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Biomedical subjects

G J Slotman

Publications and source records attributed to G J Slotman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Platelet activating factor mediates cardiopulmonary dysfunction during graded bacteremic shock.

OBJECTIVE: To determine whether or not platelet activating factor (PAF) is a necessary mediator of cardiovascular dysfunction during graded bacteremia, and to identify PAF interactions with eicosanoids and tumor necrosis factor-alpha (TNF-alpha). METHODS: Seventeen anesthetized, hemodynamically monitored adult swine were studied for 4 hours in three groups. Group 1 (ANES, n = 5) were anesthesia controls; group 2 (septic control, SC, n = 6) received intravenous Aeromonas hydrophila (109/mL) at rates incrementally increased from 0.2 to 4.0 mL/ kg/h; group 3 (WEB, n = 6) received the PAF receptor antagonist WEB 2086, 3.0 mg/kg intravenously, then A. hydrophila. Cardiopulmonary parameters and plasma thromboxane B2 (TXB2), prostaglandin 6-keto F1 alpha (PGI2), leukotriene B4 (LTB4), leukotrienes C4D4E4 (LTC4D4E4), and TNF-alpha were measured hourly. Statistical analysis was carried out using two-way analysis of variance (ANOVA) for repeated measurements, Dunnett's t test, and Student's t test, where appropriate. Statistical significance was determined at the 95% confidence interval. Values are presented as the mean +/- SEM. RESULTS: Pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure heart rate, VO2 and O2ER decreased significantly after WEB 2086 infusion, compared with SC, and mean arterial pressure, systemic vascular resistance index, stroke volume index, and left ventricular stroke work index increased. Arterial pH decreased significantly in SC animals, but was maintained at normal levels during bacteremia in the WEB group. Differences between WEB and SC for cardiac index, pulmonary vascular resistance index, right ventricular stroke work index, PaO2, SaO2, and PcO2, were not significant. The addition of WEB 2086 significantly decreased plasma levels of TXB2, PGI2, LTB4, and TNF-alpha compared with the SC group. LTC4D4E4 was decreased in WEB compared with SC animals, in which LTC4D4E4 increased during graded bacteremia. CONCLUSIONS: PAF is necessary to the development of systemic vasodilation and hypotension, pulmonary hypertension, decreased stroke volume, metabolic acidosis, and increased oxygen uptake during graded bacteremia. PAF-induced eicosanoid and cytokine release may be involved.

Aeromonas hydrophila↗
PubMed1996

Evaluation of enzyme-linked immunosorbent assays for quantitation of eicosanoid mediators of sepsis syndrome.

Thromboxane, prostacyclin, and the leukotrienes are eicosanoids that have been implicated as mediators of the host inflammatory response to infection and injury. Commercial enzyme-linked immunosorbent assays (ELISA) are being increasingly utilized to quantitate plasma eicosanoid concentrations in both clinical and experimental systemic inflammatory conditions. The objectives of this study were to 1) critically examine the performance characteristics of commercial ELISA kits for thromboxane B2, 6 keto-prostaglandin F1 alpha, leukotriene B4, and leukotrienes C4, D4, and E4; 2) apply the four ELISA kits in obtaining actual eicosanoid plasma values under both baseline and septic conditions; and 3) recommend quality control measures for general use. Although averages of multiple standard curves from individual assays were variable, there was a strong linear regression relationship between the backfit dose and nominal dose for each level of standard. Precision profiles constructed for each assay type defined a working range where the intra-assay coefficient of variation is less than 10%. Backfit doses deviated most from nominal doses at both extremes of the standard curves and this variation is reflected in the higher percentage errors in these regions. Recovery of each eicosanoid analyte was 96-103%. Calculated sensitivities were somewhat higher than the manufacturer's specifications. When applied to actual measurements in human and porcine plasma, the assays yielded values that fell within the working ranges of the standard curves with the exception of leukotriene B4. Thus, the ELISAs examined were reproducible, precise, and accurate within a specific working range for each assay type. However, internal controls were lacking in the commercial kits examined, which made assessment of intra- and inter-assay variation difficult.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Laparoscopic L5-S1 diskectomy: a cost-effective, minimally invasive general surgery--neurosurgery team alternative to laminectomy.

Laparoscopic L5-S1 diskectomy (LLD) is a promising new technique for managing disabling pain from herniated lumbar disks. It is unknown, however, whether the clinical results of LLD are superior to those of traditional laminectomy (LAM). This study was undertaken, therefore, in order to compare LLD and LAM in the management of L5-S1 disk herniation unresponsive to conservative treatment measures. Clinical records of 22 patients who underwent 23 LLD procedures and of 23 LAM patients were reviewed with respect to demographics and median age, operative blood loss, operative time, hospital stay, and time of rehabilitation to work/normal activity, as well as postoperative morbidity, recurrent symptoms, long-term functional status, and inhospital patient charges. Two LLD patients had undergone LAM previously, and one had a percutaneous microdiskectomy. All LLD patients had relief of disk pain immediately after surgery. Morbidity after LLD included transient brachial plexus neuropraxia (1), urinary retention (1), and rectus hematoma (1). No LAM complications were reported. Among LLD patients, compared with LAM, median age (34.5 years versus 40 years), estimated blood loss (12 mL versus 68 mL), hospital length of stay (1 day versus 3 days), time to normal activity (17 days versus 79 days) and mean inhospital patient charges ($5,737 +/- 283 versus $7,762 +/- 662) were reduced significantly (P < 0.05). LLD operating time was significantly longer than LAM (210 versus 160 minutes median, P < 0.01). With a median follow-up time of 11.0 months (range, 2 to 23 months) all LLD patients had returned to normal activity, whereas 7 of the LAM group (30%) remained disabled (P < 0.01). Sixty-eight per cent of LLD patients were pain-free during follow-up, compared with 39 per cent of the LAM group (P < 0.05). Sixty-four per cent of LLD patients and 57 per cent of the LAM group needed postoperatively physical therapy. One LLD and 4 LAM patients required reoperation, by LLD and LAM, respectively, for recurrent disk herniation. LLD is a safe, cost-effective, minimally invasive operation for managing disabling L5-S1 disk herniation. Compared with LAM, LLD reduces blood loss, length of stay, rehabilitation time, and patient charges, and improves long-term functional and pain-free status. LLD should be considered as an alternative to LAM for patients with herniated L5-S1 intervertebral disks unresponsive to conservative management.

Adult↗
PubMed1995

Comparison of the hemodynamic effects of gasless abdominal distention and CO2 pneumoperitoneum during incremental positive end-expiratory pressure.

Laparoscopy is used increasingly in managing critically ill patients. Carbon dioxide (CO2) pneumoperitoneum is used during these procedures. The increased intra-abdominal pressure of CO2 pneumoperitoneum, however, can affect cardiopulmonary performance adversely. Recently, gasless abdominal wall distention has been introduced as an alternative to CO2 pneumoperitoneum. The purpose of this study was to compare the hemodynamic effects of gasless abdominal distention (GAD) with those of CO2 pneumoperitoneum during mechanical ventilation with positive end-expiratory pressure (PEEP). Six anesthetized, paralyzed, mechanically ventilated adult swine were monitored with pulmonary artery and arterial catheters at incremental values of PEEP (0-20 cm H2O, by 5, Control) and then allowed to return to baseline hemodynamic status at 0 cm H2O PEEP. The animals were then randomly assigned to receive either CO2 pneumoperitoneum at 15 mm Hg intra-abdominal pressure (PNEUMO) or GAD (equal to anterior abdominal wall displacement of CO2) and PEEP was reapplied. The animals were allowed to return to hemodynamic baseline and PEEP was reapplied with the alternate method of abdominal wall distention. A complete hemodynamic profile and arterial/mixed venous blood gas measurements were monitored at each value of PEEP. With GAD, central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and PaCO2 were significantly reduced, compared to PNEUMO, and PaO2 was increased. Cardiac index was higher in GAD versus PNEUMO at baseline, but was lower for GAD at PEEP levels above 10 cm H2O. These results indicate that in its net effect, GAD does not exacerbate the adverse hemodynamic effects of PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1995

Laparoscopic laser lumbar diskectomy. Operative technique and case report.

Approximately 300,000 patients each year in the United States undergo laminectomy for disabling lumbar disc herniation. Post-laminectomy hospitalization is 3-7 days and convalescence may be prolonged. As an alternative to laminectomy, we have developed a technique for performing L5-S1 lumbar diskectomy laparoscopically. Using an anterior approach, the intervertebral disc space is opened and the diskectomy is performed under direct videolaparoscopic imaging. After pneumoperitoneum is established, the patient is placed in a steep Trendelenburg position. The small bowel is retracted cephalad and the colon is moved to the left. The iliac vessels are identified visually and by Doppler probe, and the presacral space is dissected in the midline to expose the L5-S1 disc. In the case presented, the disc annulus was opened with the Nd:YAG contact laser, and diskectomy was performed under direct videolaparoscopic vision using standard neurosurgical instruments modified for laparoscopy. The posterior longitudinal ligament can be visualized directly to define the posterior limits of the completed diskectomy. In the case described, pain relief was confirmed immediately after the procedure. The patient was discharged after 2 hospital days, and returned to normal activity in 8 days.

Adult↗
PubMed1995

Interleukin-1 mediates increased plasma levels of eicosanoids and cytokines in patients with sepsis syndrome.

The purpose of this was to study evaluate the effects of interleukin-1 (IL-1) inhibition by human recombinant IL-1 receptor antagonist (IL-1ra) on plasma prostaglandin, leukotriene, and cytokine levels in sepsis syndrome. As part of a multisite, prospective, randomized, double-blind, placebo-controlled clinical trial, 19 septic patients received IL-1ra in a 100 mg bolus followed by 2.0 mg/kg/h i.v. for 72 h (n = 10) or placebo (n = 9). Plasma thromboxane B2 (TXB2), prostaglandin 6-keto-F1 alpha (PGI), leukotriene B4 (LTB4), leukotrienes C4D4E4 (LTC4D4E4), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF) were measured by ELISA before study drug infusion (baseline) and at 24, 48, 72, and 96 h after the beginning of the study drug infusion. Differences between placebo and IL-1-ra for plasma LTB4 and TNF were not significant. Plasma TXB2, PGI, LTC4D4E4, and IL-6, expressed as % baseline, were significantly lower in patients receiving IL-1ra than in the placebo group (p < .05), while plasma IL-1 was increased significantly. IL-1 may be a necessary mediator of increased circulating PGI, TXB2, LTC4D4E4, and IL-6 levels in patients with sepsis syndrome. Plasma IL-1 is increased with infusion of IL-1ra. The clinical significance of IL-1 in modifying circulating eicosanoid and cytokine concentrations in clinical sepsis is not clear from the data.

Adolescent↗
PubMed1995

Laparoscopic lumbar diskectomy: preliminary report of a minimally invasive anterior approach to the herniated L5-S1 disk.

Approximately 300,000 patients each year in the United States undergo laminectomy for disabling lumbar disk herniation. Postlaminectomy hospitalization is 3-7 days and convalescence may be prolonged. As an alternative to laminectomy, we have developed a technique for performing L5-S1 lumbar diskectomy laparoscopically. Using an anterior approach, the intervertebral disk space is opened and the diskectomy is performed under direct videolaparoscopic imaging. After pneumoperitoneum is established, the patient is placed in a steep Trendelenburg position. The small bowel is retracted cephalad and the colon moved to the left. The iliac vessels are identified visually and by Doppler probe. Then the presacral space is dissected in the midline to expose the L5-S1 disk. The disk annulus is opened with the Nd:YAG contact laser (four cases) or the harmonic scalpel (three cases). Diskectomy is performed under direct videolaparoscopic vision using standard neurosurgical instruments modified for laparoscopy. The posterior longitudinal ligament can be visualized directly to define the posterior limits of the completed diskectomy. Laparoscopy lumbar diskectomy has been performed on seven patients (five male, two female). No perioperative complications occurred. All seven patients had immediate relief of back pain after laparoscopic lumbar diskectomy. Five patients were discharged the next day and two on the second postoperative day. L5-S1 laparoscopic lumbar diskectomy is feasible and safe. It may be an effective minimally invasive alternative to laminectomy.

Adult↗
PubMed1994

Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group.

OBJECTIVE: To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) in the treatment of sepsis syndrome. STUDY DESIGN: Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. POPULATION: A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. OUTCOME MEASURE: Twenty-eight-day all-cause mortality. RESULTS: There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n = 893; generalized Wilcoxon statistic, P = .22) or among patients with shock at study entry (n = 713; generalized Wilcoxon statistic, P = .23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n = 563; linear dose-response, P = .009). Retrospective analysis demonstrated an increase in survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n = 580; linear dose-response, P = .005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n = 411; linear dose-response, P = .002). CONCLUSIONS: There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater.

Adult↗
PubMed1994

Nd:YAG laser scalpel compared with conventional techniques in head and neck cancer surgery.

Many theoretical advantages over conventional surgical techniques have been attributed to the Nd:YAG contact laser. Clinically significant differences in perioperative results between the Nd:YAG contact laser and standard surgery, however, are not well defined. The present study was undertaken to evaluate the Nd:YAG contact laser compared with standard scalpel and/or electrocautery in curative operations for head and neck cancer. Clinical records of 36 patients undergoing head and neck cancer surgery were reviewed retrospectively. Patients were studied in three groups: 9 previously irradiated patients operated upon using the Nd:YAG laser (Nd:YAG); 9 previously irradiated patients operated upon using conventional techniques (conventional/RT); 18 nonirradiated patients operated upon using conventional techniques (conventional/no RT). These groups underwent 14, 14, and 25 procedures, respectively. Differences between the Nd:YAG, conventional/RT, and conventional/no RT groups regarding cancer staging, age, procedures performed, operative time, intraoperative blood loss, and hospital and ICU stay were not statistically significant. Preoperative radiotherapy dosages in the Nd:YAG and conventional/RT groups were similar (5,127 +/- 842 vs. 604 +/- 2,373 cGy). Postoperative morbidity in Nd:YAG patients (11%) was similar to that of the conventional/no RT group (17%) and was significantly reduced compared to conventional/RT (11% vs. 56%, P < 0.05). Clinical outcome, including operative time, blood loss, and hospital and ICU stay using the Nd:YAG contact laser in curative operations on previously irradiated patients with head and neck cancer, is equal to that of conventional surgical techniques, with or without preoperative radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Loss, Surgical↗
PubMed1994

Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial.

OBJECTIVES: To evaluate the safety, pharmacokinetics, and efficacy of human recombinant interleukin-1 receptor antagonist (IL-1ra) in the treatment of patients with sepsis syndrome. DESIGN: Prospective, open-label, placebo-controlled, phase II, multicenter clinical trial using three different doses of human recombinant IL-1ra. SETTING: Twelve academic medical center intensive care units in the United States. PATIENTS: Ninety-nine patients with sepsis syndrome or septic shock who received standard supportive care and antimicrobial therapy, in addition to infusion with escalating doses of IL-1ra or placebo. INTERVENTIONS: Patients received an intravenous loading dose of either human recombinant IL-1ra (100 mg) or placebo, followed by a 72-hr intravenous infusion of either one of three doses of IL-1ra (17, 67, or 133 mg/hr) or placebo. All patients were evaluated for 28-day, all-cause mortality. MEASUREMENTS AND MAIN RESULTS: A dose-dependent, 28-day survival benefit was associated with IL-1ra treatment (p = .015), as indicated by the following mortality rates: 11 (44%) deaths among 25 placebo patients; eight (32%) deaths among 25 patients receiving IL-1ra 17 mg/hr; six (25%) deaths among 24 patients receiving IL-1ra 67 mg/hr; and four (16%) deaths among 25 patients receiving IL-1ra 133 mg/hr. A dose-related survival benefit was observed with infusion of IL-1ra in patients with septic shock at study entry (n = 65; p = .002) and in patients with Gram-negative infection (n = 45; p = .04). Patients with an increased circulating interleukin-6 (IL-6) concentration of > 100 pg/mL at study entry demonstrated a dose-related survival benefit with IL-1ra treatment (p = .009). In patients with an increased IL-6 concentration at study entry, the magnitude of the decrease in IL-6 concentration 24 hrs after the initiation of therapy was correlated with increasing the IL-1ra treatment dose (p = .052). A significant dose-related reduction in the Acute Physiology and Chronic Health Evaluation (APACHE II) score was achieved by the end of infusion (p = .038). A renal elimination mechanism for IL-1ra was suggested by the positive correlation between IL-1ra plasma clearance and estimated creatinine clearance (p = .001; r2 = .51). Human recombinant IL-1ra was well tolerated. CONCLUSIONS: This initial evaluation suggests that human recombinant IL-1ra is safe and may provide a dose-related survival advantage to patients with sepsis syndrome. A larger, definitive clinical trial is needed to confirm these findings.

Adult↗
PubMed1994

Laser-assisted laparoscopic lumbar diskectomy.

The authors report the first excision of a herniated lumbar disk using the combination of laparoscopic exposure and contact laser application. A 27-year-old patient experienced immediate complete relief of back and leg pain. Laser-assisted laparoscopic lumbar diskectomy offers unique advantages.

Adult↗
PubMed1994

Fungal sepsis: multisite colonization versus fungemia.

The indications for therapy and the best treatment regimens for systemic fungal infections are not well defined. The purpose of this study was to evaluate retrospectively patient management and outcome in critically ill patients with multiple sites of fungal colonization and/or fungemia. Medical records of 36 fungemic patients and 76 patients without fungemia who had two or more anatomic sites colonized with fungal organisms were reviewed. There were 53 males and 59 females, with a mean age of 58 years (range 15-86). Eighty-four patients (74%) underwent 238 operations (41% elective, 59% emergent). Gastrointestinal (37%), thoracic (15%), and orthopedic (13%) procedures were most common. Concomitant, nonfungal bacteremia was present in 56 patients (50%). Seventy-one patients (63%) received systemic antifungal therapy. Mortality differences between patients with fungemia (17/36; 47%) and fungus-colonized patients (31/76; 41%) were not statistically significant. Amphotericin B treatment of fungemia reduced mortality overall (26% vs 71%, P < 0.05) and compared with fungemic patients receiving other antifungals (26% vs 50%, P < 0.05). Among fungus-colonized patients, mortality was higher with amphotericin B than without (70% vs 36%, P < 0.05) and was not changed by treatment with other antifungals (37% vs 34%). Increased gastrointestinal operations, wound infections, and intraperitoneal fungi and bacteria in fungus-colonized patients receiving amphotericin B suggest that these patients were the most critically ill. The mortality of multisite fungal colonization is as high as that of fungemia. Only amphotericin B improves survival in fungemia. The best treatment for multisite colonization is not clear from the data.

Adolescent↗
PubMed1993

Detrimental effects of high-dose methylprednisolone sodium succinate on serum concentrations of hepatic and renal function indicators in severe sepsis and septic shock. The Methylprednisolone Severe Sepsis Study Group.

OBJECTIVE: To evaluate the effects of high-dose methylprednisolone sodium succinate on biochemical markers of hepatic and renal function in patients with severe sepsis and septic shock. DESIGN: Retrospective analysis of serial serum chemistries in 382 patients who were entered prospectively into a randomized, placebo-controlled, double-blind clinical trial of high-dose methylprednisolone or placebo in the sepsis syndrome. SETTING: The original study was conducted at 19 academic centers. PATIENTS: Adult patients in severe sepsis or septic shock who met the study entry criteria, which included a clinically defined source of infection and signs of systemic sepsis, were enrolled into the study. Three hundred eighty-two patients were evaluated. INTERVENTIONS: Patients received either methylprednisolone (30 mg/kg) or placebo by iv infusion every 6 hrs for four doses. Hemodynamic variables and serum concentrations of creatinine, urea nitrogen, bilirubin, and aspartate aminotransferase (AST) were recorded on entering the study, at 12 and 24 hrs, and at 3, 7, and 14 days after the first infusion of methylprednisolone or placebo. These data were analyzed retrospectively. MAIN OUTCOME MEASUREMENTS: Hemodynamic and biochemical data were analyzed to determine whether or not hepatic and renal function in the sepsis syndrome had been influenced by methylprednisolone treatment. RESULTS: Differences between methylprednisolone and placebo in hemodynamic variables, the occurrence rate of shock and recovery from shock, mortality rates and serum concentrations of creatinine and AST were not statistically significant. At 12 and 24 hrs, and at 3 and 7 days after the first drug infusion (of methylprednisolone or placebo), blood urea nitrogen was increased from baseline values in a significantly (p < .01) greater proportion of the methylprednisolone-treated patients compared with placebo-treated patients. The frequency of increased serum bilirubin concentrations was significantly (p < .01) greater among methylprednisolone patients vs. the placebo group at 12 and 24 hrs. CONCLUSIONS: The frequency of acutely increased blood urea nitrogen and bilirubin concentrations in severe sepsis was increased significantly with high-dose methylprednisolone therapy. Similar frequencies of circulatory shock in the study groups excluded differences in global perfusion as a cause of this phenomenon. Possible adverse effects of pharmacologic concentrations of methylprednisolone in critically ill patients should be considered in planning treatment.

Aspartate Aminotransferases↗
PubMed1993

Hemodynamic effects of carbon dioxide pneumoperitoneum during mechanical ventilation and positive end-expiratory pressure.

Laparoscopy is frequently used for diagnosis and treatment of critically ill trauma patients. Its effects on cardiopulmonary performance in the intensive care unit patient population, however, are not well-defined. This study evaluated the effects of positive end-expiratory pressure (PEEP) and carbon dioxide (CO2) pneumoperitoneum on hemodynamic function during mechanical ventilation. Five anesthetized, mechanically ventilated adult swine were monitored with pulmonary artery and arterial catheters at 0, 5, 10, 15, and 20 cm H2O PEEP without, and then with 15 mm Hg CO2 pneumoperitoneum. A hemodynamic profile, analyses of arterial and mixed venous blood gases and mixed venous hemoglobin oxygen saturation values were obtained at each data point. Compared with the non-insufflated group, CO2 pneumoperitoneum significantly increased central venous pressure, mean arterial pressure, mean pulmonary artery pressure, pulmonary vascular resistance index, and stroke index for the range of PEEP levels. With PEEP of 10 cm H2O, hemodynamic changes in non-insufflated animals were not statistically significant, but with CO2 pneumoperitoneum, stroke index and left ventricular stroke work index were decreased at 5 cm H2O PEEP, as was cardiac index at 10 cm PEEP. Pulmonary gas exchange was not affected by CO2 pneumoperitoneum. The results indicate that, in this paradigm, CO2 pneumoperitoneum for laparoscopy increases ventricular afterload and exacerbates the adverse effects of PEEP. These findings could be clinically significant in critically ill patients.

Animals↗
PubMed1992

Preoperative combined chemotherapy and radiation therapy plus radical surgery in advanced head and neck cancer. Five-year results with impressive complete response rates and high survival.

Radiation therapy combined with cisplatin as a chemoradiation sensitizer (CT/RT) has been reported to enhance tumor response in squamous cell carcinoma of the head and neck. In the present study, CT/RT was used preoperatively in advanced Stage III and IV head and neck cancer. Fifty-three patients were entered prospectively into a Phase II study. Treatment consisted of 4500 cGy of radiation therapy in 5 weeks combined with cisplatin 20 mg/m2 for 4 days during weeks 1 and 4 of radiation therapy. This was followed 4 to 8 weeks later by curative surgery. Pretherapy dental care; long-term nutritional support; individualized skin, mouth, and wound care; and continuous interdisciplinary communication were integral parts of this regimen. In four patients, CT/RT toxicity was seen (8%); three episodes of skin reaction or stomatitis and three episodes of leukopenia (less than 2500/microliters), causing a delay in CT/RT treatment in one patient. Three patients died of other causes during the preoperative interval, without clinical evidence of toxicity. Fifty patients (94%) had a complete (CR) or partial response (PR) to CT/RT. Clinical CR was seen in 38 of 51 (75%) primary tumors and 21 of 27 (78%) cervical nodes. Forty-one patients (77%) underwent curative surgery. In 27 of 32 (84%) resected CR primary tumors and 16 of 18 (89%) CR metastatic nodes, the surgical specimen was microscopically free of tumor. Postoperative morbidity was 32%. Five patients (12%) required additional surgery for their complications. Perioperative mortality was 5%. Five patients had tumor recurrence: three postoperatively after clinical PR to CT/RT and two in clinical CR patients who refused further treatment after CT/RT, then had a recurrence and were salvaged surgically. No patient with a CR in both the tumor and nodes who underwent surgery had a tumor recurrence. With a follow-up of 8 years (median, 40 months), the median survival for all patients was 45 months. The 5-year actuarial survival rate was 43% for all patients and 55% for patients who had CT/RT and surgery. This multimodality treatment of advanced head and neck cancer has low toxicity and impressive survival. It renders a significant number of patients tumor-free before surgery. These patients may be candidates for additional study triaging additional CT/RT for complete CR only and surgery for PR and biopsy-proved residual disease.

Adult↗
PubMed1992

Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

OBJECTIVE: To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. DESIGN: Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. SETTING: Multi-institutional medical and surgical ICUs. PATIENTS: Patients meeting predetermined criteria for severe sepsis syndrome. INTERVENTIONS: Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. CONCLUSIONS: This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

Adolescent↗