Severe intrahepatic cholestasis in primary amyloidosis: a report of four cases and a review of the literature.

Liver involvement occurs frequently in patients with systemic amyloidosis, but jaundice is rare. The clinical and histopathologic features are described in four of 78 patients (5.3 per cent) with primary amyloidosis in whom severe intrahepatic cholestasis developed. The data on an additional eight patients recorded in the literature were reviewed. Criteria for inclusion were a tissue diagnosis of amyloidosis, a serum bilirubin level greater than 5 mg/100 ml, histopathologic evidence for cholestasis and no extrahepatic biliary obstruction. Hepatomegaly was present in 12 patients (100 per cent), ascites in nine (75 per cent) and pruritus in eight (67 per cent). The serum bilirubin ranged from 9 to 44 mg/100 ml, the serum alkaline phosphatase was markedly increased in 10 patients (83 per cent) and hypercholesterolemia occurred in seven (58 per cent). Microscopic examination of the liver revealed diffuse amyloid deposition and compression atrophy in 12 patients (100 per cent). The amyloid was prominent in the periportal regions, and some sparing of the centrilobular areas was observed. Bile thrombi and bilirubin staining of hepatocytes were predominantly in the centrilobular zones. Liver cell necrosis, fibrosis or nodularity was uncommon.The pathogenesis of intrahepatic cholestasis in these patients is probably related to the deposition of amyloid in a manner that interferes with the passage of bile from the canaliculi and/or the small intrahepatic bile ducts to the septal bile ducts. Obstructive jaundice carries a poor prognosis. Nine of 12 patients (75 per cent) died of renal failure three weeks to two months after the onset of jaundice. Amyloidosis should be considered in the patient with unexplained intrahepatic cholestasis, and liver tissue should be stained with Congo red and viewed under polarized microscopy.     

Primary empty sella syndrome, ACTH hypersecretion, and normal adrenocortical function. Report of two cases

Although the primary empty sella syndrome (PESS) is associated with normal endocrine function or subtle pituitary insufficiency, pituitary hormone hypersecretion associated with PESS has also been recognized. ACTH hypersecretion and primary empty sella syndrome have previously been reported in patients with either Cushing's disease or Addison's disease. This report describes two unique patients with ACTH hypersecretion, primary empty sella syndrome, and normal cortisol dynamics. The investigators speculate that this association may have resulted from infarction of hyperplastic adenohypophyseal corticotrophes due to production of an ACTH peptide with reduced biologic activity. These two cases emphasize that primary empty sella syndrome may be associated with ACTH hypersecretion and normal adrenocortical function.     

Tuberculous arthritis: A report of two cases with review of biopsy and synovial fluid findings

Two cases of tuberculous arthritis with synovial fluid findings are presented, and the major series with culture results and synovial fluid analyses are reviewed. Synovial fluid cultures are positive for tuberculosis in almost 80 per cent of proved cases. Specimens obtained by open synovial biopsy are positive by histology or culture in over 90 per cent of proved cases. Little experience with closed needle biopsy has been published. About one-fifth of the patients with tuberculous arthritis will have a positive synovial fluid acid-fast smear for tubercle bacilli. The tuberculous synovial effusion invariably has an elevated protein level, fair to poor mucin clot formation and usually a low joint fluid sugar level. The synovial fluid white cell count is usually in the range of 10,000 to 20,000 cells/ mm³, but it varies widely. Most fluids exhibited a predominance of polymorphonuclear leukocytes. The importance of bacteriologic or histologic study of synovial fluid and membrane in establishing the diagnosis is emphasized. In general, this disease is different from tuberculous involvement of serous membranes both in the frequency of positive cultures and in the difference in cellular response.     

Renal vein thrombosis and the nephrotic syndrome. Report of two cases with successful treatment of one

A nephrotic syndrome and bilateral renal vein thrombosis developed in two women. One suffered low back pain, the other oliguric renal failure. Both suffered pulmonary emboli and had exhibited edema, proteinuria and hypertension during pregnancies several years before. Results of thrombectomy and anticoagulant therapy were successful in one patient, although she suffered serious hemorrhage at the biopsy site during anticoagulant therapy. The other patient died of pulmonary embolism. Renal interstitial changes usually associated with renal vein thrombosis were found in both, but neither showed membranous nephropathy (membranous glomerulonephritis). This study suggests that (1) although membranous nephropathy is frequently associated with renal vein thrombosis, it is probably not the result of that condition nor invariably associated with it. (2) Prognosis in renal vein thrombosis with nephrotic syndrome may be partially dependent upon underlying renal disease. (3) Renal biopsy is useful for diagnosis and assaying prognosis. (4) Treatment should consist of thrombectomy and anticoagulants. However, serious hemorrhage may occur in patients recently subjected to biopsy.     

Unusual renal manifestations of Wegener's granulomatosis. Report of two cases

Two patients with previously undescribed renal manifestations of Wegener's granulomatosis are described. A 24 year old man, who presented with typical necrotizing granulomatous sinus disease and cavitary pulmonary lesions, had multiple bilateral renal arterial aneurysms demonstrated angiographically. One of these aneurysms ruptured, leading to a massive perinephric hematoma. The bleeding artery was successfully occluded with Gelfoam embolization, thereby obviating the need for nephrectomy. A 60 year old woman presented with glomerulonephritis and mononeuritis multiplex two years before the development of classic necrotizing granulomatous inflammation of her sinuses and nose, along with pulmonary nodules. In addition, her left ureter became obstructed due to necrotizing vasculitis of the periureteral vessels. Both patients responded dramatically to cyclophosphamide therapy. The diagnosis of Wegener's granulomatosis should be considered in patients who present with multiple renal aneurysms, a spontaneous perinephric hematoma, necrotizing glomerulitis or ureteral obstruction due to vasculitis, even though the characteristic granulomatous respiratory involvement may be absent at that time. It is important to recognize these unusual renal manifestations as features of Wegener's granulomatosis because of the therapeutic efficacy of cytotoxic immunosuppressive agents in this disease.     

Antibiotic susceptibility of gram-negative bacilli isolated from blood cultures. Results of tests with 35 agents and strains from 169 patients at Boston City Hospital during 1972

Gram-negative bacilli of several of the more common species grown from the blood of 169 patients hospitalized at Boston City Hospital during 1972 were tested with 32 antibiotics and with trimethoprim and sulfamethoxazole, alone and in combination. More than half of the agents are currently under clinical trial for efficacy and safety. Chemically related antibiotics were shown to differ in varying degrees in their activity against the different species, and even against different strains of the same species. The size of the inoculum affected the activity of the agents differently, depending on the antibiotic, the species and even the strain. Polymyxin B was generally the most active antibiotic against most species, but it was essentially inactive against Proteus mirabilis and Serratia marcescens. Trimethoprim alone, and particularly when combined with sulfamethoxazole, was even more active against most species, but it was essentially inactive against Pseudomonas aeruginosa.     

Unilateral renal vein thrombosis and nephrotic syndrome: Report of a case with protein selectivity and antithrombin III clearance studies

A case of the nephrotic syndrome with unilateral renal vein thrombosis is reported. The patient, an 18 year old man, presented with a six month history of edema and the recent development of a left-sided varicocele. An enlarged left kidney and a thrombus in the left renal vein were demonstrated roentgenographically. A biopsy specimen of the right kidney was interpreted as membranous glomerulonephritis. Selective renal function studies showed nearly identical creatinine excretion, and similar total protein excretion and protein selectivity from each kidney. Thus, the thrombus in the left renal vein did not influence glomerular filtration rate or quantitative or qualitative protein excretion. A high urinary output and a decreased serum level of antithrombin III were measured. These findings suggest a mechanism to explain the increased thrombotic tendency seen in this and other patients with the nephrotic syndrome.     

Splenic abscess: Report of 10 cases and review of the literature

Ten cases of splenic abscess seen between 1964 and 1974 are reviewed. Pain referable to the abscess was the most common symptom, but was present in only five cases. Fever was present in all but one case. Tenderness in the region of the spleen was noted in six cases, in three cases the spleen was palpable and in one case a large mass in the upper left quadrant of the abdomen was palpated. Abdominal films were suggestive of the diagnosis in two cases, and the liver-spleen scan demonstrated a defect in three cases. Seven abscesses were caused by gram-negative bacilli of bowel origin; the etiologic agents in the other three were Staphylococcus aureus, Streptobacillus moniliformis and a Nocardia species. Associated conditions predisposing to splenic abscess included trauma in three cases, splenic arteritis or embolization in five cases, and foci of infection elsewhere in the body in six, including two cases of endocarditis. The mortality was 60 per cent. Half of the deaths were due to the underlying illness, but failure to diagnose splenic abscess contributed to a fatal outcome in three cases.     

Pulmonary hypertension as a presentation of hepatocarcinoma. Report of a case and brief review of the literature

A case, unique in the literature, is reported in which a primary carcinoma of the liver presented a right-sided heart failure and pulmonary hypertension. The diagnosis of hepatocarcinoma was established by needle biopsy of the liver. Later, postmortem examination demonstrated that the pulmonary arterial tree was severely compromised by multiple tumor microemboli, despite the persistent lack of characteristic roentgenographic abnormality in our patient. In reviewing the literature, we found rare cases of occult renal cell carcinoma, choriocarcinoma and one of occult hepatocarcinoma, which presented as pulmonary embolism. These were diagnosed by pulmonary embolectomy, human chorionic gonadotrophin levels or autopsy, respectively. In another small group of reported cases of known carcinoma (gastric, breast, colonic) the patients had a clinical picture of "idiopathic" pulmonary hypertension or of pulmonary hypertension with pulmonary metastases. Pulmonary hypertension in these cases resulted from carcinomatous lymphangitis and/or tumor microembolization, as in our case. We report this case to emphasize the necessity of including occult carcinoma in the differential diagnosis of pulmonary hypertension and right ventricular failure.     

Invasive external otitis: Report of 21 cases and review of the literature

We report 21 cases of invasive external otitis and review 130 cases from the English literature. Invasive external otitis is the term that most appropriately describes the locally invasive Pseudomonas infection that begins in the external ear canal, breaches the epithelial barrier and results in signs of local subcutaneous tissue invasion.Nineteen patients were diabetic. Fifteen of these 19 had pre-existent, long-standing diabetes (average 15.8 years) and 10 had microvascular disease. Studies of the skin of the temporal bone in two patients provided evidence of diabetic microangiopathy of the dermal capillaries. Pseudomonas aeruginosa was isolated from the involved area in all cases. All patients without neurologic deficits survived, compared with six of nine with deficits of the central nervous system. All 13 patients in whom initial therapy was successful received a combination of an aminoglycoside and a semisynthetic penicillin, whereas all six episodes of recurrent disease occurred when only one antibiotic was used. The overall mortality was 15 percent (three of 20 in whom the long-term outcome is known).We propose that diabetic microangiopathy of the skin of the temporal bone results in poor local perfusion and creates an environment well suited for invasion by Pseudomonas aeruginosa. There is a good correlation between the extent of disease clinically and prognosis. Effective treatment requires early diagnosis and combination therapy with an aminoglycoside and a semisynthetic penicillin.     

Nephrotic syndrome, renal vein thrombosis and renal failure. Report of case with recovery of renal function, loss of proteinuria and dissolution of thrombus after anticoagulant therapy

A case of nephrotic syndrome, renal vein thrombosis and advanced renal failure in a 52 year old woman with adult onset diabetes mellitus is reported. The diagnosis of renal vein thrombosis was established by selective renal venography. Following 15 months of anticoagulant therapy creatinine clearance increased to the level noted prior to renal vein thrombosis, and proteinuria decreased to less than 500 mg/day. Repeat renal venography demonstrated clearing of the renal vein thrombosis. Renal biopsy performed at this time revealed changes compatible with arterial nephrosclerosis on light microscopy, but there were no findings typical of diabetic intercapillary glomerulosclerosis. No immune deposits were seen on immunofluorescent microscopy. Electron microscopy revealed fusion of the foot processes, but there were no electron dense deposits in or on the basement membrane to suggest membranous glomerulonephritis. Analysis of the sequence of events suggests that the renal vein thrombosis in this patient was probably a complication of the nephrotic syndrome, the etiology of which is not clear although the biopsy findings are compatible with lipoid nephrosis.     

Correlation of plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer

A review of patients operated on for colorectal cancer disclosed poorly differentiated histologies in those whose preoperative and postoperative carcinoembryonic antigen (CEA) levels were not elevated, even in the presence of metastatic disease. CEA was, therefore, of little prognostic value or predictive of disease recurrence in these patients. The amount of CEA in tumor tissue of 17 patients with poorly differentiated colorectal cancer was estimated with the immunoperoxidase staining technique and was correlated with histology and plasma CEA levels obtained during various stages of disease. Five tumors did not stain negatively for CEA and all had predominantly poorly differentiated histologies. In all of these patients metastatic disease developed but not elevated plasma CEA levels. In contrast 12 tumors stained positively for CEA and were found to contain either differentiated areas or signet ring cells. Serial plasma CEA levels correctly monitored the postoperative courses of all 12 patients. Six of these had a relapse and all were detected by serial increases in plasma CEA. The remaining six were disease free >48 months after resection and had normal plasma CEA levels.Among poorly differentiated tumors, those that contain gland-forming areas or signet ring cells can be assumed to produce CEA, and plasma CEA levels can be used effectively for monitoring. On the other hand, undifferentiated tumors which do not stain for CEA identify those patients whose plasma CEA levels do not provide a useful monitor.     

Lymphocytes associated with renal transplantation. Report of 15 cases and review of the literature

Within a 27 month period (from July 1, 1971 to October 1, 1973), during which 83 renal allotransplantations were performed at the Cleveland Clinic, a lymphocele developed in 15 patients (18.1 per cent). Early clinical symptoms, occurring within 6 weeks after transplantation, were suprapubic or lower abdominal swelling in 14 patients, leg swelling ipsilateral to the allograft in 12, nonpitting edema in the allograft area in 10 and lymph drainage from the wound in 8.An intravenous pyelogram demonstrated a lymphocele in 13 patients from 1 to 34 weeks after transplantation (mean 7.8 weeks), although an earlier suggestion of bladder displacement and deformity was found retrospectively in 5 patients between 1 and 3 weeks after transplantation. Lymphangiograms aided in the diagnosis in nine patients.The major complication of the lymphoceles was obstructive uropathy that developed in nine patients between 2 and 34 weeks after transplantation (mean 10.3 weeks). Lymphoceles mimicked rejection, urine extravasation, pyelonephritis, thrombophlebitis and a seroma, and occurred concurrently with rejection and pyelonephritis. Treatment by external surgical drainage was more effective than aspiration both in resolving the lymphocele and in avoiding infection. Three lymphoceles drained spontaneously 1 to 2 weeks after transplantation, and three are under observation. Chemical and protein analyses were made of the lymphocele fluid obtained from seven patients.Numerous factors may contribute to the formation of a lymphocele by increasing lymph flow. The most prominent factors are the extent of surgical dissection, the occurrence of rejection, and the use of diuretics, large doses of corticosteroids, and anticoagulants. The literature on lymphoceles in renal allograft recipients is reviewed, and pertinent comparisons are made with the more numerous reports of lymphoceles in nontransplant patients.     

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.     

Resolution of renal failure with malignant hypertension in scleroderma. Case report and review of the literature.

The ominous prognosis of rapidly progressive renal failure associated with malignant hypertension in scleroderma has led to aggressive management by dialysis, early bilateral nephrectomy and renal transplantation. We describe a woman with scleroderma who recovered after the development of malignant hypertension and renal failure. Renal biopsy and arteriography demonstrated the classic vascular lesions of scleroderma with secondary cortical ischemia. Of note, plasma renin activity was normal. Review of the literature revealed 40 patients with scleroderma and rapidly progressive renal failure who have been treated by dialysis. Thirteen patients survived, four of whom did not undergo bilateral nephrectomy. In eight patients treated by transplantation, five achieved excellent allograft function although one sustained a late rejection. Analysis of our case and of five recently reported cases of reversible renal failure and malignant hypertension reveals no distinctive features identifying patients with a favorable prognosis, except for the normal plasma renin activity level in our patient. Vigorous control of hypertension and renal failure by drugs and dialysis is recommended. Bilateral nephrectomy should be considered only for patients with refractory hypertension, since recovery of renal function may follow even after months of dialysis. For patients with irreversible renal failure without other major organ system involvement, transplantation is a reasonable alternative to dialysis.     

Persisting renal insufficiency after methoxyflurane anesthesia. Report of two cases and review of literature

Persistent renal dysfunction followed methoxyflurane anesthesia in two patients. In one polyuria, hypernatremia and azotemia developed. The serum creatinine level rose from 0.9 mg/100 ml preoperatively to a peak value of 2.9 mg/100 ml. Twenty-two months postoperatively the 24 hour creatinine clearance averaged 40 ml/min, and the maximum urinary osmolality was 424 mOsm/kg after dehydration and vasopressin. In the second patient the serum creatinine level rose slowly to a peak value of 7.5 mg/100 ml on the 39th postoperative day; 14 months later it was 3.8 mg/100 ml. Renal biopsy specimens obtained on the 21st and 24th postoperative days showed tubular epithelial degeneration ranging from swelling to necrosis, deposition of birefringent crystals and increased interstitial connective tissue. Repeat renal biopsy specimens obtained at $\text{8}\text{1}\text{2}$ and 15 months postoperatively revealed more severe interstitial fibrosis.Renal insufficiency following methoxyflurane anesthesia is reviewed. The need for careful selection of patients and antibiotics, and for limitation of the anesthetic dose is apparent. The renal insufficiency can vary greatly in severity and clinical presentation, and may persist to varying degrees.     

Budd-Chiari syndrome following pregnancy: Report of 16 cases,with roentgenologic,hemodynamic and histologic studies of the hepatic outflow tract

Budd-Chiari syndrome following pregnancy is an extremely rare disease as reported in the literature. Reported here are 16 such cases in a total of 105 patients with Budd-Chiari syndrome seen at Postgraduate Institute of Medical Education and Research, Chandigarh, from 1963 to 1978. The clinical pointer to the diagnosis was sudden occurrence of abdominal pain and ascites following childbirth. Eleven patients had diuretic-resistant ascites. Percutaneous hepatography was valuable in detecting the site and the nature of the outflow block. The prognosis was uniformly bad, and eight patients died within one year from the onset of their illness. The various treatment schedules, including anticoagulant therapy, Rhodiascit ascitic fluid re-infusion and portasystemic shunt surgery, had no beneficial effect on the survival of these patients.     

Lead poisoning from a gunshot wound. Report of a case and review of the literature.

A man was hospitalized on three occasions for symptoms of lead intoxication 20 to 25 years after a gunshot wound that resulted in retention of a lead bullet in his hip joint. The potential for lead toxicity as a complication of a lead missile injury appears to be related to (1) the surface area of lead exposed for dissolution, (2) the location of the lead projectile, and (3) the length of time during which body tissues are exposed to absorbable lead. Cases of lead poisoning of immediate onset resulting from lead shot have been reported in Europe, but all documented cases of ammunition-related plumbism reported in the United States have involved synovial fluid dissolution of a single lead bullet over many years. The solvent characteristics of synovial fluid and associated local arthritis are apparently important factors in the dissolution and absorption of lead from projectiles located in joints. Awareness that lead intoxication can be a complication of retained lead projectiles should allow rapid institution of appropriate diagnostic and therapeutic modalities when such a clinical situation arises.     

Lymphocytic thymoma associated with T-cell lymphocytosis.

A 64 year old woman presented with lymphocytosis and an interior mediastinal mass, but without lymphadenopathy, hepatosplenomegaly or skin lesions. T-cell surface markers (rosette formation with sheep erythrocytes and reactivity with antithymocyte antiserum) could be demonstrated on lymphocytes from the blood, mediastinal tumor and pleural fluid; B-cell markers (surface immunoglobulin and complement receptors) were absent. The clinical and pathologic features in this case were quite different from those of known leukemias of small mature T lymphocytes, i.e., the Sézary syndrome of mycosis fungoides and T-cell chronic lymphocytic leukemia. It is concluded that this case represents the second example of a new proliferation of mature T cells, lymphocyte predominant thymoma with lymphocytosis.