Isolated cleft mitral valve: a variety of congenital mitral regurgitation identified by 2-dimensional echocardiography

Nine children with isolated cleft mitral valve, aged 1 day to 12 years, were studied. The electrocardiogram showed a normal QRS axis in 5 subjects. Cardiac catheterization was performed in 4 patients and demonstrated severe mitral insufficiency in 3 but failed to clearly demonstrate a cleft mitral valve or gooseneck deformity. The mitral cleft was confirmed at operation in 2 patients. Two-dimensional echocardiography demonstrated a cleft dividing the anterior mitral leaflet into 2 portions in each patient. The mitral anulus was normally positioned and the atrioventricular septum present. Atrial and ventricular septa were intact. Features similar to anatomic studies such as accessory chordae and thickening of the edges of the cleft with increasing age were also seen. Two-dimensional echocardiography is the only method available to reliably diagnose isolated cleft of the mitral valve.     

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.     

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.     

Formation of the very low density lipoprotein and metabolism of [1-14C]-oleate by perfused livers from rats treated with triiodothyronine or propylthiouracil

To gain insight into the mechanism(s) responsible for changes in plasma lipid concentrations in thyroid disease, the metabolism of [1-¹⁴C]-oleate by perfused livers from hypothyroid [propylthiouracil (PTU) treated], euthyroid and hyperthyroid (T₃ treated) rats was compared. Livers from hyperthyroid animals secreted decreased amounts of very low density lipoprotein (VLDL) and incorporated less [1-¹⁴C]-oleate into VLDL triglyceride, but produced more ketone bodies and incorporated more radioactivity from [1-¹⁴C]-oleate into ketones than did livers from euthyroid animals. Conversely, incorporation of [1-¹⁴C]-oleate into perfusate and VLDL triglyceride was increased in livers from hypothyroid animals, while rates of production of ¹⁴CO₂ were diminished. Plasma T₃ concentration was inversely correlated with VLDL triglyceride (r = ?0.70, p < 0.003) and VLDL apoprotein (r = ?0.72, p < 0.008), but directly correlated with ketogenesis (r = 0.71, p < 0.002). Thyroid hormone diminished esterification of fatty acids, and inhibited the hepatic production of triglyceride and secretion of VLDL and stimulated ketogenesis, whereas thyroid hormone deficiency increased hepatic esterification of fatty acid to triglyceride, tended to increase output of the VLDL, and diminished oxidation of fatty acid through the tricarboxylic acid cycle. The surface lipid (phospholipid, cholesterol) to apoprotein ratio was directly correlated with the output of VLDL triglyceride (r = 0.85, p < 0.0005). Furthermore, the lipid composition of the secreted VLDL particle was influenced by thyroid status. Plasma T₃ concentration was directly correlated with the molar ratios of phospholipid/triglyceride (r = 0.73, p < 0.001), cholesterol/triglyceride (r = 0.85, p < 0.0001), and cholesteryl ester/triglyceride (r = 0.80, p < 0.0002) in the VLDL particle. A direct correlation was also demonstrable between the ratio apoprotein/triglyceride and plasma T₃ concentration (r = 0.72, p < 0.0084), while the ratio was inversely correlated with output of VLDL triglyceride (r = ?0.76, p < 0.0038). The percentage of certain of the polymorphic forms of arginine-rich peptide was increased, while apo C-III₃ was decreased in VLDL produced by livers from hypothyroid rats. These data are consistent with the hypothesis that as output of VLDL diminished in the progression from hypothyroidism to hyperthyroidism, the VLDL particle secreted became smaller with a larger ratio of surface to core components.     

Comparison of long-term clinical outcomes of external and internal pancreatic stents in pancreaticoduodenectomy: randomized controlled study

Background

To determine the most appropriate pancreatic drainage method, by investigating differences in 12-month clinical outcomes in patients implanted with external and internal pancreatic stents as an extension to a previous study on short-term outcome.

Thyroid hormones and lipolysis in physically trained rats

In rats a single bout of exercise resulted in increased triiodothyronine (T3), thyroxine (T4), and triiodothyronine/reverse triiodothyronine ($\text{T3}\text{rT3}$) ratio 20 hr after exercise. The effect of norepinephrine on lipolysis in vitro was potentiated.In trained rats no changes were found in T4, T3 or rT3 concentrations. The $\text{T3}\text{rT3}$ ratio as well as basal and stimulated TSH concentrations decreased in comparison with sedentary, freely eating rats. Moderate food restriction to produce a body weight similar to that of trained animals caused no changes in T4, T3 or rT3 concentrations but caused a decrease in $\text{T3}\text{rT3}$ and in TSH levels. Training and moderate food restriction groups were not different. T3 in vitro caused a potentiation of catecholamine induced lipolysis in trained and food-restricted animals. With aging the serum concentration of T3 decreased and that of rT3 increased.Acute and chronic exercise both exert an effect on peripheral hormonal responses of lipolysis, while they have different and opposite effects on thyroid hormone concentrations. Physical training seems to have effects in this regard similar to those of moderate energy intake restriction. The results suggest that changes in peripheral effects of thyroid hormones during training should attract more attention.