Biomedical subjects

G M Doherty

Publications and source records attributed to G M Doherty.

At least 37 records · Page 2Linked to original sources

PubMed1996

Evaluation of somatostatin-receptor scintigraphy for detecting neuroendocrine tumors.

BACKGROUND: Somatostatin-receptor scintigraphy (SRS) has gained attention as an imaging modality for neuroendocrine tumors (NETs). The purpose of this study was to present one of the first American series evaluating the ability of SRS to detect local and distant disease caused by NETs. METHODS: Medical records were reviewed from 35 patients who underwent a total of 38 studies using 111In-pentetreotide between 1993 and 1995. Twenty-two patients had islet cell tumors, seven had carcinoid tumors, and six had other NETs. RESULTS: The overall sensitivity of SRS was 74% for detecting local disease (primary tumor +/- regional lymph node metastases) in all NETs, excluding insulinoma, 75% in gastrinoma, 0% in insulinoma, 78% in other islet cell tumors, and 50% in carcinoids. For detecting distant disease, the overall sensitivity of SRS was 67% for all NETs, excluding insulinoma, 100% for gastrinoma, 50% for other islet cell tumors, and 80% for carcinoids. Specificity and positive predictive value were 100% for all tumors. Negative predictive value ranged from 33% to 100%. CONCLUSIONS: A positive SRS study strongly predicts the presence of tumor (100% positive predictive value in our study). However, unlike the European reports of very high sensitivity (80% to 88%), we found that SRS had a lower sensitivity (67% for all NETs excluding insulinoma and 71% for noninsulinoma gastroenteropancreatic NETs). Thus negative SRS in patients with NETs must be viewed cautiously, because the false-negative rate is high, and this limits the use of this method in the most difficult patients.

Adenoma, Islet Cell↗

PubMed1996

Mammographically detected breast cancer. Benefits of stereotactic core versus wire localization biopsy.

OBJECTIVE: The authors evaluated the differences between stereotactic core needle biopsy (SCNBx) and needle localization surgical biopsy (NLBx) in cost and treatment course for patients with mammographically detected breast cancer. SUMMARY BACKGROUND DATA: Stereotactic core needle breast biopsy is a reproducible and reliable alternative to surgical biopsy for histologic diagnosis of mammographic lesions. METHODS: Records from 52 consecutive patients with invasive breast cancer diagnosed by SCNBx (n = 21) or NLBx (n = 31) over 2 years were reviewed. Episode-of-care costs were extracted from the Barnes Hospital billing system database. RESULTS: At the time of excision, surgical margins were statistically more frequently positive in patients treated with NLBx (55%) than patients treated with SCNBx (0%, p < 0.0001). Furthermore, patients in the NLBx group undergoing breast conservation surgery required re-excision more frequently (74%) than those in the SCNBx group (0%, p = 0.001). There were no complications in either group after the diagnostic procedure. All SCNBx results were correct in the diagnosis of invasive breast cancer. The median cost of SCNBx was approximately $1000 less than the median cost of NLBx. This cost difference was carried through the definitive procedure, whether it was breast conservation or mastectomy. CONCLUSIONS: This study shows the advantage of SCNBx to diagnose breast cancer and definitive operative care at a single procedure. The preoperative diagnosis of breast cancer eliminated positive operative margins and procedures to re-excise breast tissue. The use of SCNBx also saved approximately $1000 per patient compared with the use of NLBx. Our data suggest that SCNBx is the diagnostic procedure of choice for mammographically detected cancers.

Adenocarcinoma↗

PubMed1996

Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms.

BACKGROUND: Laparoscopic adrenalectomy has recently been used for removing a variety of adrenal neoplasms. The purpose of the present study was to compare results and outcomes in patients who underwent either laparoscopic or open adrenalectomy at our institution from 1988 to the present. STUDY DESIGN: The records of 66 consecutive patients with benign adrenal neoplasms who underwent adrenalectomy from 1988 through 1995 were retrospectively reviewed. Patients were divided into three groups based on the operative approach: group I (n = 25), open anterior transabdominal approach; group II (n = 17), open posterior retroperitoneal approach; and group III (n = 24), laparoscopic transabdominal flank approach. Various parameters were compared and statistical analyses were performed. RESULTS: The three groups were similar in age, gender, American Society of Anesthesiologists class, and distribution of unilateral compared with bilateral adrenalectomy. Mean tumor size was slightly larger in group I (3.4 +/- 1.4 cm) than in group II (2.4 +/- 1.4 cm) or group III (2.7 +/- 1.4 cm) (p = NS). Mean operative times for unilateral adrenalectomy were 142 +/- 38 minutes in group I, 136 +/- 34 minutes in group II, and 183 +/- 35 minutes in group III (p < 0.001, groups I and II compared with group III). For bilateral adrenalectomy, mean operative times were 205 +/- 71 minutes (group I), 328 +/- 11 minutes (group II), and 422 +/- 77 minutes (group III). Patients who underwent laparoscopic adrenalectomy had significantly less operative blood loss (mean, 104 mL compared to 408 mL in group I and 366 mL in group II, p < 0.001) and a lower incidence of perioperative blood transfusion. Laparoscopic adrenalectomy was also associated with significantly reduced parenteral pain medication requirements (p < or = 0.001) and more rapid resumption of a regular diet (p < or = 0.01) compared to open adrenalectomy. Postoperative length of stay was significantly longer in group I (8.7 +/- 4.5 days) and in group II (6.2 +/- 3.9 days) after open adrenalectomy than after laparoscopic adrenalectomy (3.2 +/- 0.9 days) (p < 0.01). Total hospital charges were similar for groups II and III but somewhat higher for group I. Patients were able to resume 100 percent activity an average of 10.6 +/- 4.9 days after laparoscopic adrenalectomy and returned to work a mean of 16.0 +/- 6.1 days postoperatively. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective procedure and has several advantages over open adrenalectomy. Laparoscopic adrenalectomy should become the preferred operative approach for the treatment of patients with small, benign adrenal neoplasms.

Adrenal Gland Neoplasms↗

PubMed1995

Prolongation of skin allografts by recombinant tumor necrosis factor and interleukin-1.

OBJECTIVE: The hypothesis is that systemic administration of recombinant tumor necrosis factor-alpha (TNF-alpha) and/or recombinant interleukin-1 alpha (IL-1 alpha) can decrease the rejection of a skin allograft. SUMMARY BACKGROUND DATA: Tumor necrosis factor and IL-1 are pluripotent cytokine hormones that are central to the host immunologic response to foreign substances. Cytokine effects and toxicity may be reduced by systemic administration of recombinant cytokines. The authors previously have demonstrated that pretreatment with cytokines such as IL-1 or TNF can reduce the lethality of endotoxin (lipopolysaccharide), gram-negative sepsis, cancer cachexia, and oxygen toxicity. METHODS: Skin grafts from the tails of Balb/c mice were placed on the backs of C57Bl/6 mice. Mice were treated with daily intraperitoneal saline, recombinant m-TNF (Genentech, South San Francisco, CA) or h-IL-1 (Hoffman LaRoche, Nutley, NJ) from postgraft day 1 to postgraft day 28. Tumor necrosis factor and IL-1 high doses were chosen because they protected mice from the lethality of lipopolysaccharide. Animals were examined daily for toxicity and graft rejection. Graft survival was plotted in a Kaplan-Meier plot and analyzed by the log-rank test. Comparison of proportions was done using the Fisher's exact test. RESULTS: Either TNF or IL-1 alone significantly prolonged skin graft survival compared with saline control. Furthermore, the combination of TNF and IL-1 prolonged skin graft survival longer than either cytokine alone. Mice on the highest dose TNF and IL-1 combination did not reject skin grafts during the 28-day treatment period. Significant toxicity was associated with cytokine treatment. Similar significant proportions of death occurred with IL-1 alone and the highest combination of TNF and IL-1. CONCLUSION: Both TNF and IL-1 can be effective as suppressors of skin allograft rejection in mice.

Animals↗

PubMed1994

Cost of unsuccessful surgery for primary hyperparathyroidism.

BACKGROUND: Surgery for primary hyperparathyroidism demands skill and experience. The monetary and personal costs of unsuccessful surgery are investigated here. METHODS: We reviewed 47 consecutive patients operated on by one surgeon during a period of 16 months, including their clinical data and medical costs of their treatment. RESULTS: All 39 patients without previous operation were normocalcemic after operation, with no recurrent nerve injury nor hypoparathyroidism. Of the eight who had undergone previous operation elsewhere, seven had abnormal glands that should have been resected at the initial operation, and hypoparathyroidism developed in two patients. Total costs of reoperative parathyroid surgery were more than twice the cost of an initial operation (median, $8383 versus $3948, p < 0.001) because of the cost of radiologic studies (median, $3378 versus $43, p < 0.001). CONCLUSIONS: (1) An experienced parathyroid surgeon can consistently cure hyperparathyroidism at the initial operation. (2) The majority of patients referred for hyperparathyroidism not cured by previous operation have glands in usual anatomic locations. (3) The cost to the patient of an inadequate initial operation includes the physical effects of remaining hyperparathyroid, additional time off work, potentially invasive localization testing, reoperative surgery with increased risk of complications, and substantial expense. Initial parathyroid surgery should be performed by surgeons experienced and proficient in its practice.

Adult↗

PubMed1993

13C-n.m.r. of the cyanylated apoflavodoxin and flavodoxin from Clostridium pasteurianum.

The thiol group of the flavodoxin from Clostridium pasteurianum has been cyanylated in a single step using [cyanato-13C]2-nitro-5-thiocyanatobenzoic acid. This chemical modification increases the dissociation constant of the apoflavodoxin-FMN complex 10-fold from 0.33 +/- 0.15 nM to 2.9 +/- 1.3 nM. The thiocyanate carbons of the cyanylated cysteine residue of apoflavodoxin and flavodoxin had chemical shift values of 114.7 and 112.3 p.p.m. respectively. From these chemical shifts we conclude that the binding of FMN by the cyanylated apoflavodoxin causes a decrease in the polarity and/or hydrogen bonding capacity of the environment of the thiocyanate group. We compare these results with those obtained from similar studies on the cyanylated apoflavodoxin and flavodoxin from Megasphaera elsdenii and we discuss how FMN binding and cyanylation perturb the structures of apoflavodoxins from Megasphaera elsdenii and Clostridium pasteurianum.

Apoproteins↗

PubMed1992

13C NMR of cyanylated flavodoxin from Megasphaera elsdenii and of thiocyanate model compounds.

Both of the thiol groups of Megasphaera elsdenii flavodoxin have been cyanylated using 13C-enriched cyanide. This chemical modification increases the dissociation constant of the apoflavodoxin-flavin mononucleotide (FMN) complex from 0.4 nM to 2 microM. The thiocyanate carbons of the cyanylated cysteine residues in apoflavodoxin had 13C chemical shifts of 109.4 ppm and 112.2 ppm, which were replaced by signals at 115.5 ppm and 109.6 ppm when FMN was bound. The signals at 109.4 ppm and 112.2 ppm due to the cyanylated apoflavodoxin were unstable at 28 degrees C, and they were slowly replaced signals at 114.5 ppm and 115.3 ppm which are attributed to an inactive form of the apoprotein, which does not bind FMN. At alkaline pH values or after prolonged incubation at neutral pH, the signals at 114.5 ppm and 115.3 ppm were replaced by signals at approximately 171 ppm. On the basis of results obtained with model compounds, the signals at 171 ppm are assigned to the 2-imino carbon of the 2-iminothiazolidine ring formed by the cyclization of the appropriate thiocyanate group. After determining the chemical shift of the thiocyanate carbon of model compounds in a range of solvents, we conclude that the thiocyanate carbons will have a minimal chemical shift of approximately 109 ppm in apolar solvents which do not contain hydrogen bond donors. In water, a more polar hydrogen-bonding solvent, the chemical shift increases to approximately 115 ppm. We also conclude that the chemical shift of a thiocyanate carbon can be used as a probe of its molecular environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

PubMed1992

Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha.

Current evidence indicates that endogenously produced peptide cytokines, most notably TNF-alpha and IL-1, mediate the lethality of experimental endotoxemia. Because circulating serum levels of IFN-gamma can be detected soon after TNF-alpha and IL-1 in response to endotoxin, we investigated the role of IFN-gamma in endotoxin and TNF-alpha lethality. Specific neutralizing antibodies to murine TNF-alpha (anti-TNF-alpha Ab) or murine IFN gamma (anti-IFN-gamma Ab) produced in our laboratory protected mice against the lethality of Escherichia coli endotoxin (LPS) administered 6 h later. Serum IFN-gamma levels 2 h after i.v. LPS were lower in mice treated with anti-TNF-alpha Ab compared to mice that received nonimmune IgG (median less than 2.5 vs 3.0 U/ml, P2 less than 0.05). In contrast, serum TNF-alpha levels 1 h after i.v. LPS peaked more than fourfold higher in mice treated with anti-IFN-gamma Ab compared to controls (median greater than 6400 vs 1405 pg/ml, p2 less than 0.05). Doses of TNF-alpha (300 micrograms/kg) and IFN-gamma (50,000 U) which were well tolerated when given individually were synergistically lethal in combination (0% lethality vs 100% lethality, P2 less than 0.001), and were associated with higher serum levels of IL-6 than with either cytokine alone. Anti-IFN-gamma Ab provided complete protection against exogenous human rTNF-alpha at the LD100 dose (1400 micrograms/kg, p2 less than 0.001), and in fact prevented lethality at doses four- to fivefold greater than the LD100 human rTNF-alpha (up to 6000 micrograms/kg). We conclude that IFN-gamma is synergistic with TNF-alpha, is essential for the lethality of LPS and TNF-alpha, and may have modulating effects on the negative control of serum levels of TNF-alpha after LPS in mice.

Animals↗

PubMed1992

Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor.

Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.

Animals↗

PubMed1992

The hydrogen-tritium exchange activity of Megasphaera elsdenii hydrogenase.

The hydrogenase of Megasphaera elsdenii was purified to a specific activity of 350 units/mg. The hydrogen-tritium exchange assay of Hallahan et al. [Hallahan, D.L., Fernandez, V. M., Hatchikian, E. C. and Hall, D. O. (1986) Biochimie (Paris) 68, 49-54] was adapted to allow its use in the study of the M. elsdenii hydrogenase preparation. Under the assay conditions routinely employed, the enzyme's exchange activity was inhibited by Tris/HCl and MgCl2; it was stimulated by ethylene glycol. Maximal activity in this standard assay occurred at pH 7.1. The effect of the concentration of molecular hydrogen (1H2 plus 3H1H) on the exchange activity was studied. The resulting double-reciprocal plot was linear; its slope and its intercepts on the ordinate and abscissa were pH-dependent. The rate equations for a number of models of the exchange activity were derived. Each model gave rise to a linear double-reciprocal plot at constant pH, but none could explain fully the observed effects of varying pH. The experimental data corresponded most closely to the predictions of models in which protons were treated both as substrates and as regulators of the enzyme's activity.

Buffers↗

PubMed1992

Interleukin-1 alpha prevention of the lethality of Escherichia coli peritonitis.

Interleukin-1 (IL-1) is an inflammatory mediator with a variety of described physiologic functions. IL-1 alpha has been shown to confer a survival advantage to experimental animals when administered before a lethal bacterial challenge. The experiments reported here were performed to define the effective pretreatment interval of a single intravenous dose of IL-1 alpha in a murine model of bacterial peritonitis, to examine the differential induction of cytokines in animals with and without IL-1 alpha pretreatment, and to assess differences in histologic evidence of end organ damage. IL-1 alpha (27 micrograms/kg iv) conferred a survival advantage to mice given a lethal challenge of live Escherichia coli (2 x 10(8) CFU/mouse ip) when the pretreatment was given 2 to 24 hr before the bacterial inoculum. Longer pretreatment intervals were not significantly protective. Treatment with IL-1 alpha at 1 hr after bacterial inoculum also did not improve survival. Mice pretreated with IL-1 alpha developed significantly lower peak serum levels of TNF-alpha after E. coli injection than did control mice. Pretreated and control mice had similar peak serum levels of IL-6 after bacterial challenge; however, IL-1 alpha-pretreated mice had a less prolonged elevation of serum levels of IL-6. IL-1 alpha-pretreated animals were protected from the histologic evidence of end organ damage seen in control animals. Thus, in this model of E. coli peritonitis pretreatment with a single intravenous dose of IL-1 alpha confers a significant protective effect when given within a limited time range. Treatment outside this interval has no apparent beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Tumour necrosis factor mediates the survival benefit of interleukin 2 in a murine pulmonary metastases model.

Antibody to tumour necrosis factor (TNF Ab) markedly decreases the toxicity of systemic interleukin-2 (IL-2) in mice but does not completely abrogate the anti-tumour response in terms of number of pulmonary metastases. Experiments were performed with a murine model of pulmonary metastases treated with high-dose IL-2 and concomitant TNF Ab or control antibody (CON Ab) to determine the effects of TNF Ab on survival. Mice were given either equal doses of IL-2 and TNF Ab or CON Ab or equitoxic doses of IL-2. In four consecutive experiments mice given TNF Ab tolerated 5 to 6 additional IL-2 doses (a 40-60% increase in total doses) in the equitoxic IL-2 dose group compared to the maximally tolerated dose with CON Ab. In all four experiments TNF Ab-treated mice had decreased survival compared to the CON Ab group given equal doses of IL-2 and in two of four experiments this difference was statistically significant (P2 < 0.01). Mice given 40-60% additional doses of IL-2 with TNF Ab had no improvement in survival compared with equitoxic doses of IL-2 with CON Ab in three of four experiments (P2 = 0.32, P2 = 0.67, P2 = 0.69). The TNF Ab preparation had no direct inhibition of IL-2 activity in an in vitro IL-2 proliferation bioassay. TNF Ab consistently blocks IL-2 toxicity and it also abrogates IL-2 therapeutic efficacy such that survival parallels treatment toxicity in this experimental model.

Animals↗

PubMed1992

Hormonal regulation of inflammatory cell cytokine transcript and bioactivity production in response to endotoxin.

Tumor necrosis factor (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6) are central mediators of the inflammatory response. We investigated the modulation of these cytokines by hormones in vitro. Murine adherent peritoneal exudate cells (PEC) were exposed to various concentrations of hormones followed by lipopolysaccharide (LPS, 10 micrograms/ml). TNF, IL-1 and IL-6 production were assessed by bioassays, enzyme-linked immunosorbent assays (ELISA) or Western blot, and specific RNA transcripts by Northern blot. Hydrocortisone in concentrations as low as 10 ng/ml had dramatic inhibitory effects on supernatant levels of TNF and IL-1 and on TNF, IL-1 and IL-6 transcript number. Supernatant levels of IL-6 were only slightly diminished by hydrocortisone. Adrenocorticotrophic hormone (ACTH) and insulin increased supernatant levels of TNF bioactivity in response to LPS, while each decreased available TNF-alpha gene transcripts. Thus TNF protein production was affected at a post-transcriptional level. ACTH and insulin increased supernatant levels of IL-6 produced in response to LPS without altering available transcripts. Corticotrophin-releasing factor (CRF), epinephrine and glucagon had no effect on supernatant levels of cytokine. Thus, physiological and pharmacological concentrations of hydrocortisone had dramatic inhibitory effects on the supernatant levels of TNF and IL-1, and on the number of available TNF, IL-1 and IL-6 transcripts in PEC exposed to LPS, but had minimal effects on supernatant levels of IL-6 bioactivity. This hydrocortisone action may be a specific negative feedback system for IL-1 and TNF, with relative sparing of IL-6.

Adrenocorticotropic Hormone↗

PubMed1992

Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism.

Persistent primary hyperparathyroidism due to mediastinal parathyroid adenoma was effectively treated by either angiographic ablation or median sternotomy in this study of 49 patients managed at the National Institutes of Health since 1977. Each patient presented here with symptomatic persistent primary hyperparathyroidism after failed initial surgical procedures done at other institutions. Each patient underwent extensive parathyroid localization procedures, including selective angiography, and most had a parathyroid adenoma localized to the mediastinum. Angiographic ablation, the deliberate injection of large doses of contrast material into the artery that selectively perfuses the adenoma, was initially successful in 22 of 30 procedures (73%) in 27 patients. Long-term control of persistent primary hyperparathyroidism was achieved in 17 of 27 patients (63%) by angiographic ablation. Each unsuccessful ablation could be easily salvaged by surgical resection. Surgical resection of the parathyroid adenoma by median sternotomy achieved immediate success in 24 of 24 procedures (p2 less than 0.02 versus ablation), and long-term cure in 23 of 23 evaluable patients (p2 less than 0.001 versus ablation). However, ablation did have benefits for the patients in whom it was successfully performed. It was associated with a significantly shorter hospital stay (median, 6 days versus 9 days for sternotomy, p2 less than 0.003), much less pain, and easier recuperation. Complications of each procedure were transient and similar in both groups. Operative resection is the most effective single means to eradicate mediastinal parathyroid adenoma; however, angiographic ablation can provide similar long-term control of hyperparathyroidism in 63% of patients with less pain and shorter convalescence than that seen in patients after median sternotomy. Our results suggest that angiographic ablation should be attempted as the initial procedure for patients with persistent primary hyperparathyroidism caused by an angiographically identified mediastinal parathyroid adenoma. Operation can be reserved for those who fail ablation.

Adenoma↗

PubMed1992

Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats.

BACKGROUND: Morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention. Interleukin-1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis. The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin-1 receptor antagonist (IL-1ra) against polymicrobial gram-negative septicemia in rats. METHODS: Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture (CLP). After 3 hours rats received either IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of vehicle intravenously for 24 hours. Heart rate, respirations, mean arterial blood pressure, and temperature were recorded at frequent intervals, and survival was assessed for 30 hours after CLP. RESULTS: There were no differences in vital signs between groups at baseline or before treatment, and all animals appeared ill with huddled posture, piloerection, and hyperventilation. Twenty-four hours after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly improved (71% vs 20%, p less than 0.05). CONCLUSIONS: IL-1ra lessens the acute hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by CLP in rats. These data suggest that IL-1 receptor blockade may be an important new treatment strategy against overwhelming bacterial sepsis.

Animals↗

PubMed1992

A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas.

BACKGROUND: Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. METHODS: Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. RESULTS: Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. CONCLUSIONS: Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas.

Adult↗

PubMed1991

The roles of gamma-interferon and tumor necrosis factor alpha in an experimental rat model of cancer cachexia.

Administration of repetitive sublethal doses of either recombinant human tumor necrosis factor (TNF) or recombinant murine gamma-interferon (IFN) to non-tumor-bearing (NTB) rats caused a significant decline in food intake and body weight. After 3 days rats became resistant to the anorectic and weight loss effects of TNF but maintained persistent diminished food intake and diminished body weight gain while receiving recombinant murine IFN. Passive immunization against recombinant rat gamma-interferon allowed cachectic tumor-bearing (TB) rats to eat more food, have a lesser decline in body weight, live longer, and tolerate larger tumors than similar TB rats given nonspecific control antibody. TB rats treated with an antisera to recombinant murine TNF, which was 100% protective when given to NTB rats 6 h before a lethal endotoxin challenge, did not differ significantly from TB rats treated with control antibody with respect to food intake, body weight, survival, or tumor size. Serum levels of TNF or IFN were not detectable in cachectic tumor-bearing rats. The data indicate that the administration of exogenous IFN can simulate cachexia in NTB rats and that passive immunization against it can partially reverse the cachectic changes associated with cancer and prolong survival. These findings suggest that gamma-interferon may be an important mediator of cachexia in this rat tumor model.

Animals↗

PubMed1991

A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice.

Interleukin 1 (IL-1) is an endogenously produced cytokine that mediates a variety of physiological effects that may be beneficial or deleterious to the host. C57Bl/6 mice treated intravenously with a recently characterized human recombinant receptor antagonist protein to IL-1 (IL-1ra) had improved survival when treated after a lethal Escherichia coli endotoxin (lipopolysaccharide [LPS]) challenge. IL-1ra was effective when treatment was initiated after LPS, and intravenous administration every 4 h for 24 h was required. Serum levels of tumor necrosis factor (TNF) activity after LPS and in vitro TNF cytotoxicity were not altered by treatment with IL-1ra. These experiments provide direct evidence that the lethal effects of LPS may be mediated through the action of IL-1 and that the IL-1ra can provide a new treatment strategy for disease processes mediated via this cytokine.

Animals↗