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Pancreatic transplantation in diabetic rats: renal function, morphology, ultrastructure, and immunohistology.

Serial renal morphologic, ultrastructural immunohisotlogic and functional studies were done on diabetic Lewis rats to evaluate the course of nephropathy and to study the effects of early pancreatic isografts on renal disease associated with streptozotocin diabetes. Three groups of experimental animals and one group of agematched controls were used. Group 1 consisted of 12 animals which were made diabetic with streptozotocin and which did not receive transplants. Early in the course of diabetes, these animals developed an increase in mesangial matrix, electron-dense material in themesangium, with immunoglobulin G, C3, and occasionally fibrinogen deposits in the glomerular mesangium. Alterations were progressive and mesangial bars, proximal tubular degeneration, tubular vacuolization, and myeloid figureswere present later. Progressive increase in protein excretion and increase in glomerular filtration rate were observed. Persistent glycosuria, hyperphosphaturia, andhypercalcuria. In contrast, only an occasional animal from Groups 2 and 3 with a pancreatic transplant showed renal in age-matched controls. These studies have demonstrated the evolution of renal glomerular and tubular changes in streptozotocin diabetic rats, and they have showed functional, and immunohistochemical changes.

Animals↗

CLINICAL STUDIES OF TOLAZAMIDE AND TOLBUTAMIDE: COMPARATIVE EFFECTIVENESS OF CONTROL OF DIABETES MELLITUS.

Tolazamide, a new oral hypoglycemic agent, was compared with tolbutamide, a related chemical compound, for stability of control of 12 patients suffering from maturity-onset diabetes mellitus. A short 12-week study was conducted which incorporated a cross-over design and the results were examined by variance analysis after dosage was individualized to the patient's requirements. Greater stability of fasting blood sugar was found on tolazamide; patients also had less glycosuria and lower fasting blood sugar on tolazamide. Tolazamide appeared to be between five and six times as potent as tolbutamide, mg. for mg.No hepatic, renal, hematologic or symptomatic toxic reactions were observed during the total of 72 person-weeks of tolazamide therapy.

Biomedical Research↗

[Median-term (4 months) treatment with glibenclamide + metformin substituting for glibenclamide + fenformin lowers the lacticemia levels in type-2 diabetics (NIDDM)].

60 NIDDM patients, mean age (68 +/- 3 years), BMI (25 +/- 5.1 kg/m2), fasting blood glucose (FG) (170 +/- 10 mg/dl), mean daily blood glucose (MDBG) (180 +/- 10 mg/dl), daily glycosuria (GLU) (15.6 +/- 9 g/24 hours), HbA1c (7.9 +/- 0.6%), basal (1.2 +/- 0.2 ng/ml) and stimulated (3.89 +/- 1.3 mg/ml) C peptide (CP) treated by ASS (7.5 +/- 75 mg), after a strict 4 months follow-up period, were assigned to G + M treatment (7.5 +/- 1.500 mg) during a 4 months period. During G+M treatment FG (171 +/- 13 at t0 to 165 +/- 11 mg/dl: p < 0.01 at t4) varied significantly. MDBG (180 +/- 10 at t0 to 175 +/- 12 mg/dl at t4:p < 0.05), GLU (16 +/- 9 at t0 to 11 + 6 g/24 hours at t4; p < 0.01), HbA1c (8.1 +/- 0.4 at t0 to 7.6 +/- 0.3% at t4; p < 0.01). Basal CP remained unchanged in G+M period and varied significantly during ASS period (1.3 +/- 0.3 ng/ml at t4; p < 0.01) and stimulated CP (unchanged during ASS) was reduced during G+M (4.19 +/- 0.4 to 4.04; p < 0.05). Highly significant variations were observed for LAC (28.4 +/- 2.1 at t0 to 14.9 +/- 0.6 mg/dl: p < 0.01 during G+M treatment). G+M therapy was found to be more effective and safer than ASS therapy in regard to glucose metabolism and lactate production in a selected group of NIDDM patients.

Aged↗

Double-blind, randomized, acyclovir-controlled, parallel-group trial comparing the safety and efficacy of famciclovir and acyclovir in patients with uncomplicated herpes zoster.

This randomized, double-blind, parallel-group study compared the efficacy and safety of famciclovir administered at 250 mg thrice daily with acyclovir 800 mg 5 times daily for the treatment of acute uncomplicated herpes zoster in immunocompetent adults. A total of 55 patients participated in this trial. Twenty seven patients (49.1%) were randomized into the famciclovir plus placebo treatment group and 28 (50.9%) into the acyclovir plus placebo group. Six of the 55 patients did not complete the study. Two of these patients were in the famciclovir plus placebo group and dropped out due to deviation from the study protocol. Four patients in the acyclovir plus placebo group did not complete the study protocol due to adverse events (n = 2), deviation from the protocol (n = 1), or loss to follow-up (n = 1). Treatment was initiated within 72 h of onset of the zoster rash and was continued for 7 days. When treatment was initiated within 72 h, famciclovir was as effective as acyclovir for healing the cutaneous lesion, as indicated by the time to full crusting, loss of acute phase pain, loss of vesicles, and loss of crusts. Famciclovir was well tolerated and had a more favorable adverse event profile compared to acyclovir. Constipation, hematuria, and glycosuria were the most commonly reported adverse events, but only constipation was considered to have a possible relationship to the treatment. In conclusion, famciclovir, administered less frequently and at lower unit doses than acyclovir, is an effective treatment for uncomplicated herpes zoster.

2-Aminopurine↗

Bone mineral content, 25-hydroxycalciferol and zinc serum levels in insulin-dependent (type I) diabetic patients.

To determine the relationship between bone mineral content (BMC), 25-Hydroxycalciferol (25OHD) and zinc serum levels in young insulin-dependent diabetics, we performed photon absorptiometry on a poorly controlled group of 22 patients. Zinc, 25OHD and alkaline phosphatase were measured in fasting serum. Ca, P, Mg, glucose and cAMP were determined in serum and in 24 hours urine collection. The diabetic group showed a significant decrease in BMC (less than 0.001) with raised urinary excretion rate of calcium (p less than 0.001). On the other hand, serum levels of zinc and 25OHD showed a significant decrease (p less than 0.001, both). We found a positive and significant correlation between glycosuria and urinary excretion rate of calcium (r = 0.77; p less than 0.001) and negative one for 25OHD and urinary excretion rate of calcium (r = -0.77; p less than 0.001). We conclude that decreased zinc and 25OHD serum levels in poorly controlled insulin-dependent (Type I) diabetic patients, in addition to raised urinary excretion rate of calcium, as result of the osmotic diuresis, contribute to bone loss in these patients.

25-Hydroxyvitamin D 2↗

Fanconi's syndrome in an adult. A case history.

A case of the Fanconi syndrome in an adult presenting with life-threatening hypokalaemia is described. Amino-aciduria, glycosuria, high phosphate and uric acid clearances with reduced plasma levels of these two substances, reduced urinary concentrating power and abnormal urinary potassium loss with a systemic acidosis, were the essential biochemical abnormalities. Osteomalacia was shown by a radiological bone survey.

Adult↗

[The effect of Sinecal fiber on compensation in type 2 diabetics].

The authors investigated in 28 type 2 diabetics the effect of addition of 21 g Sinecal fibre to the normal diet on the glucose and lipid metabolism. The value of C,peptide was significantly influenced after breakfast and a single dose of Sinecal. The other investigated parameters (blood sugar on fasting and after a meal, glycosuria, glycosylated proteins, C-peptide on fasting and after a meal, triacylglycerol and cholesterol) were not influenced by a single nor by long-term intake of Sinecal. Further development of fibre preparations with better tolerance and a greater effect on the glucose metabolism is desirable.

Aged↗

Spectral analysis of urinary reactions: a preliminary study based on a novel concept.

The concept of spectral analysis of urinary reactions (a range of simple chemical tests combined with pattern analysis) is described. A preliminary study in which we used 10 nonspecific tested on untimed urine specimens from 20 controls and 20 diabetics, matched for age and sex, suggested that a combination of these tests could be used to separate diabetics from healthy subjects. This combination, however, did not prove satisfactory for a further group of 13 diabetics. Closer examination revealed that factors such as therapy and glycosuria affected the results of these tests. This approach, which should extend the usefulness of urinalysis, may prove viable when larger groups, and possibly a different set of tests, are used to establish a more robust combination of tests.

Adult↗

Mesangial glomerulonephropathy with deposition of IgG, IgM, and C3 induced by mercuric chloride: a new model.

A mesangial glomerulonephropathy, characterized by the deposition of rat IgG, IgM, and C3 in the glomerular mesangium, was produced in Wistar rats by a prolonged administration of mercuric chloride (HgCl2). The HgCl2 was dissolved in sterile distilled water (0.2 mg. per ml.), and a group of 15 male Wistar rats was given injections subcutaneously three times a week on alternate days at a dosage of 0.15 mg. per 100 gm. of body weight for 27 weeks. A control group of nine rats was given injections of distilled water only. Mesangial glomerulonephropathy developed in 12 of 15 rats injected with HgCl2 and was characterized by the following: (1) coarse granular and nodular deposition of rat IgG, IgM, and C3 in the mesangium of all glomeruli, (2) absence of staining for rat albumin, IgA, and fibrin, (3) presence of electron-dense deposits in the mesangium, (4) focal and segmental proliferation of the mesangial matrix, (5) interstitial inflammation, (6) tubular atrophy, and (7) deposition of periodic acid-Schiff-positive material in the medulla adjacent to the thin limbs of the loops of Henle. Glycosuria and a slight increase in proteinuria were observed transiently in some rats. The blood urea nitrogen levels were normal in all rats. Eluates from the kidneys with heavy mesangial deposits contained rat IgG. However, the eluted antibody failed to react with normal rat kidney tissue components. None of the above findings were present in the control rats. The study provides a model of a mesangial nephropathy that seems to be immunologically induced; however, the mechanism for the formation and deposition of the immune deposits containing rat IgG, IgM, and C3, and the nature of the antigen(s) have not been elucidated.

Animals↗

[Our experience with biosynthetic human insulin].

Biosynthetic Human Insulin (BHI) was administered to 20 diabetics for six months. A clinical examination, glycaemia before and after eating, total glycosuria-ketonuria, and glycosylated haemoglobin tests were performed at fixed intervals, and the results were statistically analysed. It is concluded that human insulin produces no significant side effects. More important that the type of insulin treatment is effective outpatients surveillance of the diabetic, to ensure an adequate metabolic compensation.

Adult↗

[Cyclic parenteral nutrition in children and glucose metabolism].

The effect of cyclic perfusion on glucose metabolism and insulin secretion was determined in 10 children under prolonged parenteral nutrition according to glycosylated hemoglobin (HbA1c) levels and C-peptide urinary excretion. Lack of glycosuria and increase in HbA1c levels (m: 4.4 +/- 0.7%) indicates a good regulation of glycemia. A ten times increase in urinary C-peptide (m: 47.2 +/- 33.3 nmol/m2-1) as compared with controls shows an hypersecretion of insulin induced by the high infusion delivery of glucose. This hypersecretion of insulin, which probably involves long-term risks, may be reduced if parenteral nutrition does not contain more than the energetic requirements for growth and if about 30% of the energetic intake is given as a lipid perfusion.

Adolescent↗

Fast fraction haemoglobin (HbA1) in the assessment of diabetes control.

The degree of control of 132 diabetic patients was assessed using historical data, urine glucose and blood glucose measurements. These were then related to HbA1, taken as the final arbiter of glycaemic control. Symptoms of hyperglycaemia and glycosuria were found to be not sensitive or specific indices of control, though symptomatic glycosuric patients tended to have higher HbA1. Fasting blood glucose correlated modestly with HbA1 (r = 0.60, p less than 0.001) but if used alone to determine degree of control, 21% and 9% of patients could be expected to be over or under assessed respectively. The assessment value of timed post-breakfast blood glucose applied only to 120 and 150 minutes post-breakfast blood glucose as they correlated well with HbA1 (r = 0.73, p less than 0.001 and r = 0.96, p less than 0.001 respectively). Clinically impression of degree of control based on a combination of historical data, urine glucose and blood glucose led to "undertreatment" in 41% and "overtreatment" in 27% of patients. The complementary value of a knowledge of HbA1 was thus highlighted.

Adolescent↗

Electrolyte changes in plasma and urine during tender coconut water infusion in dogs.

Intravenous infusion of tender coconut water to paraldehyde and chloralose-urethane anaesthetised dogs at a rate of 0.5 ml/kg/min to a total dose of 100 ml/kg body weight decreased serum Na and increased K and Ca levels. Simultaneously, urinary Na excretion decreased and K and Ca excretion increased and there was glycosuria. Serum electrolyte changes were more prominent in paraldehyde anaesthetised dogs.

Anesthesia↗

[Blood concentration in glycosylated hemoglobin. Index in diabetic control time (author's transl)].

To estimate during which period of time the degree of diabetes control is integrated by the level of glycosylated hemoglobin two approachs were used. Hb-g was assayed by cellulose acetate electrophoresis in insulin-dependent diabetics and compared to the degree of control over a 3 months period. Control was evaluated by the semiquantitative urine test for sugar "Clinitest" three time a day. Hb-g correlated highly with last month glycosuria, but not as well with those of the two preceding months. These later correlation in fact reflected the stability of control over the three months. In 7 incipient insulin dependent diabetics in whom normal glycaemia was achieved abruptly and maintained for more than one month, Hb-g fell to normal within one month and therefore did not reflect the prexisting hyperglycemia. Hb-g integrates precisely the degree of diabetes control, but over a one month period only.

Adolescent↗

City-wide screening for urinary abnormalities in schoolgirls.

Screening for urinary tract infection was carried out in 23,427 schoolgirls, aged 5 to 14 years, using Uricult and, for hematuria, glycosuria and proteinuria using Hema-combistix. Cultures of 10(5) colonies per ml. or more on two occasions were obtained in 2.3% and a positive culture was confirmed by the family physician using standard culture techniques in 82.7% of cases, giving an overall incidence of infection of 1.9%. Fifty-eight percent of these children had no previous history of any urinary tract symptoms. Of the infected group 9.5% had pyelonephritic scarring, 58.7% chronic cystitis and 58.7% urethral stenosis. Two additional cases had unilateral ureteropelvic junction obstruction with hydronephrosis. Reflux occurred in 26.6% of those investigated by voiding cystogram. In 58% of cases the urinary tract infection was not accompanied by significant proteinuria, hematuria or pyuria.Proteinuria was detected on two occasions in 1.6% of the children and confirmed by the family physician in 33% of cases, giving an overall incidence of 0.5%. In this group 9.2% had evidence of pyelonephritic scarring without a positive urine culture.Hematuria was detected on two occasions in 0.6% of the children and was confirmed by the family physician in 53%, giving an overall incidence of 0.3%. Only one case with pyelonephritic scarring was seen in this group.Of the 25 cases with pyelonephritic changes only six had been previously diagnosed radiologically.Four previously unrecognized diabetics were also detected.

Adolescent↗

Selected biological values of the African white-tailed sand rat (Mystromys albicaudatus).

Forty-three female and 44 male, sexually mature normal African sand rats (Mystromys albicaudatus) provided serum and urine for determining normal ranges of selected serum chemistry and electrolyte determinations and for routine nonfasted urinalyses. Serum chloride and serum glucose levels were greater and serum sodium levels lower for female rats. An unusually high physiological level of urine protein was detected, and it was determined that standard dipstick methods for determining urine protein levels in this species gave artificially high results. Ketouria and glycosuria were more common in males than in females, but these determinations were not correlated to blood urea nitrogen or to serum glucose levels. No association was found between body weight and any of the serum chemistry, electrolyte or urinalysis variables examined.

Animals↗

Gycosuria as an indication for glucose tolerance testing during pregnancy.

The indications for and results of all glucose tolerance tests (GTTs) performed at the Antenatal Clinic, Groote Schuur Hospital, Cape Town, over a period of 1 year, and the indications for a GTT in the first 80 newly diagnosed diabetics over a 4-year period are analysed. Out of 558 GTTs, only 17 tentative diagnoses of 'gestational diabetes' were made. The most rewarding single indication for a GTT was repeated glycosuria, which was an indication in 61 out of the 80 newly diagnosed diabetics. A combination of two indications in the same patient was related to twice as many abnormal GTTs as a single indication, while reported previous diabetes or hyperglycaemia certainly merited confirmation. Reasons for repeating GTTs are discussed, as well as the management of 'borderline' and 'potential' diabetics. It is emphasized that 'diabetes' or 'hyperglycaemia' diagnosed during pregnancy is not equivalent to a definite diagnosis of diabetes in the non-pregnant state.

Female↗

[Appearance and metabolic development of diabetes mellitus in the sand rat, Psammomys obesus].

The aim of this study was to examine the long-term effects of synthetic chow diet on the metabolic pattern of diabetic syndrome in a large group of sand rats. Few animals had a fulminating reaction with markedly decreased glucose tolerance, low plasma insulin levels and death within 3-4 weeks. But the most of sand rats developed obesity and elevated plasma insulin levels. From the third month, 40% of sand rats presented a diabetic syndrome with hyperinsulinemia, hyperglycemia, markedly decreased glucose tolerance and insulin resistance. Plasma lipids were increased; the lipid and glycogen accumulation in the liver was high. So this diabetic syndrome can be compared to maturity onset diabetes. If this synthetic chow diet lasted more than 6 months, the most of animals lost considerable weight with a strong lipid depletion of fat stores. Serum immunoreactive insulin levels fall and the blood glucose rose over 500 mg/100 ml with glycosuria and ketonuria . The elevated triglyceride content of plasma and the lipid deposits in the liver were exaggerated; glycogen had disappeared. Animals developed an overtly insulin- dependent diabetes, the latter phase of the disease. The sand rat appears to us as a potentially interesting model for investigation both maturity onset and ketotic-type diabetic syndrome.

Animal Feed↗