Effect of dialyzer geometry on granulocyte and complement activation

During hemodialysis with cuprophan membranes, the complement system as well as leukocytes become activated. In order to clarify the role of dialyzer geometry, the effect of hollow-fiber versus flat-sheet dialyzers and of different surface areas on C3a generation and leukocyte degranulation was investigated. Plasma levels of leukocyte elastase in complex with alpha 1-proteinase inhibitor were significantly increased after 1 h (+55%) and 3 h (+62%) of hemodialysis with flat-sheet dialyzers as compared to hollow-fiber devices. In addition, plasma levels of lactoferrin, released from the specific granules of leukocytes during activation, were significantly higher (+42%) 3 h after the onset of dialysis treatment with flat-sheet than with hollow-fiber dialyzers. With respect to surface area, larger dialyzers tended to cause more release of leukocyte elastase as compared to dialyzers with smaller surface areas, irrespectively of the configuration of the dialyzer used. On the other hand, activation of the complement system, as measured by the generation of C3a-desarg, did not differ with both types of configurations. The same held true for leukopenia, which was almost identical for hollow-fiber and flat-sheet dialyzers. From these findings two lines of evidence emerge: First, not only the type of membrane material used in a dialyzer may influence its biocompatibility, but the geometry of the extracorporeal device also determines the degree of compatibility. Hence, the extent of leukocyte activation correlated with both configuration of the dialyzer and surface area of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Idiopathic retroperitoneal fibrosis. A retrospective analysis of 60 cases

Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.     

Decreased sensitivity to phalloidin of aged F344/DuCrj rat hepatocytes

The phalloidin sensitivity of hepatocytes resulting in the formation of cytoplasmic blebs was examined with cells isolated from 73- to 74-week-old and 99- to 100-week-old F344/DuCrj rats of both sexes by a collagenase perfusion method. The cells isolated from aged rats were less sensitive to the toxin than those obtained from 10- to 14-week-old rats. The decrease in the sensitivity was more marked in males than in females, and it appeared at an earlier age in the former than in the latter. Phalloidin consumption experiments showed decreases in the cellular uptake of the toxin in aged rats, and these were more marked in males than in females. The low cellular uptake of the toxin seemed to play an important role in the low sensitivity of the cells in aged rats. Although histological and histochemical examinations showed the development of foci of altered hepatocytes in the aged rat liver, the foci were estimated to account for less than 1.5% of liver tissues. Thus, the decrease in the sensitivity of the cells isolated from whole liver tissues might mainly be attributed to the decrease in the sensitivity of otherwise normal-looking hepatocytes.     

Characterization of hindlimb motoneuron membrane properties in acute and chronic spinal cats

The purpose of this study was to determine if changes in hindlimb motoneuron membrane electrical properties occur 4–6 months after spinal transection in the adult animal. Eight acute and nine chronic animals were spinalized at T₁₂. Intracellular recordings from motoneurons innervating the triceps surae were performed. Membrane electrical properties, including resting potential, action potential peak amplitude, afterhyperpolarization duration, rheobasic current, input resistance and axonal conduction velocity were measured. There were no statistical differences found between group means or frequency distributions in the membrane properties of motoneurons assessed from acute and chronic spinal animals. Thus, alteration of motoneuron membrane properties does not appear to be a major contributing factor to the hyperexcitable hindlimb reflex activity demonstrated by chronic spinal animals.     

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.     

Significance of coupling intervals of spontaneous ventricular arrhythmias in long-term ECG in patients with coronary heart disease

Coupling intervals of premature ventricular beats and complex arrhythmias were studied by 24-h ambulatory electrocardiographic recordings in 76 patients (35 sudden death patients and 41 survivors) with coronary artery disease. A first Holter (HM 1) was recorded at the time of left ventricular angiography and a second Holter (HM 2) after a mean interval of 34.4 +/- 11.2 months (range 2-61 months). All patients were only treated medically. The mean heart rate was significantly faster in patients who died suddenly than in survivors in both HM 1 and HM 2 (p less than 0.01). In HM 1, there were no significant differences in mean coupling intervals between patients who died suddenly and survivors, whereas in HM 2, coupling intervals of premature ventricular beats and couplets were significantly shorter in patients who died suddenly than in survivors (p less than 0.05). Patients with coupling intervals for couplets less than 500 ms died significantly earlier than those patients with coupling intervals greater than 500 ms (p less than 0.05). Our data show that there is a relationship between heart rate, coupling intervals and sudden death. Patients with fast heart rates and coupling intervals for couplets less than 500 ms represent a group at high risk of sudden death.     

Fate of TR-2, the hepatic metabolite of the tremorgenic mycotoxin verruculogen, in sheep

1. Verruculogen is eliminated in bile after transformation to TR-2, only a trace of which was excreted as such in faeces of sheep given verruculogen per os. Negligible TR-2 was present free in urine; no glucuronide was found. 2. An isomer of TR-2, a minor component of the bile of sheep given verruculogen, has been defined by 1H-n.m.r. spectroscopy and the isomerism involves the disposition of the two adjacent hydroxyl groups with a concomitant change in the conformation of the ring adjacent to the indole. 3. 14C-TR-2, added to the perfusate of isolated rat liver, was excreted unchanged in the bile, implying no significant loss of any biliary TR-2 subject to enterohepatic recycling in vivo. 4. 14C-TR-2 incubated anaerobically in sheep ileum contents was 95% transformed into more polar metabolites, the majority of the radiolabelled metabolites isolated being water soluble. 5. The principal fate of biliary TR-2 is as a metabolic substrate for the intestinal microflora.