Weber-Christian panniculitis with membranous glomerulonephritis

A case of Weber-Christian panniculitis is described in which an acute phase of the disease was accompanied by the presence of circulating immune complexes, elevated serum levels of IgA and IgM, and membranous glomerulonephritis, with concomitant spontaneous remission of both diseases. This case reinforces the view that an immunologic dysfunction may be involved in the pathogenesis of Weber-Christian panniculitis.     

The therapeutic approach to hypoparathyroidism

Hypoparathyroid patients have for decades been subjected to vitamin D therapy, in varying pharmacologic doses, with widely discrepant responses. They have been hypocalcemic on extremely large doses of the vitamin and hypercalcemic on doses that are not toxic to normal persons. The resistance to conventional forms of vitamin D and calcium supplementation therapy has produced a need for other therapeutic preparations. Dihydrotachysterol (DHT), 25-(OH)D₃ and 1α-(OH)D have been tried in short-term studies, often with limited success. More detailed analyses of long-term results of therapy with 25-(OH)D, 1,25-(OH)₂D or 1α-(OH)D are warranted before their superiority over vitamin D and DHT therapy can be established. Until such time that these substances are available in sufficient quantities for these studies, a rational approach to vitamin D therapy should include a more definitive analysis of the factors leading to the hypocalcemic hyperphosphatemic state. This knowledge should be combined with an appreciation of the effects of emotion and psychologic stress, estrogens, oral contraceptives, tranquilizers, anticonvulsants, magnesium deficiency, dietary indiscretions and diuretics on calcium homeostasis. Measurements of circulating PTH levels and para-thyroid reserve, and reservations about accepting urinary values as estimates of circulating calcium levels in treated patients would add additional sophistication to planned therapeutic approaches with vitamin D. The final result of these combined endeavors may ultimately lead to better control and a much happier patient.     

Immunoglobulin and autoantibody response in acute and chronic liver disease

Serum immunoglobulin and nonorgan-specific autoimmune responses (autoantibody response) were studied in 269 patients with a variety of acute and chronic liver disease. A majority of patients with hepatitis B antigen (HB Ag)-positive and HB Agnegative acute viral hepatitis showed a mild elevation in total globulin, gamma globulin, immunoglobulin G (IgG) levels and a moderate elevation in immunoglobulin M (IgM) levels during the first 2 weeks of illness; these levels began to subside by the 8th week of illness and were completely normal by the 12th week, concomitant with the return of normal transaminase values. Serum complement (C₃) levels were low in 20 per cent of the patients with acute viral hepatitis, during the first 2 weeks of illness and returned to normal thereafter. Of the 80 patients with acute viral hepatitis, 42.5 per cent had smooth muscle antibody (SMA), 20.5 per cent had mitochondrial antibody (MA), 10 per cent had rheumatoid factor (RA), and none had antinuclear antibody (ANA); these nonorgan-specific autoimmune markers were only transiently present (mean, 2 weeks) and became undetectable as the patient's condition improved. There was no difference in these immunologic responses between patients with HB Ag-positive and HB Ag-negative acute viral hepatitis. High levels of gamma globulin and IgG were seen in chronic active liver disease, either of viral or alcoholic etiology. Serum immunoglobulin A (IgA) levels were elevated only in those with alcoholic liver disease, whereas IgM levels were high in those with liver disease associated with an active hepatocellular damage either of alcoholic or viral etiology. HB Ag-positive blood donors with asymptomatic mild liver disease had normal immunochemistry values.     

Activation of Hageman factor in the nephrotic syndrome

The patient described had the nephrotic syndrome associated with decreased levels of plasma coagulation factors XI (35 per cent) and XII (15 per cent). The patient also had a decrease in concentration of prekallikrein and kallikrein inhibitor, suggesting that the kallikrein system was activated. Addition of purified factor XII did not correct this defect. The fibrinolytic system was activated as indicated by an increase in fibrinogen split products. Thus, it seems that three Hageman-dependent proteolytic pathways (coagulation, fibrinolysis and kallikrein) were activated in this patient with the nephrotic syndrome.Another possible cause of decreased factors XI and XII is urinary loss of these proteins. The urine did contain apparent activities of factors XI and XII. The finding of factor VIII in the urine in higher concentrations than XI or XII, however, as well as the inability to adsorb the activity with Celite®, suggested that the activity was due to a nonspecific urinary procoagulant. This hypothesis was confirmed by removal of the activity via adsorbtion of the urine with barium citrate.     

Acute viral hepatitis. Course and incidence of progression to chronic hepatitis

In a prospective study, 53 consecutive patients with biopsyproved acute viral hepatitis were observed serially and treated identically during a 15 week period following the onset of jaundice. They were divided into four groups on the basis of the presence or absence of hepatitis-associated antigen (HAA) and the presence or absence of parenteral exposure to a potential source of HAA. Even though the degree of hepatocellular necrosis was greater in the HAA-positive group, irrespective of the portal of entry of HAA, 89.2 per cent of HAA-positive and 83.3 per cent of HAA-negative subjects made equally rapid and complete recovery within 6 weeks after the onset of illness. The development of chronic active hepatitis in the remainder was associated with either the persistence of HAA in the serum beyond the 13th week of illness or the presence of a positive lupus erythematosus test during the first and subsequent weeks of illness. We conclude from this study that in the majority of patients with acute viral hepatitis recovery is complete but that chronic active hepatitis will develop in patients in whom HAA persists beyond 13 weeks of illness or in whom the lupus erythematosus test is positive and antinuclear antibody (ANA) is present at the onset of illness (11.3 per cent).     

Reliability of echocardiographic and electrocardiographic parameters in assessing serial changes in left ventricular mass

A reliable noninvasive index of left ventricular mass would be useful in following patients with valvular heart disease and left ventricular hypertrophy. We reviewed concurrent electrocardiograms and echocardiograms from 54 subjects, 39 patients with aortic or mitral valve disease and 15 normal subjects. Pre- and early postoperative echocardiographic estimates of left ventricular mass in 17 patients who had valve replacements correlated well (r = 0.96, p < 0.001) and demonstrated little change in mean values despite altered left ventricular dimensions. Echocardiographic estimates of left ventricular mass were, therefore, used as a standard for evaluating other noninvasive indices. Precordial electrocardiographic voltage showed a weak correlation with left ventricular mass in the study group as a whole (r = 0.59, p < 0.001), but no correlation in patients with volume overload (r = 0.36, p = NS). In 18 patients who had preoperative and three separate postoperative studies at least eight weeks apart, changes in left ventricular cross-sectional area (an index of left ventricular mass which corrects for changes in left ventricular volume) closely followed alterations in left ventricular mass. However, changes in posterior wall and interventricular septal thickness often resulted from altered ventricular volume and did not accurately reflect directional changes in left ventricular mass. Serial changes in electrocardiographic voltage were similarly unreliable. We conclude that left ventricular mass and cross-sectional area by echocardiography allow accurate noninvasive assessment of left ventricular mass, whereas wall thickness and electrocardiographic changes do not.     

Platelet hypersensitivity and intravascular coagulation in paroxysmal nocturnal hemoglobinuria.

The patient described had paroxysmal nocturnal hemoglobinuria associated with recurrent arterial as well as venous thrombosis. Study of platelet function revealed hypersensitivity to epinephrine, adenosine 5'phosphate (ADP) and collagen as judged by their ability to aggregate platelets as well as to release 14C serotonin. The release of total nucleotides was also markedly increased over normal with all aggregating agents. The abnormality was localized to the platelet since aggregation occurred when the patient's platelets were resuspended in normal plasma but not when normal platelets were incubated in the patient's plasma. Presumptive evidence for ongoing intravascular coagulation was an increase in fibrinogen derivatives of heavier molecular weight than the native protein presumably a result of thrombin action. However, factor XII was not activated and fibrinolysis was not increased. Complement component levels and antithrombin concentrations were also normal. The findings in this case suggest that hypersensitive platelets may contribute to the intravascular coagulation that is manifested by the increased incidence of thrombosis in patients with paroxysmal nocturnal hemoglobinuria.     

Morphologic, biochemical and physiologic alterations in a case of idiopathic hypoalbuminemia (analbuminemia).

A patient with idiopathic hypoalbuminemia is described. A study of albumin kinetics demonstrated slowed albumin degradation suggesting low albumin synthesis. Morphologic observation of hepatocellular alterations suggested decreased protein synthesis. The intra- and extravascular space was low with an abnormally large postural shift of intravascular fluid into the extravascular compartment. Disturbances in the concentration of plasma lipids and of several plasma proteins were detected. The effect of albumin infusion on these physiologic and biochemical abnormalities suggests that most occurred as a secondary response to the hypoalbuminemic state. Evaluation of the patient's kindred revealed no members with hypoalbuminemia.     

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.     

Prazosin and congestive heart failure: Short- and long-term therapy

Reviewed here are the data from 34 patients given prazosin for chronic intractable heart failure. In 13 patients in whom hemodynamics were measured after the fifth 3 mg dose of prazosin was given, no attenuation was found. The cardiac index increased from 1.77 ± 0.13 to 2.5 ± 0.13 liters/min/m² (p < 0.001), and the pulmonary capillary wedge pressure decreased from 31.46 ± 1.56 to 23.54 ± 1.11 mg Hg (p < 0.001).During long-term follow-up (15.9 ± 1.5 months) the administration of spironolactone proved to be very useful. Within three months of starting prazosin therapy, none of the 15 patients discharged on a regimen of spironolactone needed readmission for edema, but 11 of the 13 patients discharged without a spironolactone regimen did. The addition of spironolactone or an increase in furosemide to the therapeutic regimen was helpful but a change to hydralazine was not.We conclude that prazosin causes short-term hemodynamic and long-term clinical improvement in patients with intractable heart failure; that spironolactone helps to prevent clinical attenuation but that more detailed studies are required to better characterize the attenuation to vasodilators seen in patients with congestive heart failure.     

Maternal antibody to fetal light chain (Inv) antigens

We report a case of immunization by fetal light (L) chain (Inv) antigens in a primipara who had never received a transfusion. An Inv(l?a?) mother produced an immunoglobulin M anti-Inv(l) antibody in high titer to her Inv(l+a+) child. The child had an abnormal placenta and died of neonatal nephrosis at 6 months. A second child was born 3 years later. This infant's L chains were also Inv(l+a+), but the mother demonstrated no immunologic recognition of the incompatible Inv antigen as demonstrated by her anti-Inv(l) titer. The second child and his placenta were normal, and at 10 months of age he was found to have an anti-Gm(a) antibody in high titer to a maternal IgG H chain antigen. Anti-Gm antibodies in mothers and children are not uncommon and are usually not associated with noticeable disease, but the pathophysiology of maternal anti-lnv antibodies is not known.     

1,25-dihydroxyvitamin D3: a kidney-produced steroid hormone essential to calcium homeostasis

Principal among the many relationships involving the metabolism and function of vitamin D is the central role of the kidney in the production of the biologically active steroid, 1,25-dihydroxychole-calciferol. Three important topics under intensive investigation in many laboratories are (1) the role of the kidney as an endocrine organ producing the biologically active form of vitamin D, (2) the regulation of the endocrine organ and its integration in the process of calcium homeostasis, and (3) reevaluation of the wide variety of vitamin D-related disease states as they relate to the central role of the kidney in vitamin D action.     

Aspergillus species endocarditis. The new face of a not so rare disease

Aspergillus flavus endocarditis developed in a 13 year old girl after mitral valve replacement. Thirty-nine other cases of Aspergillus species endocarditis were found in the medical literature. Twenty-nine of these infections occurred in postcardiac surgery patients. Fever was the most common presenting manifestation (35 patients). Cardiac murmurs were present in 25. Lesions were in the left side of the heart in 38 (95 per cent), and there were major arterial emboli in 33 (83 per cent).The diagnosis was made antemortem in only nine patients. The diagnostic specimen in eight of these was an embolus. Aspergillus sp. were cultured from the blood of only three (8 per cent). Two (5 per cent) patients survived; in both infected prostheses were replaced, and one received antifungal chemotherapy. Aspergillus sp. endocarditis should be suspected in any postcardiac surgery patient presenting with endocarditis and emboli whose blood yields no organisms in culture.Careful surveillance and control of fungal contamination of the surgical environment is urged. Cultures of arterial blood should be obtained, and both solid and liquid microbiological media utilized. Early valve replacement and chemotherapy with both amphotericin B and flucytosine are recommended.     

The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex

To determine the value of the electrocardiogram for differentiating aberrant conduction from ventricular ectopy, findings were retrospectively reviewed from patients with a widened QRS complex during tachycardia in whom the site of origin of tachycardia was determined by His bundle electrography. Seventy episodes of sustained ventricular tachycardia from 62 patients and 70 episodes of aberrant conduction during supraventricular tachycardia from 60 patients were available for study. Findings suggesting a ventricular origin of tachycardia were (1) QRS width over 0.14 sec, (2) left axis deviation, (3) certain configurational characteristics of QRS and (4) atrioventricular (A-V) dissociation. Capture or fusion beats resulting from A-V conduction of dissociated atrial complexes during ventricular tachycardia were seen during only four of 33 episodes of sustained tachycardia.     

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.     

The effect of nitroglycerin on atrioventricular conduction in man

His bundle electrograms were performed on 10 patients with organic heart disease. Six patients had had a recent myocardial infarction. Recordings were made at various rates utilizing right atrial pacing. Nitroglycerin, $\text{1}\text{150}$ gr, was administered to all 10 subjects, and the P-A, A-H, H-Q and H-S intervals were determined before, and immediately after the disappearance of the sublingually administered nitroglycerin. A significant decrease in the A-H interval occurred with negligible effects on the P-A, H-Q and H-S intervals. At the atrial pacing rate of 100/min, the average A-H interval fell from the control value of 152 msec to 129 msec after the administration of nitroglycerin (p < 0.02); at the pacing rate of 130/min, the A-H interval decreased from 194 to 133 msec (p < 0.05). Second degree heart block occurred at higher pacing rates in six patients after nitroglycerin administration as compared to the control value. The average postsuppression sinoatrial recovery time control value of 1,083 msec decreased to 906 msec after nitroglycerin administration (p < 0.01). These findings demonstrate that nitroglycerin can improve conduction through the A-V node.     

Osteomalacia and celiac disease: Response to 25-hydroxyvitamin D

In this 54 year old woman with celiac disease, osteomalacia developed while she was on a gluten-free diet which had caused regression of her steatorrhea. She was not responsive to large doses of parenterally administered dihydrotachysterol and calcium, but she was responsive to the oral administration of 25-hydroxyvitamin D₃ (25-OHD₃). The data suggest that 25-OHD₃ Is the treatment of choice for patients with vitamin D deficiency due to intestinal malabsorption.     

Hyperparathyroidism due to clear cell hyperplasia. Serial determinations of serum ionized calcium, parathyroid hormone and calcitonin

Serial determinations of serum ionized calcium (Ca⁺⁺), serum total calcium (Ca), parathyroid hormone (PTH) and calcitonin levels were made in a patient with hyperparathyroidism due to clear cell hyperplasia. Although serum Ca declined to normal levels prior to parathyroidectomy, serum Ca⁺⁺ and PTH levels remained elevated until after operation. This suggests that the calcium ion electrode may prove valuable in the diagnosis and management of patients with hyperparathyroidism, especially when they are normocalcemic. The excised parathyroid glands yielded very low PTH concentrations upon extraction, implying that in this form of hyperparathyroidism PTH secretion is excessive whereas storage is markedly reduced. CT levels were normal in both serum and excised glands. This finding is of interest in relation to the patient's associated generalized neurofibromatosis and serves further to distinguish the present syndrome from that characterized by mucosal neuromas, hyperparathyroidism and medullary carcinoma of the thyroid.