Decreases in serum high-density-lipoprotein cholesterol and total cholesterol resulting from naturally produced and recombinant DNA-derived leukocyte interferons

A three-phase study was conducted to examine the effect of leukocyte interferon administration on serum high-density-lipoprotein (HDL) cholesterol and total cholesterol levels. In the initial phase, human leukocyte interferon decreased HDL cholesterol (P less than 0.05) and total cholesterol (P less than 0.05) levels in patients with breast carcinoma. Decreases began with initiation of the interferon administration, were sustained throughout the period of treatment, and increased toward pretreatment values with discontinuation of interferon. In the second phase of the study, in neither of two comparison groups of women receiving cytotoxic chemotherapy, excluding interferon, did any similar decrease in HDL cholesterol occur. In a third comparison group of women being treated for metastatic breast carcinoma, a predicted and significant (P less than 0.01) drop in HDL cholesterol level without a concomitant lowering of total cholesterol level occurred immediately following the initiation of androgen therapy. To confirm that the observed cholesterol level decreases were associated with interferon rather than a contaminant thereof, analyses were also carried out on samples from a study utilizing interferon rather than a contaminant thereof, analyses were also carried out on samples from a study utilizing interferon produced by recombinant DNA techniques and purified to homogeneity. A similar decrease in HDL cholesterol (P less than 0.05) and total cholesterol (P less than 0.01) was observed. A definite relationship therefore appears to exist between the administration of human leukocyte interferon and decreased plasma levels of HDL cholesterol and total cholesterol.     

Pancreas fistula risk prediction: implications for hospital costs and payments

Background

As payment models evolve, disease-specific risk stratification may impact patient selection and financial outcomes. This study sought to determine whether a validated clinical risk score for post-operative pancreatic fistula (POPF) could predict hospital costs, payments, and profit margins.

Evidence for phosphorylation of pancreatic islet pyruvate kinase

Rabbit pancreatic islet cytosol catalyzes the calcium-activated phosphorylation by [gamma 32P]ATP of a protein with a molecular weight of 57,000 that is precipitated with antipyruvate kinase antibodies. We were unable to demonstrate that phosphorylation in the presence of calcium or cAMP had any immediate effect on rat pancreatic islet pyruvate kinase activity. This finding is consistent with our inability to confirm the finding of others that pancreatic islets contain phosphoenolpyruvate carboxykinase activity (Diabetes, 34:246, 1985). Since the carboxykinase catalyzes phosphoenolpyruvate formation and pyruvate kinase catalyzes essentially the opposite reaction, if the carboxykinase were present in the beta cell, pyruvate kinase would need to be inhibited to prevent recycling of phosphoenolpyruvate.     

Infections caused by aterial catheters used for hemodynamic monitoring

Utilizing a semiquantitative technique for culturing vascular catheters, we prospectively studied the risk and profile of infection caused by arterial catheters used for hemodynamic monitoring in 95 patients with a high risk of nosocomial infection. Of 130 catheters, 23 (18 per cent) produced local infection (larger than or equal to 15 colonies on semi-quantitative culture) and five septicemia (4 per cent). Sixteen of the 23 local infections and all septicemias occurred with catheter placements exceeding four days (p less than 0.001). Other factors associated with an increased risk of infection included insertion by surgical cut-down rather than percutaneously (ninefold increased rate of bacteremia, p = 0.008) and the presence of local inflammation (12-fold increase, p = 0.009). Systemic antimicrobial therapy (given to 80 per cent of the entire group and to four of the five with septicemia) did not protect against catheter-related infection but may account for the predominance of enterococci, Candida and gram-negative bacilli in these infections. Twelve per cent of all nosocomial bacteremias occurring in this critical care unit population originated from an arterial catheter. Indwelling arterial catheters pose a significant risk of bacteremic infection to ctirically ill patients. The percutaneous mode of placement is preferred; when prolonged arterial cannulation is required, the site should be rotated every four days. Local pain or inflammation, or clinical signs of sepsis without an obvious source should prompt removal and culture of the catheter.     

Glucagon stimulation of phenylalanine metabolism. The effects of acute and chronic glucagon treatment

The effects of acute and chronic glucagon treatment on phenylalanine metabolism in vivo in the rat have been investigated. A single, large dose of glucagon (2 mg/kg, i.p.) increased metabolism of a large load of phenylalanine (1.27 g/kg) via hydroxylation and transamination. The increased metabolism was associated with increased activities of hepatic phenylalanine:pyruvate aminotransferase, tyrosine aminotransferase and phenylalanine hydroxylase. In rats administered this amount of phenylalanine, the p-hydroxyphenylpyruvate dioxygenase reaction was apparently rate limiting, as indicated by increased urinary excretion of p-hydroxyphenylpyruvate and p-hydroxyphenyllactate, in addition to urinary excretion of phenylpyruvate and phenyllactate. Chronic glucagon treatment (1.25 mg/kg every 12 hr for 8 days) increased oxidation of the large phenylalanine load and urinary excretion of phenylpyruvate and phenyllactate but not p-hydroxyphenylpyruvate or p-hydroxyphenyllactate. The increased excretion of phenylpyruvate and phenyllactate was associated with an increase in hepatic phenylalanine: pyruvate aminotransferase activity. The absence of p-hydroxyphenylpyruvate in the urine and the increased oxidation of phenylalanine imply that, in rats administered glucagon chronically, flux of p-hydroxyphenylpyruvate through the p-hydroxyphenylpyruvate dioxygenase reaction was increased. A kinetic assay for phenylalanine hydroxylase based on measurement of oxygen consumption in described.     

Nosocomial bacteremia: An epidemiologic overview

Each year nosocomial bacteremia develops in approximately 194,000 patients in U.S. hospitals ($\text{5}\text{1,000}$); 75,000 die. These infections portend $.28 to $.86 billion added costs of health care. Most nosocomial bacteremias occur endemically and are secondary bacteremias, caused by postoperative wound or intra-abdominal infections, urinary tract infections or pneumonia; primary bacteremias most frequently originate from intravascular devices, but the source is unrecognized. Between 1965 and 1978, 97 epidemics of nosocomial bacteremia, including 11 of “pseudobacteremia”, were reported. In contrast to endemic bacteremias, 78 percent of the epidemics involved primary bacteremias: 33 outbreaks stemmed from infusion therapy in some form, including seven epidemics traced to a contaminated commercial product. Two thirds of endemic nosocomial bacteremias and 79 percent of epidemics are caused by aerobic gram-negative bacilli. Pseudomonas cepacia, Pseudomonas maltophilia, Flavobacterium and Enterobacter agglomerans rarely cause endemic bacteremia and when encountered often signal an epidemic. Whereas predisposing host conditions greatly increase the risk of bacteremia endemically, nosocomial epidemics occur mainly in immunocompetent patients and are related to what therapeutic measures have been taken: segregation in a special care unit (58 percent of outbreaks) or exposure to infusion therapy or other invasive procedures involving the bloodstream (65 percent). At present only about one fourth of endemic nosocomial bacteremias are in theory preventable by more consistent application of existent knowledge of asepsis. The potential for prevention seems greatest for epidemic bacteremias, most of which are related to exposure to invasive devices, to a common source of contamination, or both.     

Endemic rate of fluid contamination and related septicemia in arterial pressure monitoring

Contamination of the fluid within intra-arterial infusions used for hemodynamic monitoring has produced epidemic bacteremias, but little data exist on endemic rates of contamination and related septicemia. We prospectively studied 102 intra-arterial infusions used in 56 high-risk patients who required prolonged monitoring. During the study, administration sets were changed every 48 hours, but transducer chamber-domes and continuous flow devices were used until the intra-arterial infusion was discontinued. Cultures were obtained from the transducer-transducer chamber-dome interface and of fluid in the transducer chamber-dome of the 102 intra-arterial infusions; 12 (11.8 percent) showed contamination of transducer chamber-dome fluid, in 8 cases (7.8 percent) associated with concordant bacteremia. In each bacteremia, transducer chamber-dome fluid contained 1 to > 10⁵ (median, 10⁴) cfu/ml. Four bacteremias are considered definitely related and four, possibly related, to the intra-arterial infusion. In all 12 contaminated intra-arterial infusions and with all eight bacteremias, the transducer chamber-dome had been used for more than two days (P = 0.006). No concordant contamination of transducer-transducer chamber-dome interfaces was identified. (1) Intra-arterial infusions for pressure monitoring cause sporadic septicemias endemically. (2) With prolonged monitoring, transducer chamber-domes and continuous flow devices should be replaced at periodic intervals, ideally with the administration set, every 48 hours; since implementing this policy, only three contaminated intra-arterial infusions and no related septicemias have been detected in 53 intra-arterial infusions monitored over four months (P = 0.02).     

Renal manifestations of the staphylococcal toxic-shock syndrome

Twenty-three women of ages 13 to 44 years were hospitalized with illnesses fulfilling the criteria of the case definition for the toxic-shock syndrome (TSS) associated with coagulase-positive staphylococci. Disease onset occurred during menses in 22, and all were oliguric when admitted. Prolonged hypotension and a reduced central venous pressure were common features. Measurements of urine volume and creatinine clearance in eight patients identified two types of acute renal failure, oliguric and nonoliguric, and prerenal azotemia related to intravascular volume depletion. Urinary sodium excretion and measurement of the renal index (U_Na divided by $\text{U}\text{P}{}_{\mathrm{Cr}}$) provided further support for the presence of both prerenal and intrinsic renal failure. Hemodialysis was required in one patient in whom findings on renal nuclide scan were consistent with acute tubular necrosis. Pyuria was frequent, but proteinuria and more than five erythrocytes per high-power field were infrequent.Other features included initial hyponatremia and the combination of hypoproteinemia, hypoalbuminemia, hypocalcemia and hypophosphatemia of several days' duration. The hypoalbuminemia was believed to be due to exudation of protein from the intra to the extravascular space. The hypocalcemia was probably related to the hypoalbuminemia. The pathogenesis of hypophosphatemia in the presence of acute renal failure is unclear.Following the intravenous administration of colloids, fluids and, in seven patients, dopamine, all recovered from the acute illness.     

Valine metabolism in vivo: Effects of high dietary levels of leucine and isoleucine

The short-term effects of feeding rats high levels of L-leucine or L-isoleucine on valine metabolism in vivo have been investigated. Consumption of a low-protein diet containing an additional 5% of leucine resulted in depression within one hour of the plasma concentrations of isoleucine, valine, α-keto-β-methylvalerate, and α-ketoisovalerate. Concurrently with these changes in blood branched-chain amino acids and branched-chain ketoacids was a rapid increase (51%) in whole-body L-[1-¹⁴C]-valine oxidation. Studies with intragastrically administered leucine solutions indicated that the depressions in blood concentrations of valine occurred over the same time period as the stimulation in valine oxidation. In contrast, consumption of a low-protein diet containing an additional 5% of isoleucine had no significant effect on the plasma concentrations of leucine, valine, and α-ketoisocaproate; a significant (P < 0.01) depression in the plasma concentration of α-ketoisovalerate was observed three hours after the diet containing excess isoleucine had been consumed. In contrast to the results obtained with excess leucine, consumption of excess isoleucine had no significant effect on the rate of valine oxidation in vivo. As part of an effort to explain the leucine-induced depletion of plasma valine and stimulation of valine oxidation, liver and muscle branched-chain aminotransferase and liver branched-chain ketoacid dehydrogenase activities were measured. Consumption of excess leucine had no significant effect on either muscle or liver aminotransferase activities, but was associated with a greater than two-fold increase in hepatic dehydrogenase activity. Also, consumption of excess leucine resulted in an increase in the percentage of active dehydrogenase from 43 ± 5% to 80 ± 4%.     

Comparison of supervised and unsupervised exercise training after coronary bypass surgery

Functional capacity and cardiovascular responses to serial graded treadmill testing (GXT) were compared in 180 patients who performed prescribed unsupervised exercise and 24 patients who were referred for supervised exercise after coronary artery bypass surgery (CABS). The groups were men similar in age range, number of bypass grafts, preoperative left ventricular impairment and number of days hospitalized. All patients received similar predischarge exercise monitoring and began a progressive home walking or cycling program. Initial GXT (T1) was performed 44 ± 9 days postoperatively. Both groups were instructed to continue prescribed exercise at 75 to 85% maximal heart rate (HR) for 30 to 40 minutes 3 days (supervised) or 5 days (unsupervised) per week. The second GXT (T2) was performed 115 ± 27 days after CABS. In each group there were significant (p <0.01) increases in exercise capacity and HR from T1 to T2. However, there were no significant differences in maximal exercise capacity and HR between groups at T1 or T2. Improvement in functional capacity was not influenced by therapeutic β blockade. These findings indicate that prescribed unsupervised exercise can be performed safely and results in similar functional improvements compared with supervised exercise after uncomplicated CABS.     

Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women

The relationship of body fat distribution to metabolic profiles was determined in 80 healthy premenopausal white women of a wide range of obesity levels [percentage of ideal body weight (% IBW) 92-251]. Distribution of fat between the upper and lower body was assessed from the waist/hips girth ratio (WHR), which varied from 0.64 to 1.02. In 23 women, in vivo insulin sensitivity was also determined from the steady-state plasma glucose (SSPG) level at comparable insulin levels of approximately 100 microU/mL attained by the intravenous infusion of somatostatin, glucose, and insulin. Increasing WHR was accompanied by progressively increasing fasting plasma insulin levels (r = 0.47, P less than 0.001), insulin and glucose areas after glucose challenge (r = 0.53, P less than 0.001; r = 0.50, P less than 0.001, respectively) and fasting plasma triglyceride concentrations (r = 0.48, P less than 0.001). Obesity level was similarly correlated with these metabolic indices. Partial and multiple regression analysis and analysis of variance with a linear contrast model revealed that the effects of body fat topography were independent of, and additive to, those of obesity level. Within obese subjects alone (%IBW: 130), %IBW had no predictive value, but WHR remained a significant predictor of plasma glucose, insulin, and triglyceride concentrations. The WHR also correlated with the plasma cholesterol level, but this association was largely dependent on its relationship to %IBW. Both WHR and %IBW correlated with the insulin resistance index, SSPG (r = 0.60, P less than 0.01; r = 0.61, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hydroxychloroquine in the treatment of rheumatoid arthritis

One hundred eight patients with rheumatoid arthritis received hydroxychloroquine for six to 24 months and were studied retrospectively to examine long-term efficacy and predictors of a favorable response to the drug. Response was classified in terms of reduction of active joint count and morning stiffness. Thirteen patients (12 percent) showed a complete remission. Fifteen patients (14 percent) had a 75 percent or greater response. Forty patients (37 percent) had a 30 to 75 percent response. Thirty-two (30 percent) had no response. Toxicity occurred in eight patients (7 percent) before clinical efficacy could be assessed. Seven of the 68 with response had a flare of disease after initial improvement. Of multiple clinical and laboratory parameters tested, only a stronger baseline grip strength was found to be statistically significant (p < 0.001) in predicting a favorable response. Thus, hydroxychloroquine is an effective drug in the management of rheumatoid arthritis.     

Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis.

Pulmonary functions of patients with allergic bronchopulmonary aspergillosis were studied during an acute episode (n = 6); during a mean follow-up period of 44 months (range four months--14.8 years) (n = 16); and for any correlation between duration of ABPA and asthma with the total lung capacity (helium dilution), 1 second forced expiratory volume (FEV1), vital capacity, 1 second forced expiratory volume-forced vital capacity ratio (FEV1:FVC per cent) and diffusing capacity of carbon monoxide (DL:CO) (single breath) for the entire group (n = 22). All patients were treated with corticosteroids (intermittent or continuous) and bronchodilators. For the 16 patients, slopes using linear regression analysis were determined from the function as per cent predicted versus time in months from diagnosis and then analyzed for significance. Significant functional loss was shown in three of 16 patients for FEV1, two of 16 patients for vital capacity, one of 16 patients for FEV1:FVC per cent, none of 10 patients for DL:CO and one of 10 patients for total lung cital capacity, FEV1:FVC per cent and the duration of asthma or allergic bronchopulmonary aspergillosis was found by multiple regression analysis correcting for age and smoking (mean 4.24 years; range 0.3 to 14.8 years). Roentgenographic criteria and blood eosinophilia were used to define a "flare" of allergic bronchopulmonary aspergillosis. The six patients during a flare showed a significant reduction in total lung capacity (P less than 0.001), vital capacity (P less than 0.05), FEV1 (P less than 0.01) and DL:CO (P less than 0.001) which uniformly returned to baseline values during steroid therapy. The FEV1:FVC per cent remained unaltered. These findings, contrary to suggestions in the literature, indicate that in the majority of our patients there was no significant progressive functional deterioration after diagnosis. However, during acute episodes of allergic bronchopulmonary aspergillosis, transient reduction of volumes and DL:CO were uniformly present.     

Ketone body production in diabetic ketosis by other than liver

To determine if ketone bodies, synthesized from fatty acids by tissues other than the liver, enter the circulation, rats in diabetic ketosis were injected with sodium [6,13-¹⁴C]palmitate. Hydroxybutyrate was isolated from the urine excreted by each rat and from an aqueous extract of its carcass. The distribution of ¹⁴C in the four carbons of hydroxybutyrate in the extract was the same as in the urine. The ratio of ¹⁴C in carbon 1 to carbon 3 of the hydroxybutyrate averaged 1.80 and averaged 1.31 in carbon 2 to carbon 4. Hydroxybutyrate when formed by perfused liver has the same carbon 1-to-carbon 3 ratio as carbon 2-to-carbon 4 ratio. The results indicate that hydroxybutyrate synthesized by tissues other than the liver mixes in the circulation with that synthesized by the liver and a portion of the mix is then excreted in the urine. The difference between the carbon 1-to-3 carbon ratio 3 and carbon 2-to-carbon 4 ratio calculates to an estimated minimum of 15% to 17% of the hydroxybutyrate in the circulation of the ketotic diabetic rat having tissues other than the liver as its source. Assuming the liver and kidneys are the sources of the ketone bodies in diabetic ketosis, the ketone bodies produced by the kidneys are not excreted into the urine without first entering the circulation.     

Importance of anti-lung antibody in farmer's lung disease

The presence of anti-lung antibody was evaluated in 20 patients with farmer's lung disease. Antibody was found in 14. In patients with disease of less than five years' duration, there was no evidence of any significant differences in vital capacity, total lung capacity, diffusion capacity, and PaO₂ between those wtth and without antilung antibody. However, in patients with disease of longer than five years' duration, the diffusion capacity was lower in the anti-lung antibody-positive group (p < 0.05). The prevalence of abnormalities of vital capacity and diffusion capacity and flbrosis on chest roentgenograms was higher in those who had anti-lung antibody and disease of more than five years' duration. The study suggests that anti-lung antibody is present before permanent measurable physiologic abnormality occurs and may potentiate the pulmonary damage during subsequent episodes.     

A comparative study of polyantibiotic and iodophor ointments in prevention of vascular catheter-related infection

Using a semiquantitative technique for culturing material from vascular catheters, we studied by random allocation the efficacy of three regimens for site care of 827 catheters used in adult patients: an iodophor ointment (PI2), ointment containing polymyxin, neomycin and bacitracin (PNB), and use of no topical agent whatsoever (control). Even though this is the largest study of this subject, there was not a sufficient number of catheter-related septicemias to permit valid comparisons (two in each group, 0.7 percent). However, the rate of local catheter-related infection (greater than or equal to 15 CFU on semiquantitative culture), the prelude to related septicemia, was significantly lower in the PNB group (2.2 percent, P = 0.02) as compared with controls (6.5 percent). Use of PI2-treated catheters resulted in one-half fewer infections (3.6 percent) than use of control catheters (P = NS). Staphylococcal infections occurred with 15 control catheters, eight treated with PI2 and two with PNB (P = 0.002). Infections by gram-negative bacilli occurred less frequently in both treatment groups than in controls, but three of four Candida infections, including one septicemia, occurred in the PNB group. Topical antimicrobial agents confer modest benefit in protection against catheter-related infection, primarily for peripheral venous catheters that must remain in place for more than four days. If an ointment is to be used, topical PNB may be preferable for peripheral venous catheters and PI2 ointment for central venous catheters used for parenteral nutrition and for arterial catheters.