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.     

Breast Biopsies with ABBI(R): Experience with 183 Attempted Biopsies

When first introduced, the advanced breast biopsy instrumentation (ABBI^®) system seemed to have many advantages as a diagnostic procedure. Problems have arisen, however, both in terms of patient unsuitability and mechanical failure. In addition, there has been uncertainty as to whether the complete lesion removal it afforded could be considered definitive treatment in malignant cases. Incision margins were looked at to investigate that possibility. Of the 183 patients we saw in our first year of experience with ABBI, 48 (26%) were rejected for being poor candidates for it. In the remaining 132 biopsies there were 31 (23%) technical difficulties. All told, 14 malignancies were discovered, all of which appeared to have pathology-free incision margins radiologically. However, 13 of these 14 (93%) proved on pathologic examination to have residual malignancy. ▪     

Indiana Children's Special Health Care Services Program: Impact of Administrative Changes on Health Care Utilization, Access to Care, and Unmet Needs

In this study we assessed the impact of administrative changes occurring in 1993 on the Indiana Children's Special Health Care Services program. Responses from a 1994-1995 survey were compared with a 199 1 survey. Unmet needs declined in 6 categories: primary medical care, hospital services, home nursing care, physical therapy, occupational therapy, and special equipment. Unmet needs remained the same in 6 categories: specialty care, speech therapy, respite care, parent support, child support, and sibling support. Unmet needs increased in 5 categories: dental care, mental health, transportation, housing modifications, and child and day care. Although program changes improved the health care needs of clients in many areas, additional efforts are still needed.     

Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction

Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5–1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes. Received: 5 May 1998/Final version: 7 July 1998     

Double β-lactam regimen compared to an aminoglycoside/β-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C±T), both agents being administered only if the initial granulocyte count was below 200/l, or ceftazidime plus piperacillin (C+P). The overall response rate was 71% (39 of 60 for C±T and 45 of 58 for C+P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C+P regimen (P=0.06), there was no difference in response for patients with bacteremia and profound (<100/gml) sustained granulocytopenia. The double -lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced execllent serum bactericidal levels (C±T geometric mean peak 1:170; C+P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C+P and in 6 of 89 trials in the C±T group (P=0.19). The incidence of secondary infections in patients with profound (<100/l) sustained granulocytopenia was lower in the C±T group (P=0.04). Alimentary canal anaerobic flora preservation with C±T, and suppression with C+P, was demonstrated. These results suggest that these regimens are of similar effectiveness and neigher is associated with major toxicity.     

Chemical allergy: considerations for the practical application of cytokine profiling.

Chemical respiratory allergy is an important occupational health problem, but there are currently available no validated methods for hazard identification. This is due in part to the fact that the relevant cellular and molecular mechanisms of sensitization of the respiratory tract have been unclear, with particular controversy regarding the role of IgE. There is now increasing evidence that respiratory sensitization is associated with the preferential activation of type 2 T lymphocytes and the expression of type 2 cytokines interleukin (IL)-4, IL-5, IL-10, and IL-13. Type 2 cell products favor immediate type hypersensitivity reactions, serving as growth and differentiation factors for mast cells and eosinophils, the cellular effectors of the clinical manifestations of the allergic responses, and promoting IgE antibody production. There has been considerable interest in the application of cytokine profiling for the characterization of chemical allergens, with cytokine phenotypes analyzed in freshly isolated tissue, or following culture in the presence or absence of mitogen at the level of protein secretion or mRNA expression. Experience to date suggests that the measurement of induced cytokine secretion profiles shows promise for the hazard identification and characterization of chemical respiratory allergens. The purpose of this brief review article is to consider the approaches available and to highlight key procedural issues.     

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.     

Liposomal irinotecan: formulation development and therapeutic assessment in murine xenograft models of colorectal cancer.

PURPOSE: The purpose is to demonstrate whether an appropriately designed liposomal formulation of irinotecan is effective in treating mice with liver-localized colorectal carcinomas. EXPERIMENTAL DESIGN: Irinotecan was encapsulated in 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (55:45 molar ratio) liposomes using an ionophore (A23187)-generated transmembrane proton gradient. This formulation was evaluated in vivo by measuring plasma elimination of liposomal lipid and drug after i.v. administration. Therapeutic activity was determined in SCID/Rag-2M mice bearing s.c. LS180 tumors or orthotopic LS174T colorectal metastases. RESULTS: Drug elimination from the plasma was significantly reduced when irinotecan was administered in the liposomal formulation. At 1 hour after i.v. administration, circulating levels of the liposomal drug were 100-fold greater than that of irinotecan given at the same dose. High-performance liquid chromatographic analysis of plasma samples indicated that liposomal irinotecan was protected from inactivating hydrolysis to the carboxylate form. This formulation exhibited substantially improved therapeutic effects. For the LS180 solid tumor model, it was shown that after a single injection of liposomal irinotecan at 50 mg/kg, the time to progress to a 400-mg tumor was 34 days (as compared with 22 days for animals treated with free drug at an equivalent dose). In the model of colorectal liver metastases (LS174T), a median survival time of 79 days was observed after treatment with liposomal irinotecan (50 mg/kg, given every 4 days for a total of three doses). Saline and free drug treated mice survived for 34 and 53 days, respectively. CONCLUSIONS: These results illustrate that liposomal encapsulation can substantially enhance the therapeutic activity of irinotecan and emphasize the potential for using liposomal irinotecan to treat liver metastases.