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Biomedical subjects

J B Hall

Publications and source records attributed to J B Hall.

At least 19 recordsLinked to original sources

A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies.

OBJECTIVE: The primary objective of this study was to determine the rate of response to matuzumab in patients with recurrent, EGFR-positive ovarian, or primary peritoneal cancer. Secondary end points included safety and tolerability, time to tumor progression, duration of response, and overall survival. METHODS: A multi-institutional single arm phase II trial. RESULTS: Of 75 women screened for the study, 37 were enrolled and treated. Median age of the treated patient population was 58 years, and most patients had more than four prior lines of chemotherapy. Therapy was well tolerated, the most common toxicities being a constellation of skin toxicities, including rash, acne, dry skin, and paronychia, as well as headache, fatigue, and diarrhea. Serious adverse events were very rare but included a single episode of pancreatitis that may have been drug related. All patients completed therapy, receiving 1 to 30 infusions of matuzumab. There were no formal responses (RR=0%, 95% CI: 0-9.5%), although 7 patients (21%) were on therapy for more than 3 months with stable disease. CONCLUSIONS: Matuzumab at the dose and schedule selected is well tolerated. In this population of very heavily pretreated patients with epithelial ovarian and primary peritoneal malignancies, there was no evidence of significant clinical activity when matuzumab was administered as monotherapy.

Adult↗

Effect of timing of prostaglandin administration, controlled internal drug release removal and gonadotropin releasing hormone administration on pregnancy rate in fixed-time AI protocols in crossbred Angus cows.

Two experiments were conducted to investigate the effects of timing of prostaglandin F2(alpha) (PGF2(alpha)) administration, controlled internal drug release device (CIDR) removal and second gonodotropin releasing hormone (GnRH) administration on the pregnancy outcome in CIDR-based synchronization protocols. In Experiment 1, suckled Angus crossbred beef cows (n = 580) were given 100 microg of GnRH+a CIDR on Day 0. Cows in Group 1 (modified Ovsynch-P) received 25 mg of dinoprost (PGF2(alpha)) and CIDR device removal on Day 8 (AM), 100 microg of GnRH 36 h later on Day 9 (p.m.), and fixed-time AI (FTAI) 16 h later on Day 10 (47.5+/-1.1 h after PGF2(alpha)). Cows in Group 2 (Ovsynch-P) received 25mg of PGF2(alpha) and CIDR device removal on Day 7 (p.m.), 100 microg of GnRH 48 h later on Day 9 and FTAI 16 h later on Day 10 (66.6+/-1.2 h after PGF2(alpha)). Pregnancy rates were 56.5% (170/301) for Group 1 and 55.6% (155/279) for Group 2, respectively (P = 0.47). In Experiment 2, beef cows (n=734) were synchronized with 100 microg of GnRH+CIDR on Day 0, 25 mg of PGF2(alpha) and CIDR device removal on Day 7 and either 100 microg of GnRH 48 h later on Day 9 (Ovsynch-P) and FTAI 16 h later on Day 10 (64.9+/-3.3 h from PGF2(alpha)) or 100 microg of GnRH on Day 10 (CO-Synch-P) at the time of AI (63.2+/-4.2 h from PGF2(alpha)). Pregnancy rates were 48.8% (180/369) for Ovsynch-P and 44.7% (163/365) for CO-synch-P groups, respectively (P = 0.11). In both experiments, there was a locationxtreatment interaction (P<0.05); pregnancy rates between locations were different (P < 0.05) in the Ovsynch-P group. In conclusion, in a CIDR-based Ovsynch synchronization protocol, delaying administration of prostaglandin and CIDR removal by 12 h, or timing of the second GnRH by 16 h, did not affect pregnancy rates to FTAI. Therefore, there may be an opportunity to make changes in synchronization protocols with out adversely affecting FTAI pregnancy rates.

Animals↗

Effects of feeding supplemental fat to beef cows on cold tolerance in newborn calves.

Our objectives were to examine the effects of added fat in late-gestation cow diets on neonatal response to cold. In Exp. 1, pregnant fall-calving heifers received control (n = 5), safflower seed (n = 5), or whole cottonseed (n = 5) diets. The hay-based, isonitrogenous, and isocaloric diets, fed for 47 d prepartum, contained 1.5, 4.0, and 5.0% fat for control, safflower, and whole cottonseed diets, respectively. At calving, calf BW and vigor score, as well as fat, lactose, and IgG in colostrum were not affected (P > 0.30) by diet. Heifers fed the safflower diet tended to have greater colostral solids (P < 0.10) than heifers fed the control or whole cottonseed diets. At 6.5 h of age, calves were placed in a 5 degrees C cold room for 90 min. Calf vigor, shivering, body temperature, and blood samples were taken every 15 min. During cold stress, calf body temperature decreased 0.7 degrees C (P < 0.03). Across all diets, shivering and serum glucose concentrations increased (P < 0.05), whereas calf vigor and cortisol concentrations decreased (P < 0.02) during cold exposure. In Exp. 2, pregnant spring-calving cows (n = 98) received a control (n = 47) or whole cottonseed (n = 51) supplement. Hay-based diets fed for 68 d prepartum contained 2.0 and 5.0% fat for control and whole cottonseed diets, respectively. Calf BW, vigor, shivering, dystocia score, time to stand, time to nurse, serum glucose concentrations, and serum IgG were not affected (P > 0.50) by diet. Between 30 and 180 min, body temperature of calves from dams fed the whole cottonseed supplement decreased (P < 0.05) more than calves from dams fed the control supplement. Serum glucose concentrations in calves were not affected by diet (P > 0.30). Serum cortisol concentrations tended (P < 0.09) to be greater for calves from dams fed whole cottonseed than control calves. When ambient temperature was < 6 degrees C, calves born to dams fed whole cottonseed had greater (P < 0.05) BW, tended (P < 0.1) to stand earlier, and had greater serum IgG concentrations. We conclude that calves from dams fed high-fat diets containing safflower or whole cottonseed respond similarly to cold stress, but these responses may not be consistent with greater cold resistance. In addition, high-fat dietary supplementation of late-gestation cows may only be beneficial during calving seasons with prolonged cold weather.

Adaptation, Physiological↗

Cost considerations in sedation, analgesia, and neuromuscular blockade in the intensive care unit.

Sedation of critically ill patients is a costly endeavor. Costs of commonly used intensive care unit (ICU) sedatives range from pennies to more than $500 per day. Although the agents account for some of this expense, complications related to the use of these drugs in the ICU produce even greater costs. Prolongation of mechanical ventilation and length of stay are some of the common complications resulting from non-ideal use of these drugs. Sedative agents also impair neurological evaluation in many critically ill patients, which may mask detection of acute delirium resulting from intercurrent illness or intracranial catastrophes and can lead to excessive diagnostic testing. Opiates may result in gastrointestinal dysfunction with resulting malnutrition and perhaps bacterial translocation and sepsis. Neuromuscular blocking agents may cause prolonged paralysis and disability in critically ill patients who receive them. Simple dosing strategies based on pharmacological principles may decrease the incidence of these costly problems.

Journal Article↗

Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation.

BACKGROUND: Conous infusions of sedative drugs in the intensive care unit may prolong the duration of mechanical ventilation, prolong the length of stay in the intensive care unit and the hospital, impede efforts to perform daily neurologic examinations, and increase the need for tests to assess alterations in mental status. Whether regular interruption of such infusions might accelerate recovery is not known. METHODS: We conducted a randomized, controlled trial involving 128 adult patients who were receiving mechanical ventilation and continuous infusions of sedative drugs in a medical intensive care unit. In the intervention group, the sedative infusions were interrupted until the patients were awake, on a daily basis; in the control group, the infusions were interrupted only at the discretion of the clinicians in the intensive care unit. RESULTS: The median duration of mechanical ventilation was 4.9 days in the intervention group, as compared with 7.3 days in the control group (P=0.004), and the median length of stay in the intensive care unit was 6.4 days as compared with 9.9 days, respectively (P=0.02). Six of the patients in the intervention group (9 percent) underwent diagnostic testing to assess changes in mental status, as compared with 16 of the patients in the control group (27 percent, P=0.02). Complications (e.g., removal of the endotracheal tube by the patient) occurred in three of the patients in the intervention group (4 percent) and four of the patients in the control group (7 percent, P=0.88). CONCLUSIONS: In patients who are receiving mechanical ventilation, daily interruption of sedative-drug infusions decreases the duration of mechanical ventilation and the length of stay in the intensive care unit.

Adult↗

Sexual dysfunction following vulvectomy.

OBJECTIVE: This is a pilot study to evaluate sexual dysfunction in women after vulvectomy. METHODS: An 88-question survey was used to assess body image and the DSM IV criteria for sexual dysfunction on women who had undergone vulvectomy. RESULTS: Forty-seven women agreed to participate in the study and 41 women (87%) returned the survey. There was a significant alteration of body image in these women after vulvectomy (P = 0.004). Sexual frequency significantly decreased after surgery (P = 0.001) and there was significant sexual dysfunction in the categories of sexual aversion disorder (P = 0.01), arousal disorder (P = 0.02), and hypoactive sexual disorder (P = 0. 001). The extent of surgery did not correlate with degree of sexual dysfunction in any category. Women who were depressed at the time of survey (as determined by the PRIME-MD scale) were more likely to suffer sexual aversion disorder (P = 0.05) and tended to have more body image disturbance (P = 0.1) and global sexual dysfunction (P = 0.06). CONCLUSIONS: Women experience significant sexual dysfunction after vulvectomy and the extent of surgery or type of vulvectomy did not correlate with degree of sexual dysfunction. There is a significant need to address sexual problems with all women after any vulvectomy. Age, depression, worsening GOG performance status, and preoperative hypoactive sexual dysfunction were risk factors for sexual dysfunction after vulvar surgery. Appropriate counseling and treatment of depression may be of benefit to this patient population.

Adult↗

Effects of propofol containing EDTA on mineral metabolism in medical ICU patients with pulmonary dysfunction.

OBJECTIVE: To determine whether the addition of disodium edetate (EDTA) to propofol significantly alters mineral metabolism, adverse events, and outcome in critically ill medical patients with acute pulmonary dysfunction. DESIGN: Multicentre, double-randomised, double-blind, comparative trial. SETTING: Medical intensive care units of 5 health centres. PATIENTS: A total of 85 haemodynamically stable men and women aged 18-81 years who had pulmonary dysfunction or adult respiratory distress syndrome as a primary diagnosis or complication and who were expected to require at least 48 hours of sedation and mechanical ventilation. INTERVENTIONS: Patients were randomised to receive propofol with or without EDTA and then to 1 of 2 sedation levels: light (Modified Ramsay Sedation Scale [MRSS] score of 2 to 3) or deep (MRSS score of 4 to 5). Propofol was administered by continuous infusion at an initial rate of 5 microg/kg per min and titrated as needed. MEASUREMENTS AND RESULTS: Approximately 63 % of patients had a high severity of illness as indicated by an Acute Physiology and Chronic Health Evaluation II score > or = 19. As expected, these patients had a higher mortality rate but did not require a higher dose of propofol or propofol with EDTA. Extensive evaluation of cation homeostasis showed that ionised calcium and magnesium concentrations remained remarkably stable during treatment. Total calcium concentration was low as a result of hypoalbuminemia. Parathyroid hormone (PTH) concentration was elevated in both study groups at baseline, on day 4, and at the end of sedation. There were no significant differences in electrolyte levels and no progression to renal dysfunction. There were also no significant differences in haemodynamic or adverse-event profiles. Treatment-related adverse events occurred in 5 patients in each group; 4 of these (in 3 patients receiving propofol and 1 patient receiving propofol with EDTA) were considered serious. Because a large percentage of patients experienced a change in sedation level, no analyses were performed using sedation level. CONCLUSIONS: The addition of EDTA to propofol does not alter calcium and magnesium homeostasis in critically ill patients with acute pulmonary dysfunction. The reason for the elevation in PTH concentrations in such patients is not known.

Adult↗

Safety and efficacy of propofol with EDTA when used for sedation of surgical intensive care unit patients.

OBJECTIVE: To compare propofol with disodium edetate (EDTA) and propofol without EDTAwhen used for the sedation of critically ill surgical intensive care unit (ICU) patients. DESIGN: Prospective, randomised, multicentre trial. PATIENTS: A total of 122 surgical ICU patients who required intubation and mechanical ventilation. INTERVENTIONS: Patients were randomised to receive either propofol or propofol plus EDTA (propofol EDTA) by continuous infusion for sedation. MEASUREMENTS AND RESULTS: The addition of EDTA to propofol had no effect on calcium or magnesium homeostasis, renal function, haemodynamic function, or efficacy when used for the sedation of surgical patients in the ICU. The most common adverse events were hypotension, atrial fibrillation, and hypocalcaemia. In this trial, a greater number of serious adverse events and adverse events leading to withdrawal occurred in the propofol group relative to the propofol EDTA group. There was a significantly lower crude mortality rate at 7 and 28 days for the propofol EDTA group compared with the propofol group. There were no statistically significant differences between groups with respect to depth of sedation. CONCLUSION: The propofol EDTA formulation had no effect on calcium or magnesium homeostasis, renal function, or sedation efficacy compared with propofol alone when used for sedation in critically ill surgical ICU patients. There was a significant decrease in mortality in the propofol EDTA group compared with the propofol group. Further investigations are needed to validate this survival benefit and elucidate a possible mechanism.

Adolescent↗

The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide.

We studied the effect of abrupt discontinuation of inhaled nitric oxide (iNO) in patients receiving this drug for treatment of acute hypoxemic respiratory failure (AHRF), in order to determine the need for continued therapy, the incidence and nature of adverse events, and the risk factors predicting these adverse events. Thirty-one patients who showed an initial increase in Pa(O(2)) of > 20 mm Hg in response to iNO underwent a discontinuation trial at 10 to 30 h after beginning iNO. Indwelling arterial and pulmonary artery catheters facilitated monitoring of hemodynamic and gas-exchange parameters. For the group, discontinuation of iNO caused a significant decrease in Pa(O2 ), arterial and mixed venous oxygen saturation, and ratio of Pa(O(2)) to fraction of inspired oxygen (FI(O(2))). Three patterns of response were observed. Eight of 31 (25.8%) patients had minimal changes in oxygenation or hemodynamics, suggesting no need for ongoing therapy. Fifteen of 31 (48%) patients had worsened gas exchange as a predominant response. Eight of 31 patients exhibited hemodynamic collapse, defined as > 20% fall in cardiac output and/or mean arterial blood pressure. In this last subgroup, the pattern of cardiovascular changes suggested that this response arose from an acute increase in right ventricular afterload, and was not a consequence of gas-exchange abnormalities. In all cases, reinstitution of iNO promptly reversed worsened hemodynamics and gas exchange. Independent factors associated with an increased risk of cardiovascular collapse included multisystem organ failure, older age, and initial blood pressure increase in response to iNO; a smaller change in the ratio of Pa(O(2)) to FI(O(2)) with initiation of iNO therapy also tended to correlate with this phenomenon. We conclude that careful and monitored discontinuation of iNO in patients with AHRF will identify substantial fractions of patients who are either receiving no benefit from this therapy or who require iNO to maintain an adequate circulation and are therefore at risk for adverse outcome with transport or inadvertent discontinuation of iNO. Future trials of iNO should recognize this complication of such therapy and include assessments for it.

Acute Disease↗

Outcomes of critically ill patients denied consideration for liver transplantation.

Patients with advanced liver disease (ALD) leading to admission to the ICU are often evaluated for possible orthotopic liver transplantation (OLT). Those deemed ineligible for listing for OLT must be managed by medical therapy. The number of patients not eligible for OLT listing will likely increase given the current organ transplant shortage. We performed a retrospective multivariate analysis of mortality predictors for patients denied listing for OLT. One hundred and eighty-three patients denied OLT listing were evaluated over a 3(1)/(2)-yr period, beginning in 1994. Overall mortality was 56% for those not listed versus 12% for those listed for OLT (p < 0.001). Independent predictors of increased mortality among those not listed were APACHE II score (p = 0.001; OR 1.11), sepsis (p = 0.04; OR 2.41), and the need for mechanical ventilation (p = 0.001; OR 3.71). Gastrointestinal (GI) bleeding was associated with decreased mortality (p = 0.02; OR 0.44). We conclude that critically ill patients with ALD denied OLT listing have substantially higher mortality than those listed for OLT. APACHE II score, sepsis, and the need for mechanical ventilation predict increased mortality in this group. Conversely, GI bleeding predicts decreased mortality; therefore, aggressive resuscitative measures seem merited in these patients.

APACHE↗

The phosphoprotein Op18/stathmin is differentially expressed in ovarian cancer.

To identify potential prognostic indicators of ovarian cancer and identify targets for therapeutic strategies, mRNA differential display was used to analyze gene expression differences in normal, benign, and cancerous ovarian tissue. One cDNA isolated by this technique, Op18/stathmin, is a highly conserved gene that is reported to have many different functions within a cell, including signal transduction, control of the cell cycle, and the regulation of microtubules. Quantitative Northern blot analysis of 12 malignant ovarian samples, 8 benign ovarian tumors, and 10 normal ovarian tissue samples demonstrated overexpression of Op18/stathmin mRNA in the malignant cancers. Immunohistochemistry showed an apparent overexpression of Op18/stathmin protein level and an association with proliferating cells.

Blotting, Northern↗

The use of adjuvant radiation therapy by members of the Society of Gynecologic Oncologists.

UNLABELLED: OBJECTIVES. The aim of this study was to determine the attitudes of the members of the Society of Gynecologic Oncologists with respect to the use of adjuvant radiation therapy in women with endometrial cancer. METHODS: An anonymous survey concerning the use of adjuvant radiation therapy in endometrial cancer was mailed to all members of the Society of Gynecologic Oncologists listed in the 1998 directory. RESULTS: Of the 767 listed members, 325 (42%) returned completed surveys. Less than 20% of respondents recommended adjuvant radiation therapy in stage IA grade 1 or 2 and stage IB grade 1 endometrial cancer. Adjuvant radiation is recommended by 40 to 50% of respondents in women with stage IA grade 3 and IB grade 2 tumors. Most recommend adjuvant radiation for all women with >50% myometrial invasion or grade 3 tumors with any myometrial invasion. Lymph node sampling is attempted in all cases by 48% of respondents. For those familiar with Gynecologic Oncology Group (GOG) Study No. 99, 20% stated that they were more likely to recommend adjuvant radiation and 27% stated that they were less likely to recommend adjuvant radiation based on the preliminary results. Except in stage IA grade 1 tumors, the chance of recommending further therapy in women with all stages and grades was significantly less if a complete staging procedure including lymph node dissection had been performed. CONCLUSIONS: Complete staging appears to decrease the chance that postoperative therapy will be recommended. The use of adjuvant radiation therapy seem to have declined slightly as a result of GOG Study No. 99. Future studies in women with endometrial cancer that do not require lymph node sampling should evaluate the frequency of adjuvant therapy in the absence of complete staging.

Adenocarcinoma↗

Is age a barrier to the aggressive treatment of ovarian cancer with paclitaxel and carboplatin?

OBJECTIVE: The objective of this study was to determine whether the toxicities associated with chemotherapy are age related in women treated for ovarian cancer. METHODS: Patients with stage II-IV epithelial ovarian cancer underwent cytoreductive surgery. Adjunctive therapy was given to each patient consisting of intravenous (IV) paclitaxel 175 mg/m(2) over 3 h with a subsequent 30-min IV infusion of carboplatin. Carboplatin dose was calculated to achieve a targeted area under the curve (AUC) of 5.0-7.5. Treatment was repeated at 21- to 28-day intervals for six cycles. Toxicities were graded after each dose of chemotherapy. Results were analyzed using the Wilcoxon rank sum test and log likelihood ratio to compare toxicities in women age <60 years old to women >/=60 years old. RESULTS: Fifty-three women, 22 of whom were >/=60 years old, were treated with 309 cycles of chemotherapy. Forty-eight patients (92%) completed all six cycles. AUC dosing of carboplatin was equivalent for both groups. Carboplatin dose reduction occurred in 75% of patients for grade 4 neutropenia or thrombocytopenia. No patient required a reduction in the paclitaxel dose. Neutropenia was less frequent in women >/=60 years old than in women <60 years old (P = 0.02). There was no difference between women <60 years old and women >/=60 years old in the incidence of anemia, thrombocytopenia, or the use of growth factors. A 68% complete clinical response rate was observed in women >/=60 years old compared to a 74% complete response rate for women under age 60 (P = 0.22). CONCLUSION: Age is not a barrier to the aggressive treatment of ovarian cancer with this regimen of paclitaxel and carboplatin.

Adult↗

Oxygenation in status asthmaticus improves during ventilation with helium-oxygen.

OBJECTIVES: To determine the effect of breathing helium-oxygen (HELIOX) mixtures on pulmonary gas exchange during severe asthma. DESIGN: A retrospective case-match control design was used to compare the changes in alveolar to arterial gradient [(A-a)gradient] in the first 2 hrs of mechanical ventilation (MV) for status asthmaticus (SA) in patients who received HELIOX with those who did not. Patients were matched for diagnosis of asthma, ventilatory failure, ventilator mode and settings, and equivalent pharmacologic therapy. SETTING: The adult and pediatric intensive care units of a tertiary-care hospital. SUBJECTS: Adult and pediatric patients undergoing MV for SA. INTERVENTIONS: Use of HELIOX or standard nitrogen-oxygen mixtures during MV. MEASUREMENTS AND MAIN RESULTS: A total of 11 patients receiving HELIOX in the first 2 hrs of MV for SA were compared with 11 case-matched controls who did not. At baseline, the HELIOX and control groups had similar (A-a)gradients (216+/-92 torr and 226+/-82 torr, respectively). The (A-a)gradient decreased significantly to 85+/-44 torr after initiation of ventilation with HELIOX (p < .0003), whereas it did not change significantly in the control group in a similar time frame and during identical treatment without HELIOX. The reduction in (A-a)gradient in the HELIOX group facilitated a reduction in F(IO)2 from 0.8+/-0.2 initially to 0.4+/-0.1 at the time of the second blood gas determination, thus permitting greater concentrations of helium to be administered. CONCLUSIONS: MV with HELIOX improves (A-a)gradient in patients with SA. Although this improvement adds little to routine therapy with supplemental oxygen, it does permit reduction in concentration of inspired oxygen to levels that maximize helium concentration and thus permit full benefits of HELIOX on lung mechanics to be realized in even the most severely ill asthmatics.

Adolescent↗