On individual reference intervals based on a longitudinal study of plasma proteins and lipids in healthy subjects, and their possible clinical application.

In a longitudinal study, we determined interindividual and intra-individual variation in 20 plasma proteins and lipids and in other blood constituents by analysis of variance. Blood from 20 healthy subjects was sampled monthly for six months, a rigorous blood-sampling technique being applied. The mean proportion of interindividual variation differed for each blood constituent, ranging from 22 to 91% of the total variation. The possible clinical application of individual reference intervals of this homeostatic model was demonstrated by the fact that they were exceeded in individual cases of upper respiratory tract infection. Concordance between individual reference intervals in healthy controls and in patients--as exemplified in two chronic diseases, multiple sclerosis and chronic inactive pyelonephritis--suggests that the use of individual intervals in (chronic) disease is valid, even when derived from healthy persons. Additionally, sex- and age-related differences were significant for some constituents.

Complement studies in adipose patients treated with intestinal bypass.

Seventeen consecutive patients subjected to jejunoileostomy for obesity have been investigated for complement abnormalities and cryoglobulinaemia. The study took place 1-9 1/2 years after the operation. A concomitant clinical examination revealed recurrent arthritis in 6 (30%) of the patients. In 6 of the patients complement abnormalities were found, as activation of the classical pathway in 3 and activation of the alternative pathway in another 3 could be suspected from immunochemical data. One patient showed activation of both the classical and the alternative pathway. Two of the patients with arthritic symptoms belonged to the group showing activation of the alternative pathway. It is suggested that deficient inactivation of bacterial products from intestinal bacteria (lipopolysaccharides) have a role in the complement abnormalities found. No patient exhibited the cryoprotein complexes found earlier in this type of patients.

Regional hypothermia in renal surgery for severe lithiasis.

An active approach to severe renal lithiasis is advocated, though operative procedures often require interruption of the blood supply. Te evaluate the effect of ischemia on the kidney the literature has been searched and we have reached the following conclusions. A warm ischemic time of more than 20 minutes causes a brief and transitory reduction in renal function. If ischemia exceeds 30-40 minutes many kidneys will not regain their previous function. If the kidney's temperature is lowered to about 15 degrees C, ischemia can be tolerated for up to 12 hours. A priori these time limits applicable to normal kidneys are to broad for use in diseased kidneys. Cooling of the kidney can be achieved by either perfusion-cooling or by external parenchymatous cooling. We describe a method using the latter system for stone removal in 14 patients with staghorn calculi or multiple stones. Preoperatively 9 patients (64%) had persistent urinary tract infection, whereas infection persisted in only 2 patients following the operation (14%). Complete stone removal was achieved in 13 patients (93%). Renal function evaluated by creatinine clearance and renography generally improved following operation. There were no deaths, but in 9 patients severe complications were seen (transient oliguria and septicemia). At follow-up investigation 1.5 years after operation renewed stone formation was found in 1 patient, while the incidence of urinary tract infection had increased to 3 patients (21%). It is concluded that extensive surgery for stone removal with the use of external parenchymatous cooling is worthwhile and promising in patients with staghorn calculi or multiple stones in the kidneys.

Host resistance to lipopolysaccharides in the pathogenesis of multiple sclerosis and membranoproliferative glomerulonephritis.

Host resistance against bacterial lipopolysaccharides (L.P.S.) and especially against its toxic part lipid A has earlier been demonstrated in biological assays. In this paper an aryl-esterase is shown to be associated with alfa-1-lipoprotein (ArE) and is probably responsible for the detoxification of L.P.S. in man. Furthermore C3 is shown to be activitated by L.P.S. From these facts it is suggested that ArE performs the initial degradation of L.P.S. followed by complement activation and trapping of the L.P.S.--complement complex in the reticuloendothelial system. It is postulated that a deficient host response against L.P.S. can be the triggering mechanism in multiple sclerosis due to the lack of ArE in myelin, and that an infectious-agent/L.P.S. syndrome can activate latent infections in connection with a severe hyperreactivity to L.P.S. Preliminary investigations in patients with membranoproliferative glomerulonephritis have shown low levels of ArE in serum. This change, together with the low C3 values in these patients, may result in deficient L.P.S. detoxification and it is suggested that L.P.S. are at least partly responsible for the production of C3 nephritic factor.

Precipitating antibodies against Micropolyspora phaeni in sera from mushroom workers.

A new method for determining precipitating antibodies in allergic alveolitis is presented. The principle used is immunoelectrophoresis, either as a counterelectrophoresis or as a crossed immunoelectrophoresis with intermediate gel. Twenty-two mushroom workers without anamnestic signs of allergic alveolitis and 15 control persons were investigated. Twelve mushroom workers (55%) had precipitating antibodies as determined by crossed immunoelectrophoresis, and nine of these persons had antibodies demonstrated with counterelectrophoresis. Thus, the sensitivity seems greater in the crossed immunoelectrophoresis, but we find that the simpler counterelectrophoresis is an excellent screening procedure in patients suspected of allergic alveolitis. In the controls only one person had precipitating antibodies, though the antigen tested for Micropolyspora phaeni exists ubiquitously. It seems probable from this study that the antigenic load is important, although it is remarkable that no mushroom worker with precipitating antibodies against M. phaeni had ever experienced symptoms compatible with allergic alveolitis.

Toxicological problems with the REDY system.

Dialysate from the REDY dialysis system was examined for toxic elements, special attention being paid to the content of zirconium and aluminium. Also investigated was the concentration of formaldehyde in the rinsing fluid of three consecutive washings. The amount of zirconium and aluminium found in the dialysate was negligible. The concentration of formaldehyde was alarmingly high after two consecutive washings, a considerable amount (less than 50 mg) still remaining after three washings. It is recommended that at least three consecutive washings be performed, and that, if possible, formaldehyde be substituted by another antiseptic. Of special interest was the finding of a very high concentration of boron in the dialysate. It is suggested that this metal, which is a potentially toxic substance, may emanate from the patient. It is concluded that use of the REDY system carries no obvious toxicological risk.

Experience with one-stage bilateral nephrectomy.

Eight patients with uremia were treated by one-stage transperitoneal bilateral nephrectomy prior to transplantation. Four of the patients had refractory hypertension with high peripheral renin activity which was unresponsive to drug treatment and vigorous hemodialysis. All obtained a normal blood pressure after operation. Two patients were nephrectomised to combat chronic infection, whilst one of the two remaining patients suffered from huge polycystic kidneys and the other had suspected Goodpasture syndrome. There were no deaths and the only complications observed were one instance of hyperkalemia necessitating acute hemodialysis and one instance of prolonged ileus. Our indications for doing the operation prior to transplantation have been very restricted, but when the operation becomes necessary, it is a safe procedure.

Diazoxide in the management of severe hypertension.

Fourteen patients with severe hypertension have been given i.v. diazoxide in a dosage of 5 mg/kg b.wt. The material comprised 2 patients with malignant nephrosclerosis, 4 with chronic nephropathy and severe reduction of renal function, 1 patient with chronic pyelonephritis, 1 with renovascular hypertension and 6 patients with essential hypertension and in malignant phase. All patients attained a controllable blood pressure. Eight patients remaining needed only one injection, while the remaining patients required 2-5 injections, and concomitant furosemide therapy. The retinopathy improved in most patients and renal function was unchanged in the azotemic patients. No serious adverse effects were seen, except one hypotensive episode. Diazoxide is easy to handle, dosage can be predetermined, monitoring is simple and we find diazoxide to be a valuable drug in severe hypertension.