Overexpression of alpha4 chain-containing laminins in human glial tumors identified by gene microarray analysis.

Differential gene expression in tumors often involves growth factors and extracellular matrix/basement membrane components. Here, 11,000- gene microarray was used to identify gene expression profiles in brain tumors including high-grade gliomas [glioblastoma multiforme (GBM) and anaplastic astrocytoma], low-grade astrocytomas, or benign extra-axial brain tumors (meningioma) in comparison with normal brain tissue. Histologically normal tissues adjacent to GBMs were also studied. All GBMs studied overexpressed 14 known genes compared with normal human brain tissue. Overexpressed genes belonged to two broad groups: (a) growth factor-related genes; and (b) structural/extracellular matrix-related genes. For most of these 14 genes, expression levels were lower in low-grade astrocytoma than in GBM and were barely detectable in normal brain. Despite normal-appearing histology, gene expression patterns of tissues immediately adjacent to GBM were similar to those of their respective primary GBMs. Two genes were consistently up-regulated in both high-grade and low-grade gliomas, as well as in histologically normal tissues adjacent to GBMs. These genes coded for the epidermal growth factor receptor (previously reported to be overexpressed in gliomas) and for the alpha4 chain of laminin, a major blood vessel basement membrane component. Changes in expression of this laminin chain have not been previously associated with malignant tumors. Overexpression of laminin alpha4 chain in GBM and astrocytoma grade II by gene microarray analysis was confirmed by semiquantitive reverse transcription-PCR and immunohistochemistry. Importantly, an alpha4 chain-containing laminin isoform, laminin-8 (alpha4beta1gamma1), was expressed mainly in blood vessel walls of GBMs and histologically normal tissues adjacent to GBMs, whereas another alpha4 chain-containing laminin isoform, laminin-9 (alpha4beta2gamma1), was expressed mainly in blood vessel walls of low-grade tumors and normal brain. GBMs that overexpressed laminin-8 had a shorter mean time to tumor recurrence (4.3 months) than GBMs with overexpression of laminin-9 (9.7 months, P = 0.0007). Up-regulation of alpha4 chain-containing laminins could be important for the development of glioma-induced neovascularization and glial tumor progression. Overexpression of laminin-8 may be predictive of glioma recurrence.

Quality of life in patients with heart failure: do gender differences exist?

OBJECTIVE: The purpose of this study was to evaluate gender differences in quality of life (QOL) in a large sample of age-matched and ejection fraction (EF)-matched patients with heart failure. DESIGN: Matched comparisons of secondary data were used. SETTING: The setting consisted of multicenter Studies of Left Ventricular Dysfunction trials. SAMPLE: The sample included 1382 patients (691 men and 691 women) who were age-matched and EF-matched. OUTCOME MEASURES: Global QOL and the QOL dimensions of physical function, emotional distress, social health, and general health were measured using the Ladder of Life, items from the Profile of Mood States Inventory, the Functional Status Questionnaire, the beta-Blocker Heart Attack Trial instrument, and an item from the RAND Medical Outcomes Study instrument. RESULTS: Women had significantly worse general life satisfaction, physical function, and social and general health scores than men. There were no significant differences found between gender groups for current life situation or emotional distress. After controlling for New York Heart Association classification, women still had significantly worse ratings for intermediate activities of daily living (a sub-dimension of physical functioning) and social activity. CONCLUSIONS: Despite controlling for age, EF, and New York Heart Association classification, women had worse QOL ratings than did men for intermediate activities of daily living and social activity. Research should focus on identifying why differences exist and developing measures to improve QOL, particularly physical functioning, in women with heart failure.

Gene expression abnormalities in human glial tumors identified by gene array.

Novel genes specific for human oligodendroglioma and glioblastoma multiforme (GBM) were detected using the gene array analysis [18,376 genes Gene Discovery Array (GDA) from Incyte Genomics, Inc.]. Eleven genes were chosen based on the highest ratios of differential expression identified by GDA between histologically normal adjacent tissue and brain tumor tissue. The differential expression of those 11 genes was verified by semiquantitative RT-PCR and Northern analysis on 22 samples of glial and other tumors of the brain, as well as of normal embryonic and adult brain tissue. Gene no. 5 (an EST) was more expressed by GDA analysis in histologically normal adjacent brain tissue than in the corresponding oligodendroglioma. By RT-PCR, this gene was expressed in a number of brain tumors but not in normal adult and embryonic brain. By GDA analysis, gene no. 7 (oligophrenin-1) gave the highest ratio compared to other genes in brain tissue adjacent to the GBM vs. GBM. By RT-PCR, oligophrenin-1 was expressed in tumors and tumor-adjacent tissue, whereas meningioma and corpus callosum were negative. Gene no. 11 (an EST) was expressed only in brain tumors but not in normal brain by Northern analysis (message size 1.5 kb) and RT-PCR. GDA analysis successfully identified genes preferentially expressed in brain tumors, which was confirmed by Northern analysis and semiquantitative RT-PCR. The validity of gene arrays for tumor-specific gene discovery is discussed. Study of differential gene expression in glial tumors should help identify the mechanism/s of transformation of normal glial cells to malignant.

Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.

In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.

Can practice guidelines be transported effectively to different settings? Results from a multicenter interventional study.

RATIONALE: Although clinical guidelines have become increasingly popular as a means to reduce variation in care, increase efficiency, and improve patient outcomes, little is known about their effectiveness when they are transported outside their original setting, or about the factors that influence their successful translation into clinical practice. This study assessed whether a clinical guideline for low-risk chest pain patients, implemented with a standardized protocol, could be effectively transported to five hospital settings. METHODS: In a prospective, interventional trial, a standardized protocol for low-risk chest pain was implemented at each site. A total of 553 consecutively hospitalized low-risk patients with chest pain were enrolled during a 3-month baseline period followed by a standardized 6-month intervention period. During the intervention period, each patient's physician was contacted about eligibility for discharge within the specified 2-day guideline period. Guideline adherence (discharged within 48 hours) and postdischarge patient outcomes were measured. Local guideline champions were interviewed about their implementation experience. RESULTS: Guideline adherence during the intervention period ranged from 61% to 100%, with only two sites achieving significant increases of > or = 10% from the baseline values. Guideline implementation did not affect clinical outcomes or patient satisfaction. Implementation factors such as preexisting hospital environment, implementation team staffing, and the rapid identification and resolution of barriers may influence the successful translation of guidelines into practice. CONCLUSIONS: Even with a standardized implementation protocol, consistent results across institutions were not obtained when a clinical guideline for chest pain was implemented beyond its original setting. These findings demonstrate the importance of understanding the local factors that influence guideline implementation.

Predictors of quality of life in women with heart failure. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

BACKGROUND: Two and one half million women have heart failure (HF). Yet little is known about quality of life (QOL) in this population and the factors influencing it. Given the importance of QOL as an outcome of care, we conducted a study to evaluate predictors of QOL in women with HF. METHODS: Using baseline QOL data collected in the Studies of Left Ventricular Dysfunction (SOLVD) trials, we studied predictors of QOL in 691 women with HF. Univariate, bivariate, and multiple regression analyses were used. Potential predictors included age, education, tobacco use, social isolation, life stresses, comorbidity index, New York Heart Association (NYHA) class, HF symptoms, etiology, and medications. We measured global QOL and QOL dimensions of physical function, emotional distress, and social and general health. RESULTS: Women were older (61+/-10.5 years), predominantly Caucasian (75%), and their mean ejection fraction was 0.27 (+/-6.51). Variables with the strongest relationship to QOL included dyspnea, NYHA class, and life stresses. As dyspnea, life stresses, and NYHA class increased, QOL decreased. Additionally, smoking behavior and vasodilator use was associated with decreased QOL. Heart failure etiology of ischemic origin was associated with decreased social life satisfaction, and use of digitalis was predictive of increased social life satisfaction. Finally, increasing age was related to an increase in general life satisfaction. CONCLUSION: Symptom amelioration, which may improve functional ability, has the greatest potential for increasing QOL in women with HF. Programs to increase physical activity in women with HF should be developed and tested. Finally, clinicians may need to optimize HF medications in women.

Can practice guidelines safely reduce hospital length of stay? Results from a multicenter interventional study.

BACKGROUND: Although practice guidelines about appropriate lengths of stay have been widely promulgated, their effects on patient outcomes are not clear. Our objective was to study the effects of length of stay practice guidelines on patient outcomes. PATIENTS AND METHODS: We performed a prospective, nonrandomized, interventional trial in six geographically distributed hospitals, among consecutively hospitalized "low-risk" patients with total hip replacement, hip fracture, or knee replacement. Case managers provided physicians with patient risk information based on guideline recommendations. We measured length of stay, compliance with recommended guideline length of stay, health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. RESULTS: A total of 560 patients were included in the study. For patients with knee replacement, there was a statistically significant increase in practice guideline compliance (27% baseline versus 53% intervention, P <0.0001) and reduction in length of stay (5.2 days versus 4.6 days, P <0.001) when compared with the baseline period. For hip replacement patients, there similarly was an increase in practice guideline compliance (66% baseline versus 82% intervention, P = 0.01) and reduction in length of stay (5.1 days versus 4.8 days, P = 0.03). Significant reductions in length of stay were not observed for patients recovering after hip fracture despite a significant increase in guideline compliance. There were few statistically significant changes in patient outcomes related to reductions in lengths of stay, including health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. For patients undergoing hip replacement, very short lengths of stay (shorter than the guideline recommendation) were associated with an increased rate of discharging patients to nursing homes and rehabilitation facilities (21% versus 7%, P = 0.01), and hip fracture patients with very short lengths of stay required more visits to the doctor after discharge (56% versus 25%, P = 0.04). CONCLUSION: Reductions in lengths of stay were most often associated with no significant change in patient outcomes. However, very short lengths of stay were associated with increased intensity of care following discharge for patients undergoing hip surgery, indicating possible cost shifting (the cost incurred by transferring patients to rehabilitation facilities may have been greater than had the patients remained in the acute care hospital for an additional 1 or 2 days and been sent directly home). These results emphasize the importance of monitoring the effects of cost containment and other systematic efforts to change patient care at the local level.

A prospective, multicenter study of a pneumonia practice guideline.

OBJECTIVE: To study the effect of a length of stay practice guideline on patient outcomes. DESIGN: A prospective, nonrandomized, interventional trial. SETTING: Six geographically distributed hospitals. PATIENTS: Two hundred forty-two consecutively hospitalized "low-risk" patients with pneumonia. MEASUREMENTS AND RESULTS: One hundred fifty-two patients (63%) completed the mailed postdischarge survey and were included in the analysis. Data were prospectively collected for 85 patients from the baseline observation period (B) and 67 patients from the intervention period (I). During the I, case managers provided physicians with patient risk information based on guideline recommendations. There was no significant change in guideline compliance (B vs I: 76.5% vs 83.6%; p=0.32) or length of stay (B vs I: 3.5 days [95% confidence interval, 3.2 to 3.8] vs 3.6 days [95% confidence interval, 3.3 to 4.0]). Also, there were no statistically significant effects of the intervention on patient outcomes, care following hospital discharge, and patient satisfaction scores. CONCLUSION: Patients in this study often had shorter lengths of stay than recommended by the practice guideline. This suggests that the external environment may have had a greater effect on physician behavior and length of stay than the practice guideline itself. Moreover, it demonstrates the importance of continuous assessment of physician practices immediately prior to, during, and after application of the clinical practice guideline.

Evaluation of a pneumonia practice guideline in an interventional trial.

There are few available data to define the medically necessary duration of stay for patients hospitalized with pneumonia. Therefore, we investigated the safety and effectiveness of a practice guideline that provided information about switching patients from parenteral to oral antimicrobials and early hospital discharge. The study was a prospective controlled study with an alternate month design. The practice guideline was studied in 146 "low-risk" pneumonia patients hospitalized during a 22-month period. Medical care consistent with the practice guideline occurred in 64% and 76% of patients during control and intervention periods, respectively (p=0.15). There were no differences in patient outcomes in the control and intervention groups when measured 1 mo after hospital discharge, including hospital readmission rates, health-related quality of life, and patient satisfaction. Explicit and implicit review revealed that 98.6% (95% confidence interval [CI]: 95.1%, 99.8%) of low-risk patients would not have benefited from continued hospitalization after the fourth hospital day. The 30-d survival rate of the low-risk pneumonia patients was 99.3% (95% CI: 96.2%, 100%) and patient outcomes appeared to be favorable compared with previously published values. We conclude that duration of hospital stay was frequently consistent with the practice guideline in both study groups, and patient outcomes remained unchanged. The guideline will require additional testing before it can be recommended for use.

Identification of low-risk hospitalized patients with pneumonia. Implications for early conversion to oral antimicrobial therapy.

PURPOSE: Few available data exist to define either the medically necessary duration of parenteral antimicrobial therapy or length of stay for hospitalized patients with pneumonia. Therefore, we investigated the potential safety and effectiveness of a practice guideline recommending early conversion of low-risk patients with pneumonia from parenteral to oral antimicrobial therapy and early hospital discharge. PATIENTS AND METHODS: The practice guideline was studied retrospectively in 503 hospitalized patients with pneumonia at a teaching community hospital. RESULTS: Thirty-three percent of patients with pneumonia were classified as at low risk for complications and potentially suitable for early conversion to oral antimicrobial therapy according to the guideline. Were the guideline to have been used to guide patient discharge decisions, 619 additional bed-days would have been made available to accommodate incoming patients. A consensus among physician reviewers led to the judgment that quality of care would not have worsened for 98.2 percent of low-risk patients had they been switched to oral antimicrobial therapy on the third hospital day, nor would quality of care have been worsened for 93.4 percent of low-risk patients had they been discharged on the fourth hospital day. CONCLUSION: The practice guideline that we studied has the potential to safely reduce the duration of parenteral antimicrobial therapy and length of hospital stay for selected low-risk patients with pneumonia. The guideline should be studied in a prospective clinical trial.

Practice guidelines and reminders to reduce duration of hospital stay for patients with chest pain. An interventional trial.

OBJECTIVE: The acceptability, safety, and efficacy of practice guidelines have rarely been evaluated. Moreover, despite the recent development of guidelines and decision aids for patients admitted to coronary care and intermediate care units, few have been tested in clinical practice. DESIGN: A prospective, controlled clinical trial with an alternate-month design. SETTING: A large teaching community hospital. PATIENTS: Patients admitted to coronary care and intermediate care units with chest pain who were considered at low risk for complications according to a practice guideline (n = 375). INTERVENTION: Physicians caring for patients with chest pain who were at low risk for complications received concurrent, personalized written and verbal reminders regarding a guideline that recommended a 2-day hospital stay. RESULTS: Use of the practice guideline recommendation with concurrent reminders was associated with a 50% to 69% increase in guideline compliance (P < 0.001) and a decrease in length of stay from 3.54 +/- 4.1 to 2.63 +/- 3.0 days (0.91-day reduction, 95% CI, 0.18 to 1.63; P = 0.02) for all patients with chest pain considered at low risk for complications. The intervention was associated with a total (direct and indirect) cost reduction of $1397 per patient (CI, $176 to $2618; P = 0.03). No significant difference was found in the hospital complication rate between patients admitted to the hospital during control and intervention periods, and no significant difference was noted in complications, patient health status, or patient satisfaction when measured 1 month after hospital discharge. CONCLUSION: These results suggest that implementation of this practice guideline through concurrent reminders reduced hospital costs for patients with chest pain considered at low risk for complications. Further study of the guideline is warranted.

A computerized expert system for outcome-validated medical practice guidelines.

Our ongoing efforts in health services research have resulted in outcome-validated medical practice guidelines for common medical conditions. These practice guidelines have been shown to substantially reduce health care costs while maintaining quality of care. We have developed a computerized expert system from our practice guidelines which enhances the ease in which they can be implemented by Utilization Management (UM) Coordinators, physicians, nurses and other health care providers.

Implementing practice guidelines through a utilization management strategy: the potential and the challenges.

Although there is currently much enthusiasm for practice guidelines, far more energy and resources have been expended on their development than on their implementation. A prospective interventional trial was performed using a previously validated explicit practice guideline (decision aid) to decrease the hospital length of stay for selected "low-risk" patients with chest pain. Utilization management (UM) coordinators (RNs) and physicians were chosen to implement the guideline since these resource people are available in most hospitals, allowing for generalization of the experience. With explicit review criteria used for 624 patients, it was found that when the guideline was applied by UM coordinators, it had a sensitivity of 0.85, a specificity of 0.90, a positive predictive value of 0.76, and a negative predictive value of 0.94. The attending physicians failed to override falsely classified low-risk patient recommendations 51% of the time. Implicit review judged that outcome might have theoretically been worsened in two of these patients. Follow-up at 30 days after admission, however, revealed no untoward sequelae in falsely categorized patients discharged according to the guideline. Utilization management appears to be a promising mechanism for guideline implementation that is available in most institutions. However, the accuracy with which UM coordinators implement guidelines should be assessed rigorously. Guidelines should be implemented in an environment of checks and balances in which physicians have the ultimate responsibility for their patients' care.

The principle of parsimony: Glasgow Coma Scale score predicts mortality as well as the APACHE II score for stroke patients.

Although the development and use of severity-of-illness measures has gained widespread enthusiasm, uncertainty remains as to the optimal measure for stroke patients. The Health Care Financing Administration recently derived a severity-of-illness measure based on the APACHE II system to explain differences in Medicare mortality rates among hospitals treating stroke patients. We hypothesized that the Glasgow Coma Scale score provides prognostic information of accuracy comparable to that of the APACHE II score for stroke patients, yet is simpler and cheaper to abstract from the medical record. We therefore studied 246 patients hospitalized with stroke, including 49 oversampled mortalities. The Glasgow Coma Scale score was as accurate as the APACHE II score in predicting stroke mortality both before (r = -0.50 and r = 0.50, respectively) and after (r = -0.40 and r = 0.38, respectively) the oversampled mortalities were excluded. The APACHE II score required abstraction of 16 variables from the medical record compared with three for the Glasgow Coma Scale score and required more than three times the time to abstract from the medical record. Therefore, in the interest of parsimonious data collection, the Glasgow Coma Scale may be a preferable severity-of-illness measure for patients with stroke.

Early "step-down" transfer of low-risk patients with chest pain. A controlled interventional trial.

OBJECTIVE: To determine whether providing private practitioners with triage criteria for their low-risk chest pain patients would safely enhance bed utilization efficiency in coronary and intermediate care units. DESIGN: Prospective, controlled, interventional trial using an alternate month study design. SETTING: A large teaching community hospital. PATIENTS: Cohort of 404 low-risk patients with chest pain for whom a diagnosis of myocardial infarction has been excluded and who have not sustained complications, required interventions, or developed unstable comorbidity. INTERVENTIONS: During intervention months, private practitioners caring for low-risk patients in the coronary and intermediate care units were contacted 24 hours after admission. Physicians were informed that the transfer of low-risk patients to nonmonitored beds could probably be done safely, based on the results of a pilot study. The practitioner had the option of agreeing to or deferring patient transfer. During control months, physicians were not contacted in this way. MEASUREMENTS AND MAIN RESULTS: Use of the triage criteria by private practitioners reduced lengths of stay in the intermediate and coronary care units by 36% and 53%, respectively. Bed availability increased by 744 intermediate and 372 coronary care unit bed-days per year. Charges decreased by $2.6 million per year and profits improved by $390,000 per year. There were not significant differences in complications between control and intervention patients and in no case (95% CI, 0% to 1.6%) did the triage criteria adversely affect quality of care. CONCLUSIONS: The early transfer triage criteria may be a safe and efficacious decision aid for improving bed utilization in intermediate and coronary care units. In addition, this study shows the feasibility of and potential benefits from applying practice guidelines at a community hospital.

Selecting the best triage rule for patients hospitalized with chest pain.

PURPOSE: During an observational study, we investigated the potential benefits and risks of the use of admission and early transfer triage rules in 498 patients hospitalized with chest pain. PATIENTS AND METHODS: Appropriateness of triage decisions was measured using explicit and implicit judgments. RESULTS: Application of an admission triage rule (partially based on the Brush electrocardiographic criteria) would have increased coronary care unit (CCU) admissions by 3%, whereas application of a triage rule 24 hours after admission would have reduced bed utilization by 860 intermediate care and 82 CCU bed-days per year when compared with actual patient triage. Although 9.5% of patients who underwent triage according to the early transfer triage rule would have experienced a minor complication after transfer, the medical care of none would have been adversely affected. CONCLUSION: Our results show that application of a triage rule 24 hours after admission may have the potential to shorten length of stay in the CCU and intermediate care unit without significantly compromising patient care. However, use of the admission triage rule would have increased CCU bed utilization. The failure of the admission triage rule to improve bed utilization illustrates the potential hazards of ignoring patient complications, interventions, and co-morbidity when predicting the efficacy of a triage rule.

Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia.

Cachexia is a common manifestation of advanced cancer and frequently contributes to physical disability and mortality. An increased metabolic rate has been suggested to be one of the causes of cancer-induced cachexia, although the mechanisms producing this hypermetabolism remain unclear. The presence and activation of brown adipose tissue, a highly thermogenic tissue, may result in a hypermetabolic state and be partially responsible for weight loss in cancer patients. To investigate this hypothesis, we examined necropsy samples of peri-adrenal tissues using light microscopy to identify the prevalence of brown adipose tissue in 25 cachectic patients who died from cancer and 15 age-matched subjects who died from other illnesses. Brown adipose tissue was observed in 20 of the cancer patients (80%) compared to 2 of the age-matched subjects (13%). Therefore, our preliminary results indicate that a high prevalence of brown adipose tissue is associated with cancer-induced cachexia and may reflect an abnormal mechanism responsible for profound energy expenditure and weight loss.

Efficacy and safety of sublingual nifedipine in hypertensive emergencies.

Hypertensive emergencies are a diverse group of disorders characterized by a marked elevation of systemic arterial pressure that is associated with acute end-organ dysfunction. The efficacy and safety of sublingual nifedipine were evaluated in 16 men and 14 women (mean age 65 +/- 14 years) who had hypertensive emergencies. Before treatment, mean systolic blood pressure was 224 +/- 23 mm Hg, mean diastolic blood pressure was 125 +/- 18 mm Hg, and the average mean arterial pressure was 158 +/- 16 mm Hg. Administration of 10 or 20 mg of sublingual nifedipine initiated a smooth and predictable decline in blood pressure values within five minutes and produced a peak effect between 30 and 60 minutes. At 30 minutes, the decreases in the systolic blood pressure, diastolic blood pressure, and mean arterial pressure for the group were 49 +/- 24 mm Hg, 31 +/- 17 mm Hg, and 39 +/- 20 mm Hg, respectively, all of which were highly significant (p less than 0.001). By 60 minutes, nifedipine had decreased the diastolic blood pressure to less than 120 mm Hg in 97 percent of patients, less than 110 mm Hg in 93 percent, and less than 100 mm Hg in 67 percent. Fourteen patients required other antihypertensive medications within the first 12 hours for the antihypertensive effect to be maintained. In this group, the systolic, diastolic, and mean arterial pressures were significantly lower than baseline values (p less than 0.001) at the time that the other drugs were started (which occurred at a mean of 4.3 +/- 3.2 hours after entry into the study). The response to nifedipine correlated with the blood pressure value prior to treatment, but did not correlate with age, gender, value prior to treatment, but did not correlate with age, gender, or the type of hypertensive emergency. Twenty mg of nifedipine produced a significantly greater antihypertensive effect than did 10 mg during the first 20 minutes (176 +/- 15 mm Hg versus 201 +/- 18 mm Hg systolic; p = 0.009) and appeared to be more efficacious clinically. In only two of 30 patients (7 percent) was the blood pressure response considered inadequate, and all 10 patients with pulmonary edema or myocardial ischemia showed clinical improvement within 60 minutes of treatment. In one patient, flushing and another symptom suggestive of transient symptomatic hypotension developed after treatment with nifedipine. These results suggest that sublingual nifedipine is a safe, effective, and practical agent for treating patients with hypertensive emergencies.

Left ventricular performance in septic shock: reversible segmental and global abnormalities.

Left ventricular dysfunction has been implicated in the pathogenesis of septic shock, but little is known about its natural history, cause, and prognostic significance. Left ventricular performance was assessed by serial radionuclide and hemodynamic studies in 35 patients with culture-proven septic shock. The mean age (+/- S.D.) of the group was 64 +/- 18 years; 16 of the subjects were women, and 15 had antecedent heart disease. On the first study, the left ventricular stroke work index was depressed in 33 (94%) patients, and nineteen (54%) had a left ventricular ejection fraction less than 0.48. Twenty-two (63%) of the patients had segmental and four had generalized wall motion abnormalities. Conventional hemodynamic parameters were of no value in predicting the patients who had a depressed left ventricular ejection fraction or segmental abnormalities. Patients with underlying heart disease had a much higher frequency (87%) of segmental dysfunction than those without underlying heart disease (45%; p = 0.016), but no differences were noted in the left ventricular ejection fraction or left ventricular stroke work index of these two groups. Segmental abnormalities and low ejection fractions were seen more often in patients with a large left ventricular end-diastolic volume index. Only five subjects had a systemic vascular resistance index greater than 2580 dynes X sec X cm-5 per m2, and the correlation between systemic vascular resistance index and left ventricular ejection fraction was poor. No difference was found in the mean coronary perfusion pressure of those with segmental abnormalities and those with normal wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)