Observations of the aetiology of primary intestinal lymphoma

The aetiology of primary intestinal lymphoma (PIL) is not known. In this paper virus capsid antibodies (VCA) in sera from 43 lymphoma patients (40 PIL, three Burkitt type lymphoma) were compared to thirty-nine control sera taken from patients who were age and sex matched to the lymphoma patients.The results indicate that VCA antibody levels are not significantly raised in patients with PIL; this contrasts with the marked rise in antibodies found in Burkitt's lymphoma.     

Syndrome of anosmia with hypogonadotropic hypogonadism (kallmann syndrome): Clinical and laboratory studies in 23 cases

We have studied 23 patients (14 men, nine women) in 18 kindreds with anosmia and hypogonadotropic hypogonadism. Seven kindreds had more than one affected member, and included five eugonadal persons with anosmia and two eusomic women with hypogonadotropic hypogonadism. Other clinical abnormalities observed included: obesity (in nine), cryptorchidism (six), osteopenia (six), mild neurosensory hearing loss (five), gynecomastia (five), diabetes mellitus (four), cleft lip or palate or both (three), high-arched palate (two), short fourth metacarpal (two), and clinodactyly, camptodactyly, shortened frenulum of the tongue, multiple facial anomalies, right-sided aortic arch, malrotation of the gut, renal diverticulum, and mild red-green color blindness (one each).Normal secondary sex characteristics developed in all 20 patients treated on a long-term basis with chorionic gonadotropin or gonadal steroids. Responses to a single injection of gonadotropin-releasing hormone were heterogeneous. Five men had no luteinizing hormone response, five had a depressed response, and one an exaggerated response; two had no follicle-stimulating hormone response, five responses were depressed, three were normal, and one was ex-aggerated. None of seven women achieved a normal luteinizing hormone response to gonadotropin-releasing hormone; two had depressed follicle-stimulating hormone response, four responses were normal, and one was exaggerated. None of 11 patients tested responded to clomiphene. Two men fathered children. Each of two other men who underwent biopsy of the testes before and after long-term chorionic gonadotropin therapy showed mildly increased spermatogenesis. Little or no maturation beyond primordial follicles was observed in two ovarian biopsy specimens. Fifteen of 17 patients had normal basal prolactin levels and 14 of 16 had normal thyrotropin-releasing hormone-induced prolactin increase, but nine of 15 tested had a decreased or absent response of prolactin to chlorpromazine. Circulating concentrations of thyroid hormones were normal, but four of 17 patients tested had depressed TSH (thyroid-stimulating hormone) responses to thyrotropin-releasing hormone, and one man had an exaggerated response. Three of 12 patients had a depressed cortisol response to insulin-induced hypoglycemia, and two of seven patients had slightly depressed deoxycortisol responses to metyrapone. Growth hormone and vasopressin release in all 14 and all 12 patients, respectively, studied were essentially normal.Patients with anosmia and hypogonadotropic hypogonadism may have hypothalamic defect(s) responsible for the hypogonadotropism and perhaps for certain additional deficiencies of anterior pituitary function found in some. The cause of less frequent phenotypic abnormalities has not been established. In certain pedigrees, the evidence suggests that the major manifestations of the syndrome are inherited as an autosomal recessive trait.     

Cardiac hypertrophy: Useful adaptation or pathologic process?

An extensive body of evidence supports the concept that cardiac hypertrophy and normal cardiac growth develop in response to increased hemodynamic loading and abnormal systolic and diastolic stresses at the myocardial fiber level. The pattern of hypertrophy reflects the nature of the inciting stress. Experimental studies indicate that if the stress is moderate, gradually applied, and the animal young and healthy, physiologic hypertrophy of muscle with normal contractility develops. In this circumstance, cardiac hypertrophy may be regarded as a useful adaptation to increased hemodynamic loading. When the inciting stress is severe, abruptly applied, or the animal old or debilitated, pathologic hypertrophy develops: in this circumstance, the cardiac muscle produced is abnormal and exhibits depressed contractility. Of particular clinical relevance is the intermediate situation which seems to develop in many patients with chronic left ventricular pressure-overload and perhaps also in left ventricular volume-overload. In this situation, chronic left ventricular pressure or volume overload is initially matched by adequate hypertrophy in the appropriate pattern. Eventually, in some patients, hypertrophy fails to keep pace with the hemodynamic overload so that a systolic stress imbalance occurs at the myocardial fiber level and left ventricular pump failure ensues. If this situation persists uncorrected, it is possible that the increasingly high wall stresses will convert physiologic to pathologic hypertrophy. The task of the clinician is to identify this intermediate stage and to correct the abnormal hemodynamic loading before the transition to pathologic hypertrophy becomes complete.     

Effect of a twelve-hour hiatus in propranolol therapy on exercise tolerance in patients with angina pectoris

To determine whether propranolol can be administered twice daily without any loss of antianginal effect, we studied nine men receiving long-term propranolol therapy for stable angina pectoris. Each patient performed bicycle exercise to the point of angina on two consecutive mornings. By means of double-blind placebo-propranolol administration before the test, the study created a situation whereby on one day the exercise took place 12 hours after the last dose of propranolol, and on the other day, $\text{1}\text{1}\text{2}\text{hours}$ after a dose. Despite markedly lower blood levels of propranolol on the day that exercise was performed 12 hours after the last dose, exercise time to angina was nearly identical on the 2 days. We conclude that long-term therapy with propranolol for angina pectoris can be administered on a twice daily basis with no loss of effectiveness.     

Demonstration of re-entry within the canine specialized conduction system.

There is suggestive evidence that bundle branch re-entry occurs in man in response to premature right ventricular stimulation. Demonstration of the activation sequence during re-entrant excitation in the in vivo dog was accomplished by placing recording electrodes on the major portions of the specialized conduction system. A temporary right heart bypass was utilized to place two or more electrodes on both right and left bundle branches and place electrodes on the His bundle and on the left and right ventricular endocardium. Premature excitation of the right ventricle was found not to retrogradely activate the right bundle but was able to cause slow right to left myocardial activation that resulted in retrograde activation within the left bundle branch. Retrograde conduction in the left bundle caused activation of the His bundle and the proximal right bundle. Activation of the right bundle resulted in antegrade conduction of the impulse across the site of previous conduction block and re-excitation of the right ventricle, to complete the re-entrant circuit. This type of re-entry, utilizing the bundle branches, was demonstrated in 19 dogs. This re-entry circuit was found to be facilitated by shortening of the right ventricular refractory period by local epicardial warming and was abolished by interruption of conduction in the right bundle by anodal blocking current applied to the right bundle. The sites of slow conduction, site of unidirectional block, and pathways of conduction were demonstrated. The validity of the concept of re-entry occurring within the specialized conduction system is substantiated.     

Aneurysms of the sinus of Valsalva. Report of seven cases and review of the literature

The aneurysms of the sinuses of valsalva are relatively rare. The first case was described by Thurnam in 1840. Since then, more than 200 cases have been reported; in most surgery was performed. The lesions of the aortic sinuses are either congenital or the result of the syphilis or of the bacterial endocarditis.Between 1967 and 1976, seven patients (four men and three women) with this pathology were admitted to the Hospital Cantonal of Geneva (HCG). Their ages ranged from 13 to 51 years. Clinical symptoms consisted of chest pain, palpitations, dyspnea, cardiac insufficiency and fever. In one patient, a sudden cardiovascular shock was present. Physical examination had revealed a systolic and/or diastolic thrill in four patients, and a systolic and diastolic murmur on the left sternal edge in all. An increase in the differential arterial pressure was found in all patients and hepatomegaly in two. The electrocardiograms showed signs of left ventricular hypertrophy in five patients, right ventricular hypertrophy in four, incomplete right bundle branch block in one and signs of a subendocardial ischemic lesion in another. The chest films indicated a severe or moderate heart dilatation in all seven patients and an enlarged hilar area in six.All patients had been subject to cardiac catheterization. Rightsided pressures were increased in the majority of patients. Arterial and pulmonary capillary pressures were increased in all. A correct preoperative diagnosis had been made only twice.Cardiac surgery had been performed with cardiopulmonary bypass in all patients. The aneurysm was ruptured into the right ventricle in four patients and unruptured in the others. The lesion originated from the right coronary sinus in six patients and from both right and left coronary sinuses in one. Ventricular septal defects (three) and aortic lesions (five) were also found. The postoperative course was uneventful and all patients are still alive.     

Valvular heart disease in osteogenesis imperfecta.

Aortic and mitral valve abnormalities have been reported which clearly appear to be related to the underlying connective tissue disorder in two patients, a father and daughter, with osteogenesis imperfecta. Although this appears to occur with a much lower prevalence and lesser severity than in the Marfan syndrome, the true prevalence of cardiac connective tissue involvement is not known, and the orthopedic complications of osteogenesis imperfecta may have overshadowed attention to cardiovascular abnormalities. In evaluating patients with osteogenesis imperfecta, careful attention should be paid to cardiovascular findings and if valvular lesions are noted, patients should be instructed regarding the need for antibiotic prophylaxis for dental and surgical procedures. The valvular lesions can progress, and regular follow-up cardiovascular evaluation should be planned. Finally, despite potential problems with tissue friability and healing and a possible tendency for increased bleeding, successful valve replacement can be carried out if necessitated by cardiac disability.     

Acute dermatomyositis-polymyositis and malignancy

A partial review of selected published case reports of AD-P associated with malignancy has been enhanced by the presentation of pertinent data on 15 unreported examples of the association. It is noteworthy that the first case in current literature of AD-P associated with a malignancy was described in 1916. The brief clinical report of a patient with proximal muscle weakness and skin lesions, with the obvious association with a malignancy (adenocarcinoma of the stomach), describes an example that has been repeated many times with different types of tumors but with essentially no variations in the clinical findings.In 1959 Williams identified 590 cases of AD with an overall tumor rate of 15%,³¹ and recently Barnes identified 258 cases of AD associated with a malignancy.³³The original designation, dermatomyositis or AD, has now been expanded to include proximal muscle polymyositis with systemic involvement, which syndrome at the current state of the art is indistinguishable clinically and pathologically from AD except for the lack of skin lesions. It may be that at some future time one or more immunologic features may differentiate the clinical entity polymyositis from AD and further subdivide each of these entities from similar clinical syndromes associated with a malignancy. However, the problem in management in either AD or polymyositis is similar.¹A number of patients with a malignancy and muscle weakness or neuropathy have been reported. These associations have been mentioned briefly, but insufficient data are available to determine whether these should be considered as a variant of AD-P or only casually related conditions with certain clinical features in common.Most of the patients described in the literature of AD-P with an associated malignancy have had skin lesions; a minority only have lacked this feature. However, unless a patient is followed carefully, it is possible for a transient or evanescent erythema or insignificant skin lesions to be present and not recorded in the case record.In the patients with malignancy and AD-P, there are no clinical features or laboratory findings unique to the malignancy in contrast to a carcinoma unassociated with AD-P, nor are the clinical features or laboratory findings of AD-P with malignancy different from those without a malignancy, except for one feature. The fatal determination, usually attributed to the malignancy, may be associated with a florid type of dermatomyositis, better described as rapidly progressive dermatomyositis, relentless muscle weakness, and failure of the respiratory and pharyngeal musculature.Approximately 15% of the patients with typical AD-P have an associated malignancy. Sometimes it precedes the symptoms of the collagen-vascular disease by one or more years. In other patients, the reverse is true by a similar period of time. In a few patients with AD-P, two related or chronologically unrelated tumors have appeared. Most reports favor a more than casual relationship, e.g., the recent study by Barnes.³³ Another recent survey casts doubt on this relationship.⁹⁷ We still lack epidemiologic information based upon statistically reliable data of cases with the combined condition, nor are there comprehensive data in this country of malignancy in patients without AD-P, in respect to decades of life, sex, and site and type of tumor.³⁴The cause either of AD-P or most malignancies is unknown. It is easy to speculate positively versus negatively as to whether or not two diseases might have had their initiating pathogenesis at the same time, with clinical symptoms or laboratory findings of one or the other predominating for weeks, months, even years. I tend to favor a concomitant pathogenesis associated with disproportionate development of clinical symptoms. At the moment a virus participating in the pathogenesis seems intriguing, but firm proof is lacking.Females tend to predominate because of the larger number of genital and breast tumors, which is not quite counterbalanced by tumors in lung and gastrointestinal tract, which are more common in the male.³³ In the newly reported cases presented in this review, the males exceeded the females by a ratio of 2:1, probably because a majority of the cases came from army or VA hospitals.The clinical appearance of a malignancy associated with AD-P, in adult life, usually comes after age 40 yr. A few examples of noninvasive tumor with AD-P in the prepuberty years have been reported. One girl age 10 yr had a chromophobe adenoma. The tumor probably was present when symptoms of AD appeared. In the second patient, a boy with hyperplasia of the adrenals, symptoms appeared at age 10 yr. Also, three examples of leukemia have been reported in children. Note should also be made of the combined appearance of AD-P and malignancy in a 17-yr-old male with reticuloendotheliosis. This is borderline between childhood and adulthood. One patient in the previously unreported cases had a probable Wilms tumor removed at age 17 yr and developed systemic symptoms of AD 7 yr later. However, not one of these observations negate the statement that AD-P with malignancy is an adult disease.The treatment of dermatomyositis in patients with an associated malignancy is the same as in those without a malignancy; the same holds for the tumor. Furthermore, one might expect that the combined use of corticosteroids and immunosuppressive drugs, useful in either AD-P or a malignancy, might have an enhanced beneficial effect. There are too few cases reported or observed unreported to make any statements in this category. One patient in my series, E.A., received large doses of corticosteroids and a course of methotrexate, but the course was inevitably regressive.Several of the clinical features frequently observed early in the course of AD-P without an associated malignancy were not reported in the cases in the literature nor seen in the series of new cases observed.¹ This concerns the incidence of arthralgias, sometimes called atypical RA, sclerodermatous changes either in the skin or subcutaneous calcinosis, or Raynaud phenomenon. The incidence of each of these three clinical findings may be assumed to be low in either the reported cases or in the cases described and previously unreported.     

Effect of hydrochlorothiazide therapy on the crystallization of calcium oxalate in urine

The effect of hydrochlorothiazide on the formation of renal stones was evaluated by quantitative assessment of the propensity of urine to undergo crystallization of calcium oxalate. In seven patients with calcium urolithiasis (three with absorptive hypercalciuria, one with renal hypercalciuria, and three with normocalciuric nephrolithiasis), the urinary activity product ratio and formation product ratio of calcium oxalate were measured both on and off therapy with hydrochlorothiazide (50 mg orally twice a day). The activity product ratio (state of saturation with respect to calcium oxalate) decreased in the majority of cases, primarily as a result of the fall in urinary calcium. The formation product ratio (limit of metastability) increased in all cases; the cause of the increase was not readily apparent. Both changes reduced the propensity of urine to undergo crystallization of calcium oxalate, and therefore may account for the clinical improvement reported during thiazide therapy in nephrolithiasis.     

Clinical course of patients following the demonstration of coronary artery spasm by angiography

The clinical course of 25 patients was determined during an average of 2.7 years following the angiographic demonstration of coronary artery spasm (CAS). Seventeen patients received medical treatment after the demonstration of coronary spasm and six patients had cardiac surgery. Twenty-three patients were living and two patients had died at the time of follow-up. Twenty-one of the 23 surviving patients has either no chest pain or markedly reduced symptoms. However, the demonstration of CAS by angiography was associated with a high incidence of subsequent cardiac complications, which included myocardial infarct (four patients), cardiac arrest (four patients), and death (two patients). We concluded from this study that after the demonstration of CAS by angiography: (1) the clinical course was variable, with most patients (21 of 25 patients, 84%) having improvement of symptoms at the time of follow-up; (2) major cardiac complications were frequent (11 of 25 patients, 44%) and; (3) although clinical and coronary angiographic features were of limited use in predicting major cardiac complications, most of the patients who had an uncomplicated course (11 of 14 patients, 79%) had either < 50% fixed coronary artery luminal diameter narrowing (CAN) or coronary artery bypass graft operations, the majority of patients with < 50% fixed CAN (8 of 11 patients, 73%) had no major cardiac complications, and myocardial infarction or death usually occurred during periods of increased angina pectoris.