The management of renal scleroderma: experience with dialysis, nephrectomy and transplantation.

In 25 of 100 patients with scleroderma seen over a five year period irreversible renal failure developed; renal support was instituted in 17. Ten of 17 received peritoneal or hemodialysis, one survived. The remaining seven received hemodialysis plus nephrectomy; three survived. Two of these three underwent renal transplantation; one survived. This experience is presented to encourage improvement of these and other technics to increase the survival rate in the otherwise uniformly fatal renal failure associated with scleroderma (systemic sclerosis).     

Skin capillary abnormalities as indicators of organ involvement in scleroderma (systemic sclerosis), Raynaud's syndrome and dermatomyositis

Forty-four study patients with scleroderma (systemic sclerosis) (28 patients), Raynaud's syndrome (13 patients) or dermatomyositis (three patients) were observed for skin capillary abnormalities by widefield microscopy and compared with three control groups of 20 subjects each: (1) patients with other rheumatic disease, (2) hospitalized patients with nonrheumatic conditions, and (3) healthy volunteers. The distinctive microvascular pattern (dilated and distorted capillary loops alternating with avascular areas) previously reported in scleroderma and dermatomyositis was observed almost exclusively in the study patients. The severity of capillary abnormalities varied among the diagnostic subgroups, and a positive correlation was found between the degree and extent of abnormal microvascular patterns and multisystem involvement.On this basis, widefield nailfold capillary observations are proposed as a simple, inexpensive, reproducible technic for making an improved early diagnosis and predicting multisystem involvement in scleroderma, Raynaud's syndrome and dermatomyositis, presently a group of loosely associated and overlapping connective tissue disorders which often defy early and precise diagnosis.     

Chorioretinitis with a combined defect in T and B lymphocytes and granulocytes: A new syndrome successfully treated with dialyzable leukocyte extracts (transfer factor)

A patient with immune deficiency, recurrent pyogenic infections and active chorioretinitis is described; in addition to agammaglobulinemia, both quantitative and qualitative T-cell deficiencies were documented. Furthermore, the patient's granulocytes (polymorphonuclear leukocytes), although normal in their bactericidal capacity for Staphylococcus, responded poorly to both leukocyte migration inhibition factor and neutrophil immobilizing factor obtained from normal cells. The immunologic features of this patient appear to comprise a new syndrome. Remarkable diminution of the ocular lesions and increased visual acuity occurred within two months after the initiation of therapy with dialyzable leukocyte extracts (transfer factor). Concurrent testing of the patient's cell-mediated immunity showed increased numbers of circulating T lymphocytes and improved T-cell function following dialyzable leukocyte extract [DLE] therapy. The dramatic clinical results indicate that similar therapy may prove to be beneficial in other patients with chorioretinitis and T-cell deficiency.     

Temporal arteritis.

Temporal arteritis, like tuberculosis and syphilis, is a disease of protean manifestations. No single clinical symptom, sign or laboratory test can be relied upon for establishing the diagnosis. Hamilton [1] emphasizes the importance of a detailed analysis of each case—“More often than not the latter (physical findings indicative of active arteritis) are absent and a history indicating the likelihood of an arteritis is obtained only when probing questions are asked by one who is fully cognizant of the varied symptoms and signs this disorder may induce.” In dealing with geriatric patients, the clinician should maintain a high index of suspicion for temporal arteritis. Unexplained fever, malaise, depression, anemia or even carpal tunnel syndrome may be the initial presentation of the disease.The erythrocyte sedimentation rate is usually an accurate aid to diagnosis and clinical monitor of disease suppression during treatment. Realizing that active arteritis can exist without an abnormality in the erythrocyte sedimentation rate in some instances, the clinician must not ignore symptoms or signs consistent with the disease when the erythrocyte sedimentation rate is normal.Palpatory abnormalities need not be present before arterial biopsy reveals active arteritis. Pathologic abnormalities may be confined to short segments thereby making unilateral arterial biopsies inconclusive in eliminating the diagnosis. Contralateral biopsies have been positive in 53 per cent of one series. With appropriate corticosteroid intervention, the clinician can prevent the major threat from temporal arteritis—blindness.     

Blood pressure, heart rate, pressure-rate product and electrocardiographic changes in healthy children during treadmill exercise.

Heart rate, systolic and diastolic blood pressure, rate-pressure product and electrocardiographic changes were measured in 288 healthy children during treadmill exercise. A constant speed (3.5 miles/hour) protocol was used to facilitate the measurements of physiologic data during exercise. Because responses to exercise vary with size, the children were separated into four groups according to body surface area. Comparisons were also made between male and female and between black and white children. The values for heart rate and systolic pressure showed excellent reproducibility in repeated tests. These data establish for clinical use reference values for children during treadmill exercise.     

Transvenous catheter ablation of a right atrial automatic ectopic tachycardia

A 10 year old patient with right atrial automatic ectopic tachycardia underwent successful transvenous catheter ablation after endocardial mapping. Tachycardia had been present for 7 years before ablation and associated with development of dilated cardiomyopathy. A single 50 J discharge at the point of earliest atrial activation was followed by the establishment of sinus rhythm that remains at 10 months' follow-up. This case represents the first reported successful catheter ablation of an atrial automatic ectopic tachycardia. Specific anatomic factors favoring successful ablation and improvement in technique are discussed.     

Structural changes in a porcine xenograft after implantation for 105 months

Morphologic studies including light microscopy and transmission and scanning electron microscopy were performed on a formaldehyde-fixed porcine xenograft prosthesis that functioned well for 8 years and had been implanted for 105 months in the tricuspid valve position. It is the oldest implanted valve studied in this manner. Although all leaflets had some gross deterioration, only one had adherent thrombus. The degenerative changes in the connective tissue from all leaflets were similar to those recently reported in glutaraldehyde-fixed porcine valves implanted for shorter periods. The surfaces of the two nonthrombosed leaflets and small portions of the surface of the thrombosed leaflet were endothelized, and the endothelium appeared to have little or no effect on the degenerative changes in the subjacent connective tissue. Further, the endothelium did not extend over the examined portion of the synthetic anulus of the prosthesis, suggesting that its origin was possibly from cells circulating in the blood.     

Mycobacterium fortuitum pulmonary infection associated with an antigen-selective defect in cellular immunity

In this study we describe the first example of a well documented case of pulmonary infection caused by Mycobacterium fortuitum shown to be associated with an antigen-selective defect in cellmediated immunity to this organism. Immunologic parameters were evaluated before, during and after antibiotic treatment with amikacin. A defect in cellular immunity to purified protein derivative from Myco. fortuitum, shown to be antigen-selective as indicated by normal responsiveness to purified protein derivative from Mycobacterium tuberculosis and several other common recall antigens, accompanied the prolonged infection by this organism. During the first three months of treatment with amikacin, the patient's clinical status improved coincident with the eradication of the organism from the sputum. During the next three months of therapy with amikacin, however, a generalized defect in cellular immunity developed, and the lung disease again progressed. The deteriorating clinical condition was presumably related to a generalized cellular immune anergy or hyporesponsiveness induced by the amikacin therapy. After three more months of treatment, the organism became resistant to the drug and reappeared in sputum cultures. Since amikacin therapy was discontinued, the patient's general immune responsiveness returned to normal. He did, however, remain unresponsive to purified protein derivative from Mycobacterium fortuitum.     

Treatment of atrial automatic tachycardia by ablation procedures

Sixteen cases of atrial focus tachycardia are described clinically, electrophysiologically and hemodynamically. In each case multiple attempts at drug treatment (average 2.5 drugs) had failed. After delineation of the electrophysiologic mechanism, the patients were treated by surgical removal or cryoablation or catheter electroablation of the focus. In two of four patients catheter ablation was successful and without complication. Surgical treatment was successful in 13 of 14 patients. Left ventricular function, which had been abnormal in 10 patients, normalized in all but 1 patient whose echocardiographic shortening fraction improved from 10 to 27%. There have been no recurrences in a follow-up period of 6 months to 5 years (mean 2.2 years). It is recommended that any atrial automatic focus tachycardia that produces hemodynamic compromise undergo definitive treatment. Patients with chronic tachycardia rates of more than 140 beats/min should be followed up closely.     

Anticytoplasmic antibodies in antinuclear antibody-negative lupus erythematosus. Correlation with clinical course

A patient with clinical manifestations of systemic lupus erythematosus (SLE) and without antinuclear antibodies was found to have anticytoplasmic antibodies. These anticytoplasmic antibodies were directed against ribosomal ribonucleoprotein, and the titer of anticytoplasmic and anti-ribosomal ribonucleoprotein antibodies correlated with the clinical course of the patient's illness. The importance of detecting anticytoplasmic antibodies and their role in producing disease in patients with SLE is discussed.     

Penicillamine-induced myositis. Observations and unique features in two patients and review of the literature

Dermatomyositis developed during treatment with penicillamine in two patients with rheumatoid arthritis. Both were male without a history of penicillin allergy. Eosinophilia was present at the start of their illness, and HLA tissue typing showed the presence of HLA-DR2 in one patient. One patient was retreated with penicillamine and remained asymptomatic after three years of therapy, and the other was able to take penicillamine in a reduced dosage.     

Stimulation of hepatic and renal ornithine decarboxylase activity by selected amino acids

The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, increases after a protein meal. The effect of amino acid mixtures on hepatic and renal ODC activity and polyamine content was studied in postabsorptive and 72-hour fasted rats. Fasting decreased ODC activity in liver and in kidney by approximately 50%. Hepatic ODC activity increased tenfold 4 hours after intraperitoneal injection of either 1 g/kg of a synthetic mixture of 17 amino acids or of casein hydrolysate to fed rats and about 20-fold in fasted rats. Renal ODC activity increased four- and tenfold respectively. A mixture of glutamate, aspartate, and alanine at concentrations given in the hydrolysate reproduced the full amino acid effect. No amino acid was effective when given alone, nor were mixtures of the other amino acid constituents of the hydrolysate. Glutamate + alanine was ineffective as were glucose or various combinations of arginine, ornithine, aspartate and NH₃. Ornithine + glutamate or aspartate + glutamate were active but stimulated less than aspartate + glutamate + alanine. Hepatic and renal putrescine content increased in parallel with ODC activity. The data suggest that specific amino acids possess the full ODC-stimulating capability of a high quality protein and that polyamine synthesis is linked to urea cycle activity.     

Allopurinol hypersensitivity: Granular deposition of IgM at the dermal-epidermal junction

A patient with allopurinol hypersensitivity, manifested by fever, lymphadenopathy and a severe erythematous, morbilliform, maculopapular rash was studied. On immunofluorescent staining of the patient's skin, heavy granular deposits of immunoglobulin M (IgM) were found at the dermal-epidermal junction. Transformation of the patient's lymphocytes could not be effected by a variety of combinations of allopurinol, allopurinol metabolites and serum. These data suggested that the hypersensitivity reaction caused by allopurinol had immune complex deposition as the central feature in pathogenesis. The predominance of IgM may provide a distinctive feature from the deposits generally seen in systemic and discoid lupus erythematosus.     

The changing clinical spectrum of primary aldosteronism

In a prospective study of 80 patients with primary aldosteronism (70 with adenoma and 10 with hyperplasia), "refractory" hypertension, hyperkinetic circulation, and hypovolemia were frequent occurrences. We found that measurements of serum potassium concentration and plasma renin activity were inadequate screening tests because of high rates of false-positive and false-negative results. The demonstration of excessive aldosterone production after three days of salt loading provided the best sensitivity (96 percent) and specificity (93 percent) in identifying patients with primary aldosteronism. Severe, persistent hypokalemia, increased plasma 18-hydroxycorticosterone values, and an anomalous postural decrease in the plasma aldosterone concentration, when present, provided the best indicators of the presence of an adenoma. Of three localizing procedures (selective adrenal venography, adrenal computed tomographic scan, and adrenal venous sampling for plasma aldosterone concentration) the measurement of adrenal venous plasma aldosterone concentration yielded 100 percent accuracy. These results indicate a wider clinical spectrum in primary aldosteronism than previously described. They also show that nonsuppressible aldosterone production is its most important diagnostic hallmark and the single best diagnostic screening procedure, and that adrenal venous sampling for plasma aldosterone concentration remains the most precise technique for identification and localization of tumors.     

Effects of phenytoin on man's immunity. Evaluation of changes in serum immunoglobulins, complement, and antinuclear antibody

To determine the effects of phenytoin on serum immunoglobulins, complement, and antinuclear antibody conversion, a prospective, five-year longitudinal study was undertaken in 118 patients. Three major diagnostic groups were evaluated: 27 patients with idiopathic epilepsy, 50 with secondary epilepsy, and 41 with neuropathic syndromes without epilepsy. In addition, 83 normal volunteers were studied in a similar manner. Evaluations were performed prior to administration of phenytoin and at six-month intervals thereafter. Prior to treatment, patients with idiopathic epilepsy had a higher than expected incidence (13.5 percent, p less than 0.01) of low serum IgA (less than 61 mg/dl). Patients with secondary epilepsy and neuropathic disorders without epilepsy had a greater than expected incidence (9.2 percent, p less than 0.01; and 12 percent, p less than 0.01, respectively) of high serum IgA (greater than 417 mg/dl). Phenytoin treatment was associated with further decreases in serum IgA in patients with idiopathic epilepsy (p = 0.063) and secondary epilepsy (p = 0.008). Total serum IgE concentrations also decreased significantly in all patient categories during treatment with phenytoin. Minor decreases in serum IgG and IgM were noted, but serum IgD and complement remained unaffected. Antinuclear antibodies were observed with essentially the same frequency (10 percent) before and after phenytoin therapy.     

The clinical spectrum of ascites associated with maintenance dialysis.

Among 197 patients being treated with maintenance dialysis, six were found to have ascites. Unlike previous reported series, the cause of ascites and the clinical course were variable. Two patients responded to definitive therapy directed against the specific cause. No consistent association was found with the etiology of renal disease or therapy of uremia including the duration of hemodialysis or prior peritoneal dialysis. Nonspecific therapy attempting to alleviate ascites was unsatisfactory. Severe hypertension was not characteristic and bilateral nephrectomy did not influence the course. An extensive diagnostic evaluation is recommended along with skepticism before declaring that idiopathic, refractory ascites exists signaling progressive deterioration.     

Triad of glomerulonephritis, antinuclear antibodies, and positive skin immunofluorescence. Variant of systemic lupus erythematosus

We are reporting findings in 13 patients who presented with glomerulonephritis without evidence of systemic disease, but who were found to have positive antinuclear antibody results and immunoglobulin and/or complement deposits at the dermal-epidermal junction of normal skin not exposed to light. There was no evidence of other organ involvement, and serologic tests for systemic lupus erythematosus (SLE) gave negative results. The renal disease is characterized by severe proteinuria, focal or diffuse proliferative glomerular lesions on biopsy, with variable patterns of immunoglobulin deposits. No clinical manifestations or serologic results typical of SLE have developed during prolonged observation. HLA phenotyping carried out in eight of the 13 patients revealed DR2 or DR3 alloantigens or both in seven of the eight patients, an incidence similar to that in patients with overt SLE. Because of the specificity of the skin biopsy immunofluorescence, the similarity of HLA-DR antigens, and a favorable response of the renal disease to therapy, we believe that these patients have a variant of SLE.