the pair was identical. Postoperatively, the incidence of pyelonephritic urinary tract infection episodes (grade 3) was significantly less (p less than 0.01) among the operated than the nonoperated cases (9 versus 29), while the number of symptomatic lower urinary tract infections (grade 2) was virtually the same (14 versus 19) in both groups. The operated cases had more asymptomatic bacteriuria (26 versus 12 episodes) so that the total numbers of episodes of bacteriuria (grades 1 through 3) were similar in both groups. Antireflux surgery did not prevent the progression of pyelonephritic renal scarring, which continued equally in operated and nonoperated cases.

[Age distribution of urinary tract infections (UTIs) and their severity grade in children (author's transl)]. / Altersverteilung der Harnwegsinfekte (HWI) bein Kindern und ihre Schweregrade.

Urinary tract infections in 339 children (77 boys and 262 girls) have been followed up. An excretory urography and a urethrocystography were done for all the children. The frequency of functional and anatomical abnormalities is given. The severity grade of UTI was determined according to the classification of Elo and Stenström. Almost all episodes of UTI among boys occurred during the first three years of life and were mostly severe. After the 3rd year of life the occurrence of UTI among the boys was sporadic. Among the girls the severe episodes dominates during the first three years of life, but after that the episodes tended to become milder in character becoming mostly asymptomatic. The peak of asymptomatic episodes among girls was at 10 years of age. After that age the number of episodes dropped abruptly. The classification used, based on the erythrocyte sedimentation rate (ESR) and on white blood cell count (WBC), has shown to be useful and makes it possible to differentiate between renal (pyelonephritic) episodes and the lower tract episodes.

Mannose-resistant haemagglutination and P antigen recognition are characteristic of Escherichia coli causing primary pyelonephritis.

Thirty-two Escherichia coli strains from 30 children with pyelonephritis were examined for their haemagglutination patterns and O and K serotypes. 29 (91%) of the strains showed mannose-resistant haemagglutination (MRHA). By use of well-defined target cells, these MRHA+ strains could be shown to recognise human cells either in a P-specific manner (recognising a specific galactosyl-galactose structure which is part of P blood groups antigens) or in a separate, X-specific manner. Both recognition mechanisms could occur separately or together on the same bacteria, the frequencies of P and X specificity being 81 and 19%, respectively. Both MRHA and P specificity were significantly associated with the O antigens 01, 04, 06, 016, and 018, and the capsular antigen K1, which have previously been associated with pyelonephritis. However, the association of MRHA and P specificity with upper urinary tract infection in children is greater than that of any other laboratory-defined bacterial characteristic.

Tobramycin-clindamycin versus cephalothin-cephalexin in the treatment of appendicular peritonitis.

Forty-seven children, ages 1 to 14 years, with appendicular peritonitis were randomly divided into two groups: 27 were treated with the combination tobramycin-clindamycin and 20 with cephalothin followed by cephalexin. The overall rate of complications was 32%. Patients who had had their symptoms for less than 48 hours before being admitted to hospital had significantly fewer complications than those whose symptoms had lasted longer. Patients treated with tobramycin-clindamycin had significantly fewer wound infections. As clindamycin is effective against anaerobes this observation supports the view that anaerobes play an important role in the infectious complications in peritonitis. In this series, 12 species of aerobes and eight species of anaerobes were cultured from peritoneal fluid. In eight patients only one species was isolated; in the remaining 39 patients 29 different combinations of bacteria were encountered. Early diagnosis and administration of antibiotics preoperatively or during surgery, including clindamycin, metronidazol or tinidazol is recommended in the treatment of children with appendicular peritonitis.

The role of vesicoureteral reflux in paediatric urinary-tract infection.

Observations are reported from a series of 284 children, 68 boys and 216 girls, who had had one or more episodes of urinary tract infection (UTI) and had vesicoureteral reflux (VUR) of grade II, III or VI. In 6 of the boys and 43 of the girls the Politano-Leadbetter operation for correction of VUR was performed. Only in grade III or IV VUR was the cure rate--considered solely as cessation of reflux--significantly higher in surgically than in non-surgically treated children. Irrespective of sex or mode of treatment, the number of episodes of UTI tended to diminish as the children grew older. For more precise comparisons, two individually matched groups of 40 girls were studied. One girl in each pair was operated on. Within these matched pairs, the frequency of UTI episodes according to age did not differ appreciably. Nor did the number of UTI episodes before and after the time of operation differ significantly when analysis was made according to grade of reflux. Thus, although disappearance of surgically treated grades III and IV VUR was more rapid and more frequent than spontaneous cessation of reflux, the observations in the matched pair series indicated that antireflux surgery does not affect the incidence of UTI.

Seasonal variations in the occurrence of urinary tract infections among children in an urban area in Finland.

The seasonal variations in the incidence of urinary tract infections (UTI) were studied in a series of 992 verified episodes of UTI treated between 1965 and 1974. The incidence was highest during November and lowest during the summer months. Summer episodes, moreover, tended to be the most severe. Seasonal variations were less marked among girls, than amond boys, except in the group of teenage girls in which peak incidences occurred in March and in September. Among the boys, a single peak incidence was recorded in July. The results of the analysis of weather type performed in this study showed that unseasonable types of weather, that is, cold and dry weather in autumn, warm and rainy weather in winter, and warm and dry weather in spring, were accompanied by a clear increase in the monthly number of episodes of UTIs. The difference in the monthly frequency of UTIs between the most and the least favourable types of weather was about two-fold.