Search PubMed⌕ Search

Biomedical subjects

P Dineen

Publications and source records attributed to P Dineen.

At least 19 recordsLinked to original sources

Elevated production of neutrophil leukotriene B4 precedes pulmonary failure in critically ill surgical patients.

Leukotriene B4, a potent neutrophil chemotactic factor, is also made by the neutrophil. Neutrophil function was studied in 12 patients at risk for the development of adult respiratory distress syndrome (ARDS) after admission to the surgical intensive care unit (ICU) to test the hypothesis that increased generation by the neutrophil generation of this mediator precedes the development of pulmonary failure. Peripheral blood neutrophils were tested for chemotaxis to f-met-leu-phe (fMLP) and leukotriene B4 (LTB4) and the generation of LTB4. Plasma was collected simultaneously for assay of C3a desArg levels. Five patients had ARDS a mean of 2.2 +/- 0.25 days after admission to the ICU. Neutrophil generation of LTB4 was significantly enhanced on ICU day 1 in these patients as compared with patients at risk for ARDS but not developing the syndrome (119.4 +/- 6.1 versus 101.0 +/- 5.1, per cent control, p less than 0.05). Chemotaxis to fMLP and LTB4 was significantly reduced in both groups of patients. However, neutrophil chemotaxis improved in patients who did not have pulmonary failure during the time in the ICU, whereas neutrophil chemotactic responsiveness worsened in patients who did have pulmonary failure. Plasma C3a desArg levels were significantly elevated over normal laboratory values on ICU day 1 in the ARDS patients (317.2 +/- 74.0 versus 132.0 +/- 16.0 milligrams per milliliter, p less than 0.01). These data indicate that LTB4 production by the neutrophil occurs concomitantly with complement activation, is a predictor of subsequent ARDS and may play a significant role in the development of pulmonary failure in critically ill surgical patients.

Chemotaxis, Leukocyte↗

Leukotriene B4 generation in patients with established pulmonary failure.

We investigated the cause of the reduced leukotriene B4 (LTB4) production seen in neutrophils from patients with established adult respiratory distress syndrome compared with control neutrophils. Lymphocytes/monocytes from controls were found to synergistically enhance the amount of LTB4 produced when incubated with neutrophils. This synergistic effect was not seen in cells from patients with adult respiratory distress syndrome. Fatty-acid analysis of neutrophils from patients with adult respiratory distress syndrome and controls showed remarkable similarity in all quantities of fatty acids measured except for arachidonic acid, where there was a 22% reduction in patients' cells compared with controls. Assay of the rate of generation of LTB4 and its degradation product, 20-hydroxy LTB4, revealed that reduced LTB4 generation in patients' neutrophils was not due to increased degradation of LTB4 by hydroxylase enzymes. When the amount of LTB4 being generated per milliliter of whole blood was analyzed in the patients with adult respiratory distress syndrome and compared with controls, it was determined that the potential to generate LTB4 in patients in the intensive care unit was three to five times greater than in controls.

Fatty Acids↗

Tumor necrosis factor-enhanced leukotriene B4 generation and chemotaxis in human neutrophils.

In an in vivo study of five normal volunteers infused with endotoxin (20 U/kg of US reference endotoxin lot EC-5), increased neutrophil (PMN) generation of leukotriene B4 and chemotaxis to leukotriene B4 were found concomitantly with elevated plasma tumor necrosis factor (TNF) levels. To clarify the role of TNF in PMN activation, neutrophil responsiveness after in vitro treatment with TNF was examined. Neutrophils from seven normal subjects were incubated with TNF for 30 minutes and tested for chemotaxis to leukotriene B4, formyl-methionyl-leucyl-phenylalanine and zymosan-activated serum, or the calcium ionophore A23187 to assess leukotriene B4 generation. A range of 10(-13) to 10(-9) mol/L of TNF was used for these assays. When 10(-9) mol/L of TNF was used, the amount of leukotriene B4 that was produced was significantly greater than in control cells. The effect of TNF on PMN chemotaxis was uniformly inhibitory for the three stimuli at 10(-10) mol/L compared with untreated cells. At a picomolar range, PMN migration to leukotriene B4, but not to zymosan-activated serum or formyl-methionyl-leucyl-phenylalanine, was significantly increased over that of PMNs not exposed to TNF. This suggests that TNF has a specific facilitatory effect on PMN responsiveness for both leukotriene B4 production and chemotaxis to leukotriene B4 and may be the same signal for this phenomenon in endotoxemic patients.

Calcimycin↗

Differential neutrophil activation before and after endotoxin infusion in enterally versus parenterally fed volunteers.

This study was done to determine whether or not increased susceptibility to infection seen in enterally versus parenterally fed patients was caused by altered neutrophil (PMN) responsiveness. To determine the differential effects of route of feeding on human PMN activation, plasma C3a levels, circulating PMN counts, PMN migration to leukotriene B4 (LTB4), the peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and zymosan activated serum (ZAS) and generation of LTB4 were assayed before and after and infusion of endotoxin. Nine normal volunteers were enterally (n=4) or parenterally (n=5) fed a diet sufficient to maintain body weight for seven days prior to a standard challenge of endotoxin. Samples were taken prior to the infusion and hourly thereafter for six hours. Prior to the injection of endotoxin, significant differences were seen in the two feeding groups. Plasma C3a levels, absolute circulating PMN counts and chemotaxis to LTB4 were all significantly (p less than 0.02) elevated in the enterally fed group. Generation of LTB4 was higher in the intravenously fed group at base line than the orally fed group (p less than 0.05). Plasma C3a levels rose in the enterally fed group, but not in the intravenously fed group, at two hours after infusion. Neutrophil counts rose in both feeding groups after endotoxin infusion; but the change in percentage was greater in the enterally fed group than in the intravenously fed group. Chemotaxis to FMLP and ZAS was not different during the study and did not differ between the two feeding can have significant impact on neutrophil function and that parenteral nutrition may impair host responsiveness.

Chemotaxis↗

Analysis of the mitogenic effects of toxic shock toxin on human peripheral blood mononuclear cells in vitro.

It has been shown previously that the staphylococcal enterotoxins A and B are T-cell mitogens and also cause inhibition of murine plaque-forming cells generated in vitro. Similarly, toxic shock toxin, a 24,000-MW protein produced by toxic shock-associated strains of Staphylococcus aureus, is mitogenic and inhibits the generation of both murine and rabbit plaque-forming cells. In this study, an analysis of the T-cell response to toxic shock toxin was performed. Human peripheral blood mononuclear cells responded to toxic shock toxin over a broad dosage range (1 ng/ml to 5 micrograms/ml) with maximum proliferation at day 4 (96 hr) of culture. Heat treatment (100 degrees C for 60 min) of toxic shock toxin attenuated its mitogenic effects by only a small amount, and this attenuation could be reversed with increasing concentration of the toxin. By cytofluorography, both untreated and toxic shock toxin-treated small lymphocytes manifested normal percentages of OKT3+, OKT11+, OKT4+, OKT8+, HLA/DR+, and Leu-7+ cells. However, toxic shock toxin-induced blasts were 99% OKT11+ and expressed the receptor for interleukin 2 (89%-100% TAC+). Approximately 85% of the blasts were OKT4+, and 25% of the blasts were OKT8+. Proliferation of purified, double-rosetted T cells was enhanced monotonically by the addition of irradiated "non-T" cells. Irradiated, monocyte-enriched non-T cells were 2.5 times more potent than unfractionated non-T cells in producing quantitatively similar proliferation by toxic shock toxin-stimulated, autologous T cells. In addition, preincubation of non-T cells for 24 hr with toxic shock toxin, followed by extensive washing and irradiation, induced substantial proliferation by unexposed, autologous T cells. These data show that toxic shock toxin is mitogenic for T cells and requires accessory cells for maximal activity. Further, this substance appears to induce both a subset of OKT4+ (Class II MHC-restricted) and OKT8+ (Class I MHC-restricted) blasts.

Antigen-Presenting Cells↗

The diagnosis and treatment of pyogenic liver abscesses.

Pyogenic liver abscesses in 106 adult patients at The New York Hospital were reviewed to define optimum treatment. Mortality in the surgically treated patients was 26% (17/65), while those treated nonsurgically had a fatality rate of 95% (39/41). Multiple abscesses treated surgically had a surprisingly low mortality of 29% (5/17). Modern noninvasive tests are highly sensitive in diagnosing liver lesions greater than 2 cm. Difficulty remains in identifying small hepatic abscesses and differentiating large abscesses from tumor. Most liver abscesses have an identifiable source outside the liver. The most common source (31%) was cholangitis secondary to extrahepatic biliary obstruction. Multiple abscesses, mixed organisms, hyperbilirubinemia, and abscess complications are all associated with a significantly increased mortality. However, the lethality of the primary disease process was the most important factor determining survival. Most patients who have the underlying pathogenesis of the abscess controlled will survive surgical treatment. Transperitoneal surgical drainage and antibiotics remain the mainstay of treatment. Percutaneous drainage is recommended for high risk patients only.

Adult↗

Increased chromium uptake in polymorphonuclear leukocytes from burned patients.

Following thermal injury neutrophil function is severely impaired and thought to be hypometabolic; however, the host is considered to be hypermetabolic. To further investigate the metabolism and the function of neutrophils following thermal injury, neutrophil migration and chromium uptake were studied using radio-labelled neutrophils. Random and directed migration were found to be significantly reduced compared to control values. Neutrophil lysozyme content was also reduced in these burn cells while serum lysozyme from the same patients was significantly elevated over control values. These data suggest lysozyme is released by the neutrophil into the circulatory system. The influx of chromium in cells from burned patients was much greater than the influx in normal cells used in studies for chemotaxis. Influx of chromium over time and over varying concentrations of chromium was linear (r2 = 0.90) in cells from burned patients and normals. Cells from burned patients, however, took up more chromium than normals. Influx velocity of chromium was also determined and found to be greater in burn cells than normal cells. Since it has been shown that chromium influx is an energy-dependent reaction it is suggested that cellular energy stores are being depleted by the influx of chromium. Whether this is a response to an intracellular deficit or uncoupling of metabolic pathways is not known at this time.

Adult↗

A fifty year experience with Meckel's diverticulum.

Four hundred and two patients with Meckel's diverticulum are reviewed. Symptoms referable to the diverticulum occurred in 68 patients or 16.9 per cent of the group. Obstruction of the small intestine, inflammation and lower gastrointestinal tract bleeding accounted for 90 per cent of the presenting symptoms. A 10.3 per cent mortality and a 17.6 per cent morbidity rate were noted for symptomatic diverticuli. Patients most likely to have symptoms develop were 40 years of age, or younger; those whose diverticuli were 2 centimeters or more in length; those whose diverticuli contained heterotopic mucosa, and, probably, those who were males. Patients more than 40 years of age with diverticuli less than 2 centimeters in length with no heterotopic mucosa and who were females constitute a lower risk group. The decision to perform an incidental Meckel's diverticulectomy should be based upon the risk of the individual patient having symptoms develop from the diverticulum.

Adolescent↗

Pancreaticoduodenectomy for benign disease.

Ten cases of pancreaticoduodenectomy (PD) performed for benign disease are reported with all patients alive and well at an average of 7.5 years. A review of the English literature reveals that 52 patients have had a PD for benign disease in which a carcinoma had originally been suspected (incidence of 1%) with an overall surgical mortality of 9.6%. Three hundred and thirty-four cases of PD done for complications of pancreatitis have been reported with an overall mortality of 4.8%. On rare occasion, despite extensive preoperative evaluation, a patient will be explored with true uncertainty as to the diagnosis of a periampullary mass. Under these circumstances, it has been considered good surgical judgement to proceed with resection, considering that the lesion may be benign, as opposed to leaving behind an early resectable malignant lesion. Results of this review support this policy only in that if the PD is done for what turns out to be benign disease, the perioperative mortality is low, and an excellent long-term survival can be expected.

Aged↗

Sepsis following burns, trauma, and intra-abdominal infections.

In the last ten years anaerobic organisms have emerged as the major infecting agent in surgical patients. While these groups of organisms including Bacteroides fragilis, clostridia, and anaerobic cocci persist, there has, in addition, developed in the last few years a virulent group of nosocomial infections, and modern management of sepsis is primarily directed at gram-negative and anaerobic infections, which include nosocomial infections, for example, those caused by the Serratia group. Much has been learned about control of infections from the patient who has sustained thermal injury. While topical water-soluble antibiotics have been a remarkable advance in the care of the burn patient, systemic and subeschar antibiotics have proved essential in the management of severe burn injury. There is increasing evidence that there is remarkable interference with host defense mechanisms in patients who have sustained burns or significant trauma or intraabdominal infection. The patient sustaining nonthermal traumatic injury also sustains reduction in host resistance. Because of this and the additional initial contamination, in the traumatized patient antibiotic therapy should be started early and as a therapeutic measure. Newer localization techniques, including sonography and computed axial tomography scanning, have helped localize abdominal infections early. Specific antimicrobial therapy may be begun as an adjunct to the surgical therapy of intra-abdominal infection.

Abdomen↗

Delayed wound infection. An 11-year survey.

A small number of patients manifest wound infections several months to several years after their operations. A study was undertaken to delineate the clinical characteristics of patients whose infections became apparent after a prolonged time interval from surgery. Twenty-six patients were admitted to the New York Hospital-Cornell University Medical Center, with wound infections that occurred more than six months postoperatively. There were three distinct groups. The first group consisted of patients with Staphylococcus aureus infections related to superficial stitch abscesses. The second group comprised patients with pacemaker infections; S epidermidis was the most frequently recovered organism. The third group consisted of patients with more clinically significant infections. These infectious complications followed genitourinary, gastrointestinal, and biliary surgery. The findings of this study suggest that most of these infections are caused by organisms introduced into the wound at the time of surgery; these organisms may become active because of alterations in the host's resistance.

Adult↗

Pancreaticoduodenectomy. A 40-year experience.

One hundred six pancreaticoduodenectomies, including 10 cases done for benign disease were reviewed, retrospectively, and 51 factors analyzed. There is a significant difference in survival based upon final pathologic diagnosis. Five-year survivals were 0% for adenocarcinoma of the pancreas, 38% for duodenal carcinoma, 24% for CBD caracinoma, 30% for ampullary carcinoma, 24% for other cancers not considered part of the ampullary carcinoma, 24% for other cancers not considered part of the ampullary region, and 100% for those with benign disease (chi 2 = 24.66, df = 5, p = 0.0002). Four statistically significant poor prognostic factors were identified, including age greater than 51 years, serum bilirubin level greater than 6 mg/dl, SGOT greater than 100, and a previous drainage procedure. Results of this study seem to indicate that the pancreaticoduodenectomy has limited indications in adenocarcinoma of the pancreas, but remains the procedure of choice for all other periampullary lesions including suspicious lesions with a negative biopsy at the time of surgery.

Adolescent↗

Carcinoma arising in pilonidal sinuses.

Pilonidal carcinoma is an infrequent complication of pilonidal disease. The surgeon's suspicion should be raised in cases of longstanding pilonidal inflammation. The disease occurs most frequently in men. The lesion is often a well-differentiated squamous carcinoma. Wide excisions at the initial procedure following a brief period of local wound care, is the optimum treatment and increases the chances for a five-year survival. Definitive closure of the defect is delayed and accomplished by rotational flaps or skin grafts. It palpable nodes are present in the inguinal region they should be biopsied even though this does not necessarily connote metastasis. When inguinal node metastasis is present, this is associated with a poor prognosis. The incidence of occult node metastasis is not known because no prophylactic groin dissections were performed. Staged groin dissections were not associated with any long-term survivals. The series was too small to determine its palliative potential. Radiation therapy may palliate local bone or soft tissue recurrences. Re-excisions of local soft tissue recurrences can provide, in some instances, long disease-free intervals. Both topical and systemic chemotherapy were administered in more recent cases with poor results, but this series is not large enough to form conclusions for this modality of treatment.

Carcinoma, Squamous Cell↗

Gastrointestinal carcinoids and the malignant carcinoid syndrome.

The records of 59 patients with gastrointestinal carcinoid tumors at The New York Hospital from 1948 to 1978 were reviewed. Forty-seven instances were diagnosed surgically; 12 were identified on autopsy specimens. The average age at diagnosis was 55.8 years. No association with duodenal ulcer or carcinoma could be made. The appendix was the mose common site of origin, followed by the ileum, rectum and colon, respectively. Jejunoileal carcinoids were multiple in 37 per cent of the patients. Primary tumors of the colon had the highest malignant potential and only two patients had the malignant carcinoid syndrome. Radical excision of all primary tumors is advocated.

Adolescent↗