Goodpasture's syndrome: Failure of nephrectomy to cure pulmonary hemorrhage

Two patients with Goodpasture's syndrome are described. The diagnosis was typical both on clinical and pathologic evidence. Both patients presented with pulmonary symptoms with hemoptysis and suffered from rapidly progressive and irreversible glomerulonephritis. Histologic study of the lungs in one patient demonstrated extensive intra-alveolar hemorrhage. Histologic examination of the kidneys in both patients disclosed changes of rapidly progressive glomerulonephritis with epithelial crescents. Immunofluorescent studies showed linear staining of the glomerular capillary basement membrane with (IgG) and (C′₃). Bilateral nephrectomy was carried out in both patients in an attempt to control the pulmonary manifestations. There was no improvement in the first patient and he died 2 days after the operation. The nephrectomy has not prevented recurrence of the pulmonary hemorrhage in the second patient in whom the lungs were less severely diseased; he is maintained on longterm hemodialysis, and the pulmonary disease is best controlled by corticosteroids. Bilateral nephrectomy is not always as successful as has been claimed in previous reports.     

A nationwide outbreak of Reye's syndrome: Its epidemiologic relationship to influenza B

Between December 15 and June 30, 1974, 379 cases of confirmed Reye's syndrome were reported to the Center for Disease Control. Of these, 316 occurred during February and March 1974. A simultaneous surveillance system for influenza B indicated that this clustering of cases of Reye's syndrome correlated both temporally and geographically with influenza B outbreaks. The incidence of Reye's syndrome was higher in rural than in urban centers. Epidemiologically, two groups of cases of Reye's syndrome emerge: those which occur in older children (median age 11 years), cluster in time and geographic region, and are associated with antecedent influenza B infection; and those which occur sporadically throughout the year, are isolated in occurrence, occur in younger children (median age 6 years), and are associated with a wide variety of antecedent viral illnesses.     

Goodpasture's syndrome in a patient with the nail-patella syndrome

A patient with the nail-patella syndrome in whom end-stage renal failure developed as the result of Goodpasture's syndrome is described. Lesions characteristic of both rare diseases were seen on renal morphology. It is postulated that the glomerular membrane alteration of the nail-patella syndrome predisposed to the development of antiglomerular basement membrane antibody and hence Goodpasture's syndrome. A review of the incidence of renal failure in the nail-patella syndrome suggests that renal involvement can no longer be regarded as benign and that immune mechanisms may be related to progressive renal disease in some cases.     

The appearance of nonlinear deposits of immunoglobulins in Goodpasture's syndrome

A twenty year old woman presented with pulmonary hemorrhage and glomerulonephritis with linear deposition of IgG on the glomerular capillary basement membrane, and high titer of antiglomerular basement membrane antibody in her serum. Without treatment, renal function, which was transiently impaired, has improved, pulmonary hemorrhage subsided, and repeat renal biopsies have revealed the appearance of nonlinear in addition to the linear deposition of IgG on the glomerular capillary basement membrane in the face of diminished serum antiglomerular basement membrane antibody titer.     

The malignant potential of the dysgenetic germ cell in Klinefelter's syndrome

We report two cases of extragonadal germ cell tumors in patients with Klinefelter's syndrome and review the other cases of germ cell tumors reported in this syndrome. Especially in choriocarcinoma, the presence of Klinefelter's syndrome may be overlooked because of the similar clinical presentations and testicular histology. We recommend karyotypes be carried out in patients with germ cell tumors since the dysgenetic gonad of Klinefelter's syndrome may be important in the pathogenesis of these malignancies. Also patients with Klinefelter's syndrome should be followed closely because of their increased risk of development of germ cell tumors.     

Mixed cryoglobulinemia: Clinical aspects and long-term follow-up of 40 patients

The clinical course of 40 patients with significant quantities of mixed cryoglobulins, but without lymphoproliferative, collagen-vascular or chronic infectious diseases, is presented. These cases comprise 51.3 percent of all mixed and 31.7 percent of all types of cryoglobulins evaluated by us over the period 1960–1978. A characteristic clinical syndrome, consisting of recurrent palpable purpura (100 percent), polyarthralgias (72.5 percent) and renal disease (55 percent), was seen. Biopsy specimens of skin lesions showed cutaneous vasculitis, and half had immune reactants in vessel walls. Seventy percent of patients had evidence of hepatic dysfunction, often subclinical, and more than 60 percent of those tested had serologic evidence of prior infection with hepatitis B virus. Hepatic lesions ranged from minimal triaditis to chronic active hepatitis and/or cirrhosis. All 22 patients in whom clinical renal disease developed had significant proteinuria; 63.6 percent had diastolic hypertension, 77.3 percent edema, 45.5 percent renal failure and 22.7 percent were nephrotic. Glomerular disease associated with deposition of immunoglobulin G, immunoglobulin M and complement, often with coexistent renal arteritis, was confirmed pathlologically in 15 cases.All cryoglobulins had rheumatoid factor activity and consisted of IgM and polyclonal IgG; five also contained IgA. Thirteen had a monoclonal IgM kappa component. Serum protein electrophoresis was unremarkable or showed diffuse hyperglobulinemia. Striking depression of early complement components was noted but did not correlate well with the cryoprotein concentration, renal involvement or clinical course.Follow-up for periods up to 21 years from onset of symptoms revealed that renal involvement has a deleterious effect on prognosis. Postmortem examinations of nine patients demonstrated widespread vasculitis in addition to renal involvement. Preterminal infection was found in eight.     

Serum glucose levels during long-term observation of treated and untreated men with mild hypertension: The Oslo study

Serum glucose levels, triglyceride levels, and body weight are reported from a controlled drug trial in men, aged 40 to 49, with uncomplicated mild hypertension. The drug treatment started with hydrochlorothiazide alone, and methyldopa was added when necessary. If side effects occurred, methyldopa was replaced by propranolol. No detailed advice about diet, smoking, or weight reduction was given to any group. The untreated control subjects had a small increase in serum glucose levels during five years, from 6.08 to 6.21 mmol/liter. Those treated with hydrochlorothiazide alone and those treated with hydrochlorothiazide plus methyldopa had a small increase in serum glucose levels of the same order as that in the control subjects. However, those receiving the thiazide/propranolol combination experienced a sizeable increase in glucose levels, from 5.96 to 6.53 mmol/liter (p < 0.001). This increase was significantly greater than the increase in the other groups (p < 0.001). The thiazide/propranolol group also showed a significant increase in serum triglyceride levels (p < 0.05). There was no difference in serum potassium levels in the different drug groups. The results indicate that moderate thiazide doses do not have significant effects on serum glucose levels in this age group. Propranolol in combination with thiazide seems to increase the level of serum glucose.     

Chest pain with angiographically insignificant coronary arterial obstruction: Clinical presentation and long-term follow-up

Among 3,242 coronary angiograms performed from November 1972 through October 1975 at the Massachusetts General Hospital, 175 patients had normal coronary arteries or luminal narrowings of less than 30 per cent. All patients were studied for chest pain, and none had experienced prior myocardial infarction. Subsequent information was available in 159 patients over a mean follow-up period of 42.7 months. There were no deaths, and only one myocardial infarction occurred during this period. However, among the patients followed, continued chest pain with episodes occurring at least once monthly was present in 54 per cent. In addition, 17 per cent of all patients required subsequent hospitalization and 44 per cent continued to receive antianginal medication. Nearly half of the group (46 per cent) suffered some limitation of activity, and 22 per cent stated that they had either changed jobs or stopped work because of chest pain. Continuing chest pain was significantly more common in women and in patients who had experienced chest pain for more than one year before angiography. However, typicality of chest pain for angina or the occurrence of electrocardiographic changes of ischemia prior to angiography did not predict continued chest pain during the follow-up period. Thus, although mortality and morbidity are low in this group of patients, the syndrome of chest pain with angiographically insignificant coronary artery obstruction has an important impact on the lives of a majority of those affected.     

Liver cysts in patients with autosomal dominant polycystic kidney disease

Liver cysts were found in 46 (29 per cent) of 158 patients over 10 years of age with documented autosomal dominant-type polycystic kidney disease (PKD) from 62 unrelated families. Hepatic cysts were not found in any patient at risk for PKD in whom renal cysts were not detected. The prevalence of liver cysts increased with advancing age and with declining rate of glomerular filtration. Results of clinical and laboratory studies indicate that polycystic liver disease in patients with autosomal dominant-type PKD is a benign condition, rarely, if ever, causing impaired liver function or portal hypertension.     

Renal function in gout. IV. An analysis of 524 gouty subjects including long-term follow-up studies.

Renal function studies were performed in 524 gouty subjects, including follow-up studies at intervals up to 12 years in 112 of them. In 49 subjects, the glomerular filtration rate was less than 70 ml/min and Curate:glomerular filtration rate ratio tended to rise as the glomerular filtration rate decreased, reflecting a relatively stable urate excretion over varying filtered urate loads. The increment in Tsurate:glomerular filtration rate was small with spontaneous Purate between 7 and 9 mg/100 ml. It was modest with Purate up to 10 mg/100 ml. The increment in Tsurate:glomerular filtration rate became much higher beyond Purate of 10 mg/100 ml. Urinary urate levels above 800 mug/min, designated as excess urate excretion, occurred more commonly in subjects with Purate above 9 mg/100 ml, and with better preserved renal function. Tophi were more frequently observed in subjects with low glomerular filtration rate and proteinuria; but incidence of urolithiasis seemed to be less affected by a decrease in the glomerular filtration rate. Hyperuricemia alone had no deleterious effect on renal function as evidenced by follow-up studies over periods up to 12 years. Deterioration of renal function was largely associated with aging, renal vascular disease, renal calculi with pyelonephritis or independently occurring nephropathy. In only very few instances was diminished renal function ascribable to gout alone.     

Acquired Gaucher's cells in Hodgkin's disease

A patient with Hodgkin's disease associated with low glucocerebrosidase levels in the peripheral leukocytes, and Gaucher's cells in the bone marrow and lymph nodes, is described. After MOPP therapy, complete remission of Hodgkin's disease was accompanied by normalization of the glucocerebrosidase level and disappearance of Gaucher's cells. This observation appears unique when compared with the four cases of combined Hodgkin's and Gaucher's disease reported in earlier literature in which Gaucher's disease remained unchanged after chemotherapy. We conclude that our patient had Hodgkin's disease and acquired Gaucher's cells with diminished glucocerebrosidase levels, rather than a combination of Hodgkin's disease and Gaucher's disease.     

Complications and consequences of endotracheal intubation and tracheotomy: A prospective study of 150 critically ill adult patients

A prospective study of the complications and consequences of translaryngeal endotracheal intubation and tracheotomy was conducted on 150 critically ill adult patients. Adverse consequences occurred in 62 percent of all endotracheal intubations and in 66 percent of all tracheotomies during placement and use of the artificial airways. The most frequent problems during endotracheal intubation were excessive cuff pressure requirements (19 percent), self-extubation (13 percent) and inability to seal the airway (11 percent). Patient discomfort and difficulty in suctioning tracheobronchial secretions were very uncommon. Problems with tracheotomy included stomal infection (36 percent), stomal hemorrhage (36 percent), excessive cuff pressure requirements (23 percent) and subcutaneous emphysema or pneumomediastinum (13 percent). Complications of tracheotomy were judged to be more severe than those of endotracheal intubation. Follow-up studies of survivors revealed a high prevalence of tracheal stenosis after tracheotomy (65 percent) and significantly less after endotracheal intubation (19 percent) (p < 0.01). Thirty-nine of 41 (95 percent) patients with endotracheal intubation and 20 of 22 (91 percent) patients with tracheotomy had laryngotracheal injury at autopsy. Ulcers on the posterior aspect of the true vocal cords were found at autopsy in 51 percent of the patients who died after endotracheal intubation. There was no significant relationship between the duration of endotracheal intubation or tracheotomy and the over-all amount of laryngotracheal injury at autopsy, although patients with prolonged endotracheal intubation followed by tracheotomy had more laryngeal injury at autopsy (P = 0.06) and more frequent tracheal stenosis (P = 0.05) than patients with short-term endotracheal intubation followed by tracheotomy. Adverse effects of both endotracheal intubation and tracheotomy are common. The value of tracheotomy when an artificial airway is required for periods as long as three weeks is not supported by data obtained in this study.     

Fatal pulmonary hypertension and resolving immune-complex glomerulonephritis in mixed connective tissue disease: A case report and review of the literature

Mixed connective tissue disease (MCTD) has been characterized as a benign rheumatic syndrome with a favorable response to immunosuppressive therapy. Serious renal and pulmonary involvement are reported to be rare in MCTD. We are describing a female adolescent with MCTD in whom fatal cor pulmonale developed due to recurrent thromboembolic primary pulmonary hypertension. Death occurred after two years of therapy with prednisone and azathioprine for an immune-complex glomerulonephritis. Paramesangial and intramembranous electron-dense deposits had been identified in several glomeruli at the start of treatment. Improved renal function and apparent histologic improvement were demonstrated four months after the institution of prednisone and azathioprine therapy, and stable renal function was maintained until death. The pulmonary hypertension was progressive and apparently not altered by either the prednisone or azathioprine. At necropsy, there was no evidence of a pulmonary arteritis or vascular immune-complex deposition to account for the recurrent thromboembolic lesions in the small pulmonary arteries and arterioles. This is a clinical course not previously described in patients with MCTD and may represent an extreme of the clinical spectrum of this syndrome.     

Immunoglobulin E (IgE) multiple myeloma: A case report and review of the literature

A case of immunoglobulin E (IgE) myeloma with clinical features of “classic” myeloma is presented. Skeletal roentgenograms showed osteoporosis and compression fractures of the vertebrae but no osteosclerosis. Protein analyses revealed an M component of the IgE kappa type with a concentration of 3.1 g/dl. Although morphologic examination revealed that the plasma cells were not so differentiated, well-developed Golgi apparatus and abundant rough-surfaced endoplasmic reticulum were observed. An indirect immunofluorescence technique showed characteristic apple green fluorescence. The E myeloma protein of our patient had no antibody activity. Treatment with melphalan or cyclophosphamide resulted in a decrease in the serum IgE level and in the level of Bence Jones protein in the urine. The clinical and laboratory features of IgE myeloma were summarized and compared with those of other classes of myeloma.     

Neurologic involvement in seven patients with Behçet's disease

Of 25 patients with Behçet's disease seen in five years at the Mayo Clinic, seven had central nervous system involvement. The mean interval from onset of Behçet's disease to central nervous system involvement was 1.3 years, and the mean period of observation thereafter was 3.8 years. All patients had headache and fever during or preceding exacerbations of the central nervous system disease, and all had cerebrospinal fluid pleocytosis (white cell counts ranged from 6 to 490/mm³) with predominant lymphocytosis. The mean cerebrospinal fluid protein level was 55 mg/dl, and gamma globulin was less than 15 per cent in six patients. Results of cerebrospinal fluid, lesional and serologic studies for bacterial, fungal and viral agents were negative. Clinical findings included corticospinal tract disease (five patients), cerebellar ataxia (four patients), pseudobulbar palsy (three patients) and transient ocular palsies (three patients). All these occurred in concert with the systemic phases, especially aphthosis. Corticosteroid therapy was used in six patients, cyclophosphamide therapy in two and azathioprine therapy in two. The neurologic manifestations tended to recur when dosages of the drugs were lowered and established central nervous system damage could not be reversed. The case histories suggest that steroids, when used promptly and in sufficient dosage (up to 60 mg prednisone), are effective in reducing or preventing progression of central nervous system disease.Three patients died, one from Pneumocystis carinii infection, one from neurologic disease and another from presumed myocardial infarction. The central nervous system involvement in Behçet's disease should be diagnosed earlier, and it can be if attention is given to other systemic criteria, that is, aphthous stomatitis, aphthous genital lesions, cutaneous vasculitis, uveitis and synovitis.     

Response of Paget's disease to porcine and salmon calcitonins: effects of long-term treatment

Multiple clinical, biochemical and immunologic variables were measured in 49 patients with Paget's disease during 4 to 41 months (mean, 25 months) of treatment with porcine (PCT) or synthetic salmon calcitonin (SCT) or both. Mild nausea and dermal reactions occurred in 20 per cent of the patients and were generally transient. Skeletal and radicular pain, and overt neurologic deficits were moderately to dramatically relieved in 75 per cent of the patients. Maximal clinical benefits were achieved during the first 6 to 12 months of treatment, with only one fifth of the patients experiencing intermittent exacerbations of pain during the 2nd and 3rd years of treatment. Three examples of dramatic roentgenologic improvement were observed. SCT doses of 50 MRC units three times a week generally were as effective as 100 MRC units three times a week or daily. Dissociation among the clinical effects, the decrease in serum alkaline phosphatase and the decrease in urinary hydroxyproline were common.Binding antibodies developed in 60 per cent of the patients treated with PCT and in 30 per cent of those treated with SCT; however, SCT-binding antibodies usually were present in higher titer and with a greater frequency of SCT neutralization activity. No correlations were present between the development of antibodies and the incidence of biochemical rebounds or the failure of increased doses of SCT to renew biochemical effects. No evidence of increased secretory activity of the parathyroid glands was observed in 10 patients with biochemical rebounds.These data demonstrate the feasibility and efficacy of continuous long-term therapy with calcitonin on an outpatient basis, and SCT may be the treatment of choice for Paget's disease.     

On the various forms of corticosteroid withdrawal syndrome

Five patients who had received corticosteroids for periods of years experienced steroid withdrawal symptoms when attempts were made to reduce or discontinue the drugs. Summarized herein are studies of hypothalmic-pituitary-adrenocortical (HPA) function in these five people during corticosteroid withdrawal. Analysis of these data and of data in previous reports discloses four subgroups of corticosteroid withdrawal syndrome: Type I, symptomatic and biochemical evidence of HPA suppression; type II, recrudescence of the disease for which the drug was originally described; type III, dependence upon Corticosteroids, either physical or psychological, with demonstrably normal HPA function and no recrudescence of underlying disease; and type IV, biochemical evidence of HPA suppression without symptoms and without recurrence of underlying disease. Any combination of types I, II and III may exist. The major conclusions are these five. (1) Some syndromes that clinically suggest HPA suppression are not. (2) Some syndromes that resemble drugdependence are not. (3) The rapid ACTH test is a clinically useful way to assess HPA function; this test should govern the rate of corticosteroid withdrawal in the absence of steroid-treatable disease. (4) If disease is present, the rate and degree of corticosteroid withdrawal are governed by the status of the disease. (5) Patients have an unpredictable tendency to abuse corticosteroids; physicians should guard against inattentively permitting long-term, unnecessary overdosage to continue.     

A familial glucagonoma syndrome: Genetic,Clinical and Biochemical Features

A family with multiple endocrine neoplasia type I (MEN-I) is described in which three members had A-cell pancreatic tumors. Two of these members had classic glucagonoma syndromes. The proband, a 62 year old woman, had a high (≤9.2 ng/ml) basal plasma glucagon level, most of which eluted in the 3,500 dalton fraction. Plasma glucagon increased following the ingestion of mixed meals and arginine. Secretin, which, in the dog, has been reported to inhibit normal glucagon secretion, provoked a twofold increase in 3,500 dalton plasma glucagon concentration. Increased plasma glucagon in the proband was associated with mild hyperglycemia and insulin resistance. Somatostatin infusion suppressed peripheral glucagon and insulin levels, and increased blood glucose levels. The unique responses to secretin and somatostatin observed in this patient may be diagnostically important in syndromes of inappropriate or autonomous glucagon secretion.     

Fatal disseminated adenovirus infection in a renal transplant recipient.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.     

Emphysematous pyelonephritis. A report of two cases

Emphysematous pyelonephritis is a suppurative infection of the renal parenchyma characterized by the production of gas by bacteria through fermentation. Although seemingly rare, this condition occurred in two diabetic patients on general medical wards over a two year period. Diagnosis, in an appropriate clinical setting, is confirmed roetgenologically. Escherichia coli is the most common etiologic organism. Despite appropriate medical and surgical intervention, this severe form of renal parenchymal infection carries a high mortality.