Improved quality of care for patients undergoing an abdominoperineal excision for rectal cancer.

INTRODUCTION: New diagnostics, the emergence of total mesorectal excision and neoadjuvant treatments have improved outcome for patients with rectal cancer. Patients with distal rectal cancer undergoing an abdominoperineal excision seem to do worse compared to those treated with sphinctersparing techniques. The aim of this study was to evaluate the quality of care for patients undergoing an abdominoperineal excision for distal rectal cancer during the last 15 years. MATERIALS AND METHODS: All patients with rectal cancer, who underwent an abdominoperineal excision between December 1996 and December 2010 in 5 Dutch hospitals were analysed. Patients were divided into three cohorts; 1996-2001, 2001-2005 and 2006-2010. All data was extracted from medical records. RESULTS: 477 patients were identified. There was no significant difference in sex, age, BMI, prior pelvic surgery and ASA stages between the cohorts. MRI became a standard tool in the work-up, the use increased from 4.5% in the first, to 95.1% in the last cohort (p < 0.0001). Neoadjuvant treatment shifted from predominantly none (64.9% in cohort 1) to short course radiotherapy (66.7% in cohort 2) and chemoradiation therapy (55.7% in cohort 3). There was a trend towards a decreased circumferential resection margin involvement in the cohorts (18.8%, 16.7% and 11.4%; p = 0.142). Accidental bowel perforations have significantly decreased from 28.6%, and 21.7% to 9.2% in cohort 3 (p < 0.0001). CONCLUSION: Significant improvements in work-up, neoadjuvant and surgical treatment have been made for patients with low rectal cancer, undergoing an abdominoperineal excision. These improvements result in improved short term outcome.

Improvement of microbial strains and fermentation processes.

Improvement of microbial strains for the overproduction of industrial products has been the hallmark of all commercial fermentation processes. Conventionally, strain improvement has been achieved through mutation, selection, or genetic recombination. Overproduction of primary or secondary metabolites is a complex process, and successful development of improved strains requires a knowledge of physiology, pathway regulation and control, and the design of creative screening procedures. In addition, it requires mastery of the fermentation process for each new strain, as well as sound engineering know-how for mediaoptimization and the fine-tuning of process conditions. This review focuses on the various options that may be employed to improve microbial strains and addresses the complex problems of screening, the tools and technology behind the selection of targeted organisms, and the importance of process optimization. Furthermore, this review discusses new and emerging technologies and designing optimized media for tracking mutants with enhanced productivity or other desired attributes.

Serotonergic stimulation of the genioglossus and the response to nasal continuous positive airway pressure.

In obstructive sleep apnea (OSA), abnormal pharyngeal collapsibility may be offset by increased mechanoreflex-mediated activity of dilator muscles while awake, but this reflex is inhibited during sleep and during application of nasal continuous positive airway pressure (CPAP). Direct activation of upper airway (UA) motor neurons in the hypoglossal nucleus by a selective serotonin reuptake inhibitor (SSRI), paroxetine hydrochloride, may increase genioglossal electromyographic (EMG) activity (EMGgg) in a manner resistant to mechanoreflex inhibition. We studied the effects of paroxetine on EMGgg using an intraoral surface electrode during eupnea or room air breathing (RA), hypercapnia (HYP), and CPAP application in the presence of hypercapnia (CPAP + HYP) in 11 normal volunteers, using a double-blind, placebo-controlled crossover design. After 5 d of paroxetine, EMGgg activity increased significantly within each condition (p = 0.02). EMGgg during the conditions of HYP and HYP + CPAP were significantly greater than during RA for both placebo and paroxetine treatments (p = 0.006). EMGgg activity in HYP persisted during HYP + CPAP on paroxetine (183% versus 182% of placebo, respectively). We conclude that paroxetine produces an augmentation in EMGgg in normal subjects during wakefulness and that this effect persists during mechanoreflex inhibition. This is consistent with a central serotonergic effect.

Force production of the genioglossus as a function of muscle length in normal humans.

Resting muscle length affects both maximum force production and force maintenance. The strength and force maintenance characteristics of the genioglossus as a function of resting muscle length have not been described. We hypothesized that genioglossus optimum length (L(o)) could be defined in vivo and that the ability of the genioglossus to sustain a given workload would decrease as resting length deviated from L(o). To test this, 11 normal men repeated maximal isometric genioglossus protrusions at different muscle lengths to determine L(o). L(o) was also obtained by using submaximal efforts while simultaneously recording electromyographic activity of the genioglossus, with L(o) defined as the length at which the force-to-genioglossus electromyographic activity ratio was maximum. Both methods provided similar results. Force maintenance was measured at four muscle lengths on separate days. Target efforts representing 60% of each subject's maximum at L(o) and lasting 5 s were performed at 12-s intervals. Time limit of endurance of the genioglossus was defined as the time from trial onset at which 90% of the target could not be maintained for three consecutive efforts. Time limit of endurance was greatest at L(o) and fell to 47.5% at L(o) + 1 cm, 53.8% at L(o) - 1 cm, and 47.4% at L(o) - 1.5 cm. We conclude that L(o) of the genioglossus can be determined in vivo and that force maintenance of the genioglossus is decreased when operating length deviates from L(o).

Novel naphthoquinones from a Streptomyces sp.

Cdc25A assay-guided fractionation of a fermentation broth derived from a Streptomyces sp. resulted in the isolation of four novel naphthoquinones 1-4. Structures of these compounds were deduced by NMR and mass spectrometry. Two of them, 3 and 4, incorporate a modified cysteine residue which is observed for the first time in this class of natural products. Naphthoquinones 1-4 showed weak activity against cdc25A phosphatase.

[Preoperative diagnosis with stereotactic biopsy is a good predictor of breast cancer in radiologically non-benign breast lesions]. / Preoperatieve diagnostische stereotactische biopsie goede voorspeller van mammacarcinoom bij radiologisch niet-benigne mamma-afwijkingen.

OBJECTIVE: To evaluate histological needle biopsy in breast lesions classified radiologically as 'non-benign'. DESIGN: Prospective, descriptive. SETTING: Hospital Velp, Velp, the Netherlands. METHODS: 232 women with an 'uncertain', 'suspicious' or 'malignant' result of mammography, if necessary supplemented by echography, were subjected to histological biopsy from a breast between 1 January 1994 and 1 January 1997. The earlier biopsies were made with a 16 Gauge (G) needle, those after April 1996 with a 14 G needle, as a rule under stereotactic control. In principle, operation was performed after a positive result. Concerning the women operated after the biopsy, the results of the histological examinations were compared in a 2 x 2 table. RESULTS: 165 of the 232 patients (71%) had breast cancer. Of the 59 patients classified roentgenologically as 'uncertain', 15 (25%) had breast cancer, of the 'suspicious' cases this ratio was 44/67 (66%) and of the 'malignant' results it was 106/106 (100%). Operation was performed in 186 women. The biopsy findings and the surgical preparation were in agreement in 169 patients (91%). The sensitivity of the stereotactic biopsy was 90%, its specificity 93%. One woman was over-treated (axillary lymph node resection) because of a biopsy classified as malignant performed on a rare tumour ultimately diagnosed as 'adenomyo-epithelioma with epithelial atypia'. The proportion of false-negative results was 36%. The predictive value of a positive result was 99%, that of a negative result 63%. CONCLUSION: A diagnostic stereotactic biopsy after roentgenological classification based on mammography and echography had a good predictive value regarding the probability of breast cancer.

Joint NASA-ESA-DARA Study. Part three: characterization of sleep under ambient CO2-levels of 0.7% and 1.2%.

An experiment was conducted to study sleep quality and sleep architecture in volunteers living in a closed system under elevated ambient CO2 levels of 0.7% and 1.2%. In a closed system, human life is possible only if the CO2 level is permanently adjusted. For the Russian space station MIR, for example, the CO2 levels of the present study are actual upper limits for the adjustment. Sleep architecture was found to be altered in astronauts on the orbiting MIR station. Sleep quantity and quality were reduced. The latency to the first REM sleep was shorter in space and slow wave sleep was redistributed from the first to the second sleep cycle. The elevated CO2 concentration in the atmosphere on MIR may be one of the reasons for those observations regarding sleep in space. Thus, this experiment was also conducted in order to clarify the interpretation of data obtained from astronauts on MIR. In this study sleep polygraphies could be recorded in 4 subjects who lived for 23 d under 0.7% and then for the same period of time under 1.2% CO2. Findings suggest that these levels of ambient CO2 do not reduce sleep quality. Sleep architecture, however, was slightly changed and showed that the amount of slow wave sleep increased with the duration of the exposure to CO2. But it can be excluded that findings on MIR were caused by elevated CO2-levels.

A new UHV angle encoder for high-resolution synchrotron radiation monochromators.

The high precision of 0.1 arcsec required for the positioning of optical elements in new two-axes monochromators at the undulator beamlines at BESSY II has led to the development of UHV-compatible high-precision angle encoders. Mounted directly on the rotation axes, they provide substantial advantages over measuring systems connected outside the vacuum vessel. Making use of a fast closed-loop control system, an accuracy of 0.1 arcsec at a resolution of less than 0.01 arcsec has been experimentally verified.

Replication and extension of a risk profile for Amerasian youth.

The relationship between number of risk factors and symptoms of anxiety and depression was examined in a cohort of Vietnamese Amerasians, replicating a study done with a previous cohort. One hundred forty seven subjects awaiting U.S. placement completed the Hopkins Symptom Checklist, the Vietnamese Depression Scale, and a questionnaire which included items found to be risk factors for psychological distress among Amerasians. Number of risk factors was linearly related to symptoms of both depression and anxiety. Results are consistent with previous findings of the relationship between risk factors and symptoms of psychological distress. The profile may be helpful in anticipating which refugees may be at risk for future psychological distress, and thus be useful in preventively allocating scarce treatment resources.

The prevalence of psychiatric disorders among Vietnamese Amerasians: a pilot study.

A pilot study of the prevalence rate of DSM-III psychiatric disorders among Vietnamese Amerasians prior to migration from Vietnam found current prevalence of such disorders to be lower than previously reported among Vietnamese refugees in the United States and Australia. Methodological and cultural factors contributing to the lower than expected prevalence rate are discussed, and implications for clinical assessments and future research are noted.

Chicken oviductal ecto-ATP-diphosphohydrolase. Purification and characterization.

An ecto-ATP diphosphohydrolase (ATPDase) was purified to homogeneity from vesiculosomes shed from chicken oviduct. First, the ecto-ATPDase-enriched vesiculosomes were concentrated by filtration, differential centrifugation, and exclusion chromatography. Next, the nonionic detergent, Nonidet P-40, was used to extract the ecto-ATPDase from vesiculosomal membranes, and the solubilized enzyme was further purified by ion exchange (DEAE-Bio-Gel) and lentil-lectin-Sepharose 4B chromatography. In the final stage, immunoaffinity chromatography was utilized to obtain purified ecto-ATPDase. More than 25,000-fold purification was achieved. Specific activity of the purified enzyme was greater than 800 micronol/min/mg of protein with MgATP as the substrate, the highest ever reported for an ATPDase. The enzyme also hydrolyzed other nucleoside triphosphates in the presence of magnesium at similar rates and CaATP and MgADP at lower rates. The molecular mass of the purified glycoprotein was 80 kDa as determined by SDS-polyacrylamide gel electrophoresis and Western blot analysis. Based on its enzymatic properties, the relationship of the chicken oviduct ecto-ATPDase with other reported ATPDases and ecto-ATPases is discussed.

Aneurysm formation in modified human umbilical vein grafts.

OBJECTIVES: Aneurysm formation in Human Umbilical Vein Grafts has been reported to be as high as 65% after 5 years. One of the causes might be the structure of the Biograft-wall and in 1985 a new method of processing the graft was begun. In Groningen this new improved Biograft has been used since late 1986. DESIGN: Duplex scanning was used to examine the frequency of aneurysm formation in the new improved Biograft. MATERIALS: Sixty-nine patent Biografts have been examined in a period up to 6 years after implantation. MAIN RESULTS: Aneurysms were found in only 17% of grafts although the frequency increased with time. Dilatation was common but may be due to a more elastic graft. CONCLUSION: These findings justify the continued use of the new Biograft as a substitute for arterial femoropopliteal reconstructions.

Obesity and weight loss in obstructive sleep apnea: a critical review.

Clinic-based and epidemiological studies demonstrate a strong association between obesity and obstructive sleep apnea. However, defining the causal relationship between excess body weight and sleep-disordered breathing remains difficult. Potential mechanisms to be considered include: (1) alterations in upper airway structure; (2) alterations in upper airway function; (3) alterations in the balance between ventilatory drive and load and (4) obesity-induced hypoxemia. Additional evidence for the role of obesity in obstructive sleep apnea comes from clinical studies of weight loss in patients with sleep-disordered breathing. Significant weight loss has been reported in most studies, which has been associated with varying degrees of improvement in sleep-disordered breathing, oxygen hemoglobin saturation, sleep architecture and daytime performance. Surgical and nonsurgical approaches to weight loss have been evaluated, although most studies to date suffer from methodological limitations including lack of random assignment to treatment groups, confounding of treatment interventions, absence of untreated controls and lack of adequate follow-up assessment. Implications for research and clinical practice are discussed.

Identification and immunolocalization of ecto-ATPDase in chicken stomach.

The distribution of the extracellular adenosine tri- and di-phosphatase (ecto-ATPDase) in adult chicken tissues was investigated using a monoclonal antibody (MC18) generated previously from chicken oviduct. Ecto-ATPDase was determined to be most abundant in stomach by Western blot analysis of crude tissue homogenates. The ecto-ATPDase activity from solubilized stomach microsomes and a purified oviduct control was depleted 64% and 72%, respectively, by immunoprecipitation with MC18. Both oviduct and stomach ecto-ATPDases had an M(r) of approximately 80 kDa based on SDS-PAGE analysis. In addition, the enzymology of the ecto-ATPDase from both tissues was very similar. It is concluded that the same ecto-ATPDase is present in stomach and oviduct. Furthermore, immunolocalization of the stomach ecto-ATPDase with MC18 showed the enzyme to be localized in the apical membranes of the oxyntico-peptic cells, suggesting a role for the ecto-ATPDase in secretion.

Genotoxicity of 17 gyrase- and four mammalian topoisomerase II-poisons in prokaryotic and eukaryotic test systems.

The genotoxic potency of certain classes of topoisomerase II poisons is correlated with their affinity to the topoisomerase protein rather than with the presence of 'classical' structural alerts for DNA reactivity: bacterial topoisomerase II poisons (specifically named gyrase inhibitors) are highly genotoxic in prokaryotic systems; mammalian topoisomerase II poisons are potent mutagens/clastogens in eukaryotic systems. Studies with bacterial, lower eukaryotic and mammalian genotoxicity tests were performed to draw structure-activity conclusions and address risk-benefit considerations for the class of quinolone gyrase inhibitors. All 17 gyrase inhibitors investigated in this study showed genotoxic activity in Salmonella typhimurium strain TA102 and the SOS test. The genotoxic and the toxic activities increased in a highly parallel fashion from the parent compounds, nalidixic acid and oxolinic acid, to the new generation fluoroquinolones. Generally, the most potent fluoroquinolones also show clear-cut positive effects in eukaryotic test systems, although at concentrations 100-1000-fold higher than those effective in bacteria and also 100-1000-fold higher than the minimal genotoxic concentrations of antitumour topoisomerase II inhibitors (ellipticine, teniposide, mAMSA) used as reference compounds. However, subtle structural modifications of the quinolones can strongly diminish the preferential genotoxicity in the prokaryotic test systems.

Properties of and proteins associated with the extracellular ATPase of chicken gizzard smooth muscle. A monoclonal antibody study.

The chicken gizzard smooth muscle extracellular ATPase (ecto-ATPase) is a low abundance, high specific activity, divalent cation-dependent, nonspecific nucleotide triphosphatase (NTPase). The ATPase is a 66-kDa glycoprotein with a protein core of 53 kDa (Stout, J.G. and Kirley, T.L. (1994) J. Biochem. Biophys. Methods 29, 61-75). In this study we evaluated the characteristics of a bank of monoclonal antibodies raised against a partially purified chicken gizzard ecto-ATPase. 18 monoclonal antibodies identified by an ATPase capture assay were tested for effects on ATPase activity as well as for their Western blot and immunoprecipitation potential. The five most promising monoclonal antibodies were used to immunopurify the ecto-ATPase. The one-step immunoaffinity purification of solubilized chicken gizzard membranes with all five of these monoclonal antibodies isolated a 66-kDa protein whose identity was confirmed by N-terminal sequence analysis to be the ecto-ATPase. Several of these monoclonal antibodies stimulated ecto-ATPase activity similar to that observed previously with lectins. Western blot analysis revealed that three of the five monoclonal antibodies recognized a major immunoreactive band at 66 kDa (53-kDa core protein), consistent with previous purification results. The other two antibodies recognized proteins of approximately 90 and 160 kDa on Western blots. The 90-kDa co-immunopurifying (and presumably associated or related) protein was identified by N-terminal analysis as LEP100, a glycoprotein that shuttles between the plasma and lysosomal membranes. The approximately 160-kDa co-immunopurifying protein was identified by N-terminal analysis as integrin, a protein involved in extracellular contacts with adhesion molecules. Extended N-terminal sequence analysis of the immunopurified 66-kDa ecto-ATPase revealed some sequence homology with mouse lysosomal associated membrane protein. Tissue distribution of the ecto-ATPase showed that the highest levels of protein were expressed in muscle tissues (cardiac, skeletal, and smooth) and brain.

Photomutagenesis test development: I. 8-Methoxypsoralen, chlorpromazine and sunscreen compounds in bacterial and yeast assays.

Two in vitro genotoxicity tests have been adapted to the evaluation of photomutagenic activity of test compounds. The study was initiated to obtain an experimental basis relating to newly proposed guidelines of the EC which request the screening of UV-absorbing compounds, for example, those employed in sunscreen preparations, for their photomutagenic potential. The well established photomutagens 8-methoxypsoralen and chlorpromazine were used to define relevant test protocols. The compounds were evaluated with the Ames test and the Saccharomyces cerevisiae D7 test for gene conversion. The influence of various parameters such as UV light sources, spectral composition, UV sensitivity of the test systems, absorbance by test materials and different exposure conditions is indicated. Two exemplary screening experiments with cosmetic ingredients are presented. Both test systems can be employed for the evaluation of compounds for photomutagenic activity although the standard excision-deficient strains of S. typhimurium pose problems because of their high UV sensitivity. The present experience in this complex field suggests that rigid test protocols and a restrictive test battery would be inadequate.

Evaluation of a saliva alcohol test stick as a therapeutic adjunct in an alcoholism treatment program.

This study was designed to evaluate the clinical usefulness of a saliva alcohol dipstick by comparing dipstick saliva alcohol concentrations to simultaneous blood and urine alcohol concentrations. The sample consisted of 211 saliva tests and blood alcohol concentrations and 189 urine alcohol concentrations. The dipsticks had a specificity of 0.965, a sensitivity of 0.895, a positive predictive value of 0.850, a negative predictive value of 0.977 and a Pearson's product moment correlation coefficient of 0.609 for blood alcohol concentrations and salivary alcohol concentrations, suggesting that the saliva dipstick is useful as a qualitative test in certain settings but is less useful than previously reported as a semiquantitative test.