Prospective comparison among three intrarectal anesthetic treatments combined with periprostatic nerve block during transrectal ultrasonography-guided prostate biopsy.

BACKGROUND: Recent trends in prostate biopsy analgesia suggest a combination anesthetic to provide better pain relief than periprostatic nerve block (PPNB) alone. This study aimed to demonstrate the efficacy and safety of three intrarectal local anesthesia (IRLA) combined with PPNB in patients undergoing transrectal ultrasonography (TRUS)-guided prostate biopsy. METHODS: In this prospective, randomized study, 120 prostate biopsy patients were equally divided into four IRLA groups: group 1 (placebo) received simple lubrication; group 2 received 2% lidocaine gel; group 3 received 100 mg indomethacin suppository and group 4 received 5% prilocaine/lidocaine (EMLA) cream. PPNB with 2% lidocaine was applied in all groups. A ten-point visual analog scale evaluated both pain associated with the probe insertion and pain associated with prostate sampling. Adverse effects or complications due to anesthesia during and after the procedure were documented. RESULTS: Compared with group 1, groups 3 and 4 had significantly lower pain scores at both probe insertion and prostate sampling while group 2 showed no significant differences at both pain scores. Moreover, group 4 showed significantly lower pain scores at probe insertion compared to group 3, while no significant difference was observed at prostate sampling. Mild complications were observed in all groups with no significant difference in the incidence of complications between groups. CONCLUSION: Intrarectal application of EMLA cream is a more efficient pain reduction than either 2% lidocaine gel or 100 mg indomethacin suppository when applied combined with PPNB. This combination represents an effective option of pain relief for patients undergoing TRUS-guided prostate biopsy.

Outcomes from Autologous Hematopoietic Cell Transplantation versus Chemotherapy Alone for the Management of Light Chain Amyloidosis.

Light chain amyloidosis (AL) results in tissue deposition of misfolded proteins, causing organ dysfunction. In an era of modern therapies, such as bortezomib, reassessment of the benefit of autologous hematopoietic cell transplantation (AHCT) should be considered. In this study, we compared outcomes between patients with AL receiving chemotherapy alone (CT) and those undergoing AHCT. Seventy-four patients with AL were analyzed retrospectively. Two cohorts of patients were studied, those receiving CT (n = 31) and those undergoing AHCT (n = 43). Of the 43 patients in the AHCT cohort, 29 received induction chemotherapy before AHCT, whereas 14 proceeded straight to AHCT without induction therapy. Compared with the CT cohort, patients in the AHCT cohort were younger and had higher ejection fractions, lower brain natriuretic peptide levels, and more severe proteinuria. The majority (87%) of patients in the CT cohort received bortezomib-based treatment. Transplantation-related mortality (TRM) was 7%. Patients receiving AHCT were more likely to achieve complete or very good partial response (P = .048). The median progression-free survival (PFS) and overall survival (OS) were superior in the AHCT cohort (not reached versus 9 months; P < .01 and 74 months versus 8 months; P = .03, respectively). Multivariable analysis demonstrated that improved PFS (hazard ratio, 3.86; 95% confidence interval [CI] 1.3 to 11.5; P = .02) and OS (hazard ratio, 5.6; 95% CI, 1.9 to 16; P < .001) were associated with use of AHCT compared with CT. Patients in the AHCT cohort had deeper and longer durations of response, with superior PFS and OS, compared with those in the CT cohort. Despite the limitations of this study, AHCT should be considered for eligible patients with AL at experienced transplantation centers that can offer this therapy with a low risk of TRM.

Mapping pain activation and connectivity of the human habenula.

The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e.g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e.g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain.

Reference measurement procedure for total glycerides by isotope dilution GC-MS.

BACKGROUND: The CDC's Lipid Standardization Program established the chromotropic acid (CA) reference measurement procedure (RMP) as the accuracy base for standardization and metrological traceability for triglyceride testing. The CA RMP has several disadvantages, including lack of ruggedness. It uses obsolete instrumentation and hazardous reagents. To overcome these problems the CDC developed an isotope dilution GC-MS (ID-GC-MS) RMP for total glycerides in serum. METHODS: We diluted serum samples with Tris-HCl buffer solution and spiked 200-µL aliquots with [(13)C(3)]-glycerol. These samples were incubated and hydrolyzed under basic conditions. The samples were dried, derivatized with acetic anhydride and pyridine, extracted with ethyl acetate, and analyzed by ID-GC-MS. Linearity, imprecision, and accuracy were evaluated by analyzing calibrator solutions, 10 serum pools, and a standard reference material (SRM 1951b). RESULTS: The calibration response was linear for the range of calibrator concentrations examined (0-1.24 mmol/L) with a slope and intercept of 0.717 (95% CI, 0.7123-0.7225) and 0.3122 (95% CI, 0.3096-0.3140), respectively. The limit of detection was 14.8 µmol/L. The mean %CV for the sample set (serum pools and SRM) was 1.2%. The mean %bias from NIST isotope dilution MS values for SRM 1951b was 0.7%. CONCLUSIONS: This ID-GC-MS RMP has the specificity and ruggedness to accurately quantify total glycerides in the serum pools used in the CDC's Lipid Standardization Program and demonstrates sufficiently acceptable agreement with the NIST primary RMP for total glyceride measurement.

Proposed serum cholesterol reference measurement procedure by gas chromatography-isotope dilution mass spectrometry.

BACKGROUND: Our purpose was to establish a mass spectrometry reference measurement procedure (RMP) for cholesterol to use in the CDC's standardization programs. We explored a gas chromatography-isotope dilution mass spectrometry (GC-IDMS) procedure using a multilevel standard calibration curve to quantify samples with varying cholesterol concentrations. METHODS: We calibrated the mass spectrometry instrument by isotope dilution with a pure primary standard reference material and an isotopically enriched cholesterol analog as the internal standard (IS). We diluted the serum samples with Tris-HCl buffer (pH 7.4, 0.05 mol/L, 0.25% Triton X-100) before analysis. We used 17 serum pools, 10 native samples, and 2 standard reference materials (SRMs). We compared the GC-IDMS measurements with the CDC's modified Abell-Levy-Brodie-Kendall (AK) RMP measurements and assessed method accuracy by analyzing 2 SRMs. We evaluated the procedure for lack of interference by analyzing serum spiked with a mixture of 7 sterols. RESULTS: The mean percent bias between the AK and the GC-IDMS RMP was 1.6% for all samples examined. The mean percent bias from NIST's RMP was 0.5% for the SRMs. The total %CVs for SRM 1951b levels I and II were 0.61 and 0.73%, respectively. We found that none of the sterols investigated interfered with the cholesterol measurement. CONCLUSIONS: The low imprecision, linear response, lack of interferences, and acceptable bias vs the NIST primary RMP qualifies this procedure as an RMP for determining serum cholesterol. The CDC will adopt and implement this GC-IDMS procedure for cholesterol standardization.

Lenalidomide vs bortezomib maintenance choice post-autologous hematopoietic cell transplantation for multiple myeloma.

Maintenance therapy post-autologous hematopoietic cell transplantation (AHCT) with either lenalidomide or bortezomib for multiple myeloma (MM) have separately been shown to improve progression-free survival (PFS), but have never been directly compared. We performed a retrospective study to investigate progression-free and overall survival outcomes and toxicities of lenalidomide maintenance therapy compared with bortezomib maintenance in MM patients post-AHCT. This study included 156 patients who received post-AHCT lenalidomide or bortezomib maintenance therapy for MM. The primary outcome was PFS. Ninety-two patients received lenalidomide maintenance and 64 received bortezomib maintenance post-AHCT. By multivariable analysis, maintenance therapy choice and cytogenetics risk did not impact PFS or OS. Staging by International Staging System and pre-maintenance disease response were the greatest predictors for PFS. Treatment-related toxicities were as anticipated with 5.4% of patients receiving maintenance lenalidomide experiencing secondary primary malignancies (SPMs) compared with 3% for bortezomib. These findings suggest there were no differences in PFS or OS between lenalidomide and bortezomib maintenance therapy options for post-transplantation MM patients. These data should be validated in a larger, prospective cohort to determine if maintenance choice should be guided by side effect profile and patient anticipated tolerance rather than by disease biology alone.

Cardiac events during treatment with proteasome inhibitor therapy for multiple myeloma.

BACKGROUND: Proteasome inhibitors (PI) bortezomib and carfilzomib are cornerstone therapies for multiple myeloma. Higher incidence of cardiac adverse events (CAEs) has been reported in patients receiving carfilzomib. However, risk factors for cardiac toxicity remain unclear. Our objective was to evaluate the incidence of CAEs associated with PI and recognize risk factors for developing events. METHODS: This was a descriptive analysis of 96 patients with multiple myeloma who received bortezomib (n = 44) or carfilzomib (n = 52). We compared the cumulative incidence of CAEs using a log rank test. Patient-related characteristics were assessed and multivariate analysis was used to identify risk factors for developing CAEs. RESULTS: PI-related CAEs occurred in 21 (22%) patients. Bortezomib-associated CAEs occurred in 7 (16%) patients while carfilzomib-associated cardiac events occurred in 14 (27%) patients. The cumulative incidence of CAEs was not significantly different between agents. Events occurred after a median of 67.5 days on PI therapy. Heart failure was the most prevalent event type. More patients receiving carfilzomib were monitored by a cardiologist. By multivariate analysis, a history of prior cardiac events and longer duration of PI therapy were identified as independent risk factors for developing CAEs. CONCLUSIONS: AEs were common in patients receiving PIs. Choice of PI did not impact the cumulative incidence of CAEs. Early involvement by a cardiologist in patients at high risk for CAEs may help to mitigate the frequency and severity of CAEs.

Chemical composition and physicochemical properties of Phaeodactylum tricornutum microalgal residual biomass.

The production of photosynthetic biofuels using microalgae is a promising strategy to combat the use of non-renewable energy sources. The microalgae residual biomass is a waste by-product of biofuel production; however, it could prove to have utility in the development of sustainable nutraceuticals and functional foods. In this study, a comprehensive characterisation of the under-utilised Phaeodactylum tricornutum microalgae residual biomass is presented. Proximal composition, antioxidant capacity (using three different antioxidant assays; oxygen radical absorbance capacity; radical cation activity, ABTS; and radical scavenging activity, DPPH), and total phenolic content of free and bound polyphenols were determined. Additionally, the physicochemical properties of water activity, pH, water absorption index, water solubility index, and dispersibility were evaluated. Results revealed that P. tricornutum microalgae residual biomass exhibits a relatively high protein and carbohydrate content, with values of 36.67% and 46.78%, respectively; and most carbohydrates were found as total dietary fibre (45.57%), of which insoluble dietary fibre was the most predominant (43.54%). Antioxidant capacity values for total phytochemicals of 106.22, 67.93, 9.54 µM TE g-1 dw were determined by oxygen radical absorbance capacity, ABTS, and DPPH assays, respectively. Total phenolic content was found to be 2.90 mg GAE g-1 dw. Interestingly, antioxidant capacity and total phenolic content were higher in bound than in free phytochemical extracts. The physicochemical analysis showed P. tricornutum microalgae residual biomass to have suitable properties for the generation of a beverage with Aw, pH, water absorption index, water solubility index, and dispersibility values of 0.45, 7.12, 3.40 g gel g-1 dw, 2.5 g solids 100 g-1 dw, and 90%, respectively. Hence, P. tricornutum microalgae residual biomass could be considered a potential source of bioactive compounds suitable for the production of functional food exhibiting antioxidant capacity and high dietary fibre content.

Passive smoking affects endothelium and platelets.

Blood was obtained before and after ten healthy male nonsmokers sat for 20 minutes in open hospital corridors beside men who were already there smoking by their own initiative. Mean values before and after passive smoking were 0.87 and 0.78 for the platelet aggregate ratio, 2.8 and 3.7 per counting chamber for the endothelial cell count, 0 and 2.8 ng/mL for the plasma nicotine concentration, and 0.9% and 1.3% for the carboxyhemoglobin level. No variable changed significantly during control periods in which the subjects sat in a room where smoking was prohibited. Passive exposure to tobacco smoke affected the endothelial cell count and platelet aggregate ratio in a manner similar to that previously observed with active smoking.

Effects of tobacco and non-tobacco cigarette smoking on endothelium and platelets.

Endothelial damage and platelet activation may mediate increased cardiovascular morbidity and mortality in tobacco cigarette smokers. Our study was designed to determine whether acute effects of tobacco smoking on endothelium and platelets could be avoided by the substitution of non-tobacco cigarettes. Twenty healthy nonsmokers smoked two tobacco cigarettes in 20 minutes and on another occasion (separated by 1 week) smoked two cigarettes made from wheat, cocoa, and citrus plants. Mean endothelial cell counts from venous blood before and after smoking tobacco cigarettes were 2.3 and 4.8 and before and after smoking non-tobacco cigarettes counts were 2.5 and 3.0. Mean platelet aggregate ratios before and after smoking tobacco cigarettes were 0.80 and 0.65 and before and after smoking non-tobacco cigarettes they were 0.81 and 0.78. Much greater effects of tobacco smoking on endothelial cell counts and platelet aggregate ratios suggest the possibility that non-tobacco cigarette smoking may be less harmful to the cardiovascular system than is tobacco cigarette smoking.

The organization of the diencephalon and the pretectum in the cichlid fish, Haplochromis burtoni.

Although teleost fish comprise the largest vertebrate radiation, surprisingly little is known about the structure and development of their central nervous systems. Since teleosts are being used much more frequently as model systems in neurobiological research, particularly in understanding visual function, detailed information is needed about central nervous system structures and interconnections. By using the Bodian method with Nissl counterstaining we have analyzed the major nuclei in the diencephalon and pretectum of a cichlid fish, Haplochromis burtoni, which is dependent on vision for its survival. Although our results are broadly comparable with those from other teleost species, there are clear differences, particularly among the visual nuclei. By using animals of a range of sizes to confirm our descriptions we were able to identify possible developmental relationships among several nuclei.

Acid hydrolysis of monoclonal antibodies.

For analysis of monoclonal antibodies using polyacrylamide gel electrophoresis, two hydrolytic fragments derived from the heavy chain of mouse IgG1 were produced during incubation of the antibodies in Laemmli reducing sample buffer at 100 degrees C for 5 min. The cleavage sites were identified by amino terminal sequencing. Results indicate that the final pH of the mixture is critical for the production of the fragments which are generated when the pH is approximately 6.0. At pH 8.0, no fragments are detected. The relevance of this finding to those working with monoclonal antibodies is discussed.

Antibodies to hepatocyte membrane antigens in chronic liver disease: detection by immunofluorescence after Bouin's fixation.

Using a modified indirect immunofluorescent (IF) technique in which cryostat tissue sections were fixed in Bouin's solution for ten minutes prior to reaction with sera under test, we have looked for antibodies to the hepatocyte membrane (HMA) in the sera of patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). Samples were tested initially in parallel on unfixed and Bouin's-fixed rat composite blocks (kidney, stomach, liver) at a titer of 1:100 and those found to be positive were diluted further and reexamined. Conventional unfixed sections of rat composite block showed no liver membrane immunofluorescence although antinuclear (ANA), mitochondrial (AMA), and smooth muscle antibodies (SMA) were detected as anticipated. By contrast, prior Bouin's fixation abolished most of the fluorescence due to ANA, AMA and SMA but resulted in brilliant fluorescence of rat hepatocyte membranes in eleven of twelve patients with CAH (93%) and all ten patients with PBC. Only one of 22 normals (5%), one of 20 with collagen-vascular diseases (5%), and one of seven with nonimmunologic liver disease (14%) were positive for this hepatocyte membrane antibody. Bouin's fixation prior to IF is a simple technique which appears to alter the hepatocyte membrane so that HMA become detectable. The strong association of HMA with CAH and PBC suggests that this test might be of value and may contribute towards a further understanding of the pathogenesis of these conditions.

A trial of dipyridamole and aspirin in the prevention of smoking-induced changes in platelets and endothelium in men with coronary artery disease.

A random-order, double-blind crossover study compared the effects of placebo, dipyridamole and dipyridamole plus aspirin on smoking-induced changes in endothelium and platelets. Each of 12 male habitual smokers with coronary artery disease was given dipyridamole (75 mg) and aspirin (324 mg), dipyridamole (75 mg) and placebo for aspirin, or a placebo for each drug 3 times daily for 1 week before each of three 20-minute periods (separated by 2 weeks) of smoking 2 cigarettes after a 12-hour period of abstinence. During each period of smoking there were increases in the mean values of the plasma concentrations of beta-thromboglobulin, platelet factor 4 and nicotine, the endothelial cell count and the blood level of carboxyhemoglobin. In addition, the mean platelet aggregate ratio decreased during each period. After administration of placebos for both dipyridamole and aspirin, the respective mean values +/- standard deviations before and after smoking were 28 +/- 8 and 30 +/- 7 ng/ml (beta-thromboglobulin), 7.4 +/- 1.0 and 8.2 +/- 1.4 ng/ml (platelet factor 4), 3.7 +/- 0.6 and 15.7 +/- 3.5 ng/ml (nicotine), 4.2 +/- 1.4 and 5.4 +/- 1.7/counting chamber (endothelial cell count), 5.0 +/- 2.2 and 6.6 +/- 2.2% (carboxyhemoglobin) and 0.80 +/- 0.07 and 0.68 +/- 0.10 (platelet aggregate ratio). Each of the differences between the means before and after smoking was statistically significant (p less than or equal to 0.02). Neither dipyridamole alone nor in combination with aspiring significantly affected the mean smoking-induced change in any of these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic features of children with idiopathic dilated cardiomyopathy.

The presenting features and long-term outcome of 39 children (median age 6.5 months, range 1 day to 16 years) with idiopathic dilated cardiomyopathy (IDC) were reviewed to help determine the appropriate management of these patients. Four outcome groups were identified: those who died, improved, had IDC resolved or received transplants. Presenting clinical features of age, sex, race, congestive heart failure, cardiomegaly, and degree of systolic ventricular dysfunction did not predict final outcome. Left ventricular hypertrophy on the electrocardiogram was seen significantly more often in children who improved than in those who died or in whom IDC resolved (p = 0.002). A rhythm disturbance was also seen more often in those who died than in those who survived (p = 0.025). Of 36 patients treated medically, 12 (33%) died, 15 (42%) improved and 9 (25%) resolved. Eighteen of 26 (69%) patients presenting at age less than or equal to 2 years survived, whereas 6 of 10 patients greater than 2 years survived. There were no differences based on age at presentation, in the time to death or time of follow-up. Three patients received orthotopic heart transplants, 1 of whom died from graft failure. Thus, no clinical feature including age at presentation consistently predicts ultimate outcome in children with IDC.

Y-grafts and sequential grafts in coronary bypass surgery: a critical evaluation of patency rates.

In a series of 584 patients undergoing coronary bypass, 425 patients received Y-grafts, sequential grafts, or a combination of the two. The saphenous veins from the legs frequently had Y- or double Y-branches suitable for bypasses. As many as 5 grafts have been served satisfactorily by a single proximal anastomosis. Simultaneous procedures included 45 left ventricular aneurysmectomies, 18 valve replacements, 7 carotid endarterectomies, repairs of a ventricular septal defect, an acute dissection, and coronary arteriovenous fistulas, with a total surgical mortality of 6 (1.4%). Restudy to determine graft patency was undertaken only in the 59 patients with unsatisfactory surgical results. These patients represent the worst 10% of the series in terms of surgical results. The patency rate for proximal anastomoses was 93%; Y-branchings, 93%; distal end-to-side anastomoses, 89%; and distal side-to-side anastomoses, 89%. Fifty-eight patients (98%) had at least 1 patient graft, and in 47 patients (80%) all anastomoses were patent up to six years after operation. Six patients underwent reoperation without any deaths.

Blood loss and bank blood requirement in coronary bypass surgery.

With the use of nonblood prime and refinement in perfusion and surgical techniques, blood requirement for coronary bypass operations has been reduced to a minimum. Of 240 patients (average number of bypasses, 3.07; average pump time, two hours and 22 minutes), no blood was used in pump prime or before perfusion. During perfusion, 29 patients (12%) received 34 units of blood in the pump-oxygenator, and after bypass 64 patients (27%) received 65 units of blood in the operating room (average intraoperative use, 203 ml per patient). For the total hospital stay, the blood requirement was 728 ml per patient. For the last 60 patients operated on, the figure was 328 ml. There were no surgical deaths, and only 1 reexploration for postoperative hemorrhage (0.4%). Discharge hemoglobin level averaged 11.8 gm, whereas the admission hemoglobin level had averaged 13.8 gm. Autotransfusion, avoidance of entry into the pleural space, shorter perfusion time, postoperative platelet count of more than 150,000, and normal partial thromboplastin time tend to reduce blood requirement, but not to a striking degree. Bank blood requirement for the coronary bypass program accounted for 3.7% of the hospital need and 2% of the community need.

Developmental level as a predictor of alcoholism treatment response: an attempted replication.

Over 12 years ago, a developmental level (DL) cognitive measure derived from the Rorschach was found to be a powerful predictor of alcohol-related outcomes following behaviorally oriented inpatient alcoholism treatment. These findings represent the strongest evidence of a relationship between cognitive functioning and treatment response. The current pilot study attempted to determine whether the large effects previously obtained with the DL measure could be replicated. The Rorschach was administered during the first week of treatment to 20 male alcoholic patients attending 1-month day hospital rehabilitation program. The Addiction Severity Index (ASI) was administered upon entry into treatment and a follow-up ASI was also administered 7 months after treatment entry. A higher DL was found to be significantly related to less recent drinking and intoxication at baseline as well as to lower alcohol-related problem levels in general. However, all of the relationships between DL and alcohol-related behaviors at follow-up were found to be either small or in a direction opposite to that hypothesized. Some of the reasons for the discrepancy between the findings of the current study and the earlier study are discussed.

Acute venous obstruction from a mediastinal cystic lymphangioma.

We report a case of acute symptomatic obstruction of the right innominate vein caused by mediastinal cystic lymphangioma, which was dissected completely free and excised from the surrounding tissues. The patient's postoperative course was uneventful. We stress the need for timely surgical excision of such masses upon diagnosis to prevent life-threatening clinical presentations resulting from sudden increase in the cyst size.

Self-reported medical problems of adult female survivors of childhood sexual abuse.

BACKGROUND: Childhood sexual abuse has been established as an antecedent to specific psychological disorders in adulthood. Only recently have researchers begun to consider the effects of this early trauma on subsequent physical health status. The current study sought to explore the relationship between a history of childhood sexual abuse in female adults and subsequent self-reported medical complaints. METHODS: This consecutive sample study used a questionnaire to distinguish subjects with a sexual abuse history and those without such a history. Subjects were female patients over 18 years of age at a primary care health center. RESULTS: Twenty-six percent of the 523 subjects who completed the entire questionnaire acknowledged a history of sexual abuse in childhood. This percentage is consistent with estimates for the population at large. The abused group reported more problems in respiratory, gastrointestinal, musculoskeletal, neurological, and gynecological functions. Statistically significant discriminating variables for those who had been abused were (1) total medical complaints reported, (2) previous mental health treatment, and (3) age of first sexual intercourse. Among the abused group, only 5.1% had ever disclosed information about their sexual abuse experiences to a physician. CONCLUSIONS: At least one in four women are survivors of childhood sexual abuse. These women rarely spontaneously reveal this history to a physician, yet they are more likely than nonabused patients to report multisystemic medical complaints. To avoid misdiagnosis and misuse of medical services, physicians should routinely obtain a thorough sexual history, particularly when the patient has multisystem complaints.