Chronic kidney disease and end-stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to assess the clinical outcomes of Clostridium difficile infection (CDI) in patients with chronic kidney diseases (CKD) and end-stage renal disease (ESRD). METHODS: A literature search was performed from inception through February 2015. Studies that reported relative risks, odds ratios or hazard ratios comparing the clinical outcomes of CDI in patients with CKD or ESRD and those without CKD or ESRD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS: Nineteen studies (a case-control and 18 cohort studies) with 116,875 patients assessing clinical outcomes of CDI were included in the meta-analysis. Pooled RR of severe or complicated CDI in CKD patients was 1.51 (95% CI: 1.00-2.28). The risk of recurrent CDI is significant higher in patients with a pooled RR of 2.73 (95% CI: 1.36-5.47). The pooled RR of mortality risk of CDI in patients with CKD, ESRD and CKD or ESRD were 1.76 (95% CI: 1.26-2.47), 1.58 (1.37-1.83) and 1.76 (1.32-2.34) respectively. CONCLUSION: This meta-analysis demonstrates poor outcomes of CDI including severe and recurrent CDI in CKD patients. History of CKD and ESRD are both associated with increased mortality risk in patients with CDI.

Highlights and discoveries from the Chandra X-ray Observatory.

Within 40 years of the detection of the first extra-solar x-ray source in 1962, NASA's Chandra X-ray Observatory has achieved an increase in sensitivity of 10 orders of magnitude, comparable to the gain in going from naked-eye observations to the most powerful optical telescopes over the past 400 years. Chandra is unique in its capabilities for producing sub-arcsecond x-ray images with 100-200 eV energy resolution for energies in the range 0.08 < E < 10 keV, locating x-ray sources to high precision, detecting extremely faint sources, and obtaining high-resolution spectra of selected cosmic phenomena. The extended Chandra mission provides a long observing baseline with stable and well-calibrated instruments, enabling temporal studies over timescales from milliseconds to years. In this report we present a selection of highlights that illustrate how observations using Chandra, sometimes alone, but often in conjunction with other telescopes, have deepened, and in some instances revolutionized, our understanding of topics as diverse as protoplanetary nebulae; massive stars; supernova explosions; pulsar wind nebulae; the superfluid interior of neutron stars; accretion flows around black holes; the growth of supermassive black holes and their role in the regulation of star formation and growth of galaxies; impacts of collisions, mergers, and feedback on growth and evolution of groups and clusters of galaxies; and properties of dark matter and dark energy.

High-resolution x-ray imaging of a globular cluster core: compact binaries in 47Tuc.

We have obtained high-resolution (approximately 1") deep x-ray images of the globular cluster 47Tucanae (NGC 104) with the Chandra X-ray Observatory to study the population of compact binaries in the high stellar density core. A 70-kilosecond exposure of the cluster reveals a centrally concentrated population of faint (Lx approximately 10(30-33) ergs per second) x-ray sources, with at least 108 located within the central 2' x 2.5' and greater, similar half with Lx approximately 10(30.5) ergs per second. All 15 millisecond pulsars (MSPs) recently located precisely by radio observations are identified, though 2 are unresolved by Chandra. The x-ray spectral and temporal characteristics, as well as initial optical identifications with the Hubble Space Telescope, suggest that greater, similar50 percent are MSPs, about 30 percent are accreting white dwarfs, about 15 percent are main-sequence binaries in flare outbursts, and only two to three are quiescent low-mass x-ray binaries containing neutron stars, the conventional progenitors of MSPs. An upper limit of about 470 times the mass of the sun is derived for the mass of an accreting central black hole in the cluster. These observations provide the first x-ray "color-magnitude" diagram for a globular cluster and census of its compact object and binary population.

Vulnerability in palliative care research: findings from a qualitative study of black Caribbean and white British patients with advanced cancer.

INTRODUCTION: Vulnerability is a poorly understood concept in research ethics, often aligned to autonomy and consent. A recent addition to the literature represents a taxonomy of vulnerability developed by Kipnis, but this refers to the conduct of clinical trials rather than qualitative research, which may raise different issues. AIM: To examine issues of vulnerability in cancer and palliative care research obtained through qualitative interviews. METHOD: Secondary analysis of qualitative data from 26 black Caribbean and 19 white British patients with advanced cancer. RESULTS: Four domains of vulnerability derived from Kipnis's taxonomy were identified and included: (i) communicative vulnerability, represented by participants impaired in their ability to communicate because of distressing symptoms; (ii) institutional vulnerability, which referred to participants who existed under the authority of others--for example, in hospital; (iii) deferential vulnerability, which included participants who were subject to the informal authority or the independent interests of others; (iv) medical vulnerability, which referred to participants with distressing medical conditions; and (v) social vulnerability, which included participants considered to belong to an undervalued social group. Participants from both ethnic groups populated all these domains, but those who were black Caribbean were more present among the socially vulnerable. CONCLUSIONS: Current classifications of vulnerability require reinterpretation when applied to qualitative research at the end of life. We recommend that researchers and research ethics committees reconceptualize vulnerability using the domains identified in this study and consider the research context and interviewers' skills.

Neck Grasp Predicts Obstructive Sleep Apnea in Type 2 Diabetes Mellitus.

AIMS: Obstructive sleep apnea (OSA) is a common disorder with high morbidity, mortality, and an increasing prevalence in the general population. It has an even higher prevalence among individuals with type 2 diabetes mellitus (DM). The snoring, tiredness, observed apnea, high blood pressure, body-mass-index, age, neck circumference and male gender (STOP-BANG) questionnaire and Berlin Questionnaire can be cumbersome in clinical practice and require subjective data on sleepiness. We proposed prospectively studying a primary care population with type 2 DM comparing neck grasp, neck circumference, and common screening questionnaires to identify OSA. METHODS: Persons with a diagnosis of type 2 DM were recruited from a primary care clinic. Participants were screened using Easy Sleep Apnea Predictor (ESAP), STOP-Bang questionnaire, and Berlin questionnaire. A positive ESAP was defined as a 1cm gap when a patient encircled their hands around the neck. All subjects underwent in-laboratory PSG testing. RESULTS: Forty-three participants were enrolled and the prevalence of OSA was 90.7% (AHI ≥ 5). The median BMI was 38.0. The prevalence of mild OSA by PSG (AHI 5-14) was 27.9%, moderate OSA (AHI 15-29) was 25.6%, and severe OSA (AHI >30) was 37.2%. For mild OSA both ESAP and neck circumference showed 100% specificity. CONCLUSIONS: This study reinforces the need for screening diabetic persons for obstructive sleep apnea. ESAP and neck circumference are useful for identifying persons with type 2 DM who are at risk for OSA. Together these findings could improve recognition of OSA in persons at risk for cardiovascular disease. Trial Registration of "Neck grasp as a predictor of Sleep Apnea," https://clinicaltrials.gov/ct2/show/NCT02474823, Clinical Trials.gov Identifier, is NCT02474823.

End-of-life care in end-stage renal disease: renal and palliative care.

The numbers of patients with end-stage renal disease are growing, with a disproportionate increase among those who are elderly, dependent and with multiple co-morbidities. More of these patients are choosing to be managed conservatively, without dialysis. Palliative provision for these patients within UK renal services is limited, but the recent National Service Framework for Renal Services (Department of Health, 2005) has promoted service development. However, few models of service provision have been described. This article describes a retrospective review of a new service for conservatively-managed patients with end-stage renal disease. The range and complexity of the health needs of this population is demonstrated, and an example of service development described. A model of the stages of the conservative pathway and appropriate interventions was developed. The absence of research evidence prevented development of formal audit standards, and highlighted the urgent need for evaluation of models of care.

Associations of sugar- and artificially sweetened soda with nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the major concern of public health worldwide. The risk of NAFLD in subjects who regularly drink soda is controversial. The aim of this study was to assess the association between consumption of sugar-sweetened soda and NAFLD. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through June 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of NAFLD in patients consuming a significant amount of either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Seven observational studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and NAFLD. The pooled RR of NAFLD in patients consuming sugar-sweetened soda was 1.53 (95% CI: 1.34-1.75, I(2) = 0). When meta-analysis was limited only to studies with adjusted analysis, the pooled RR of NAFLD was 1.55 (95% CI: 1.36-1.78, I(2) = 0). The data on association between consumption of artificially sweetened soda and NAFLD were limited; one observational study reported no significant increased risk of NAFLD in artificially sweetened soda consumption. CONCLUSIONS: Our study demonstrates statistically significant association between sugar-sweetened soda consumption and NAFLD. This finding may impact clinical management and primary prevention of NAFLD.

The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis.

BACKGROUND: The objective of this meta-analysis was to evaluate the association between a history of kidney stones and kidney cancer. METHODS: A literature search was performed from inception until June 2014. Studies that reported odds ratios or hazard ratios comparing the risk of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the upper urinary tract in patients with the history of kidney stones versus those without the history of kidney stones were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULT: Seven studies were included in our analysis to assess the association between a history of kidney stones and RCC. The pooled RR of RCC in patients with kidney stones was 1.76 (95% CI, 1.24-2.49). The subgroup analysis found that the history of kidney stones was associated with increased RCC risk only in males (RR, 1.41 [95% CI, 1.11-1.80]), but not in females (RR, 1.13 [95% CI, 0.86-1.49]). Five studies were selected to assess the association between a history of kidney stones and TCC. The pooled RR of TCC in patients with kidney stones was 2.14 (95% CI, 1.35-3.40). CONCLUSION: Our study demonstrates a significant increased risk of RCC and TCC in patients with prior kidney stones. However, the increased risk of RCC was noted only in male patients. This finding suggests that a history of kidney stones is associated with kidney cancer and may impact clinical management and cancer surveillance.

High alcohol consumption and the risk of renal damage: a systematic review and meta-analysis.

BACKGROUND: The risk of renal damage in patients with high alcohol consumption is controversial. The objective of this meta-analysis was to evaluate the associations between high alcohol consumption and progression of kidney damage including chronic kidney disease (CKD), end-stage renal disease (ESRD) and proteinuria. METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Databases from inception through August 2014 to identify studies investigating the association between high alcohol consumption and CKD, ESRD or proteinuria. Studies that reported odds ratios, relative risks or hazard ratios comparing the risk of CKD, ESRD or proteinuria in patients consuming high amount of alcohol versus those who did not consume alcohol were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Twenty studies with 292 431 patients were included in our analysis to assess the associations between high alcohol consumption and progression of kidney damage. The pooled RRs of CKD, proteinuria and ESRD in patients with high alcohol consumption were 0.83 (95% CI: 0.71-0.98), 0.85 (95% CI: 0.62-1.17) and 1.00 (95% CI: 0.55-1.82), respectively. Post hoc analysis assessing the sex-specific association between high alcohol consumption and CKD demonstrated pooled RRs of 0.72 (95% CI: 0.57-0.90) in males and 0.78 (95% CI: 0.58-1.03) in females. CONCLUSIONS: Our study demonstrates an inverse association between high alcohol consumption and risk for developing CKD in males. There is no significant association between high alcohol consumption and the risk for developing proteinuria or ESRD.

Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: should it be tested in a randomized trial against radiotherapy?

PURPOSE: Underpinned by increased confidence in cure of metastatic seminoma by chemotherapy during the past 12 years, three management strategies for Stage I seminoma have been evaluated by six collaborating centers within the Anglian Germ Cell Tumor Group. This paper evaluates the efficacy of surveillance, prophylactic radiotherapy and adjuvant chemotherapy, and discusses these differing management approaches. METHODS AND MATERIALS: Patients were recruited into the study between 1982 and 1992. There was no randomization between treatment groups. Seventy-nine patients received prophylactic radiotherapy (median follow-up = 51 months), 67 patients had surveillance alone (median follow-up = 61 months) and 78 patients were treated with adjuvant single agent platinum (median follow-up = 44 months). Fifty-three of these patients received two courses of platinum (median follow-up = 51 months) and 25 patients received one course (median follow-up = 29 months, range 22-72 months). RESULTS: There were 18 (27%) recurrences on surveillance, five (6%) after radiotherapy, one (1%) after two courses of adjuvant single agent platinum and none after one course of carboplatin. There was one death from testis cancer after radiotherapy and none after adjuvant chemotherapy treatments. Two patients died with drug resistant disease after relapse on surveillance. There was one death from a myocardial infarction after prophylactic radiotherapy and one death from suicide in the surveillance group. A retrospective quality of life questionnaire reviewing the incidence of early and late toxicity revealed no major differences though they suggest that those treated with one course adjuvant carboplatin had somewhat less sickness and an earlier return to work. CONCLUSION: Single agent carboplatin appears well tolerated and is an effective adjuvant treatment for Stage I seminoma. A multicenter randomized trial of the different treatment modalities is required to further evaluate its use.

Evaluation of a chemiluminescent DNA probe assay for the rapid confirmation of Listeria monocytogenes.

A Listeria monocytogenes-specific, acridinium-ester-labelled DNA probe was evaluated in a chemiluminescent homogeneous protection assay (HPA) for the rapid confirmation of suspect L. monocytogenes colonies from blood agar plates. The HPA uses an acridinium-ester-labelled chemiluminescent DNA probe in a free-solution hybridization format. After the DNA probe hybridized with the target ribosomal RNA, the acridinium label on the unhybridized probe was inactivated by a chemical differential hydrolysis step. Formation of a hybrid between probe and target was detected in a luminometer after the addition of a detection reagent. The assay can be completed in 30 to 45 min and allows for simultaneous processing of several (50-100) samples. The probe showed 100% sensitivity and 100% specificity for L. monocytogenes when evaluated in the HPA against L. monocytogenes, other Listeria species and other Gram-positive bacteria. The lower detection limit of the HPA was between 10(4) and 10(5) cells. In an evaluation with 296 bacterial colonies isolated from food, the HPA colony confirmation showed 100% agreement with conventional biochemical characterization. HPA will be useful for the rapid confirmation of L. monocytogenes isolated from food and clinical specimens.

Flow cytometric analysis of DNA content in Hürthle cell adenomas and carcinomas of the thyroid.

Paraffin-embedded surgical biopsy material from 17 Hürthle cell tumors of the thyroid was examined for DNA content by flow cytometry to assess the diagnostic and prognostic utility of ploidy determinations in these rare tumors. Both adenomas (11 cases) and carcinomas (6 cases) were studied. As a control for methods, ten randomly selected normal autopsy thyroids were analyzed, all of which demonstrated normal diploid DNA content. Among the Hürthle cell tumors, however, aneuploid peaks were present in six adenomas (55%) and in four carcinomas (67%). Similarly, polyploid DNA peaks in the absence of other aneuploid peaks were present in two adenomas and two carcinomas (18% and 33%, respectively). These findings demonstrate the limited value of aneuploidy or polyploidy as diagnostic features for malignancy in Hürthle cell tumors of the thyroid. As for prognosis, there does not appear to be any unfavorable prognostic significance for abnormal DNA content in histologically benign Hürthle cell tumors treated by surgical excision because no metastases or recurrences occurred in this group at a mean disease-free follow-up of 50 +/- 19 months for six aneuploid lesions and 19 +/- 7 months for two polyploid adenomas. Preliminary data suggest that aneuploidy may, however, have an important prognostic value for histologically defined Hürthle cell carcinomas, because the only patient to die from the tumor in this series had an aneuploid Hürthle carcinoma. Thus, the authors' data indicate that the diagnostic utility of DNA content in Hürthle cell tumors is extremely limited and that there does not appear to be any negative prognostic significance for aneuploidy in histologically defined Hürthle cell adenomas.

Treatment of stress urinary incontinence due to paravaginal fascial defect.

This study supports the thesis that the physical findings of pelvic relaxation, such as cystourethrocele, are the results of isolated defects in the pelvic fascia rather than the results of generalized stretching or attenuation of the supporting structures. The most frequently encountered defect resulting in cystourethrocele with stress urinary incontinence was a paravaginal break in the pubocervical segment of the endopelvic fascia between the lateral edge of the vagina and the pelvic sidewall. The operative approach to this paravaginal defect is described. The overall results in 233 procedures performed by 2 separate groups are analyzed. Functionally satisfactory results were obtained in over 95% of patients with 2 to 8 years of follow-up. The use of an indwelling urethral catheter was found to be unnecessary, and all patients experienced a rapid return of normal bladder function. The average length of the postoperative hospital stay was 5 days.

A systematic review of the role of bisphosphonates in metastatic disease.

OBJECTIVES: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity. DATA SOURCES: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). REVIEW METHODS: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios (OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi-squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. RESULTS: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs (doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. CONCLUSIONS: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

Rare pancreatic malignancies.

The incidence of pancreatic malignancy in most countries is increasing, and the overall prognosis for nonendocrine pancreatic cancer is grim. The majority of nonendocrine pancreatic malignancies are duct cell adenocarcinomas with no special features. However, several morphologic subtypes have been fairly recently recognized and classified, some of which appear to have a different inherent biologic behavior and a chance for a longer survival after resection. This article describes the rare nonendocrine pancreatic malignancies, emphasizing those clinical, pathologic, and radiologic features that serve to differentiate these entities from the more common duct cell adenocarcinoma of the pancreas.

Is the presence of dyspnea a risk factor for morbidity in cancer patients?

Data collected from six home palliative care teams in Ireland were analyzed to determine the prevalence of dyspnea in the population studied and to identify factors associated with the presence of dyspnea that might impact on future care. The prevalence of mild, moderate, or severe dyspnea, as measured by the Support Team Assessment Schedule (STAS), fell from 39% at referral in 327 evaluable patients to 23%. The presence of dyspnea at referral was positively correlated with severity of patient spiritual distress (Spearman rho = 0.110, P = 0.042) and weakness (Spearman rho = 0.105, P = 0.008) at referral. In analysis of contingency tables, dyspnea was also significantly associated with low patient (chi 2 9.5, P = 0.002) and family (chi 2 50.78, P < 0.001) well-being, high staff anxiety (chi 2 4.14, P = 0.04), male sex (chi 2 8.9, P = 0.003), a diagnosis of lung cancer (chi 2 59.88, P < 0.001), and dying in hospital rather than hospice or nursing home (chi 2 18.03, P = 0.001). In adjusting for covariates using a logistic regression analysis, however, only the presence of low family well-being, a diagnosis of lung cancer, and increased likelihood of a hospital death remained significantly associated with the presence of dyspnea at referral. These data suggest that the presence of dyspnea may be associated with increased family distress, which may influence place of death.

The use of the Rotterdam Symptom Checklist in palliative care.

The Rotterdam Symptom Checklist (RSCL), which measures both physical and psychological aspects of quality of life (QOL), was given to all new patients admitted to a palliative care unit who were thought capable of filling out a questionnaire as an outcome measure of symptom control. Assessments were obtained from 52 patients at baseline (week 1). This represented only 53% of the new patients admitted to the unit. Thirty-one patients completed a second questionnaire at week 2, and only 28 patients completed a third (week 3). In these selected patients, the median overall RSCL scores were 57, 52, and 49 at weeks 1, 2, and 3. There was a significant improvement in QOL scores across the three measurements with a significant difference between weeks 1 and 3 (P = 0.05) but not between weeks 1 and 2. Primarily because of the inability of many patients to complete the questionnaire and the high attrition rate, the appropriateness of this tool as a symptom control measure in palliative care patients is questioned.

Margin status and excision of cervical intraepithelial neoplasia: a review.

UNLABELLED: Excisional biopsy of the cervix for diagnosis and treatment of cervical neoplasia is common. Management of patients with involved margins of resection is unresolved. Data concerning use of thermal techniques show that this technique yields equivalent results in most cases. Important exceptions are microinvasive squamous disease and adenocarcinoma. Conservative management of involved squamous margins is possible. Techniques for follow-up include cytology, colposcopy, and endocervical curettage. Adenocarcinoma in situ (AIS) should be treated with cold-knife conization. The standard of care for AIS is hysterectomy except in certain specific indications. Data concerning technique, follow-up, use of endocervical curettage, and the need for reexcision will be presented. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to compare the efficacy of the various excisional procedures in the treatment of cervical dysplasia, list the indications for additional surgery after positive margins on cervical excisions, and describe the proper management of a patient with adenocarcinoma in situ.

Protein synthesis by neuroblastoma cells is enhanced by exposure to burst-mode ultrasound cavitation.

We observed enhancement of protein synthesis, compared to control cells, 24 h after exposing C1300 neuroblastoma cells (N2A) in rotating tubes at 37 degrees C to 1-MHz ultrasound tone bursts [1:1; durations from 6 to 600 ms; 3.4 W/cm2 spatial-peak burst-average intensity; 5 min total treatment duration (on + off periods)]. Protein synthesis was measured by uptake of 3H-leucine and normalized for cell proliferation by measured uptake of 14C thymidine. The similarity between results for enhanced cavitation-stimulated iodine-release reported by Ciaravino and our results for cellular protein synthesis suggests that cavitation causes this biological effect.

Acoustic emission as a measure of exposure of suspended cells in vitro.

Cell viability, survival, and growth of C1300 mouse neuroblastoma cells were assayed by trypan blue dye exclusion, clonogenesis, and culturing, respectively, after exposure in suspension to therapeutic levels of ultrasound (1 MHz; continuous wave; spatial peak intensity 0.9, 1.7, and 2.6 W/cm2; 5 min at 37 degrees C). Acoustic emission from the cavitating cell suspensions was recorded as the rms value of the half-harmonic and noise components combined. Cell viability and survival appeared better correlated with acoustic emission than with spatial peak intensity, implying that acoustic emission may provide a more direct measure of insult to the cells in a cavitating field than the incident intensity. Biological assay results of growth were well correlated with spatial peak intensity but not with acoustic emission levels, which seems to imply that for this end point incident intensity is a more directly interacting parameter than cavitational activity, provided however that the latter is present. Further refinement of the technique for measuring acoustic emission from cell suspensions should permit separate measurements of the half-harmonic and noise components. When thus refined, it may provide the means to demonstrate cavitational action without resorting to additional experiments to suppress cavitation.