Ectopic production of lipotropin by cancer.

Lipotropin (LPH) has been evaluated as a potential tumor marker using a sensitive beta melanocyte-stimulating hormone (beta MSH) radioimmunoassay. All 79 acetic acid extracts of carcinomas of lung, colon, stomach, esophagus and breast contained LPH in concentrations greater than blood; 61 of 79 extracts contained LPH in larger amounts than control tissues from patients without cancer. In a blind prospective study, plasma LPH was quantified in 107 patients admitted for work-up because of an abnormality on a chest roentgenogram. Thirty-one of 33 patients subsequently diagnosed as having benign lesions had plasma LPH within the 95 per cent confidence limits of normal subjects whereas 28 (36 per cent) of the 74 patients subsequently diagnosed histologically as having primary lung carcinoma had elevated levels. In control studies, 13 of 100 patients with chronic obstructive pulmonary disease had elevated plasma LPH levels; three of the 13 with elevated levels and four with normal levels have been diagnosed, during the two years of follow-up, as having lung carcinoma. In control studies of 23 patients with granulomatous lung disease, 22 had normal levels of LPH. In those with carcinoma of the colon elevated plasma LPH levels were observed in two of 21 untreated patients and in 11 of 61 patients receiving noncurative chemotherapy. Elevated plasma LPH levels were also observed in 10 of 59 patients with breast cancer, eight of 28 with pancreatic cancer, eight of 22 with gastric or esophageal cancer, six of 16 with renal cancer, four of eight with prostatic cancer, one of seven with cervical cancer and one of six with ovarian cancer. We conclude, an elevated LPH level is frequently observed in blood and tumor tissue from patients with various types of carcinoma.     

Sepsis associated with decubitus ulcers

Among 21 patients with sepsis attributed solely to decubitus ulcers, bacteremia was documented in 16 (76 per cent). Bacteremia involved obligate anaerobes in eight patients (50 per cent) and was polymicrobial in eight patients (50 per cent). Twelve of 17 patients who received appropriate antibiotics had persistent bacteremia; in five patients, bacteremia was terminated only after surgical debridement. Ten of these 21 patients died, eight despite appropriate antibiotics. Among 14 patients who underwent surgical debridement, only four patients died. Surgical debridement and antibiotics effective against aerobic as well as anaerobic bacteria are both important in the treatment of this serious complication.     

Candida peritonitis: Report of 22 cases and review of the english literature

Thirty-one patients with Candida isolated from peritoneal fluid were examined. Twenty-two were considered to have Candida peritonitis. The data on these 22 patients, plus 12 additional patients described in the literature, were reviewed. This infection was observed as a complication of peritoneal dialysis, gastrointestinal surgery or perforation of an abdominal viscus. Recent antibiotic administration seemed to be an important predisposing factor. The disease usually remained localized intra-abdominally, although disseminated candidiasis was also noted in three cases. Clinically significant infection could be differentiated from peritoneal contamination with Candida by the presence and persistence of fever, peritoneal signs, peripheral leukocytosis, positive peritoneal cultures for Candida, abnormal films of the abdomen and purulent ascitic fluid. Surgical interventions and removal of infected peritoneal fluid were the cornerstones of therapy. Short-term, low-dose systemic and/or intraperitoneally administered amphotericin B appeared promising in the treatment of unremitting infection. Mortality in treated patients was low and was comparable to that in patients with bacterial peritonitis.     

Serious infections in adults due to group B streptococci: Clinical and serotypic characterization

Serious infections in adults due to group B streptococci have been infrequently reported. We describe 24 such patients. Bacteremic pyelonephritis, pneumonitis and endometritis were the most common clinical syndromes observed. Group B streptococcal infections tended to occur in patients with underlying illnesses, particularly genitourinary disorders and diabetes mellitus. Mortality was surprisingly low (8 per cent). Type III was the serotype most commonly isolated, and there was no significant correlation of different serotypes with specific organ-system involvement. Group B streptococcal isolates from these patients were uniformly sensitive to penicillin, ampicillin, cephalothin, chloramphenicol, erythromycin and clindamycin; all were highly resistant to kanamycin. Eighty-seven per cent were resistant to tetracycline. Although consistently sensitive to penicillin, the minimal inhibitory concentrations were significantly higher for group B than group A streptococci (p < 0.0005).     

Bacteroidaceae bacteremia with disseminated intravascular coagulation

Three patients with Bacteroidaceae bacteremia and disseminated intravascular coagulation (DIC) are described. The association of DIC with this anaerobic infection has been infrequently reported. Septic shock due to Bacteroidaceae appears to involve endotoxin as in aerobic gram-negative bacillary sepsis. Similarly, endotoxin may be the trigger mechanism for initiating DIC in both aerobic and anaerobic gram-negative bacillary sepsis.     

Role of anaerobic bacteria in subdural empyema: Report of four cases and review of 327 cases from the english literature

Anaerobic bacteria were isolated from the subdural space in all four cases of subdural empyema encountered over a $\text{2}\text{1}\text{2}$ year period. Only one aerobe was isolated in these cases. The bacteriology of subdural empyema was further analyzed from a review of 327 cases reported in the English literature. Anaerobes accounted for 12 per cent of 234 cases. In addition, 27 per cent of cases were reportedly “sterile.” These data support our finding that anaerobic bacteria may play a far more important role in subdural empyema than was previously appreciated.     

Necrotizing pneumonia and empyema due to Clostridium perfringens. Report of a case and review of the literature.

Clostridia are rare causes of pleuropulmonary infections in the absence of penetrating chest injuries; only 10 previous cases have been reported from civilian practice. An additional case of a rapidly progressive, necrotizing pneumonia and empyema is reported. Clostridial pneumonia is more likely to occur in patients with underlying pleuropulmonary disease. Unlike clostridial myonecrosis, it is rarely associated with toxemia; its mortality rate is comparable to that of nonclostridial pleuropulmonary infections. Appropriate antimicrobial therapy with surgical drainage of the empyema is the treatment of choice. Among the cases reviewed, an iatrogenic cause of infection involving an invasive procedure into the pleural cavity could be identified in seven of 11 cases. Aspiration of oropharyngeal contents was the likely route of infection in three other cases. In the remaining case, bacteremic seeding of the pleural cavity was the most probable mode of infection.     

Effect of uremia on incorporation of acetate into rat plasma and tissue lipids

Experimental uremia was induced in rats by means of bilateral nephrectomy or bilateral ureteral ligation. Incorporation of acetate-1-¹⁴C into expired ¹⁴CO₂ and into plasma and tissue lipids was studied immediately after surgery and at 48 hr, when the rats were uremic. In rats studied immediately after surgery, bilateral nephrectomy, but not bilateral ureteral ligation, significantly decreased the conversion of acetate-1-¹⁴C metabolism to ¹⁴CO₂ was not significantly altered in either group. Plasma triglyceride concentrations and ¹⁴C-acetate incorporation into triglycerides were increased in the 48-hr uremic groups, but plasma and liver triglyceride specific radioactivities were not significantly altered. Plasma free fatty acid concentrations and incorporation of acetate into free fatty acids were lower in the 48-hr uremic groups than in controls. Plasma cholesterol concentrations and specific radioactivities were increased in these uremic groups, as were liver free cholesterol specific activities. These results suggest that increased triglyceride and cholesterol synthesis from acetate may contribute to the hypertriglyceridemia and hypercholesterolemia observed in uremic rats.     

Serious infections due to group G streptoccocci: Report of 15 cases with in vitro-in vivo correlations

Serious infections due to group G streptococci have been infrequently reported. Fifteen such cases are described. Endovascular infection, particularly endocarditis, and septic arthritis were the most common clinical syndromes observed. Despite exquisite in vitro sensitivity of group G streptococci to penicillin G, the in vivo clinical response was disappointing in six of nine patients with either endocarditis or septic arthritis. The group G streptococcal isolates from the patients in this study were uniformly sensitive to the inhibitory and killing action of penicillin G, ampicillin, cefotaxime, cephalothin, cefoxitin, and vancomycin. In contrast, clindamycin, erythromycin, and chloramphenicol had relatively poor bactericidal activity against these strains, including several “tolerant” strains. Timed-kill studies with penicillin G revealed impaired killing of group G streptococci at in vitro conditions of high inocula and stationary growth phases. This may partially explain the poor clinical responses in cases of group G streptococcal endocarditis.     

Metabolic factors in the control of energy stores

We have examined some of the factors involved in the control of food intake and integrated the data using methods of systems analysis from biomedical engineering. The central hypothesis is that energy stored in the body is a regulated variable. Alterations in the quantity of stored calories initiates changes designed to restore the store of calories to its original level. These responses are both short-term and long-term in nature. They involve integrating data on the quantities of protein, carbohydrate, and lipid stores in the body, probably through such feedback signals as amino acids, glucose, glycerol, and free fatty acids.     

Spontaneous and experimental human obesity: effects of diet and adipose cell size on lipolysis and lipogenesis.

We examined the hypothesis that adipose tissue from lean and obese subjects might provide different internal signals in response to changes in stored calories. Adipose tissue was obtained before weight gain in nonobese subjects and after weight gain in five of the same individuals. Adipose tissue was removed before and after weight loss in seven obese patients. Two isocaloric diets were fed to both groups for 2–3 wk each; one diet was high in carbohydrate, and the other contained a low carbohydrate content. Incorporation of radioactivity from pyruvate into fatty acids in vitro was lower with the low-carbohydrate diet than with the high-carbohydrate diet. It was also significantly reduced after weight gain in the nonobese subjects but was not significantly altered in the obese. There were no significant effects of diet or weight gain on the enzymatic activities in the nonobese subjects. The large fat cells from both groups of subjects had an increased sensitivity to the lipolytic effects of isoproterenol as compared with the smaller fat cells. Variations in carbohydrate intake had no effect on the lipolytic response to isoproterenol. The dose response of fat cells to dibutyryl-cyclic-3′,5′-AMP did not change after weight gain in the nonobese males, but was significantly reduced on both levels of carbohydrate after weight loss in the obese (i.e., when studying the smaller fat cells). These studies suggest that differences in the metabolism of adipose tissue between obese and lean subjects persist when differences in the size of fat cells and caloric intake are controlled.     

Genetic obesity in rats. II. The effect of food restriction on the metabolism of adipose tissue

The metabolism of adipose tissue from genetically obese rats (Fatty) and lean animals was studied in two experiments. In the first experiment, food intake was regulated at three levels in Fatty rats. One group ate ad lib., a second group was pair fed to lean controls, and the third group received two-thirds of the food eaten by the lean rats. Serum insulin was reduced by restricting food intake. Fat cells were largest in the ad lib.-fed Fatties and smallest in the lean rats. Lipolysis, as measured by glycerol release, was comparable in lean and Fatty rats. Several lipolytic drugs were as effective in fat from the obese as the lean animals. Metabolism of ¹⁴C-glucose with or without insulin was reduced in the tissue from Fatty rats and was not corrected by restricting food intake. In the second experiment, lipolysis and lipogenesis were studied by serial biopsies during starvation-induced weight loss. Rats were allowed to eat for 3 days before each biopsy. Reduction of fat cells to the same size as normals did not restore lipogenesis or lipolysis to normal. Reesterification of fatty acids remained high in all experiments with tissues from Fatty rats.     

Genetic obesity in rats. I. The effects of food restriction on body composition and hypothalamic function

The effect of controlled food intake was compared in genetically obese rats of the “Fatty” (Zucker) strain and lean animals. One group of six Fatty rats were fed ad lib., another six were pair fed to lean controls, and a third group were fed two-thirds the intake of lean animals. All rats were trained to eat in 6 hr each day. Weight gain was abolished in the Fatties fed a restricted diet, but these animals did not reduce their body fat. Fatty rats fed ad lib. or pair fed were more efficient than lean rats in storing calories as fat. Pituitary, ovary, and uterus were significantly smaller in the Fatty rats. Limiting food intake did not restore these organ weights toward normal. Among the three groups of Fatty rats, body weight was positively correlated with the weight of the adrenal, pituitary, ovary, uterus, and liver. Urine volume was higher in the ad-lib. and pair-fed Fatties than in the lean animals but restriction of food intake reduced urine output below controls. The uptake of ¹²⁵I by the thyroid was significantly reduced in all groups of Fatties, but thyroid weights did not differ. Serum FSH was higher in the restricted Fatties but LH was not. These studies suggest that previously observed differences in hypothalamic endocrine function do not result from hyperphagia.     

ProACTH: use for early detection of lung cancer.

ProACTH was identified by radioimmunoassay and column chromatography in extracts of 38 lung carcinomas. One hundred patients were evaluated because of abnormalities on chest roentgenograms; 53 (72 per cent) of 74 with lung cancers had increased plasma ACTH immunoreactivity; all 26 with benign abnormalities had normal ACTH. Of 101 patients with obstructive lung disease, five of 20 with elevated plasma ACTH levels and two of 81 with normal plasma ACTH levels had lung cancer within two years. In three of 31 patients with granulomatous lung disease plasma ACTH levels were elevated during acute exacerbation of the disease, but they returned to normal after recovery. We conclude that plasma ACTH immunoreactivity is frequently increased early in the course of lung carcinoma.     

Some respiratory and metabolic effects of exercise in moderately obese men.

The effects of varying levels of exercise on oxygen uptake, CO2 production, blood pressure, arterial blood gasses, and arterial concentrations of glucose, insulin, and growth hormone were examined in ten normal weight and ten moderately overweight young men. At comparable external work loads with a bicycle ergometer, the lean men required less oxygen than the obese men. When oxygen uptakes were matched during exercise on a treadmill, the lean men were walking on a steeper grade or at a higher rate than the obese men. The efficiency of exercise as assessed by the relation between oxygen uptake and work did not differ between the two groups. Blood pressure rose more in the obese during exercise than in the lean. The fall in lactate and rise in bicarbonate was of greater magnitude during cycle ergometry than during treadmill exercise. Obese and lean men, however, showed similar changes. With each level of exercise, there was a fall in arterial insulin levels, but the concentrations in the blood of overweight men always remained significantly above that of the normal men. Growth hormones tended to be higher in the normal weight men, but the differences were usually not significant, and there was no significant rise with exercise in either group until the highest levels of work were achieved. Glucose concentrations tended to be higher in the obese men, but fell to constant levels in both groups during exercise. Blood pressure rose to a greater extent in the overweight men during exercise.     

The incidence and significance of contraction bands in endomyocardial biopsies from normal human hearts

With increasing use of myocardial biopsy as a diagnostic tool, different criteria of pathology have evolved from tissues obtained from biopsy and postmorten specimens. We reported that contraction bands may be produced artifactually by the biopsy procedure in the fresh, but not the postmorten or perfused fixed normal rat and dog hearts. Contraction bands have been used as a morphological index of pathology. From 12 normal human transplant donors endomyocardial biopsy samples were obtained from the right ventricle, were fixed immediately and then processed for light and electron microscopy. Contraction bands were quantitated by assigning 0, 1, 2, and 3 to represent 0, 1 to 5, 6 to 10, and 11 or more cells per square millimeter with contraction bands. A large number of contraction bands were present in 11 out of 12 hearts; 3rd, 2nd, 1st, and zero degrees of contraction bands were present in 11, 0, 1, and 0 samples, respectively. We conclude that contraction bands may be produced artifactually in normally human hearts, and based upon the rat and dog study, that the determinants of contraction band formation are activation of the contractile machinery by the biopsy procedure, together with sarcomeres capable of hypercontraction because their shortening is unopposed.Furthermore, contraction bands may be considered a morphological index of pathology in tissue obtained postmortem and after perfusion fixation, but not in tissue obtained from biopsies.     

Focal renal cortical necrosis associated with zomepirac

Anaphylactoid shock, disseminated intravascular coagulation, and anuric renal failure requiring dialysis occurred in a patient receiving zomepirac sodium for toothache. Although renal function showed gradual improvement after seven days of anuria, the recovery was slow and incomplete. Renal biopsy three weeks after the onset of renal failure revealed evidence of focal renal cortical necrosis. Association of zomepirac administration with renal cortical necrosis is not known to have been previously demonstrated. This observation adds another dimension to the previously reported renal complications of nonsteroidal anti-inflammatory agents, especially zomepirac. The proportions of lymphocyte subsets, as defined with monoclonal antibodies, and the proliferative response to mitogens were normal. The patient's lymphocytes showed no proliferative response to zomepirac. Serum complement components and immunoglobulin levels were within normal limits, and radioallergosorbent testing gave negative results. The mechanism of anaphylactoid reaction to zomepirac in this case, therefore, remains unclear.