Rickets and the pathogenesis of impaired tubular transport of phosphate and other solutes

This discussion concerns the nature of the renal tubular disorders in acquired vitamin D deficiency and in two forms of so-called vitamin D-resistant hereditary rickets (autosomal recessive vitamin D dependency and X-linked hypophosphatemia). The first of the three conditions yields information of use in interpreting the second, and the first two yield information relevant to the third disease; all three are instructive about tubular transport mechanisms in general. Resistance to vitamin D in the autosomal recessive disease probably reflects an inborn error of vitamin D biosynthesis, whereas the primary abnormality in the X-linked condition appears to be an impairment of transepithelial transport of phosphate.     

Occupational carcinogenesis: The Louisville experience with vinyl chloride-associated hepatic angiosarcoma

Hepatic angiosarcoma in man was first associated with exposure to vinyl chloride in Louisville, Kentucky, where it was identified in 10 persons from a single vinyl chloride polymerization plant; clinical manifestations are summarized herein. Following prolonged exposure to vinyl chloride, the onset of this disease is insidious and the clinical picture is that of nonspecific hepatic injury with mildly abnormal biochemical liver test results. Carcinoembryonic antigen and alpha fetoprotein are undetectable. Radionuclide and angiographic studies of liver show characteristic but nondiagnostic abnormalities. A definite diagnosis is usually made only by open liver biopsy. Treatment is unsatisfactory but chemotherapy seems to prolong survival. Average survival from diagnosis is about 12 months. Overt liver failure usually occurs only as a preterminal event and was the major cause of death in all of our patients. Preventive measures are now in effect in the plant. This experience illustrates the importance of the clinician in occupationally-related cancer.     

Gram-negative bacillary endocarditis. Interpretation of the serum bactericial test.

Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.     

Serum thyroglobulin levels predict total body iodine scan findings in patients with treated well-differentiated thyroid carcinoma

Forty-eight consecutive patients with treated thyroid carcinoma were studied with 131-I total body scans and serum thyroglobulin (hTg) levels. Serum hTg levels during thyroxine treatment accurately predicted scan results (chi square = 18.6, p < 0.001). All patients with negative scans (24 patients) had serum hTg levels (< 7 ng/ml whereas in patients with metastatic thyroid cancer (eight patients) they ranged from 11 to 690 ng/ml. In patients with iodine uptake confined to the thyroid bed (16 patients) serum hTg values ranged from 2 to 17 ng/ml. Serum hTg levels rose in patients with negative scans during hypothyroidism or after exogenous TSH suggesting that hTg levels are more sensitive than iodine scans in detecting residual thyroid tissue. Serum hTg levels could replace total body iodine scans in many patients with treated thyroid carcinoma.     

Guillain-Barré syndrome following administration of live measles vaccine.

In a 19 month old girl and a 10 month old girl the Guillain-Barre syndrome developed within a week after they received, respectively, live measles-rubella vaccine and live measles vaccine. The older child was immune to the rubella at the time of vaccination, but both girls demonstrated a primary measles antibody response. Serum obtained during the acute and convalescent stages from the younger child was tested for antibodies against the herpes viruses (herpes simplex, Epstein-Barr virus, cytomegalovirus and varicella-zoster) and found to be negative.     

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.     

Underutilization of Aspirin in Patients With Advanced Colorectal Polyps

BackgroundColorectal cancer is the third-most common cause of cancer deaths in the United States, and advanced colorectal polyps are a major risk factor. Although there are no large-scale individual trials designed a priori to test the hypothesis, in meta-analyses of trials in primary prevention of cardiovascular disease, aspirin reduces risk of colorectal cancer. The US Preventive Services Task Force used a microsimulation model, including baseline risk factors, and concluded that aspirin reduces risk of colorectal cancer by 40%. Their guidelines suggest that without a specific contraindication, clinicians should routinely prescribe aspirin to patients with advanced colorectal polyps.MethodsWritten informed consent was obtained, and brief telephone interviews were conducted by trained interviewers for 84 men and women with biopsy-proven advanced colorectal polyps from 55 clinical practices.ResultsOf the 84, 39 (46.4%) were men. The mean age was 66 with a range from 41 to 91 years. Among the 84, 36 (42.9%) reported taking aspirin.ConclusionsThese data suggest underutilization of aspirin by patients with advanced colorectal polyps. These data pose major challenges that require multifactorial approaches by clinicians and their patients, which include therapeutic lifestyle changes, adjunctive drug therapies, and screening. Lifestyle changes include treating overweight status and obesity and engaging in regular physical activity; adjunctive drug therapies include aspirin. These multifactorial approaches will be necessary to achieve the most good for the most patients with regard to prevention, as well as, early diagnosis and treatment of colorectal cancer in patients with advanced colorectal polyps.     

Bilateral nonfistulous congenital coronary arterial aneurysms

A 15 year old boy collapsed and died after participating in a basketball game. Autopsy revealed bilateral congenital coronary arterial aneurysms. The diagnosis was made post mortem but, retrospectively, might have been suspected during life, even before angiography. The clues to the correct diagnosis were chest pain, a systolic and diastolic murmur and a mass on the right heart border in the chest roentgenogram.     

Left ventricular function during isometric exercise (handgrip): significance of an atrial gallop (S4)

The clinical significance of an atrial (S₄) gallop remains controversial. The present study was undertaken to investigate whether the development of an atrial gallop (S₄) during stress correlated more closely with an abnormal left ventricular function than the presence of an S₄ at rest. Left ventricular function was assessed by relating changes in SWI to left ventricular enddiastolic pressure during isometric exercise at 25 per cent and 50 per cent of a maximum voluntary handgrip contraction. A phonocardiogram was recorded continuously during the procedure.Six patients with no S₄ at rest or during isometric exercise all had normal ventricular function curves. Six patients had no atrial gallop at rest but developed an S₄ during isometric exercise. In this group, all but one patient had an abnormal left ventricular function curve. Finally, nine patients had an S₄ at rest as well as during isometric exercise. Seven of these patients had a normal left ventricular function curve.The results suggest that the development of an atrial gallop during isometric stress may be a more reliable indicator of left ventricular dysfunction than the presence of an S₄ at rest. Therefore, isometric exercise can be employed as a bedside procedure for evaluation of left ventricular function.     

Bilateral arteriosclerotic coronary arterial aneurysms successfully treated with saphenous vein bypass grafting

A man with ischemic heart disease was discovered to have bilateral coronary arterial aneurysms that were successfully treated with saphenous vein grafting. Preoperative coronary arteriograms revealed a tight luminal stenosis at the proximal end of the large aneurysm in the left anterior descending artery, suggesting poststenotic dilatation as an etiologic or contributing factor. The right coronary artery was totally occluded proximally, but was noted to be aneurysmal at operation. This is the 14th published case of nonfistulous coronary arterial aneurysm diagnosed in vivo, and the first associated with proximal luminal stenosis.     

Crystal deposition disease

Calcium pyrophosphate dihydrate crystal deposition disease and HA crystal deposition disease are two common disorders that may come to the attention of a physician because of a variety of clinical symptomatology patterns. In CPPD crystal deposition disease, characteristic radiologic features include articular and periarticular calcification and an arthropathy consisting of joint space narrowing, bone sclerosis, often prominent subchondral cyst formation, occasional severe and progressive destructive bone changes, and variable osteophyte formation. These findings are often seen in a characteristic distribution with involvement of non-weight-bearing as well as weight-bearing joints and with involvement of distinctive intraarticular sites such as the patellofemoral compartment of the knee and the radiocarpal compartment of the wrist. In HA crystal deposition disease, characteristic radiologic features consist of calcific tendinitis and periarthritis as well as a more recently described arthropathy. Awareness of the distinctive roentgenographic appearance of these two diseases should allow a specific diagnosis to be made, and an understanding of their pathologic features should aid in appropriate therapy and guide future investigation of possible etiologic factors.     

The significance of mitral valve prolapse in middle-aged and elderly men.

The clinical, roentgenographic, phonocardiographic, ECG, and echocardiographic data were evaluated in 40 consecutive middle-aged and elderly male patients with echocardiographically detectable systolic prolapse of mitral valve leaflets. Prolapse was present during more than half of systole in 31 patients and was holosystolic in six patients. In most instances, both leaflets prolapsed during systole. The closing velocity and excursion of the anterior leaflet were frequently increased particularly in association with evidence of mitral insufficiency. A majority of the patients had cardiac symptomatology. Moreover, roentgenographic and/or ECG evidence of cardiac enlargement or hypertrophy was evident in 45 percent of patients with mitral valve prolapse.     

Initial and delayed right ventricular thallium-201 rest-imaging following dipyridamole-induced coronary vasodilation: Relationship to right coronary artery pathoanatomy

The relationship of coronary anatomy to right ventricular (RV) appearance on serial thallium-201 myocardial imaging (TI) following dipyridamole (DP)-induced coronary vasodilation was examined in 71 consecutive patients undergoing coronary angiography for the evaluation of chest pain. Transient defects of the RV were found in 18 patients. All 18 had significant (≥ 50%) stenosis of the proximal right coronary artery (RCA). Nonvisualization of RV activity occurred in 13 patients. Six of these 13 (46%) had proximal RCA disease (p < 0.05 compared to transient defects). Normal RV appearance was seen in 40 patients, of whom only six (15%) had proximal RCA disease (p < 0.001 compared to transient defects). RV appearance was not affected by left anterior descending or left circumflex artery disease or by the thallium-201 uptake in the left ventricle. Thus with serial (initial and delayed) TI following DP (1) a transient RV defect appears to indicate significant proximal RCA disease; (2) normal RV appearance suggests the absence of proximal RCA disease; and (3) however, nonvisualization of the RV appears to be nondiagnostic.     

Precordial honk due to tricuspid regurgitation

A systolic honk developed in a woman with idiopathic cardiomyopathy and congestive heart failure. The honk was present only during deep inspiration, disappeared as her cardiovascular status improved, but recurred when her cardiovascular function declined. Further investigation indicated that the honk was the result of tricuspid regurgitation.