Evidence for a postsynaptic effect of captopril in isolated perfused rabbit kidney

The influence of captopril (SQ 14225) on the vascular and norepinephrine-releasing responses to nerve stimulation (2, 5 and 10 Hz) was assessed in isolated blood-free perfused rabbit kidney. At a concentration of 0.23 and 0.46 mM in the perfusion medium, captopril markedly attenuated the vasoconstrictor response but did not influence the release of norepinephrine produced by nerve stimulation. These results suggest that captopril may act as an alpha-antagonist at a postjunctional level.     

Nonmalignant monoclonal immunoglobulinemia, pernicious anemia and gastric carcinoma. A model of immunologic dysfunction: Report of two cases and review of the literature

The association of an autoimmune disease with a monoclonal immunoglobulin is not exceptional and most probably results from a dysfunction of the immunologic apparatus.This study describes two patients with monoclonal immunoglobulin A (IgA) and M (IgM) gammopathy, respectively, in whom pernicious anemia and finally gastric carcinoma developed. One patient had autoantibodies to gastric parietal cell and to thyroid microsomal antigen which could not be identified with the M-component. This observation, together with the fact that pernicious anemia occurred in one case before and in the other case after the discovery of M-component, suggests that different clones of cells were responsible for both disorders. Sixteen cases in which the patients had the same association have been collected from the literature and the data are compared with ours.     

The biochemistry of the renin-angiotensin system and its role in hypertension.

The renin-angiotensin system has an important role in maintaining elevated blood pressure levels in certain forms of experimental and human hypertension. Renin, an enzyme produced by the juxtaglomerular cells of the kidney, acts on a protein substrate found in the alpha 2-globulin fraction of the plasma to produce a decapeptide, angiotensin I. This decapeptide is not directly pressor, but on passage through the pulmonary circulation is converted to an octapeptide, angiotensin II, a very potent pressor substance which acts by causing constriction of arteriolar smooth muscle. In addition to its direct action which increases blood pressure, angiotensin II acts on the adrenal cortex to cause the release of the sodium-retaining hormone aldosterone. Recent evidence suggests that this action may be mediated by the heptapeptide, angiotensin III. Both renin and its protein substrate exist in multiple forms and renin may also exist as a high molecular-weight "pro-hormone," although the physiologic significance of these forms is not clear. The elucidation of the biochemistry of the renin-angiotensin system has provided us with inhibitors which allow the system to be blocked effectively in vivo. Thus, angiotensin antagonists such as Sar 1, IIe 8-angiotensin II and converting enzyme inhibitors such as BPP 9a (SQ 20881) have proved useful in the study of experimental and human hypertension.     

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.     

Autoimmune hematologic diseases associated with infraclinical systemic lupus erythematosus in four patients. A human equivalent of the NZB mice

In four patients with a diagnosis of autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura antinuclear antibodies and circulating immune complexes (Clq-BA test) have developed at some time in their history. Renal biopsy material was assayed with different methods. Immunofluorescence studies revealed granular deposits of immunoglobulin G (IgG), immunoglobulin M (IgM) and third component of complement (C3). Upon optic microscopy, three patients had mild mesangial proliferation, one a focal glomerulonephritis. Upon electron microscopy, all patients exhibited mesangial and/or subendothelial deposits. The patients have been followed for 18 to 37 years since the beginning of their disease. There has been no clinical evidence of systemic lupus erythematosus (SLE), although they present in their glomeruli immunologic and anatomic features compatible with this disease. These patients seem to be a human equivalent of the black NZB mouse which presents immunohematologic disorders and some biologic markers of SLE without having a full clinical picture of SLE.     

Age,race, sex and other indices of risk in hypertension

Among the various criteria used in evaluating the prognosis of hypertensive patients the level of the diastolic blood pressure averaged over three or more visits is the most important index. Other indices also are useful and are essential in deciding on treating patients with average diastolic blood pressures below 105 mm Hg. Included among these are sex, age and race. Male sex, young age and black race are all associated with increased risk of morbidity and mortality.The lability of the hypertension is another indicator of risk. Patients with labile hypertension—high casual in relation to basal blood pressure—have a better prognosis than those who do not. Family history also should be considered. A history of premature death from hypertensive complications in a parent or sibling suggests that the patient may be at increased risk. Finally, the presence and extent of detectable target organ damage provides a major criterion of prognosis and indication for treatment.     

Blood in the lymph (hemochylia) and intestinal lymphangiectasia associated with Lutembacher's syndrome

A 31 year old man presenting with Lutembacher's syndrome and protein-losing enteropathy is described. Reversal of the protein-losing enteropathy 7 months after cardiac surgery suggested that it was secondary to the cardiac disorder. Spontaneous rupture of a congenital aneurysm of the splenic artery created a spleno-portal arteriovenous fistula which caused a massive sequestration of blood into the dilated abdominal lymphatic system, severe hypovolemic shock and death.The pathogenesis and relation of two rare disorders of the lymphatic system, contamination of the lymph with blood (hemochylia) and intestinal lymphangiectasia are discussed.     

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.     

Autonomic complications in a case of severe tetanus

Severe tetanus developed in an elderly white man and he was treated with tracheostomy, therapeutic paralysis with curare and intermittent positive pressure ventilation. Over the initial few days, labile hypertension and tachycardia developed, which were eventually controlled with a trimetaphan infusion and intravenous propranolol. These drugs were withdrawn when profound hypotension developed, and over the next 5 days frequent physical stimulation was necessary to maintain an adequate level of cardiovascular activity. At this time the patient appeared comatose, his muscle tone was flaccid, and there was a marked similarity between the levels of cardiovascular and electroencephalographic activity. The end of the period was marked by a spontaneous increase in electroencephalographic activity and a better maintained blood pressure. Over the next 2 days, muscle spasms and hypertension reappeared, body temperature increased and consciousness returned. Eventual recovery was complete but delayed by a prostatic operation.It appears that in some elderly patients with severe tetanus a transient phase of sympathetic overactivity is followed by a phase when spontaneous sympathetic activity is minimal. During this second phase, massive sympathetic activation can be evoked by various stimuli provided drug-induced depression is avoided.     

Effects of streptozotocin on an islet cell carcinoma with hypercalcemia

A 57 year old man had an inoperable pancreatic islet cell carcinoma with liver metastases. Biochemical studies indicated the possibility of a circulating parathyroid hormone-like substance; exploration of the neck revealed normal parathyroid glands. Biochemical studies of family members revealed no evidence of familial endocrine adenomatosis. The patient's hypercalcemia could not be controlled with the usual calcium lowering measures. He was treated with streptozotocin, with temporary increases in his hypercalcemia after each of the first three treatments. After four doses of streptozotocin, the size of the tumor decreased and the serum calcium fell to hypocalcemic levels. The serum calcium subsequently stabilized at low normal levels, and the tumor has remained in partial remission for 14 months after administration of the last dose of streptozotocin.     

A case of lymphoproliferative disease presenting as juvenile rheumatoid arthritis. Diagnosis by synovial fluid examination

Lymphoproliferative disease can present as arthritis, most commonly mimicking acute rheumatic fever. The finding of arthritis rarely leads to the correct diagnosis, in fact, it frequently suggests inflammatory rheumatic diseases. We present a case closely resembling juvenile rheumatoid arthritis in which the diagnosis was made by demonstration of malignant cells In the synovial fluid at a time they were absent from the peripheral blood and initial bone marrow specimen. Closed synovial and bone biopsy specimens, the latter of an osteopenic area, revealed the infiltrative character of this disorder.     

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.     

Biologic and clinical significance of cryoglobulins. A report of 86 cases

Eighty-six patients with cryoglobulinemia repeatedly underwent complete immunochemical and clinical evaluation during the course of their disease. Immunochemical analysis of the purified cryoglobulins allowed us to classify them into three groups. Type I cryoglobulins are made of isolated monoclonal immunoglobulin: IgM (11 cases), IgG (7 cases), IgA (2 cases) or Bence Jones protein (1 case). Type II cryoglobulins are mixed cryoglobulins with a monoclonal component possessing antibody activity towards polyclonal IgG. These cryoglobulins were mainly IgM-IgG (19 cases), sometimes IgG-IgG (2 cases) or IgA-IgG (1 case). Type III cryoglobulins (43 cases) are mixed polyclonal cryoglobulins, i.e., composed of one or more classes of polyclonal immunoglobulins and sometimes nonimmunoglobulin molecules such as beta₁C or lipoprotein. Most of these type III cryoglobulins are also immunoglobulin-anti-immunoglobulin immune complexes. This classification enabled us to establish correlations between the biologic findings and the clinical features as well as the underlying diseases.Cutaneous and vasomotor symptoms were most severe in patients with type I and II cryoglobulins. The usual clinical picture in patients with type II or III cryoglobulins consisted of chronic vascular purpura and mild Raynaud's phenomenon. Renal and neurologic involvement were more frequent in patients with type II and III cryoglobulins, and were of major prognostic significance. In our series, immunoproliferative and autoimmune disorders were the most frequent diseases associated with cryoglobulinemia. The former were associated with type I or II cryoglobulins and the latter mainly with type III cryoglobulins. Of note is that idiopathic cryoglobulinemia accounted for nearly 30 per cent of the cases despite repeated careful clinical evaluation and a mean follow up of 9 years.In 10 per cent of the cases, acute and severe symptoms necessitated emergency treatment with plasmapheresis and chemotherapy which allowed a satisfactory initial remission in all but one patient. Conversely, no treatment was definitively effective in patients with chronic symptoms such as vascular purpura.     

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.     

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.     

Repeat hemodynamic determinations in borderline hypertension

Repeat hemodynamic determinations were performed in 37 young men with borderline hypertension. The duration of the follow up study was 47 ± three months. At each determination, those with borderline hypertension were compared to a group of matched normal subjects. Blood pressure increased from the first to the second determination, but the increase was significant only for systolic (P < 0.001) and mean (P < 0.01) arterial pressures. Cardiac index and heart rate, which were initially increased, decreased significantly (P < 0.02; P < 3.01, respectively) and decreased to normal values; total peripheral resistance increased (P < 0.01); blood and plasma volumes decreased (P < 0.01). At the first determination, the cardiac index-heart rate correlation was significant (P < 0.01) and the cardiac index-blood volume correlation was not. At the second determination, on the contrary, the cardiac index-total blood volume correlation was significant (P < 0.001) whereas the cardiac index-heart rate correlation was not. The study provides evidence that patients with borderline hypertension, over a short-term period, show (1) a greater increase in systolic than in diastolic pressure, (2) a return of cardiac output toward normal values through a decrease both in heart rate and blood volume, and (3) an increased importance of volume factors in the cardiac output control.     

Long-term prognosis of idiopathic membranous glomerulonephritis. Study of 116 untreated patients.

One hundred sixteen patients, mainly adults, with idiopathic membranous glomerulonephritis were studied to evaluate their clinical course and long-term prognosis.The onset was marked by a nephrotic syndrome in 88 patients (75.8 per cent) and by a proteinuria without the nephrotic syndrome in 28 patients (24.2 per cent). Clinical remission occurred in 23.4 per cent of cases, clinical improvement in 14.6 per cent, renal insufficiency in 19 per cent (with end-stage renal failure in 9.5 per cent) and the condition remained unchanged in 43 per cent. The actuarial survival curve shows that 76 per cent of the patients were alive at 10 years. Twenty-five per cent of the patients had hypertension during the course of the membranous glomerulonephritis. Seven women had nine pregnancies after the diagnosis of membranous glomerulonephritis was made, with successful deliveries in seven. Renal vein thrombosis was present in five of 16 patients examined for it.Glomerular lesions were classified into three groups, according to the classification of Bariety et al. At the first biopsy, 22 patients were classified as having type I lesions, 79 as having type II lesions and 15 as having type III lesions. The mean interval between discovery of the disease and renal biopsy according to the type of glomerular lesions, is shorter in patients with type I lesions than in those with type II and III lesions. Clinical improvement and clinical remission are more frequent in those with type I lesions than in those with type II and type III lesions. End-stage renal failure was never encountered in those with type I lesions and was present in 13 per cent of those with type II lesions and 7 per cent of those with type III lesions. The different histologic types can correspond to a progression of lesions with time but not to a progressive severity of the disease. In two cases there was complete resolution of the lesions and recovery of the normal appearance of the capillary wall.     

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.