Total parenteral nutrition during acute pancreatitis: Clinical experience with 156 Patients

Over a 3-year period, 156 of 815 patients admitted to a single institution with acute pancreatitis received total parenteral nutrition (TPN) for 2,572 patient days. Seventy had simple acute pancreatitis (group I) and 86 (group II) developed local complex disease (pseudocyst, abscess, or necrotic gland). In groups I and II, respectively, days without oral intake (NPO) were 13.6±1.5 (SEM) and 24.0±2.1 (p<0.005), hospital days were 19.8±1.7 and 35.8±3.2 (p<0.005), and duration of TPN was 10.9 ±1.0 and 21.0±2.3 days (p<0.005). Thirty-three patients in group I and 53 in group II required exogenous insulin. Alteration of standard formulas was necessary in 87 patients, but cessation of therapy was necessary in only one instance. Twenty catheters were removed for suspected sepsis with only 3 confirmed cases. Fat-based formulas were well tolerated in 15% of patients. During TPN, body weight rose from 95.0±2.4% to 97.4±4.3% of ideal in group I and remained at 90.5±1.8% in group II. Albumin rose from 3.36±0.10 to 3.50±0.08 g/dl in group I and from 3.01±0.07 to 3.35±0.07 g/dl in group II. The entire cohort differed from 10 randomly chosen patients who did not receive TPN in terms of days NPO (2.8±0.3) and hospital days (5.5±0.6). Variables associated with prolongation of hospital stay and time NPO were number of prognostic criteria, local complex disease, and underlying chronic pancreatitis only in select groups. We conclude that during acute pancreatitis, TPN can be administered safely but with careful monitoring and we recommend early aggressive therapy in the subgroups noted above and when underlying malnutrition exists. In the borderline patient, TPN may be administered by peripheral vein until the severity of disease is manifest.

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Resumen En el curso de un período de 3 años, 156 de 815 pacientes hospitalizados en una sola institución por pancreatitis aguda recibieron nutrición parenteral total (NPT) durante 2,572 paciente-días. Setenta presentaban pancreatitis aguda simple (grupo I) y 86 (grupo II) desarrollaron enfermedad local complicada (pseudoquiste, absceso, o necrosis de la glándula). Las siguientes fueron las características de los grupos I y II, respectivamente: días sin ingesta oral (NPO) 13.6±1.5 (SEM) y 24.0±2.1 (p<0.005), días de hospitalización: 19.8±1.7 y 35.8±3.2 (p<0.005), y duración de la NPT: 10.9±1.0 y 21.0 ±2.3 días (p<0.005). Trienta y tres pacientes en el grupo I y 53 en el grupo II requirieron insulina exógena. Se requirió alterar la fórmula estándar en 87 pacientes, pero sólo fue necesario cesar la terapia en un caso. Veinte catéteres fueron retirados por sospecha de sepsis, pero sólo en 3 se confirmó. Las fórmulas a base de grasa fueron bien toleradas en 15% de los pacientes. En el curso de la NPT el peso corporal ascendió de 95.0±2.4% a 97.4±4.3% del peso ideal en el grupo I y se mantuvo a un 90.5±1.8% en el grupo II. La albúmina ascendió de 3.36±0.10 a 3.50±0.8 g/dl en el grupo I y de 3.01±0.07 a 3.35±0.07 g/dl en el grupo II. Toda la cohorte se diferenció de un grupo de 10 pacientes escogidos al azar que no recibieron NPT en términos del número de días NPO (2.8±0.3) y de días de hospitalización (5.5±0.6). Las variables que aparecieron asociadas con prolongación de la hospitalización y el tiempo NPO fueron el número de criterios de pronóstico, la enfermedad complicada, y la presencia de pancreatitis crónica subyacente sólo en grupos seleccionados. Nuestra conclusión es que en el curso de la pancreatitis aguda, la NPT puede ser administrada con seguridad pero bajo monitoría cuidadosa, y recomendamos terapia agresiva precoz en los subgrupos anotados anteriormente y cuando exista mal nutrición concomitante. En el paciente limitrofe se puede administrar la NPT por vía periférica hasta cuando la gravedad de la enfermedad se haga manifiesta.

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Résumé Pendant une période de 3 ans, 156 des 815 patients admis pour pancréatite aiguë ont reçu une alimentation parentérale totale (APT), soit en tout 2,572 jours patient. Soixante dix patients (groupe I) avaient une pancréatite simple et 86 (groupe II) avaient aussi une maladie locale complexe (pseudokyste, abcès ou nécrose du pancréas). La durée du jeûne était respectivement de 13.6±1.5 (ET) et de 24.0±2.1 (p<0.005), la durée moyenne de séjour était respectivement de 19.8±1.7 et de 35.8 ±3.2 (p<0.005) alors que la durée d'APT était respectivement de 10.9±1.0 et de 21.0±2.3 jours (p<0.005). Trente-trois patients dans le groupe I et 53 dans le groupe II avaient besoin d'insuline exogène. Un changement dans la formule standard a été nécessaire chez 87 patients mais l'APT n'a du être arrêté complètement que chez un patient seul. Vingt cathéters ont été enlevés avec suspicion de sepsis, confirmée cependant dans 3 cas seulement. Les compositions à base de lipides ont été bien tolérées chez 15% des patients. Pendant l'APT, le poids du corps s'est élevé de 95.0±2.4% à 97.4±4.3% du poids idéal chez les patients du groupe I et est resté à 90.5±1.8% chez ceux du groupe II. L'albumine s'est élevée de 3.36±0.10 à 3.50 ±0.08 g/dl dans le groupe I et de 3.01±0.07 à 3.35±0.07 g/dl dans le groupe II. La durée du jeûne (2.8±0.3) et la durée moyenne de séjour (5.5±0.6) de l'ensemble des patients différaient de ces mêmes données chez 10 autres patients choisis au hasard. Les facteurs associés avec un séjour hospitalier prolongé et sans alimentation orale étaient le nombre de critères pronostiques, l'existence de complications locales, et de pancréatite chronique sous-jacente chez certains patients. Nous concluons que pendant la pancréatite aiguë, l'APT peut être administrée sans danger sous contrôle permanent et nous conseillons un traitement agressif et précoce dans le sous groupe mentionné plus haut ou quand existe un état de nutrition déficient. Chez le patient limite, on peut se contenter d'APT par une veine périphérique tant que des signes de gravité ne se manifestent pas.

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Presented at the Société Internationale de Chirurgie in Toronto, Ontario, Canada, September, 1989.     

Social support, social selection and self-assessed health status: results from the veterans health study in the United States

This study provided a comprehensive assessment of the association between social support and health using longitudinal data from the Veterans Health Study. Unlike previous studies which examined the relationship between one single domain of social support with either mental or physical health, the present study assessed the effects of three different domains of social support on multiple measures of health. The findings of the study indicated that social support tended to mediate the deleterious effects of non-military traumatic events; whereas the adverse consequences of traumatic events experienced in the military were not affected by social support, suggesting that stressors associated with combat had a long lasting effect on the health status of veterans. The study results revealed that compared with those with better health, respondents with poor health were more likely to have lower levels of social support, suggesting that poor health might be a barrier to a person's ability to participate and/or maintain social relationships. The study also showed that different types of social support had varying beneficial effects on different measures of health. While perceived support had a strong effect on all the measures of health (except alcoholism) included in the study, living arrangement had a significant effect on post-traumatic stress disorder or physical health and participation in group activities had a strong effect only on physical functioning. The results of the study highlight the need for future research to determine whether particular types of social support affect various aspects of health differently. This simultaneous focus on multiple support functions and health outcomes is important because it provides insight into the mechanisms linking social support to health.     

Phase II study of intravenous adenosine 5''-triphosphate in patients with previously untreated stage IIIB and Stage IV non-small cell lung cancer

Fifteen patients with Stage IIIB or IV non-small cell lung cancer gave informed consent to receive three or more 96-hour infusions of ATP at a dose of 50 mcg/kg/min or higher to determine whether ATP has antineoplastic activity against this tumor type and to better define the spectrum of toxicity for ATP given as a single agent. There were no objective complete or partial responses observed. The median survival of the overall group was 187 days and the median time to tumor progression was 113 days. The major toxic side effects were chest pain and dyspnea, leading to the cessation of treatment in 5 patients. We conclude that ATP at this dose and schedule of administration is an inactive agent in patients with advanced non-small cell lung cancer.     

The Gastric Bypass for Failed Bariatric Surgical Procedures

Background: Revision of failed bariatric surgical procedures is a significant challenge for every bariatric surgeon. Methods: Evaluated are surgical difficulties, management problems and weight loss in patients with distal gastric bypass as a revisionary procedure. Eighty patients were followed up to 3 years; four were lost to follow-up. Mean age was 43; mean prebariatric surgery weight 134 kg; height 1.65 meters; body mass index 40.1; ideal body weight 62.7 kg; excess weight 70.5 kg; per cent excess weight 214%. A 250 cm stomach-to-ileocecal valve segment of small bowel was used, and the biopancreatic secretions were brought into the terminal ileum 100 cm from the ileocecal valve. Mean pouch size was 63 cc; length of hospital stay 5 days; operative blood loss 616 cc; operative time 130 min. Results: Intraoperative complications included three splenic injuries (without splenectomy). Early complications included one deep vein thrombosis, two marginal ulcers, one GI hemorrhage, one wound dehiscence, one pouch outlet obstruction and one pancreatitis. Late complications included: one death from protein malnutrition/ARDS; 21 hypoproteinemia; six protein malnutrition, and of these, three had hyperalimentation; three cholecystitis; 27 anemia; 22 incisional hernia; two staple-line disruption (reoperated); 26 low serum iron; 11 prolonged (> 6 months) diarrhea; three prolonged frequent vomiting; and two unrelated deaths (chronic myelogenous leukemia and amyotrophic lateral sclerosis). Mean excess weight loss was 83% at 12 months; 89% at 24 months; and 94% at 36 months. Conclusion: The distal gastric bypass is fraught with the operative and immediate post-operative complications experienced in any revisionary bariatric surgery. Distal gastric bypass is very effective in producing long-term weight loss. Nutritional problems are common but usually easily corrected. The most serious nutritional complication is protein malnutrition, which must be identified and corrected early. Success of this procedure is dependent upon patient compliance with proper nutrition and supplements, and regular office follow-up with monitoring of laboratory data. Patients who are noncompliant are at significant risk for complications.     

Psychological characteristics of males with secondary erectile failure

This study was designed to obtain objective data on the personality profiles of two groups of males with a primary complaint of erectile failure and compare them to a group of psychiatric patients unselected for sexual dysfunction and to a sexually normal control group. Utilizing the Eysenck Personality Inventory, the Institute of Personality and Ability Testing Anxiety Scale, Symptom Checklist, and the Minnesota Multiphasic Personality Inventory, it was determined that males applying to a university/county hospital sex-dysfunction clinic appeared similar to patients seen in the same clinic who were unselected for sex dysfunction and more psychologically disturbed than patients with the same complaint applying for treatment at a private clinic. All three groups showed more psychopathology than sexually normal males. The implications of these findings are discussed.     

Pharmacokinetics and metabolism of β-2′-deoxythioguanosine and 6-thioguanine in man

Summary Resistance to the antileukemic agent 6-thioguanine (TG) inevitably develops in animal tumors. However, a new agent, -2-deoxythioguanosine (-TGdR) can overcome TG resistance in animal tumor models and is therefore of potential clinical use. The pharmacokinetics of radiolabeled TG were compared with those of -TGdR in patients with cancer after intravenous administration. [³⁵S]--TGdR (5.4 mg/kg, 200 mg/m², 200 Ci total) was administered to five patients; the radiolabel in the plasma declined with an initial half-life (t_1/2) of 14 min and a terminal t_1/2 of 19.3 h. Within 24 h, 65% of the radiolabel was excreted in the urine. In contrast, after administration of [³⁵S]-6-TG (3.4 mg/kg, 125 mg/m², 200 Ci total) the average initial t_1/2 was 40 min while the terminal phase t_1/2 was 28.9 h. Urinary excretion of the radiolabel was 75% of the dose 24 h after administration. Both thiopurines were rapidly and extensively degraded and excreted as 6-thioxanthine, inorganic sulfate, S-methyl-6 thioxanthine, and 6-thiouric acid in addition to other products. Small amounts of unchanged drug were also excreted. These studies suggest that -TGdR is merely a latent form of TG.Deceased, to whose memory this paper is dedicated     

Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer.

PURPOSE: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. EXPERIMENTAL DESIGN: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Results and CONCLUSIONS: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.     

Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort.

High circulating concentration of insulin-like growth factor-I (IGF-I) and low circulating concentration of IGF binding protein-3 (IGFBP-3) have been associated with increased risk for breast, prostate, and colorectal cancers. Building on previous work in the Multiethnic Cohort (MEC) showing significant differences in IGF-I levels across racial/ethnic groups, we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a random sample of 1,000 MEC participants, which included Native Hawaiian, African American, Japanese, Latino, and White men and women. Crude analyses confirmed the existence of differences in protein levels with race/ethnicity, sex, age, and body size. Reproductive, physical activity, smoking, and diet variables had less consistent effects. In multivariate analyses, IGF-I levels were lower and IGFBP-3 were higher in females versus males. IGF-I and IGFBP-3 declined with increasing age in both genders. Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels; in men, height was significantly positively associated with both proteins. In women, alcohol was directly associated with IGFBP-3. Both proteins were lowest among female Latinos. IGF-I was highest among female African Americans. In men, IGFBP-3 was lowest among African Americans. Overall, although these factors were statistically significant determinants of IGF-related protein levels, they did not explain much of the variation in these levels. A positive correlation was found between IGF-I levels (ng/mL) and colon cancer incidence rates (per 100,000) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer.