Induction of bone morphogenetic protein-2 by interleukin-1 in human fibroblasts.

Rheumatoid arthritis and periodontitis are chronic inflammatory diseases associated with tissue destruction that is mediated in part by elevated levels of cytokines (e.g., interleukin-1 and tumor necrosis factor). Differential screening of a human synovial fibroblast cDNA library for interleukin-1 induced genes revealed a clone identical to the gene encoding human bone morphogenetic protein-2. Northern blot analysis of human synovial fibroblast mRNA confirmed up-regulation of bone morphogenetic protein-2 in the presence of interleukin-1. Utilizing a specific antibody, levels of bone morphogenetic protein-2 protein in conditioned medium from synovial fibroblasts were also up-regulated in the presence of interleukin-1. This is the first report of the production of bone morphogenetic protein-2 by synovial fibroblasts, and the first report of its up-regulation in response to interleukin-1. However, interleukin-1 did not induce bone morphogenetic protein-2 mRNA in human gingival fibroblasts.

Phlebotomy for pulmonary edema in dialysis patients.

STUDY OBJECTIVE: To assess the efficacy of phlebotomy in the treatment of pulmonary edema in hemodialysis patients. PROCEDURE: Maintenance hemodialysis patients presenting to the emergency room in respiratory distress from apparent pulmonary edema were assessed with regard to clinical response, change in blood pressure, change in hematocrit, and interval until the next hemodialysis treatment, RESULTS: Twenty-one patients underwent phlebotomy and seventeen improved markedly and did not require intubation or emergent dialysis. Hemodialysis was initiated 15.6 +/- 13.6 SD hours later. Four were able to have their treatment 24 or more hours later. Thirteen of 21 (62%) were hypertensive at the time of treatment and blood pressure tended to normalize in this subset. Four of 21 (19%) developed transient hypotension without permanent sequelae. Pre-mean hematocrit = 25.0 + 6.0 and post phlebotomy = 22.6 + 4.6 SD. All patients receiving phlebotomy survived to hospital discharge. CONCLUSION: Phlebotomy can often obviate the need for intubation or emergent dialysis in ESRD patients presenting with pulmonary edema.

The role of thrombolysis in hemodialysis access occlusion.

Thirty-eight occluded hemodialysis accesses were infused with urokinase on 43 occasions. In 49% of the cases, the access patency was reestablished for a week or longer, although 38% of this subset subsequently rethrombosed. Postthrombolysis angiography detected a stenotic segment in 14 of 22 angiograms (64%). Local bleeding was common, but the thrombolytic therapy was generally well tolerated. Percutaneous thrombolysis in conjunction with angiography and access revision provides a clinically useful means of access preservation.

Intestinal mucormycosis in hemodialysis patients following deferoxamine.

Two maintenance hemodialysis patients receiving deferoxamine to chelate iron and aluminum developed intestinal mucormycosis. One patient had pulmonary mucormycosis as well. The patients lacked the usual predisposing factors to mucormycosis, ie, diabetes and acidosis, but both had liver disease. The role of siderophores such as deferoxamine in promoting certain infections is discussed with reference to this particular clinical setting.

Progressive systemic sclerosis with the nephrotic syndrome and acquired factor X deficiency.

A patient with progressive systemic sclerosis (PSS) involving skin, digit, esophagus, and lung developed the nephrotic syndrome and rapidly progressive renal insufficiency. Renal pathology revealed capillary collapse, cellular crescents, arteriolar hyaline deposition, and mesangial proliferation. On immunofluorescence IgM, C3, and fibrinogen were present in mesangium and capillary walls. Prebiopsy coagulation screening revealed a factor X deficiency which caused substantial prolongation of the partial thromboplastin time without an overt bleeding diathesis. The acquired factor X deficiency resolved after fresh frozen plasma and vitamin K administration, although some spontaneous improvement was noted. Nephrotic syndrome may occasionally be seen in the acute fulminant form of PSS and should not deter diagnosis of PSS.

Angiographic visualization for percutaneous renal biopsy.

Fifteen patients underwent visualization of the kidney for percutaneous biopsy by selective renal angiography. Biopsies were performed in 11 patients, and adequate renal tissue was obtained in all instances. Postbiopsy angiogram revealed pinpoint bleeding in ten patients and significant extravasation in one case, which was controlled with a selective epinephrine infusion. In four cases, biopsy was not performed when the cortex was found to be less than 5 mm thick.

Patients surviving 10 years of hemodialysis.

Experience with 37 patients surviving 10 years of hemodialysis therapy was reviewed. These patients were compared with 103 patients who began hemodialysis between 1967 and 1971 and who subsequently died. Males had an excess risk of death. Patients with polycystic kidneys survived longer. There was more uncontrolled hypertension among a control group than in 10-year survivors. In survivors, the hematocrit level increased over time and averaged 30.4 percent at 10 years. Over 10 years, many complications arose including parathyroidectomy (24), pericarditis (13), gastrointestinal bleeding (11), myocardial infarction (10), septicemia (eight), and active tuberculosis (six). Despite complications, most patients are now stable. Between their eighth and 10th years they required an average of only one hospitalization with a mean stay of 9.7 days. Eighteen patients were not hospitalized. Excluding housewives, 67 percent of patients between ages 20 and 59 years are employed full-time and 10 percent part-time. Patients surviving 10 years are not progressively deteriorating and may look to the future with cautious optimism.

Nephronophthisis with massive proteinuria.

A 23-year-old male whose uncle died of nephronophthisis, and whose pathology is also discussed, presented with 5 g of protein in a 24-hour urine collection. Nephrogenic diabetes insipidus and salt wasting were present in addition to azotemia. Characterization of the proteinuria, including elevated alpha globulins by electrophoresis and markedly elevated urinary beta-microglobulins by radioimmunoassay (49.55 mg/L) indicated predominantly tubular proteinuria. A percutaneous renal biopsy showed normal glomeruli, interstitial inflammation and fibrosis, and tubular atrophy. Electron microscopy revealed notable alterations of the tubular basement membrane.

Acute myoglobinuric renal failure. A consequence of the neuroleptic malignant syndrome.

Neuroleptic malignant syndrome and acute myoglobinuric renal failure developed in three patients after they had received a combination of a major tranquilizer and a tricyclic antidepressant or after a large dose of haloperidol. Rhabdomyolysis was demonstrated by biochemical methods as well as by a muscle biopsy. Myoglobinuria was confirmed by radioimmunodiffusion and also was verified in a necropsy specimen. Dehydration and drug interaction with tricyclic antidepressants seem to be predisposing factors. Renal function recovered when the patient survived the acute episode, but neurologic sequelae persisted. Recommendations that may avert further cases are made.

Cure of cryptococcemia in an immunocompromised patient with lupus nephritis.

The first documented cure of cryptococcosis with cryptococcemia is reported. The patient had systemic lupus erythematosis and had received corticosteroids and immunosuppressive drugs for diffuse proliferative nephritis. She had additional poor prognostic factors including high serum cryptococcal antigen titer, low cerebrospinal leukocyte count, and absence of anticryptococcal antibody. Pulmonary tuberculosis was diagnosed concurrently and subsequently she developed disseminated herpes zoster. During amphotericin B therapy, renal function worsened. Cure of cryptococcosis with cryptococcemia was accomplished despite multiple concurrent infections and transient worsening of renal function.

Contrasting alterations in pulmonary gas exchange during acetate and bicarbonate hemodialysis.

We studied 10 patients during acetate and 10 patients during bicarbonate hemodialysis to assess changes of minute ventilation; oxygen consumption (VO2); and carbon dioxide production (VCO2) as well as pO2, pCO2 and pH. We also measured the extent of pulmonic shunting by administering 100% O2. Our studies revealed that VO2 increased significantly during acetate dialysis, while it decreased slightly during bicarbonate dialysis. Since VCO2 decreased with both baths, the respiratory exchange ratio (R) decreased during acetate dialysis but did not change during bicarbonate dialysis. By the alveolar gas equation, these changes in R could account for a difference in alveolar pO2 and consequently arterial pO2. The fact that pO2 fell during bicarbonate dialysis may relate to decreased minute ventilation paralleling decreases in VCO2. The degree of intrapulmonic shunting was not altered during dialysis with either bath. We conclude that hypoxemia during dialysis relates to decreases in minute ventilation and that a greater decrease during acetate dialysis is a consequence of enhanced VO2 and its effect on R. Bicarbonate dialysis does not increase VO2.

A comparison of androgens for anemia in patients on hemodialysis.

To compare the erythropoietic effects of nandrolone decanoate, testosterone enanthate, oxymetholone, and fluoxymesterone, we performed a randomized clinical trial in patients with anemia who were receiving maintenance hemodialysis (the women were not given testosterone enanthate). After a control period of at least two months, patients received one of the drugs for six months and then returned to control status; a second and third drug were administered in a similar fashion. Seventy-seven patients completed the first drug period, 56 the second, and 35 the third. The response to nandrolone and testosterone enanthate, the two drugs given by injection, was clearly superior to the response to oxymetholone or fluoxymesterone, given by mouth, in terms of the percentage of patients responding and the mean rise in hematocrit. Approximately half the patients had an increase of at least 5 percentage points in hematocrit after an injectable androgen was given; more than half the women responded. Patients who required transfusions regularly and those who had bilateral nephrectomies did not respond.

A wearable artificial glomerulus.

We have shown that hemofiltration can be conducted for 16 hrs/day for more than 3 continuous days by connecting an Amicon 0.2 M2 hemofilter to an arteriovenous shunt. We can produce over 8 ml/min of ultrafiltrate with no external pump, and this ultrafiltrate can be replaced by having the patient drink an electrolyte-glucose solution. Anticoagulation can be attained with heparin, warfarin and cyproheptadine. Each filter can be expected to function at least 48 hrs before it must be replaced.

Bilateral nephrectomy for hypertension in patients with chronic renal failure on a dialysis program.

During the last 6 years 33 bilateral nephrectomies have been performed for severe hypertension in patients with chronic renal failure on a dialysis program. Nephrectomy resulted in a prompt and sustained reduction in blood pressure, an improved sense of well-being and a gain of weight. Despite the fact that the mean hematocrit decreased from 25 to 18 per cent all patients thrived. The nephrectomy group showed an 85 per cent 5-year cumulative survival rate compared to 55 per cent in the non-nephrectomy group. There was 1 mortality and low morbidity. Simultaneous nephrectomy by 2 teams, using a posterior approach, proved more satisfactory than an anterior or bilateral flank apprach. The indications for and arguments against bilateral nephrectomy are discussed.

Uremic pleural effusion. A study in 14 patients on chronic dialysis.

During a 21/2-year period, studies were done on 14 patients with chronic renal failure to evaluate pleural effusions which we believe were secondary to the uremic process. The patients with uremic pleural effusions closely resembled those in the group with chronic renal failure as a whole with respect to diagnosis and clinical features. Fever and pericarditis were noted in half the patients. The pleural fluid appeared serosanguineous or hemorrhagic in 10 of 14 patients and contained a predominance of lymphocytes more often than of neutrophils. Elevated protein and lactic dehydrogenase (LDH) levels gave the effusion characteristics of an exudate. Pleural tissue obtained by pleural biopsy or autopsy showed chronic fibrinous pleuritis in every patient. With continued dialysis the effusions resolved in 4 to 6 weeks after thoracentesis in 11 patients and recurred in 3 patients.