"Big, big insulin"

The presence of a new form of immunoreactive insulin, “big, big insulin”, was first detected in the plasma of an insuloma suspect. On Sephadex gel filtration the elution volume of this insulin is approximately that of ¹²⁵I-γ-globulin. Its sedimentation velocity on ultracentrifugation is between that of labeled albumin and labeled γ-globulin. Thus, it appears to have a molecular weight of about 100,000. Studies with starch gel and starch block electrophoresis reveal that it is a more basic protein than porcine or crystalline human insulin. It is immunochemically identical with crystalline human insulin, maintains its identity on refractionation on Sephadex gel filtration and is rapidly transformed by trypsin to an insulin-like component. “Big, big insulin” is a minor component (<1%) in extracts of normal pancreas and of insulomas. These observations suggest that insulin is the daughter product not only of proinsulin but of an even larger precursor, “big, big insulin”.     

"New" treatment for chronic intractable congestive heart failure.

The use of hexamethonium injected intravenously in successive 2.5 mg. doses resulted in alpha-adrenergic sympathetic nerve blocking and associated peripheral vasodilation with dramatic improvement of the symptoms and signs in patients with marked chronic intractable CHF. The vasodilatating effect of the drug is simple to monitor at the bedside and serves as an effective, simple means to "bleed" the patient intravenously by decreasing systemic venous tone and reducing the wall stress in the vessels. This intravenous "bleeding" results in a shifting of excessive blood from the lungs and central systemic venous areas to the larger volume of the more peripheral systemic venous reservoirs. Rheoplethysmorgraphic recordings of digital blood flow in the fingertips of the patients revealed marked constriction of all vessels of the fingers during CHF. Hexamethonium dilated all these vessels and increased digital blood flow even though arterial blood pressure was reduced by the drug. Theoretic discussions of aspects of the mechanism of congestive heart failure of the two-pump system of the heart of man and the mechanical or hemodynamic advantages of the small veins over the larger centrally located veins tend to explain why the use of hexamethonium benefits the circulation by producing vendoilatation. These studies indicate the therapeutic usefulness of hexamethonium in the management of acute and chronic intractable CHF and provides physiologic and theoretic data to explain why the drug is effective.     

Competitive radioassays and "specific" tumor markers

Competitive radioassays have been used to detect ectopic production of hormones and other polypeptides by various non-endocrine neoplasms. Some of these proteins, particularly those whose synthesis is normally restricted to fetal or placental tissue, may serve as specific tumor markers when detected in the serum of a male or nonpregnant female. However, the true incidence of these markers and their specificity for cancer are not yet established and related to the sensitivity and specificity of the assay methods employed.     

Effect of isoproterenol on the "early repolarization" syndrome.

A study has been carried out on a group of subjects with RS-T segment elevation, a normal variant of early repolarization. Following isoproterenol administration, the RS-T segment became isoelectric. In most cases this was accompanied by shorter QT and longer QTc intervals. The same effects were observed after physical exertion but not after atropine or amyl-nitrite. Propranolol administration exaggerated RS-T elevation. Considering the mechanism with which isoproterenol acts and some analogies with the electrocardiographic picture experimentally obtained by means of the unilateral stimulation of the stellate ganglions, the hypothesis is advanced that the normal variant of early repolarization is related to an enhanced activity of the right sympathetic nerves.     

Marrow granulocyte reserves in black Americans. Hydrocortisone-induced granulocytosis in the "benign" neutropenia of the black.

The bone marrow granulocyte reserves of nine black patients with "benign" neutropenia were estimated by measuring the maximum neutrophil increment after the administration of hydrocortisone. Thirty control subjects, including 16 black and 14 white adults, were also studied. The mean neutrophil increment in the black patients with neutropenia was significantly less than that in the control subjects. The mean increment in the black control was also significantly less than that in the white control subjects. Four of the 16 black control subjects had neutrophil counts below 2,000/microliter; if these four are excluded from the analysis, the difference between the black and white control subjects is no longer significant. These data suggest that there is a subpopulation of healthy black adults with neutrophil counts below 2,000/microliter with reduced marrow granulocyte reserves as tested by corticosteroids. Bone marrow aspirates in four of the neutropenic patients showed normal cellularity and myeloid maturation suggesting that the lower increments are due to a difference in granulocyte release rather than to a difference in granulocyte production.     

Augmentation mammoplasty and "silicone-osis"

BACKGROUND: Claims have been made that breast augmentation induces a previously unrecognized disease ("silicone-osis"). AIMS: To confirm the existence of "silicone-osis", qualify and quantify its characteristics. METHODS: In this population-based retrospective cohort study, the health status of 458 female Sydney residents who had augmentation mammoplasty for cosmetic reasons ("augmentation mammoplasty-exposed" or "exposed" cohort) between 1979 and 1983 was compared with the health status of 687 female Sydney residents who had non-silicone-associated plastic surgery ("augmentation mammoplasty-nonexposed" or "non-exposed" cohort). Both groups were matched for age (+/- 5 years), year of plastic surgery (+/- 2 years), plastic surgeon, anaesthetist and mode of anaesthesia. Outcome measures comprised dummy symptoms to assess reporting bias, as well as symptoms and symptom clusters from a comprehensive 78-symptom list. RESULTS: Dummy variables were not over-reported by the exposed cohort. The following individual symptoms developed more commonly in the exposed cohort after index plastic surgery: "memory loss/confusion", "altered bowel habit", "chest pain made worse by deep breathing", "shortness of breath after walking up 10 steps", "breast pain", "sweating mainly at night" and "tunnel vision". Of eight identified symptom clusters, three were rejected as biologically unimportant: "joint swelling of the bunion joint", "haemorrhoids" and "breast lumps" (the latter two occurring more commonly in the non-exposed cohort). In contrast, five symptom clusters were thought to have potential biological importance and occurred more commonly in the exposed cohort. The symptom "night sweats" was common to all five clusters, and comprised the sole symptom in one instance. The other four multisymptom clusters were also characterized by "low energy" (lethargy) and "pins and needles", whereas "breast pain", "impaired memory", "muscle pain" and "reflux", occurred in three of the four clusters. CONCLUSION: Cluster analysis suggested the existence of a multisystem disorder occurring more commonly in the exposed cohort and characterized by night sweats, lethargy, breast pain, impaired mentation, reflux, paraesthesiae, hand muscle weakness and myalgia. The argument against this being a new disease entity --"silicone-osis"-- however, was its presence, albeit at lower frequency, in the silicone-unexposed cohort. Thus this study did not confirm the existence of a new disease entity "silicone-osis" uniquely and causally associated with silicone exposure. The possible interpretations of these findings are discussed.     

Exercise and heart disease. Epidemiology of the "exercise hypothesis"

The "exercise hypothesis" states that exercise protects against coronary heart disease. Reviewed herein is the epidemiologic evidence for and against the "exercise hypothesis." The weight of evidence supports the view that exercisers have a lower risk of coronary disease, but that vigorous exercise cannot always prevent progression of coronary atherosclerosis and does increase the risk of sudden death in persons with advanced coronary atherosclerosis. It is concluded that the "exercise hypothesis" is plausible, even likely, but still unproved.     

Acquired "storage pool disease" of platelets associated with circulating antiplatelet antibodies

This study reports the first example of acquired “storage pool disease” in a patient with nephritis, polyarthralgia, chondritis, thrombophlebitis, Raynaud's phenomenon and circulating antiplatelet antibodies. Studies of platelet function showed a long bleeding time, decreased aggregation to collagen, thrombin and adenosine diphosphate (ADP), and depleted platelet stores of ADP and serotonin. These findings are similar to those found in a congenital disorder of platelets characterized by a deficiency of the storage pool of adenine nucleotides and serotonin. It is suggested that in this patient the circulating antibodies induced a release of the storage pools of adenine nucleotides and serotonin of the circulating platelets, leading to a state of defective hemostasis. The patient responded well to steroid therapy, and platelet function returned to normal concomitant with the disappearance of the antiplatelet antibodies. It is possible that “storage pool disease” with or without a thrombotic tendency may occur in other acquired disorders, especially the myeloproliferative disorders and those associated with circulating antibody.     

Multiple adenocarcinomas and premalignant changes in "backwash" ileitis.

In a patient with long-staning ulcerative colitis and "backwash" ileitis, multiple carcinomas developed in the colon and ileum. In both locations premalignant mucosal changes of the basal cell proliferation type were seen adjacent to and remote from sites of carcinoma. Although the frequency of such premalignant and malignant changes in "backwash" ileitis is unknown, their concurrence in this case suggests that ulcerative colitis involving the terminal ileum increases the risk of small bowel carcinoma.     

Malignant lymphoma of plasmablastic identity. A neoplasm with both "immunoblastic" and plasma cellular features

A solitary extramedullary lymphoid neoplasm had characteristics of plasma cell precursors or plasmablasts. Conventional microscopic study classified this tumor as a diffuse large cell lymphoma of "immunoblastic sarcoma" type. Immunologic cell surface markers could not be detected, but cytoplasmic immunoglobulin G (IgG)-kappa was demonstrated by immunoperoxidase technic, and IgG was present in the supernatant of the tumor tissue culture. The distinction between lymphoid and plasma cellular neoplasms is made.     

Arrhythmias and the "Holiday Heart": alcohol-associated cardiac rhythm disorders

An association between excessive alcohol use and cardiac rhythm disorders is often difficult to establish in the absence of overt cardiomyopathy. We studied 32 separate hospital admissions for dysrhythmias in 24 patients (20 men, 4 women) with heavy recent alcohol ingestion and prolonged excessive alcohol use. None had evidence of overt heart disease after treatment of arrhythmia. Episodes usually followed heavy weekend or holiday sprees, resulting in hospitalization between Sunday and Tuesday or in proximity to the year-end holidays, a relationship not observed in other alcohol-associated illnesses. Atrial fibrillation was most common, but atrial flutter, atrial tachycardia, junctional tachycardia, multiple APC's, multiple PVC's and ventricular tachycardia were also observed. Transient hypokalemia was present in four of 30. The mean $\text{PEP}\text{LVET}$ ratio after treatment was 0.412 ± 0.014 (normal 0.299 ± 0.008, P < 0.001). High-speed ECG's showed prolongation of PRc, QRS, and QTc. At cardiac catheterization, intracardiac pressures and volumes, coronary arteriograms and ventricular wall motion were normal at rest and mean cardiac index was slightly low, but the left ventricular response to angiotensin was abnormal. Cardiac arrhythmias presenting during weekend or holiday drinking episodes are associated with conduction delays and depressed cardiac performance indicative of early cardiomyopathy and suggest a “holiday heart” syndrome.     

Cardiac sarcoma causing "ASH" and simulating coronary heart disease.

A patient is described in whom primary cardiac sarcoma preferentially infiltrated the ventricular septum while essentially sparing the left ventricular free wall, resulting in striking echocardiographic and morphologic asymmetry between septum and free wall (ASH). No reports have appeared previously of a patient with an intramural cardiac neoplasm demonstrated by echocardiogram. Additionally, the patient clinically had features typical of coronary heart disease, yet at necropsy the extramural coronary arteries showed insignificant (< 75 per cent) cross-sectional area luminal narrowing by atherosclerotic plaques.     

"Paradoxical" prolongation of sinus nodal recovery time after atropine in the sick sinus syndrome.

A case of symptomatic sick sinus syndrome is presented with confirmation of sinus nodal dysfunction established by functional testing. The validity of such provocative testing and the criteria for abnormality are discussed. A newly recognized, seemingly "paradoxical" and potentially detrimental effect of atropine noted in this patient is examined. Despite an increase in sinus rate and an improvement in sinoatrial conduction time after administration of atropine, a markedly prolonged sinus recovery time after rapid atrial pacing occurred, and atrial quiescence for more than 10 seconds was seen. Possible electrophysiologic mechanisms for this phenomenon, such as decreased atriosinus entrance block, concealed sinoatrial reentry or enhanced intranodal depolarization, are discussed and potential clinic correlates are made.     

家兔对小鼠抗血吸虫靶抗原单克隆抗体的抗抗体应答

本文报告从分泌具血吸虫保护性IgG_(2a)表型1E2McAb的杂交瘤培养上清液中,应用蛋白A-葡聚糖柱层析法纯化的McAb免疫家兔,采用纯化McAb分别进行Dot-ELISA、免疫双扩散和免疫印迹试验、ELISA观察免疫血清中抗McAb和抗-抗McAb的产生及其动态变化规律。主要结果表明:(1)1E2McAb免疫后,20d开始出现抗McAb,若不加强免疫,抗McAb逐渐减弱:若加强免疫,则抗McAb水平较高,且持续30-50d。(2)免疫血清中的抗-抗McAb,能起抗-抗Id的作用,可识别不同的血吸虫抗原及血吸虫抗原中不同抗原决定簇(90,68和45kD_a),而且免疫后不同时期抗-抗McAb识别不同抗原的水平不同(滴度1:100-1:1600)。对抗血吸虫肥抗原McAb免疫后抗抗体应答的观察,可为研制不同抗独特型McAb创造条件。     

"Floating" catheter for temporary transvenous ventricular pacing

A technique for the placement of a flow-directed balloon electrode catheter for right ventricular endocardial pacing was utilized successfully in 15 of 17 patients. The catheter is capable of being passed either percutaneously, or by cut-down procedure, at the bedside under electrocardiographic control. It was successfully positioned in 6 cases after other semifloating electrodes failed. This new catheter provides stable, reliable pacing and is an excellent alternative to X-ray image intensification for placement under urgent or emergent conditions.     

The functional defect in amyloid heart disease. The "stiff heart" syndrome.

Left ventricular performance was studied in three patients with heart failure due to amyloid deposits. The diagnosis of amyloidosis was proved by cardiac biopsy in two patients and by rectal biopsy in the third. One patient had myelomatosis, but the other two had no other identifiable disease. The investigative technique allowed simultaneous measurements of pressure and volume in the left ventricle. The functional defect with slow cardiac filling at high pressure and greatly reduced left ventricular contraction differed from that of constrictive pericarditis and other heart muscle disease. These features of a "stiff heart" are probably unique to amyloidosis and should make possible positive recognition of the condition on the basis of echocardiographic, angiographic and hemodynamic findings.     

Neurological complications of connective tissue and other "collagen-vascular" diseases

A variety of neurological complications may occur in the various connective tissue and "collagen-vascular" diseases. Most of these complications are due to vasculitis affecting various sites in the central or peripheral nervous system. While the evidence for definitive vasculitis in SLE is not strong, small vessel damage usually is present in anatomic sites which correlate well with clinical features. Although patients with rheumatoid arthritis also may have vasculitis, neurological complications are usually related to nerve compression by rheumatoid nodules or the arthritic process itself. Considerable controversy exists regarding the accuracy of various diagnostic tests. While corticosteroids are the mainstay of therapy for these conditions, there are no definitive studies proving their efficacy.     

"Malignant" hypertension resulting from atheromatous embolization predominantly of one kidney

The presence of left-sided renal ischemia in a 57 year old man with malignant hypertension was suggested by an abnormal intravenous pyelogram and radioisotopic evidence of reduced blood flow to the left kidney. Plasma renin activity was higher in the left renal vein than in the right renal vein (ratio 2.3:1), despite a normal renal arteriogram, implying occlusion of small arteries or arterioles in the left kidney. The patient died and at autopsy was found to have an ulcerated plaque of atheroma overlying the orifice of the left renal artery, whence atheromatous embolization, predominantly of the left kidney, had taken place, causing ipsilateral renin release and hypertension.     

Significant associations of adrenal cortical abnormalities with "essential" hypertension

A study of the records of 35,000 consecutive autopsies yielded 870 patients with adrenal cortical abnormalities: 690 with adenomas and 180 with hyperplasia alone. A highly significant excess (p < 0.001) of all forms of hypertension was found in these patients compared with carefully matched controls. The excess was significant for essential (p < 0.005) and essential accelerated (p < 0.001) hypertension. Further analyses by age and race revealed excesses of similar significance to be confined to the younger Negro patients (twenty to fifty-nine years old), whereas among the younger white patients there was an excess only of essential hypertension (p < 0.05). These data suggest that adrenal cortical adenomas and hyperplasia may contribute to the development of essential hypertension in a significant proportion of younger and middle-aged adults, especially Negro adults.     

"Mitral stenosis" secondary to combined "massive" mitral anular calcific deposits and small, hypertrophied left ventricles. Hemodynamic documentation in four patients.

Certain observations are described in four elderly women with massive mitral anular calcific deposits, small thick-walled left ventricles and diastolic gradients between pulmonary artery wedge position (or left atrium) and left ventricle. All four patients had some degree of obstruction to left ventricular outflow. Examination at necropsy (two patients) or at operation (one patient) disclosed only focal fibrous thickening of the mitral leaflets without commissural or chordal fusion. By auscultation, none had mitral opening snaps, only two had loud first heart sounds and only one had a mitral diastolic rumble. Hemodynamic documentation of a diastolic gradient between pulmonary artery wedge position (or left atrium) and left ventricle in the presence of massive mitral anular calcific deposits and in the absence of diffuse disease of the mitral leaflets has not been demonstrated previously. The diastolic gradients are considered to result from the combination of the large mitral anular calcific deposits and the small, thick-walled, noncompliant left ventricles.