Comparison of propofol deep sedation versus moderate sedation during endosonography.

BACKGROUND: The purposes of this study are: (1) to prospectively evaluate clinically relevant outcomes including sedation-related complications for endoscopic ultrasound (EUS) procedures performed with the use of propofol deep sedation administered by monitored anesthesia care (MAC), and (2) to compare these results with a historical case-control cohort of EUS procedures performed using moderate sedation provided by the gastrointestinal (GI) endoscopist. MATERIALS AND METHODS: Patients referred for EUS between January 1, 2001 and December 31, 2002 were enrolled. Complication rates for EUS using MAC sedation were observed and also compared with a historical case-control cohort of EUS patients who received meperidine/midazolam for moderate sedation, administered by the GI endoscopist. Logistic regression analysis was used to isolate possible predictors of complications. RESULTS: A total of 1,000 patients underwent EUS with propofol sedation during the period from January 1, 2001 through December 31, 2002 (mean age 64 years, 53% female). The distribution of EUS indications based on the primary area of interest was: 170 gastroduodenal, 92 anorectal, 508 pancreaticohepatobiliary, 183 esophageal, and 47 mediastinal. The primary endpoint of the study was development of sedation-related complications occurring during a performed procedure. A total of six patients experienced complications: duodenal perforation (one), hypotension (one), aspiration pneumonia (one), and apnea requiring endotracheal intubation (three). The complication rate with propofol was 0.60%, compared with 1% for the historical case-control (meperidine/midazolam moderate sedation) group. CONCLUSIONS: There does not appear to be a significant difference between complication rates for propofol deep sedation with MAC and meperidine/midazolam administered for moderate sedation.

Metronidazole single versus multiple daily dosing in serious intraabdominal/pelvic and diabetic foot infections.

The purpose of the study was to compare the clinical efficacy of once-daily versus multiple dose regimens of metronidazole in inpatients with serious/systemic Bacteroides fragilis infections, i.e., intraabdominal/pelvic and diabetic foot infections. A retrospective chart review was performed on 145 adult inpatients who received combination therapy with metronidazole for B. fragilis abdominal/pelvic infection or diabetic (deep) foot infections/osteomyelitis. Exclusion criteria included metronidazole given for indications other than those mentioned, patients who received only one dose of metronidazole, and patients who received oral metronidazole only. The 145 patients were in two groups: 66 patients in the metronidazole 1 g (i.v.) q24h (Group A) and 79 patients who received metronidazole 500 mg (i.v./p.o.) q6-8h dosing (Group B). Patient demographics included age, gender, indications of metronidazole, concomitant, antibiotics, and co-morbidities. Data collection also included length of stay (LOS), antibiotic days, and clinical outcomes. The 145 patients in our study had a mean age of 66 years, 61% were female and 39% male. Most patients were being treated for definitive intraabdominal/pelvic infections (82%), or probable intraabdominal/pelvic infections (22%). Only 6% had deep diabetic foot infections of osteomyelitis (percentages exceed 100% since a patient can have more than one indication) and were included since B. fragilis is also and important pathogen in diabetic osteomyelitis. Group A patients had more concomitant antibiotics and co-morbidities (p < 0.0001 and p < 0.05 respectively, chi-square test for trend) than Group B patients. There were no statistically significant differences between groups A and B for LOS and antibiotic days (p = 0.42 and p = 0.92 respectively, by rank-sum test), but after adjusting for concomitant antibiotics and co-morbidities Group A patients had clinically shorter LOS and fewer antibiotic days. Unadjusted mortality and failure rates were non-significantly higher in group A (relative ratios of 12.1%/6.3% = 6.3% = 1.91 and 18.2%/ 10.1% = 1.80 respectively), but after adjusting for concomitant antibiotics and co-morbidities with stratification analysis, groups A and B were virtually the same (risk differences of

Survival of patients who had salvage castration after failure on bicalutamide monotherapy for stage (D2) prostate cancer.

Patients with hormone-naive stage D2 prostate cancer often benefit from castration. This treatment, however, frequently produces many unacceptable physical and psychological side effects, especially in younger and sexually active patients. Bicalutamide is an oral antiandrogen with excellent tolerance and preservation of sexual function. Three institutions participated in phase II and III trials of bicalutamide monotherapy (50 mg daily) as primary therapy in hormone-naive patients with stage D2 prostate cancer. Upon bicalutamide failure, all patients underwent castration and were followed until death. Fifty-four patients received bicalutamide 50 mg orally once a day. One patient (2%) had complete response, 9 patients (17%) had partial response, and 27 patients (50%) had stable disease. Seventeen patients (31%) had progressive disease. The median time to bicalutamide failure was 47.4 weeks, 70.5 weeks for the responders vs. 25.4 weeks for the nonresponders (p < 0.001). The median survival time after the sequential use of bicalutamide and castration was 119.2 weeks for all 54 patients, 162.0 weeks for the responders, and 73.5 weeks for nonresponders (p < 0.0001). The median survival time after initiation of castration was 71.1 weeks for all 54 patients, 91.4 weeks for bicalutamide responders, and 42.1 weeks for nonresponders (p < 0.01). In hormone-naive patients with stage D2 prostate cancer, sequential treatment with bicalutamide monotherapy followed by castration upon failure may produce survival time within the range reported for initial treatment with castration. Thus, considering the favorable quality of life profile of bicalutamide, further studies are needed to define the role of sequential hormonal therapy in younger sexually active patients.

The memorial symptom assessment scale short form (MSAS-SF).

BACKGROUND: The Memorial Symptom Assessment Scale Short Form (MSAS-SF), an abbreviated version of the Memorial Symptom Assessment Scale, measures each of 32 symptoms with respect to distress or frequency alone. A physical symptom subscale (PHYS), psychologic symptom subscale (PSYCH), and global distress index (GDI) can be derived from the Short Form. We validated the MSAS-SF in a population of cancer patients. METHODS: Two hundred ninety-nine cancer patients examined at the Section of Hematology/Oncology completed the MSAS-SF and the Functional Assessment Cancer Therapy (FACT-G). The Karnofsky performance status (KPS), extent of disease (EOD), and demographic data were assessed. The Cronbach alpha coefficient was used to assess internal reliability. MSAS-SF subscales were assessed against subscales of the FACT-G, the KPS, and EOD to determine criterion validity. Test-retest analysis was performed at 1 day and at 1 week. RESULTS: The Cronbach alpha coefficients for the MSAS-SF subscales ranged from 0.76 to 0.87. The MSAS-SF subscales showed convergent validity with FACT subscales. Correlation coefficients were -0.74 (P < 0.001) for the PHYS and FACT-G physical well-being subscales, -0.68 (P < 0.001) for the PSYCH and FACT emotional well-being subscales, and -0.70 (P < 0.001) for GDI and FACT summary of quality-of-life subscales. The MSAS-SF subscales demonstrated convergent validity with performance status, inpatient status, and extent of disease. The test-retest correlation coefficients for the MSAS-SF subscales ranged from 0.86 to 0.94 at 1 day and from 0.40 to 0.84 for the 1 week group. CONCLUSIONS: The MSAS-SF is a valid and easy to use instrument for symptom assessment.

Differences in skeletal and muscle mass with aging in black and white women.

Previous cross-sectional studies using delayed gamma neutron activation analysis and whole body counting suggested that the relationship of total body calcium (TBCa) to total body potassium (TBK) (muscle mass, body cell mass) remained constant with age. This led to the hypothesis that the muscle mass and skeletal mass compartments are integrated in their response to aging. It had also been hypothesized that loss of skeletal and muscle mass was similar between races. In the current study, delayed gamma neutron activation analysis and whole body counting were performed on 90 black and 143 white women 20-69 yr of age. Black women had higher TBCa and TBK values than white women, even when the data were adjusted for age, height, and weight. TBCa was correlated with height and TBK with weight. The estimated decline of skeletal mass (TBCa) from 20 to 70 yr was 18% in black women and 19% in white women. However, the lifetime decline of TBK was only 8% for black women, compared with 22% for white women. Black women may lose TBK more slowly than TBCa with aging, compared with white women. In particular, correlation of TBCa and age was similar for blacks and whites (r = -0.44 and r = -0.54, respectively). However, for TBK these correlations were r = -0.14 and r = -0.42. These data confirm a higher musculoskeletal mass in black women and suggest that the loss of muscle mass with age may be lower in black than in white women. These ethnic differences do not support the hypothesis of an integrated musculoskeletal system, so that these two components should be considered separately. A prospective study is needed to confirm these findings.

Validation of the Edmonton Symptom Assessment Scale.

BACKGROUND: The Edmonton Symptom Assessment Scale (ESAS) is a nine-item patient-rated symptom visual analogue scale developed for use in assessing the symptoms of patients receiving palliative care. The purpose of this study was to validate the ESAS in a different population of patients. METHODS: In this prospective study, 240 patients with a diagnosis of cancer completed the ESAS, the Memorial Symptom Assessment Scale (MSAS), and the Functional Assessment Cancer Therapy (FACT) survey, and also had their Karnofsky performance status (KPS) assessed. An additional 42 patients participated in a test-retest study. RESULTS: The ESAS "distress" score correlated most closely with physical symptom subscales in the FACT and the MSAS and with KPS. The ESAS individual item and summary scores showed good internal consistency and correlated appropriately with corresponding measures from the FACT and MSAS instruments. Individual items between the instruments correlated well. Pain ratings in the ESAS, MSAS, and FACT correlated best with the "worst-pain" item of the Brief Pain Inventory (BPI). Test-retest evaluation showed very good correlation at 2 days and a somewhat smaller but significant correlation at 1 week. A 30-mm visual analogue scale cutoff point did not uniformly distinguish severity of symptoms for different symptoms. CONCLUSIONS: For this population, the ESAS was a valid instrument; test-retest validity was better at 2 days than at 1 week. The ESAS "distress" score tends to reflect physical well-being. The use of a 30-mm cutoff point on visual analogue scales to identify severe symptoms may not always apply to symptoms other than pain.

Symptom and quality of life survey of medical oncology patients at a veterans affairs medical center: a role for symptom assessment.

BACKGROUND: The current study was conducted to assess symptom prevalence and symptom intensity and their relation to quality of life in medical oncology patients at a Veterans Affairs medical center. METHODS: Consecutive inpatients and outpatients were asked to complete the Functional Assessment Cancer Therapy (FACT-G), Memorial Symptom Assessment Scale (MSAS), and the Brief Pain Inventory. Symptoms then were analyzed by their relation to Karnofsky performance status (KPS) and quality of life. RESULTS: Two hundred forty patients participated. The median number of symptoms was 8 per patient (range, 0-30 symptoms). The 5 most prevalent symptoms were lack of energy (62%), pain (59%), dry mouth (54%), shortness of breath (50%), and difficulty sleeping (45%). Patients with moderate intensity pain had a median number of 11 symptoms and patients with moderate intensity lack of energy had a median number of 13 symptoms. The number of intense symptoms increased as the KPS decreased (P < 0.001). Patients with moderately intense pain or fatigue also were more likely to experience nausea, dyspnea, and lack of appetite. The number of symptoms rated as present on the MSAS was found to correlate significantly with the FACT-G Sum Quality of Life score. CONCLUSIONS: Intense symptoms were highly prevalent in this population. The presence of pain, lack of energy, or poor performance status should lead to comprehensive symptom assessment. Patients free of disease nevertheless still may experience intense symptoms. The number of symptoms present may be a helpful guide to quality of life. Routine comprehensive symptom assessment may identify a significant fraction of patients who urgently require intensive symptom palliation.

Effect of combined kinetic therapy and percussion therapy on the resolution of atelectasis in critically ill patients.

BACKGROUND: Some critically ill patients have difficulty in mobilizing their respiratory secretions. These patients can develop pulmonary atelectasis that may result in hypoxemia. There are some data to show that atelectasis may be prevented by turning a patient from side to side utilizing special beds. STUDY OBJECTIVES: To determine the role of kinetic therapy (KT) combined with mechanical percussion (P) in the resolution of established atelectasis of the lungs and hypoxemia in critically ill, hospitalized patients. (KT was defined as rotation of a patient along the longitudinal axis of > or = 40 degrees to each side continuously.) DESIGN: Prospective and randomized study (2:1 test to control group). PATIENTS: Twenty-four patients with respiratory failure, either mechanically ventilated or spontaneously breathing, who demonstrated segmental, lobar, or unilateral entire lung atelectasis were studied. SETTING: Medical ICU and adult respiratory ward in a county hospital in New York. INTERVENTIONS: Seventeen patients were treated with KT combined with mechanical P using a KT system (Triadyne Kinetic Therapy System; KCI; San Antonio, TX). Seven patients received manual repositioning and manual P every 2 h. Both groups received similar conventional therapy with inhaled bronchodilators and suctioning. RESULTS: Partial or complete resolution of atelectasis was seen in 14 of 17 patients (82.3%) in the test group as compared with 1 of 7 patient (14.3%) in the control group. The median duration to resolution of atelectasis was 4 days in the test group. Bronchoscopy was performed in 3 of 7 patients in the control group, but in none of the patients in the test group. A cost of $720 was incurred per patient for utilizing the specialty beds for a mean duration of 4 days. An improvement in oxygenation index occurred in the test group (change in baseline PaO2/fraction of inspired oxygen from 207.4+/-106.7 mm Hg to 318+/-100.7 mm Hg) at the end of therapy, while the control group showed a reduction over a similar duration of time (181.3+/-96.3 mm Hg to 112+/-21.2 mm Hg). CONCLUSIONS: KT and mechanical P therapy resulted in significantly greater partial or complete resolution of atelectasis as compared with conventional therapy. There was a generalized trend toward statistical significance in the improvement of oxygenation and a reduced need for bronchoscopy in the group receiving KT and P therapy.

Total-body calcium estimated by delayed gamma neutron activation analysis and dual-energy X-ray absorptiometry.

Total body calcium (TBCa) in 270 black and white women age 21-79 years was measured concurrently by delayed gamma neutron activation analysis (DGNA) and dual-energy X-ray absorptiometry (DXA). The mean value for TBCa calculated from DXA was 933 g compared with 730 g for DGNA. By regression, TBCa(DXA(g)) = 1.35 x TBCa(DGNA(g)) -54 (r = 0. 90, r(2) = 81.4%, SEE = 66.9 g). This remarkable difference of 203 g suggests that one or both these methods is not accurate. Adjustment of the regression of DXA versus DGNA for body mass index or trunk thickness explained 8.5-10% of the variability between methods. The unadjusted slope for the DXA values regressed against the DGNA values was 1.35, indicating significant discordance between the methods. There is greater agreement between the two DGNA facilities (Brookhaven National Laboratory and Baylor College of Medicine) and between the various DXA instruments. Either DGNA underestimates TBCa or DXA overestimates total-body bone mineral content. Resolution of these disparate results may possibly be achieved by concurrent measurement of whole human cadavers of different sizes with chemical determination of the calcium content of the ash. In the interim, cross-calibration equations between DGNA and standardized values for DXA for total-body bone mineral content may be used, which will permit reporting of consistent values for TBCa from the two technologies.

alpha-Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration.

alpha-fetoprotein (AFP) gene expression occurs in the yolk sac, in the fetal liver and gut, and in the adult liver during regeneration and tumorigenesis. Two unlinked genes determine the level of AFP gene expression in adult mice: Afr1 regulates the basal level of expression in the normal adult liver, and Afr2 regulates the increase in expression during liver regeneration. It has been shown that AFP-derived transgenes, including the sequences between -1,010 and -838 bp and between -118 bp and the transcriptional start site were induced appropriately during liver regeneration and were Afr2-regulated. To assess the role of the distal sequence in gene expression during liver regeneration, a new transgene with 7.6 kilobases of 5'-flanking sequence deleted between -1,010 and -838 bp was designed. We show that this transgene was subject to characteristic AFP tissue-specific and developmental regulation, in that it was highly expressed in the yolk sac and the fetal liver and gut but not in normal adult tissues. Expression was induced in response to liver regeneration as observed for the endogenous gene. The genetic regulation of the basal level of AFP gene expression in adult liver by the Afr1 gene was undisturbed. However, transgene expression was not regulated by Afr2 during liver regeneration. Our data suggest that Afr2 regulation of AFP gene expression during liver regeneration requires the sequence between -1,010 and -838 bp and is independent of other regulatory mechanisms.

Stressful life events and risk of symptomatic kidney stones.

BACKGROUND: It has been reported that a substantial proportion of cases of hypercalciuria and nephrolithiasis are idiopathic. Several studies suggested that stressful life events increase lithogenic urinary constituents (calcium, oxalate and uric acid). OBJECTIVE: To test the hypothesis that there is an association between stressful life events and symptomatic kidney stone. METHODS: A case-control study of 200 symptomatic kidney stone cases and 200 matched controls was designed to test the hypothesis. In this study, the stressors include those life events that the subjects perceived as highly stressful and inflicted upon them an intense emotional impact with apprehension and distress for at least one week in duration. RESULTS: Ten of eleven (91%) categories and 41 of 60 (68%) subcategories of stressful events occurred more frequently among cases than controls. Eighteen stressful events had odds ratios of 1.5 or greater. Of the seven significant (P < 0.05) variables that were entered into a multivariate logistic regression model, the following three remained statistically significant between cases and controls: annual family income (lower for cases); stressful morgage problems; and emotional life events. CONCLUSION: The overall prevalence rate of stressful life events was significantly (P < 0.00001) higher among cases than controls. The data support the hypothesis that there is an association between stressful life event(s) and symptomatic kidney stones.

p53-independent induction of p21WAF1/CIP1 expression in pericentral hepatocytes following carbon tetrachloride intoxication.

The cyclin-dependent kinase, proliferating cell nuclear antigen, and stress-activated protein kinase/c-jun NH2 terminal kinase inhibitor p21WAF1/CIP1 can induce G1 arrest, and its expression coincides with the cessation of replication in many systems. We examined expression of p21 during the early stages of carbon tetrachloride intoxication in the mouse liver and observed a dramatic increase in p21 RNA levels between 4 and 8 h after administration. p21 expression, visualized by in situ hybridization, is induced in pericentral hepatocytes before carbon tetrachloride-induced necrosis. Examination of c-fos and c-myc expression patterns confirm that these immediate-early genes are induced in similar regions of the mouse liver. p21 induction is not dependent on p53; we observed similar levels and localization of p21 in wild-type and p53 null animals. Immunohistochemical localization of p21 and CCAAT/enhancer-binding protein expression shows that p21 protein accumulation is limited to a subset of CCAAT/enhancer-binding protein-positive hepatocytes. A second peak of periportal and intermediate zone-specific p21 gene expression, appearing 1-2 days after injection, is also p53 independent and may represent cell cycle checkpoints or postmitotic growth arrest. Sporadic p21 expression was also detected in pairs of hepatocytes distributed throughout the liver acini in healthy animals. Together, these data suggest several roles for p21 in the liver in response to toxicity, regeneration, and growth inhibition.

Characterization of the myosin heavy chains of avian adult fast muscles at the protein and mRNA levels.

High resolution anion-exchange chromatography of myosin subfragment-1 in avian fast muscles revealed five fast heavy chains (I-V) expressed in muscle-specific patterns. Sequence analysis of a unique peptide established that the proteins differed in primary structure and suggested correlation with heavy chain genes identified independently by Robbins and coworkers. The identities of the isoforms and their expression patterns were confirmed at the mRNA level by a reverse-transcription, 5'-anchored PCR procedure. The fast white pectoralis major muscle possessed heavy chain I, the posterior latissimus dorsi muscle, of similar fibre type, expressed heavy chains I, III and IV. The fast red adductor superficialis muscle expressed either, or both, of heavy chains II and IV. The lateral gastocnemius muscle, of mixed fibre type, expressed heavy chains II-V. In general, heavy chains I, III and V appeared to be favoured in fast white fibres, while heavy chains II and IV were characteristic of fast red fibres. These results imply a greater subtlety of fast muscle function than has previously been appreciated.

Patterns of smoking among inner-city teenagers: smoking has a pediatric age of onset.

OBJECTIVES: (1) To test the hypothesis that the prevalence of smoking among African-American teenagers is lower than among whites and Hispanic inner-city senior high school students; (2) to assess the patterns of smoking among inner-city teenagers; and (3) to ascertain the relationship between smoking status and their knowledge, attitudes, beliefs, and behaviors. METHODS: All students attending inner-city senior high schools in two cities in New Jersey were included in the survey (n = 8,900). Response Rate was 85%; 89% of respondents were minority teenagers. RESULTS: The overall point prevalence rate of cigarette smoking was 9%. Almost all smoking began before the age of 16 years. The factors that significantly (p < .001) contributed to the initiation of cigarette smoking were: peer influence, self-initiation, and the influence of relatives' cigarette smoking. The factors that were stated to play a major role in progression to regular smoking were: perceptions that smoking relieves stress and feelings of induced pleasure while smoking. In addition, smokers were significantly (p < .0005) less knowledgeable about smoke-related diseases than exsmokers or nonsmokers. Over two-thirds of smokers and exsmokers believed that it is the physician's responsibility to advise patients to quit smoking and the majority of the current smokers contemplated quitting smoking. The data support the hypothesis that smoking prevalence among African-American teenagers is significantly lower than among white and Hispanic teenagers who attended the senior high school and resided in the inner city. CONCLUSION: These data suggest that multidimensional antismoking strategies are needed to address the smoking among predominately minority teenagers. This includes supportive messages from physicians, relatives, friends along with public policy to act as motivating factors to discourage early smoking.

Cigarette smoking among patients with mental retardation and mental illness.

Among 136 adults with mental illness and mental retardation who were consecutively treated at a developmental disabilities clinic, 25 reported that they currently smoked cigarettes. Among those with mild and borderline retardation, smoking rates were 30 and 37 percent, respectively. Smokers were significantly more likely than nonsmokers to drink alcohol, use other drugs, and be sexually active. Multiple regression analysis found that a mild or borderline level of retardation and a diagnosis of schizophrenia were significant predictors of smoking. Mentally retarded persons with mental illness are at risk of tobacco-related disease and may benefit from prevention and smoking cessation interventions.

Sequence requirements for Afr-2 regulation of alpha-fetoprotein gene expression during liver regeneration.

Alpha-fetoprotein (AFP) gene expression occurs in the yolk sac, fetal liver and gut, and in the adult liver during regeneration and tumorigenesis. Polymorphism at a single genetic locus, Afr-2 (formerly known as Rif) between inbred mouse strains C3H/He and C57B1/6, results in different levels of AFP expression during liver regeneration. We examined AFP, histone H3, and albumin gene expression during liver regeneration and found that the strain-specific variance in AFP gene expression could not be attributed to a difference in the numbers of dividing cells. Experiments with transgenic mice revealed sequences required for Afr-2 regulation included 172 bp between -1010 and -838 bp and 118 bp immediately upstream of the AFP transcriptional start site-the same regions required for induction during liver regeneration. This suggests that the Afr-2 phenotype may stem from an allelic difference in a gene regulating gene expression during liver regeneration.

Caries experience and cariogenic markers in HIV-positive children and their siblings.

The purpose of this cross-sectional, masked study was to compare the oral status of perinatally HIV-infected children with their uninfected siblings living in the same environment. A secondary purpose was to compare HIV-positive children for differences in oral health with respect to disease advancement. One hundred forty-seven children were examined in their homes and meeting places, using NIH criteria for caries diagnosis. Significant differences were found in the number of caries-free children (P < 0.05), past caries experience (P < 0.003), subsurface demineralizations (P < 0.0001), and caries-related bacteria (P < 0.05). However, differences in caries prevalence were not found in the 3- to 6-year-old subgroup. Caries prevalence (P < 0.001) and levels of caries-related flora in saliva were correlated to years since diagnosis (mutans streptococci P < 0.008, lactobacilli P < 0.02). Children with a more advanced disease stage had significantly more caries (P < 0.02). Among the HIV-infected children, the frequency of carbohydrate intake was clearly correlated to caries (P < 0.003) and to lactobacilli levels (P < 0.0001). It is concluded that children with perinatally acquired HIV are at greater risk for caries than their siblings, more so with advancing disease.

Reduction of left ventricular spontaneous echo contrast in cardiomyopathy by acute inotropic intervention or aggressive therapy.

The purpose of this study was to determine whether improvement of left ventricular (LV) systolic function could reduce the severity or eliminate LV spontaneous echo contrast found with transthoracic echocardiography in a group of patients with advanced cardiomyopathy. A successful reduction of this by hemodynamic means might indicate an additional beneficial method of helping prevent thromboembolism in advanced cardiomyopathy. Six patients with advanced cardiomyopathy and demonstrating spontaneous echo contrast on transthoracic echocardiography were treated with acute inotropic drug infusions or aggressive medical therapy to improve LV systolic function to determine whether reduction in spontaneous contrast could be achieved by such means. A spontaneous echo contrast scoring system was devised: 0 to 4, indicating absent to severe. Six observers, unacquainted with the study plan, were blinded as to the source of the 12 pre- and post-therapy two-dimensional echocardiograms obtained and re-recorded in a random sequence, and were asked to grade the degree of spontaneous echo contrast. In all six patients, LV spontaneous echo contrast was reduced by improvement in LV systolic function (average score lowered from 2.94 to 1.25, p < 0.005). Among patients with cardiomyopathy at high risk for LV thromboembolism, as indicated by the presence of LV spontaneous echo contrast, improvement in LV systolic function may serve as an adjunct to anticoagulation or, in some cases, as a substitute when the latter is contraindicated in the prevention of thromboembolism. The results obtained suggest merit in prospective, long-term studies of a larger group of such patients.

Sequence requirements for alpha-fetoprotein gene expression during liver regeneration.

The alpha-fetoprotein (AFP) gene is expressed in fetal liver and in adult liver undergoing regeneration or tumorigenesis. It has been shown previously that three distal enhancers, a proximal promoter, and a dominant negative postnatal repressor element are required for the tissue-specific and developmental regulation of AFP gene expression. Using transgenic mice, we have determined the sequence requirements for AFP gene induction during liver regeneration. Two DNA sequences were found in all transgenes appropriately regulated in response to liver regeneration: a distal sequence between 1010 and 838 bp upstream of the structural gene and a proximal sequence within 118 bp of the transcriptional initiation site. In situ hybridization analysis showed that transgene expression during liver regeneration was first found in all hepatocytes and then localized to perinecrotic hepatocytes surrounding the central vein. This pattern of expression is reminiscent of that observed after birth for the transgenes, suggesting that repression of AFP gene expression after birth and liver injury may be regulated by similar mechanisms.