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The effect of chronic cholesterol loading and lovastatin administration in renal artery clamping acute renal failure in rats is not known. Acute renal failure was induced by 60-min left renal artery clamping immediately afer right nephrectomy. The changes in renal function after renal artery clamping in the hyperlipidemic rats were unexpected. The acute renal failure in the cholesterol-loaded groups was less severe than in the nonhyperlipidemic rats. The lovastatin administration had some favorable effect on renal function afi ter ischemia; however, this effect was not additive to the high dietary cholesterol administration. Our results seems to favor the concept that in this special form of experimental renal ischemic acute renal failure, serum cholesterol levels, elevated through diet, may have protective effects with respect to renal tubular lesions during or following the acute ischemic insult.

Chronic renal failure was induced in 3-month-old male rats by 5/6 nephrectomy. Potency and fertility studies were performed after 3 months of chronic uremia. The mean serum testosterone at the end of the experiments was significantly lower: 0.96 +/- 0.14 ng/mL compared to a control group of sham-operated male rats, 2.86 +/- 0.59 ng/mL, p.001. All the uremic male rats had normal accessory gland weights at the end of the study. Fertility and, in most animals, sexual behavior and mating were not different from the normal control group. It is concluded that in 5/6-nephrectomized uremic male rats, in spite of low testosterone level, fertility and reproductive system are maintained similar to normal control male rats.

The renin-aldosterone system and plasma insulin were studied in 19 patients with familial Mediterranean fever (FMF). Their relationships to serum potassium level at rest and before and after oral glucose loading are described. An interesting finding is the occurrence of hyperkalemia in the absence of oliguria, in the advanced stages of renal failure. No differences were found in the activity of the renin-angiotensin-aldosterone system to explain these variations in serum potassium found in some of the patients. The response of the renin-aldosterone system to glucose loading showed no abnormality, and the regular relationship between serum potassium, plasma renin activity (PRA), aldosterone, insulin, and plasma pH is maintained. Levels of insulin, potassium, and bicarbonate in serum or plasma pH were found similar in FMF patients with normal renal function with and without proteinuria. Further decrease in renal function due to the progression of the underlying disease is manifested by an increase in FENa+ and FEK+ and a hyperchloremic metabolic acidosis, as is the case in other patients with chronic renal failure.

A case of prolonged urinary tract infection caused by Mycobacterium fortuitum in a 56-year old female patient is reported. The infection, which was resistant to therapy with conventional antituberculous agents, responded well to a combination of trimethoprim, sulfamethoxazole and doxycycline.

Changes in nitric oxide (NO) levels were determined in ischaemic acute renal failure in streptozotocin-induced diabetes mellitus rats. Two weeks after streptozotocin administration and immediately after right nephrectomy, the left renal artery was occluded for 60 min. Similar procedures were carried out in non-diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma and urine. The effects of chronic oral supplementation with L-arginine and an NO synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic and non-diabetic rats before and after renal artery clamping. The rats with diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22 microliters.min-1. 100g body weight-1, p0.005), and higher fractional excretion of sodium (FENa)% (10.90 +/- 4.2, p0.001) and protein excretion (2078 +/- 69 micrograms/ml creatinine clearance, p0.001) compared with the respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/- 31). The plasma and urine NO2 + NO3 levels were significantly higher in the untreated diabetic rats compared with the untreated normal rats before ischaemia (p0.001). The ischaemic acute renal failure in non-diabetic rats increased the plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of these metabolites decreased significantly and their plasma levels remained unchanged in the ischaemic diabetic rats. The L-arginine administration resulted in a small but significantly higher creatinine clearance after clamping in the non-diabetic rats. The NO synthase inhibitor caused deterioration in renal function in all ischaemic and non-ischaemic groups. In summary, the greater vulnerability to ischaemia of the diabetic kidney seems to be associated with both impaired response to and impaired production of NO.

EDRF results from the metabolism of L-arginine. N-omega-nitro-L-arginine is a nitric oxide synthase inhibitor (L-arginine competitive inhibitor). Acute renal failure was induced by i.m glycerol (50%) 5 ml/kg bw. L-arginine: 3 mg/kg bw/min for 60 min before and 60 min after glycerol administration. L-arginine inhibitor (150 micrograms/kg bw/min for 120 min). Cin, Cpah and FENa% were measured immediately or 24 h after glycerol (mean of three periods of 20 min). A second series of similar experiments was done in dehydrated (16 h) rats with a high dose of glycerol (50% solution, 10 ml/kg bw). L-arginine ameliorates the severity of ARF immediately after glycerol administration and enhances the recovery of glycerol-induced ARF. The L-arginine inhibitor resulted in a more severe ARF. Urinary cGMP decreased significantly after glycerol administration. It is concluded that nitric oxide has an important pathogenetic role in the glycerol induced ARF.

To study the effect of pregnancy on kidney function in patients with familial Mediterranean fever (FMF) with amyloidosis.A retrospective analysis relating kidney function at term to kidney function at conception and to blood pressure and colchicine treatment before and during pregnancy in 17 patients with 29 pregnancies found among more than 3000 patient files in our FMF clinic.Following pregnancy, 7 patients (24% of pregnancies) experienced a decline in renal function. Urine proteinor = 2 g/24 h at conception was present in all pregnancies which sustained deterioration in contrast to 6 of 22 which did not (p0.001). Serum creatinineor = 1.5 mg/dl at conception was present in 3 patients, all of whom experienced deterioration of renal function during pregnancy (p0.01). Neither colchicine dose nor elevated blood pressure correlated with status of renal function at term.Our findings suggest a possible deleterious effect of pregnancy on amyloid nephropathy and that this effect may be associated with more advanced renal disease at conception.

Calcium channel blockers decrease the plasma potassium concentration in acutely nephrectomized rats exposed to an acute potassium load. We examined the effect of verapamil on the plasma potassium concentration during an acute potassium load in anephric-uremic diabetic and non-diabetic rats. The plasma potassium concentration was measured at 15-min intervals during 60 min of continuous KCl infusion, with and without verapamil. The baseline potassium concentrations were higher in diabetic rats vs. nondiabetic controls. Verapamil blunted the increase in plasma potassium in diabetic and nondiabetic rats compared with the respective controls. The pH and hematocrit were similar in all groups. We conclude that the effect of verapamil on extrarenal potassium disposal are independent of insulin and the renin angiotensin system in the uremic state.

The cardiovascular and renal effects of intravenous (i.v.) and intra-arterial (i.a.) infusions of isoproterenol (ISP, 0.1–0.2 μg/kg/min) were evaluated in 17 two-week-old swine anesthetized with pentobarbital. The glomerular filtration rate (GFR) of each kidney and blood flow and vascular resistance (RVR) of the left kidney were determined in all animals. In the 8 animals given ISP i.v., right ventricular pressure and dP/dtmax were also determined via a thoracotomy. In 9 animals, ISP was given i.a. after stabilization of constant-flow perfusion of the left kidney in situ. During i.v. infusion of ISP, the positive inotropic and chronotropic effects and the decrease in arterial pressure were maintained; renal blood flow and GFR increased and RVR decreased. During i.a. infusion of ISP in the constant-flow perfused kidney, similar changes in RVR and GFR were observed despite the higher effective concentrations of drug reaching the kidney. We conclude that, at this stage of postnatal renal development, the infusion of cardiotonic doses of ISP lowers RVR and produces a small increase in GFR.

Evidence has been accumulated which shows an association between renal disease and hepatitis B virus (HBV), as reviewed in recent articles by Levy et al. (1982) and Eknoyan (1983). However, the mechanism of renal pathology has not yet been elucidated clearly. Ten centres in Japan and one in Korea (Seoul) have been performing a multicentre co-operative study to investigate the natural history and the pathogenesis of the nephropathy associated with HBV antigenaemia. The purpose of the present paper is to describe the association between the seroconversion of HBV antigens and favourable clinical evolution in children with HBV nephropathy.

In this analysis of 43 patients with IgA nephropathy, renal morphology was correlated with clinical data. Gross hematuria and mild proteinuria were typical among younger patients. Among older individuals the clinical spectrum was wider. A comparison with data previously obtained from the normal population indicated that disease-related glomerular sclerosis was present in 1/3 of initial biopsy specimens. The prevalent pattern of glomerular sclerosis was that of global tuft collapse, the type of sclerosis known to result from ischemia. Intrarenal vascular sclerosis was present in 1/3 of initial biopsies. Follow-up specimens from 6 patients showed progression of glomerular sclerosis, vascular sclerosis or both. Hypertension occurred in over 1/4 of patients. It is proposed that progressive renal damage in IgA nephropathy may not be solely immunologically mediated. Glomerular sclerosis may also be mediated by vascular sclerosis, or alterations in intrarenal hemodynamics in glomerulonephritis may have a direct damaging effect on both the glomerulus and the intrarenal vasculature.

Pathophysiological effects of exposure to Finnish sauna (80 to 90 C, 30 to 40% relative humidity) were investigated in 60 volunteers--33 men and 27 women aged between 18 and 63 years. The volunteers entered the sauna after a rest period of 20 min, and remained there for 20 min or until they suffered discomfort. Weight, height, rectal and skin temperatures, blood pressure, heart and respiratory rates and ECG were recorded 20 min prior to the sauna, during the sauna, and 20 min after leaving the sauna. Marked physiological changes appeared in the first few minutes in the sauna without any prodromal warning. At the 20th min the mean heart rate was 143 +/- 25 (SD) beats/min (greater than 160 beats/min in 32% of the subjects). Mean rectal temperature was 38.6 +/- 0.6 (SD) C (greater than 39 C in 22%): mean skin temperature was 40.4 +/- 1 (SD) C (greater than 40 C in 35%); mean systolic blood pressure was 130.5 +/- 26.6 (SD) mm Hg (greater than 160 mm Hg in 17%); and mean diastolic pressure was 66.6 +/- 15.9 (SD) mm Hg (greater than 50 mm Hg in 17%). The mean total sweat loss was 457 +/- 264 (SD) g. Three subjects experienced syncope, and one developed an anginal attack; ECG changes suggestive of coronary insufficiency were recorded. No decrease in blood pressure occurred in patients with preexisting high blood pressure. It is concluded that sauna bathing involves dangers to the bather's health, which may appear suddenly, without prodromal warning signs.

Fibrosing peritonitis and constrictive pericarditis occurred in an 18-year-old patient who manifested the classic features of familial Mediterranean fever (FMF). Pericardial calcification had been present in chest X-rays taken when the patient was five years old. Intermittent intestinal obstruction and congestive heart failure were relieved by appropriate surgical intervention, but attacks of FMF subsided only after colchicine therapy. This is the first instance of nonuremic pericarditis in our experience with over 1,000 FMF patients. Critical analysis of the reported cases in which pericarditis was attributed to FMF strengthens our belief that the occurrence of pericarditis in a patient with FMF probably represents a fortuitous intercurrent disease.

A family with familial combined hyperlipidaemia in which affected members had nonsymmetric subcutaneous lipomatosis (NSSCL) is described. Affected members had high serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. By contrast, family members without NSSCL had normal lipid levels. There was also a correlation between the degree of hyperlipidaemia and the amount of subcutaneous lipomas. The occurrence of hyperlipidaemia in family members with NSSCL suggests the existence of a genetic linkage between these two characteristics, but did not show any association with HLA haplotyping. To our knowledge this association between lipid abnormalities and NSSCL has not been previously reported.

A prospective study among unselected patients hospitalized in an internal medicine ward showed that 46 patients, 6.9% of total admissions, had serum concentrations of sodium less than 132 mEq/l. In 28.3% of hyponatremic patients (n = 13), the cause was the syndrome of inappropriate antidiuretic hormone secretion; 21.7% of the cases (n = 10) developed hyponatremia during hospitalization, mainly because of hypotonic solution administration. The mortality rate among the hyponatremic patients was high (30.4%) and was not influenced by treatment of hyponatremia. In our opinion, the high mortality reflects the severity of the underlying diseases, although 82.5% of the patients were asymptomatic or had mild neurological signs. There was no significant correlation between the degree of hyponatremia and neurological signs, or mortality.

Renal and cardiac effects of norepinephrine and dopamine were evaluated in swine aged 1 wk, 2 wk, and 6 mo. The swine were anesthetized with pentobarbital (20-30 mg/kg). Aortic pressure, right ventricular pressure and its first derivative, and heart rate were recorded, together with carotid and renal (RBF) arterial flows. Glomerular filtration rate (GFR) was determined by [14C]inulin clearance. After a control period, norepinephrine or dopamine was infused intravenously for 10-20 min before and then during another clearance period. After a second control period, the second catecholamine was infused. GFR increased in piglets given either catecholamine. Norepinephrine at equipressor doses (2.0 micrograms.kg-1.min-1 in piglets and 1.0 micrograms.kg-1.min-1 in mature swine) decreased RBF and increased renal resistance. Dopamine at equi-inotropic doses (10 micrograms.kg-1 min-1 in piglets and 20 micrograms.kg-1.min-1 in mature swine) increased RBF and decreased renal resistance only in mature swine. Infusions of dopamine at a low dose (5 micrograms.kg-1.min-1) also failed to increase RBF or decrease renal resistance in piglets. The results suggest that maturation of the mechanism of renal vasodilation by dopamine occurs later than that for vasoconstriction by norepinephrine.

In order to investigate a possible immune regulation imbalance in familial Mediterranean fever (FMF), the T-cell subsets and interleukin (IL)-1 and -2 production were examined in 39 patients (32 consecutive; 7 previous) and 14 controls. Results in the FMF group indicated no change in total T-cells and B-cells. The number of supp T-cells and helper cells were significantly decreased, as compared to the controls (14 +/- 5.2, 19 +/- 4.6 vs. 31 +/- 4.6, 41 +/- 5.3, respectively), and the NK cells were significantly increased (16 +/- 4.8, 36 +/- 2.1). Peripheral blood monocytes from the patients with FMF produced higher amounts of IL-1 and lower amounts of IL-2 than those from the control subjects. The latter results were enhanced when the FMF group was subdivided on the basis of pretreatment with colchicine and presence of amyloidosis. This study, although preliminary, indicates an immune regulation imbalance in FMF patients. Further research is necessary to understand the interrelation of amyloidosis and colchicine treatment.

Since Goldfinger’s observation in 1972 that daily administration of colchicine may prevent the attacks of familial Mediterranean fever [1], the drug has become the mainstay of therapy and is recommended to all of our many afflicted. On a dose of 102 mg/day, 95% of patients experience complete remission or marked amelioration of their attacks. The remainder do not respond to even higher doses. Children as a rule respond only to full adult dosage. Side-effects are uncommon and usually mild but have occasionally required and always responded to desensitization, permitting continuation of the drug. Non-compliance is promptly punished by renewal of attacks.

The total incidence of untoward reactions to chlorpropamideis about 6% (Sayers and Travis, 1965). Gastrointestinal symp-toms, skin reactions, and blood dyscrasias constitute the majorgroups (Stein et al., 1964; Dinsdale et al., 1968; Aecker andHynes, 1969; Norman et al., 1970). The anaphylactic reactionto chlorpropamide as described in the following case has

We have described a 35-year-old woman who had had recurrent episodes of swelling of the lips since the age of 14. The patient had a complete remission of symptoms between the ages of 20 to 30, but the swelling recurred, and she has had permanent swelling of both lips and cheeks for the past four years. Various treatments were ineffective. Biopsy of the lip mucosa showed histologic findings of Melkersson-Rosenthal syndrome. This case probably represents an oligosymptomatic form of the syndrome.