Treatment of severe hypothyroidism in a patient with progressive renal failure leads to significant improvement of renal function.

The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy.

Acute renal failure caused by Klebsiella pneumoniae pyelonephritis.

We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function recovered to near normal after intermittent hemodialysis and antibiotic therapy. We believe that it is important to include this entity in the differential diagnosis of acute renal failure since proper diagnosis and treatment is essential for recovery of renal function. Furthermore, we would like to draw attention to Klebsiella pneumoniae as an important potential pathogen in such cases, in addition to Escherichia coli.

A randomised, multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory tract infections.

In this study the efficacy and cost-effectiveness of i.v. ceftriaxone 1 g once daily (CTX) was compared with standard i.v. antibiotic treatment (STD) for lower respiratory tract infections (LRTI). STD was given according to the guidelines of the American Thoracic Society and consisted of either cefuroxime 1500 mg three times daily (q8h), amoxicillin/clavulanic acid 1200 mg q8h or ceftriaxone 2 g once daily; each with or without a macrolide. After a minimum of 5 days i.v. therapy, patients could be switched to oral therapy. One hundred patients were enrolled in the study; 52 patients received CTX and 48 STD. Groups were comparable with respect to demographic and baseline characteristics. Seventy patients had a confirmed diagnosis of pneumonia. Twenty-nine patients had a severe type I exacerbation of chronic bronchitis. In one patient the diagnosis of LRTI could not be confirmed. In approximately 50% of the patients a microbiological diagnosis could be made. The most important isolated pathogens from sputum and blood were (positive blood cultures in brackets): Streptococcus pneumoniae 14 (9) and Haemophilus influenzae 16. Mean duration of i.v. therapy was 7.4 days in both groups. Average duration of hospitalisation was 15.0 days for CTX patients and 15.9 days for STD patients. Overall cure and improvement rate at the end of treatment was 47 (90%) for patients receiving ceftriaxone 1 g compared to 37 (77%) for patients receiving standard therapy. Pathogens were eradicated or presumed to be eradicated in 84% of the CTX patients and in 76% of the STD patients. Mean total costs per treatment were lower for CTX than for STD treatment: NLG 169 versus 458. These results show, that i.v. ceftriaxone 1 g once daily is as effective as standard therapy in the treatment of LRTI and that its use reduces treatment costs, in view of the multiple daily dosing regimens of most standard therapies.

Hyperamylasaemia in multiple myeloma.

A 71-year-old woman, known to have multiple myeloma, was admitted because of fever, abdominal pain and hyperamylasaemia and hyperamylasuria. She was diagnosed as having acute pancreatitis. Because the diagnosis could not be confirmed, and serum lipase was normal, it appeared that this patient had developed an amylase-producing myeloma lesion in the pelvis.

Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia.

Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

IgG autoantibodies to C1q do not detectably influence complement activation in vivo and in vitro in systemic lupus erythematosus.

The influence of IgG antibodies to C1q (C1qAb) on activation of the classical pathway of the complement system was investigated in patients with systemic lupus erythematosus (SLE). In in vivo experiments, a prototype for immune complexes was administered intravenously to 14 patients and 9 healthy controls. Eight SLE patients had increased C1qAb titers. The increase of C3a levels, which was measured as a parameter of C1 activation, was significantly lower in SLE patients than in the healthy controls (p = 0.01). No correlation was found between C3a increases and C1qAb titers. In in vitro experiments the influence on C1 activation of monomeric IgG isolated from serum of 11 SLE patients, 7 of whom had increased C1qAb titers, was measured in a C4 consumption assay. The presence of C1qAb did not influence C4 consumption. The results demonstrate that C1qAb do not influence C1 activation by immune complexes in SLE patients.

Elimination of soluble 123I-labelled aggregates of human immunoglobulin G in humans; the effect of splenectomy.

To study the role of the spleen in the elimination of immune complexes we examined mononuclear phagocyte system function in eight healthy controls and eight splenectomized patients, with soluble 123I-labelled aggregates of human immunoglobulin G (AIgG). No differences were found between the two groups in elimination and degradation of AIgG. The loss of splenic function was compensated for by increased uptake of AIgG by the liver. With the dose of 123I-AIgG used in this study (10 micrograms/kg body weight), significant generation of C3a was observed. No correlation was found between erythrocyte CR1 number and the fraction of aggregates that bound to erythrocytes.

Diminished clearance of soluble aggregates of human immunoglobulin G in patients with rheumatoid arthritis.

Investigation of the capacity of the mononuclear phagocyte system to remove immune complexes from the circulation was performed by the administration of 125I-labelled aggregates of human immunoglobulin G (AIgG) to patients with seropositive rheumatoid arthritis and healthy volunteers. It was found that the rate at which AIgG disappeared from the circulation was significantly prolonged in patients with RA, t1/2 61 +/- 49 min, versus 26 +/- 8 min in healthy volunteers (p less than 0.01). We were not able to establish a correlation between the t1/2 of AIgG and immune complex levels in the circulation, or between t1/2 and articular disease activity (Ritchie index). The sites of removal of AIgG from the circulation were analysed by determining radioactivity levels detectable over liver, spleen and heart. No correlation was found between t1/2 and liver/spleen uptake ratios. We have demonstrated that the removal of AIgG from the circulation of patients with RA is abnormal, though the biological significance of this finding remains to be determined.

Abnormal clearance of soluble aggregates of human immunoglobulin G in patients with systemic lupus erythematosus.

In the present study, we tested mononuclear phagocyte system function in nine healthy controls and 15 SLE patients with complement activating 123I-labelled aggregates of human IgG (AIgG). Clearance half-time of AIgG was 26 +/- 8 min in controls, compared to 58 +/- 27 min in patients (P less than 0.005). Binding of AIgG to erythrocytes was significantly lower in patients, 9.3 +/- 8.1 vs 24 +/- 20% (P less than 0.05). The increase of C3a-levels in plasma was significantly lower in patients than in controls (P less than 0.05 at 3 and 8 min), suggesting less complement activation. Liver and spleen uptake of 123I-AIgG was measured with a gamma camera and expressed as liver/spleen uptake ratios. In patients, the liver/spleen uptake ratios were significantly higher than in controls at 15 min, 3.8 +/- 2.0 vs 2.31 +/- 0.7 (P less than 0.05), due to less splenic uptake of AIgG. Correlations between clearance half-time or liver/spleen uptake ratios and immune complex levels or disease activity were not found. This study indicates that clearance of soluble AIgG is abnormal in patients with SLE, due to decreased splenic uptake of AIgG.

Clearance of soluble aggregates of human immunoglobulin G in healthy volunteers and chimpanzees.

Using aggregates of IgG (AIgG) obtained by heat aggregation of a 16 g% human IgG solution, we sought a method for measuring the function of the mononuclear phagocyte system with a probe that bears more resemblance to soluble immune complexes than erythrocytes coated with anti-rhesus IgG (EIgG). It was found that intravenous administration of 10 micrograms AIgG/kg body weight did not cause any detectable side effects in chimpanzees. In nine healthy volunteers, a dose of 10 micrograms AIgG/kg body weight was used without any adverse reactions. AIgG is cleared from the human circulation with a t1/2 of 26 +/- 8 min (mean +/- SD). The site of clearance is predominantly the liver, as shown by an average liver spleen uptake ratio of 230:100. In whole blood obtained from the volunteers, it was found that erythrocytes bound significant amounts of AIgG, suggesting that CR1 on erythrocytes is involved in the clearance of complement activating immune complexes in humans. In five of the volunteers, clearance studies with EIgG had been done in a previous study. EIgG was cleared from the circulation with a t1/2 of 30 +/- 6.2 min (mean +/- SD). The predominant site of clearance of EIgG was the spleen. These data indicate that sensitized red blood cells are cleared from the circulation differently from soluble IgG aggregates.

Mononuclear phagocyte system Fc-receptor function in patients with seropositive rheumatoid arthritis.

Mononuclear phagocyte system (MPS) Fc-receptor function in 20 patients with seropositive rheumatoid arthritis (RA) was investigated using radiolabelled autologous erythrocytes coated with an average of 5,800 molecules of anti-rhesus IgG (E. IgG). Although clearance times (T1/2) of E. IgG tended to be longer in RA patients than those in healthy controls (46 +/- 6 min vs 38 +/- 5 min, mean +/- s.e.m., P = 0.38), this did not reach statistical significance. Liver spleen uptake ratios (LS ratios) were increased in patients with RA (13/100 +/- 1/100 vs 7/100 +/- 1/100, P less than 0.05). There was no correlation of T1/2 or LS ratios with articular disease activity, vasculitis, ESR, IgM containing immune complex levels or Clq-binding immune complex levels. Although Clq-binding immune complex levels were significantly higher in patients with vasculitis than in those without (P less than 0.01), T1/2 and LS ratios did not differ in these two groups of patients. The T1/2 and LS ratios of E.IgG did not reveal a defect in MPS Fc-receptor function and did not correlate with one of the above-mentioned clinical and immunological parameters. We suggest that in order to establish a possible defect in Fc-receptor function correlating with disease activity and immune complex levels in RA patients, soluble immune complexes or immune complex-like material should be used as probes.

Renal failure due to granulomatous interstitial nephritis after pulmonary sarcoidosis.

Two patients, who had had pulmonary sarcoidosis, developed renal failure due to sarcoid granulomatous interstitial nephritis after their original pulmonary symptoms had subsided. Treatment with prednisone resulted in almost complete recovery of renal function. Lysozyme and angiotensin-converting enzyme levels and gallium scintigraphy can be of diagnostic value.

Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis.

Immunoglobulin G (IgG) autoantibodies against extranuclear components of polymorphonuclear granulocytes were detected in 25 of 27 serum samples from patients with active Wegener's granulomatosis and in only 4 of 32 samples from patients without signs of disease activity. In a prospective study of 19 patients these antibodies proved to be better markers of disease activity than several other laboratory measurements used previously. The autoantibodies were disease specific and the titres were related to the results of an in-vitro granulocyte phagocytosis test, in which 7S IgG antibodies were internalised after specific binding to the cell, resulting in gradual formation of ring-like cytoplasmic structures. This autoantibody may have a pathogenetic role in Wegener's granulomatosis. The detection of this antibody is valuable for diagnosis and estimation of disease activity.

Hepatic sinusoidal dilatation with portal hypertension during azathioprine treatment after kidney transplantation.

An unusual hepatic disease developed in 3 patients with a well-functioning kidney graft 16-24 months after transplantation. Vague abdominal pain, increased bleeding tendency and edema were initial complaints, and hepato- or splenomegaly and ascites were found as well. Liver function tests were not or only mildly disturbed; hemolysis and pancytopenia were always present. Colloid uptake was absent at liver scintigraphy and the hepatic venous wedge pressure was increased. Esophageal varices were demonstrated. Liver biopsy showed extensive midzonal and pericentral sinusoidal dilatation. After discontinuation of azathioprine the symptoms and the extent of sinusoidal dilatation disappeared gradually, but after 1-3 years fibrosis or micronodular cirrhosis had developed and splenomegaly with hypersplenism remained. These observations strongly suggest an association between chronic use of azathioprine and the development of venous congestion of the liver with sinusoidal dilatation, eventually resulting in chronic liver disease.

Hyperimmunoglobulinaemia D and periodic fever: a new syndrome.

Six patients of Dutch ancestry with a long history of recurrent attacks of fever of unknown cause were found to have a high serum IgD level and a large number of plasma cells with cytoplasmic IgD in the bone marrow. Because the clinical picture in some ways resembled that of familial Mediterranean fever (FMF), sera of patients with FMF were also investigated; only one of eight such patients had a raised serum IgD.