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Biomedical subjects

D Horak

Publications and source records attributed to D Horak.

8 recordsLinked to original sources
PubMed2001

Identification of poor prognostic features among patients requiring mechanical ventilation after hematopoietic stem cell transplantation.

Patients who develop respiratory failure requiring mechanical ventilation after hematopoietic stem cell transplantation (HSCT) have very high mortality. Several investigators have identified prognostic features that can be used to identify a subset of these patients who are virtually certain to die, yet these have never been prospectively assessed. The objectives of this study were to determine the accuracy of published prognostic features for mortality and to determine the survival of patients who recover from respiratory failure. A systematic review of the literature was undertaken to identify reported poor prognostic features and survival rates. The study validated the reported poor prognostic features on a prospective, multicenter inception cohort of 226 patients with respiratory failure requiring mechanical ventilation after HSCT. The main outcome measures were determination of a baseline probability of death, drawn from literature review; likelihood ratio of mortality for each prognostic feature determined from the validation cohort; conditional probability of death in the presence of each feature; and 6-month survival of those who recover. Patients requiring mechanical ventilation after HSCT have a baseline probability of death of 82% to 96%. In the setting of combined hepatic and renal dysfunction, the probability of death rises to 98% to 100%. Other previously reported prognostic features are less strongly associated with mortality. For patients who recover from respiratory failure, the proportion surviving 6 months or longer ranges from 27% to 88%. It was concluded that in patients requiring mechanical ventilation after HSCT, the presence of combined hepatic and renal dysfunction is highly predictive of death. The presence of this feature may justify the recommendation to withdraw life-sustaining measures.

Adult↗
PubMed2000

The short prodomain influences caspase-3 activation in HeLa cells.

Proteolytic activation of caspases is a key step in the process of apoptosis. According to their primary structure, caspases can be divided into a group with a long prodomain and a group with a short prodomain. Whereas long prodomains play a role in autocatalytic processing, little is known about the function of the short prodomain, for example the prodomain of caspase-3. We constructed caspase-3 variants lacking the prodomain and overexpressed these in HeLa and yeast cells. We found that removal of the caspase-3 prodomain resulted in spontaneous proteolytic activation of the protein when expressed in HeLa cells. This processing was only partially autocatalytic, as demonstrated by a catalytically inactive caspase-3 mutant. Co-expression of the anti-apoptotic protein XIAP (X-chromosome-linked inhibitor of apoptosis protein) completely blocked the observed spontaneous activation, which excluded a direct involvement of caspase-8. Our findings indicate that the short prodomain of caspase-3 serves as a silencing component in mammalian cells by retaining this executioner caspase in an inactive state.

Apoptosis↗
PubMed1999

Outcome for cancer patients requiring mechanical ventilation.

PURPOSE: To describe hospital survival for cancer patients who require mechanical ventilation. MATERIALS AND METHODS: A prospective, multicenter observational study was performed at five academic tertiary care hospitals. Demographic and clinical variables were obtained on consecutive cancer patients at initiation of mechanical ventilation, and information on vital status at hospital discharge was acquired. RESULTS: Our analysis was based on 782 adult cancer patients who met predetermined inclusion criteria. The overall observed hospital mortality was 76%, with no statistically significant differences among the five study centers. Seven variables (intubation after 24 hours, leukemia, progression or recurrence of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence of disseminated intravascular coagulation, and need for vasopressor therapy) were associated with an increased risk of death, whereas prior surgery with curative intent was protective. The predictive model based on these variables had an area under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow goodness-of-fit statistics of 7.19; P = .52. CONCLUSION: This model can be used to estimate the probability of hospital survival for classes of adult cancer patients who require mechanical ventilation and can help to guide physicians, patients, and families in deciding goals and direction of treatment. Prospective independent validation in different medical settings is warranted.

Critical Care↗
PubMed1998

Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model.

PURPOSE: To develop prospectively and validate a model for probability of hospital survival at admission to the intensive care unit (ICU) of patients with malignancy. PATIENTS AND METHODS: This was an inception cohort study in the setting of four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 1,483 patients and then validated on an additional 230 patients. Multiple logistic regression modeling was used to develop the models and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analysis. The main outcome measure was hospital survival after ICU admission. RESULTS: The observed hospital mortality rate was 42%. Continuous variables used in the ICU admission model are PaO2/FiO2 ratio, platelet count, respiratory rate, systolic blood pressure, and days of hospitalization pre-ICU. Categorical entries include presence of intracranial mass effect, allogeneic bone marrow transplantation, recurrent or progressive cancer, albumin less than 2.5 g/dL, bilirubin > or = 2 mg/dL, Glasgow Coma Score less than 6, prothrombin time greater than 15 seconds, blood urea nitrogen (BUN) greater than 50 mg/dL, intubation, performance status before hospitalization, and cardiopulmonary resuscitation (CPR). The P values for the fit of the preliminary and validation models are .939 and .314, respectively, and the areas under the ROC curves are .812 and .802. CONCLUSION: We report a disease-specific multivariable logistic regression model to estimate the probability of hospital mortality in a cohort of critically ill cancer patients admitted to the ICU. The model consists of 16 unambiguous and readily available variables. This model should move the discussion regarding appropriate use of ICU resources forward. Additional validation in a community hospital setting is warranted.

Academic Medical Centers↗
PubMed1990

Poly(2-hydroxyethyl methacrylate) beads for the preoperative endovascular occlusion of branches of the hepatic artery in focal alterations of the liver.

Spherical particles of porous poly(2-hydroxyethyl methacrylate) have been used in the treatment of patients suffering from focal alterations of the liver, namely haemangioma and hypervascular tumour. The treatment consisted of the preoperative endovascular occlusion of branches of the hepatic artery using these spherical particles, and was followed by an operation. The main merit of the preoperative occlusion of blood vessels is that it substantially reduces blood loss during surgery. In order to determine the optimal time for the operation on the liver, indicators of the coagulation system were examined in successive terms of the postemboilization period. Reaction of the organism to endovascular occlusion is reflected in hypercoagulation changes in the coagulation system.

Blood Loss, Surgical↗
PubMed1983

Sensitive indices of improvement in a pulmonary rehabilitation program.

It is often difficult to demonstrate objective evidence of physiologic improvement following a pulmonary rehabilitation program, despite subjective increases in exercise tolerance. In an attempt to identify sensitive indices of improvement, we studied resting and exercise lung function extensively in 15 patients (age range 45 to 73) with severe chronic obstructive lung disease before and after a pulmonary rehabilitation program. The six-week outpatient rehabilitation program consisted of exercise at 70 percent of the maximum predicted heart rate and diaphragmatic breathing for 20 minutes three times weekly. There were no significant changes in resting pulmonary function following exercise training. Exercise measurements were unchanged after completion of the program, with the exception of two parameters: heart rate and arterial lactate levels. The observed small but significant reductions in exercise heart rate and blood lactate levels following training may be due to conditioning of skeletal muscles, although respiratory muscle conditioning may be a contributing factor. Measurements of blood lactate may be a useful marker of conditioning in patients with chronic obstructive pulmonary disease who complete a pulmonary rehabilitation program.

Exercise Test↗