Randomized study of the influence of two-dimensional versus three-dimensional imaging using a novel 3D head-mounted display (HMS-3000MT) on performance of laparoscopic inguinal hernia repair.

BACKGROUND: 3D laparoscopy has proven to be superior to the 2D approach in experimental settings. The aim of the present study was to investigate the influence of 3D laparoscopy using a novel head-mounted display on the performance of defined steps within a laparoscopic inguinal hernia repair. This effect was investigated both in laparoscopically advanced surgeons and in beginners. METHODS: Patients suffering from symptomatic inguinal hernia were randomly assigned to laparoscopic hernia repair using either a head-mounted 3D display or a conventional 2D laparoscopic approach. Operative performance of both groups was compared in terms of the time taken for mesh placement and for peritoneal suturing. Additionally, quality of imaging and physical discomfort were assessed. RESULTS: The use of a head-mounted 3D display was able to shorten the time required for placement of the mesh as well as that for peritoneal suturing, both for experienced and novice surgeons when compared to the conventional 2D approach. 3D laparoscopy was significantly superior to 2D laparoscopy in terms of depth perception, image sharpness and image contrast. Additionally, increased impairment caused by ghosting effects could not be detected in 3D laparoscopy. Evaluation of image quality was independent of experience in laparoscopic surgery. However, use of a head-mounted 3D display resulted in a significant impairment of surgeon's comfort when compared to 2D laparoscopy. Thereby, the greatest impairment was caused by ear discomfort. CONCLUSIONS: This is the first study examining the effect of a head-mounted 3D system on the performance of laparoscopy in a randomized controlled trial (RCT) showing a clear advantage of this system in surgical performance as well as in depth perception and image quality.

Education as Risk Factor of Mild Cognitive Impairment: The Link to the Gut Microbiome.

BACKGROUND: With differences apparent in the gut microbiome in mild cognitive impairment (MCI) and dementia, and risk factors of dementia linked to alterations of the gut microbiome, the question remains if gut microbiome characteristics may mediate associations of education with MCI. OBJECTIVES: We sought to examine potential mediation of the association of education and MCI by gut microbiome diversity or composition. DESIGN: Cross-sectional study. SETTING: Luxembourg, the Greater Region (surrounding areas in Belgium, France, Germany). PARTICIPANTS: Control participants of the Luxembourg Parkinson's Study. MEASUREMENTS: Gut microbiome composition, ascertained with 16S rRNA gene amplicon sequencing. Differential abundance, assessed across education groups (0-10, 11-16, 16+ years of education). Alpha diversity (Chao1, Shannon and inverse Simpson indices). Mediation analysis with effect decomposition was conducted with education as exposure, MCI as outcome and gut microbiome metrics as mediators. RESULTS: After exclusion of participants below 50, or with missing data, n=258 participants (n=58 MCI) were included (M [SD] Age=64.6 [8.3] years). Higher education (16+ years) was associated with MCI (Odds ratio natural direct effect=0.35 [95% CI 0.15-0.81]. Streptococcus and Lachnospiraceae-UCG-001 genera were more abundant in higher education. CONCLUSIONS: Education is associated with gut microbiome composition and MCI risk without clear evidence for mediation. However, our results suggest signatures of the gut microbiome that have been identified previously in AD and MCI to be reflected in lower education and suggest education as important covariate in microbiome studies.

Strychnine- and pentylenetetrazol-induced changes of excitability in aplysia neurons.

In Aplysia neurons isolated from their synaptic input strychnine induces doublet discharges associated in voltage clamp with a decrease in the threshold for the inward current and a reduction and delayed onset of the outward current. Pentylenetetrazol causes oscillations and bursting behavior in normally silent cells together with an increased inactivation of the delayed outward current and induced or enhanced anomalous rectification.

Palliative irradiation of bone metastases.

Painful bone metastases is a common feature in patients with advanced cancer. The application of radiotherapy is often used as palliative treatment. A review of available data from the literature reveals that irrespective of the primary diagnosis palliation is achieved in 70-100% of cases. The biological basis of pain and the effects of radiotherapy is discussed. Treatment schedules for patients with single-bone lesions are reviewed. It is concluded that single-shot treatment in doses ranging from 5 to 8 Gy is as effective as multi-fractionated treatment. In addition, the possible role of radiotherapy in relation to patients with multiple lesions, and the use of combined surgery and radiotherapy in patients with impending and manifest fractures are discussed. It is concluded that the literature does not allow a definitive conclusion concerning an optimal use of radiotherapy.

The action of a phorbol ester on voltage-dependent parameters of the sodium current in isolated hippocampal neurons.

The action of a phorbol ester (phorbol-12,13-diacetate) on the voltage-activated sodium current has been investigated by the voltage-clamp method in acutely isolated pyramidal neurons from rat hippocampus. The intracellular perfusion of isolated pyramidal neurons for 30-40 min induced a gradual 10-15 mV shift in both the current-voltage relationship and voltage-dependent steady-state inactivation to more negative potentials. The application of phorbol ester (1-10 microM) to isolated neurons for the same time increased the amplitude of sodium current by 15-20%, shifted the above-mentioned voltage-dependent parameters for an additional 10-15 mV in the same direction and changed the slope of the steady-state inactivation curve. In contrast, after prolonged incubation of slices in the phorbol ester-containing solution (1-10 microM) for 0.5-3 h, subsequent application of phorbol ester at the same concentration caused neither the addition shift of the voltage-dependent characteristics of sodium channels nor the change of the slope of the steady-state inactivation curve. However, in this case an increase in the amplitude of sodium current by 15-20% during 30-40 min intracellular perfusion was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement.

Patient-rated questionnaires are increasingly used to assess health-related quality of life. We studied one aspect of the validity of such measures that has rarely been investigated do patients interpret questionnaires in the same way as do the researchers reporting the results? If not, there may be a problem. We employed the EORTC QLQ-C30 quality-of-life questionnaire to study 95 cancer patients and measured the agreement between (1) the patient's self-assessment and (2) an observer's rating of the patient's open-ended responses to the same questionnaire administered as an interview. The observer made qualitative recordings describing potential misinterpretations. The agreement between patients' and observers' ratings was high (median kappa = 0.85, range 0.49-1.00). The qualitative data revealed a few minor validity problems. One of these, selective reporting, may lead to systematic errors; some patients reported only what they considered "relevant" symptoms. The combination of quantitative and qualitative methods proved useful for questionnaire validation.

Test for item bias in a quality of life questionnaire.

Item bias (differential item functioning) analysis examines whether the construction of an index from two or more variables results in bias in relation to sex, age, or other criteria. Item bias may lead to erroneous conclusions because of distortion or dilution of the effects measured. In comparing groups, item bias analysis, tests whether the information about possible differences between groups, obtained by the variables constituting an index, are correctly passed on by the index score. We examined a quality of life questionnaire answered by 1189 breast cancer patients. We found age-bias or bias in the comparison of groups receiving different treatments in three out of nine indexes. Recommendations for the interpretation of these indexes are made. Item bias analysis is a useful method examining an issue not covered by traditional psychometric tests.

Anxiety and depression in breast cancer patients at low risk of recurrence compared with the general population: a valid comparison?

Breast cancer and its treatment have been associated with psychological morbidity. In this study our aim was to quantify the excess anxiety and depression resulting from breast cancer. We compared 538 newly diagnosed breast cancer patients at low risk of recurrence (87.0% responded) to 872 women randomly selected from the Danish general population (69.7% responded) using the Hospital Anxiety and Depression Scale (HADS). Contrary to expectations, the proportions classified as "cases" of anxiety and depression were not significantly different in the two groups. The breast cancer patients' mean HADS scores were significantly lower than those in the general population sample (anxiety, P = 0.021; depression, P < 0.001), indicating less anxiety and depression. However, we question the validity of this comparison. The HADS may not be suitable for use in the general population and there may be methodological problems in comparisons of groups whose life situations are very different.

Single electrode voltage clamp by iteration.

A technique for providing conditions of voltage clamp which differs considerably from other voltage clamp schemes has been developed. The feedback network which determines the current which will clamp the cell to the desired voltage does not operate in real time. Instead, the system uses a form of discontinuous feedback. The event to be clamped, which must be one which can be made to repeat itself without change, is elicited and allowed to run to completion without the intervention of feedback. During each repetition of the event, a current waveform is injected whose shape is based on the foregoing trials (iterations). Successive repetitions of this process develop a current waveform which ever more closely clamps the voltage to the desired value. Implementation involves a means of converting the intracellular voltage signal to digital form (a transient recorder), a means of processing the digitalized voltage signal (a digital computer), and a means of delivering the clamping current back to the preparation. The system has two advantages over other voltage clamp techniques. First, that the feedback loop is open in real time confers great stability. This advantage is exploited in the use of iterative voltage clamp in single electrode preparations. Secondly, iterative voltage clamp is essentially unlimited in the speed with which it can respond to transients. This would make the technique of interest even in preparations such as squid giant axon, where two electrodes are used and very fast responsiveness is desired.

Bridge balance in intracellular recording; introduction of the phase-sensitive method.

Passing current through the microelectrode during intracellular recording produces an artifactual voltage-drop across the electrode's resistance. In modern biological amplifiers, the means of removing this artifact is through what is no more than an analog arithmetic unit which subtracts a voltage, having some fixed proportion to the current being injected, from the voltage appearing at the input to the amplifier. Various techniques have evolved for determining that fixed proportion, an operation which has come to be referred to as bridge balance, and these are reviewed. A new method is presented for determining bridge balance and another amplifier parameter which affects current injection, capacitance neutralization. Essentially, a sinusoidal current is passed through the electrode and preparation at a frequency high enough so that the cellular membrane presents negligable impedance but low enough so that the electrode appears as nearly a pure resistance. A set of analytical formulations is presented which describes the system and which is useful in choosing the best frequency of the test sinusoidal signal. This choice, part of the experimental design, is based on the predicted time constants of the recorded cell and the recording electrode. In using the phase-sensitive method, the capacitance neutralization of the recording amplifier is adjusted until there is no phase error in the injected current. Bridge balance can then be adjusted until no sinusoidal signal is visible at the output of the amplifier. Both bridge balance and correction of capacitance compensation can be automatically and continuously performed during intracellular recording by incorporating a phase-sensitive alternating current (AC) voltmeter (i.e. a lock-in amplifier) into the system. This permits accurate measurement of intracellular potential during current injection even though the resistance of the electrode might be changing.

Ovarian carcinoma: care and survival in a community-based population.

BACKGROUND: Previous studies of the management and costs of ovarian cancer have been based on data from oncology practices. Such studies may exclude patients who are not candidates for treatment and may not account for costs incurred during diagnosis or primary treatment. OBJECTIVE: The purpose of this study was to describe the epidemiology, management, and costs of care of ovarian cancer in a geographically defined population to better reflect the total spectrum of the disease and its care. METHODS: We conducted a retrospective review of the medical records of all residents of Olmsted County, Minnesota, who received a first diagnosis of epithelial ovarian carcinoma (including postmortem diagnoses) between 1985 and 1997. RESULTS: Of the 107 women with a new diagnosis of ovarian cacinoma, 42 (39%) had stage I or II tumors at the time of diagnosis. The mean age of the patients at the time of diagnosis was 64.7 years, and 20% were nulliparous. The diagnostic assessment for ovarian carcinoma was initiated by a family physician or internist in 50% of cases and by an obstetrician or gynecologist in 16% of cases. One hundred two patients (95%) underwent surgical treatment, and 80 (75%) received primary chemotherapy. The 5-year survival rate was 88% in those with stage I or II tumors and 17% in those with stage III or IV tumors. The mean charges for secondary care were higher than those for primary care ($36,110 vs $32,367; P < 0.05) in those receiving both types of therapy. Fifty percent of those dying of ovarian cancer received hospice care for a mean of 39.0 days before death. CONCLUSIONS: Most assessments leading to a diagnosis of ovarian carcinoma were initiated by primary care physicians. In this community-based population, early-stage and low-grade tumors were common (> or = 30%) and were associated with lower costs of care and higher 5-year survival rates. Total treatment costs for those requiring secondary therapy were approximately twice the costs for those requiring primary treatment only, with approximately 50% of costs associated with inpatient care.

Piperidine discriminates between the transient and the persistent components of the ACh-induced chloride current in Aplysia neurons.

ACh-induced Cl- -current (ICl) is well known to desensitize with two components: an initial fast phase followed by a second, more slowly developing phase. In the present study, the influence of piperidine, a normal constituent in vertebrates and invertebrates, on ACh-induced ICl in isolated neurons of Aplysia was investigated by using the concentration clamp in combination with the voltage clamp technique. Pretreatment with piperidine in doses greater than 2 X 10(-4)M depressed the transient ACh-induced ICl but had little effect on the persistent ICl. Kinetic study of the desensitization phase of ACh-induced ICl showed that the slow time constant of the desensitization phase of ACh-induced ICl was not altered by pretreatment with piperidine. The present results indicate that piperidine can discriminate between the fast transient and slow persistent components of ACh-induced ICl in Aplysia neurons, and also suggest that two components of the desensitization phase of ACh-induced ICl function in an independent manner.

Alterations in the action potential of Aplysia neurons evoked by a phorbolester are mediated by protein kinase C.

Alterations in the parameters of action potentials upon changes in protein kinase C (PKC) activity were studied on neurons of the visceral ganglion of Aplysia californica. The amplitude and maximum speed of the up-and downstroke of the action potentials (APs) were measured. Intracellularly injected PKC and intra- and extracellularly applied phorbol-12,13-diacetate (PDAc) had similar effects on the Aplysia neurons, the most prominent being an increase of the upstroke speed of the AP in every neuron. The non-PKC-activating 4 alpha-phorbol didecanoate had no effect, and the effects of the PKC blocker H-7 were opposite to those of PDAc. It was concluded that the changes of the AP evoked by PDAc are mediated through PKC activation.

Valproate enhances inhibitory postsynaptic potentials in hippocampal neurons in vitro.

Effects of sodium valproate (0.5-10 mM) on hippocampal cells (CA3 pyramidal cells and granule cells) of the guinea pig in vitro were studied by intra- and extracellular recording. Inhibitory postsynaptic potentials were markedly and reversibly augmented. Their shunting action as well as duration increased by more than 150%. Effects of locally administered gamma-aminobutyric acid (GABA) did not change significantly. Membrane characteristics such as membrane potential, membrane input resistance and action potential did not alter. Valproate suppressed spontaneous spiking and repetitive discharges evoked by GABA antagonists. It is concluded that valproate enhances GABAergic synaptic transmission by a presynaptic mechanism. However, postsynaptic mechanisms might be involved in the limitation of repetitive firing.

Effect of temperature on postsynaptic potentials of cat spinal motoneurones.

The effect of spinal cord temperature on excitatory postsynaptic potentials (EPSP) and inhibitory postsynaptic potentials (IPSP) were measured by means of intracellular recordings from lumbar motoneurones of 43 cats. While body temperature and oil bath temperature were maintained between 37 and 38 degrees C, the temperature of the spinal segment under investigation was changed separately in the range between 30 and 42 degrees C. Cooling consistently produced an increase in amplitude and duration of both, mono- and poly-synaptic EPSPs and recurrent and direct IPSPs. Warming caused the opposite effect. The input resistance of the motoneurones was inversely related to the spinal cord temperature, while the latency of action potentials produced by intracellular injection of outward current was directly and exponentially related to spinal temperature. Although the data do not provide a quantitative differentiation of pre- versus postsynaptic temperature effects, they are consistent with the notion that temperature dependent changes on postsynaptic membrane properties contribute to the observed PSP changes. It is further suggested that similar postsynaptic temperature effects may be concerned in temperature sensitivity of proposed specific central neurones.

Differential blockade of bicuculline and strychnine on GABA- and glycine-induced responses in dissociated rat hippocampal pyramidal cells.

The inhibitory effects of bicuculline (BIC) and strychnine (STR) on GABA- and glycine-induced responses were studied in the rat dissociated hippocampal CA1 pyramidal neurons in whole-cell mode by using the conventional patch-clamp technique. Both GABA and glycine elicited inward Cl- currents in a dose-dependent manner and had almost the same maximal responses. The half-maximum dose (Ka) and Hill coefficient were 6.4 microM and 1.1 for the GABA response, and 74 microM and 1.5 for the glycine response. BIC and STR antagonized both GABA and glycine responses in a competitive manner. The blocking potency of BIC and STR on the GABA response was comparable. The half inhibition dose (IC50) was 2.7 microM for BIC and 6.7 microM for STR. STR blocked the glycine response about 3,000 x more effectively than BIC. The IC50 was 28 nM for STR and 100 microM for BIC. The BIC and STR did not have voltage-dependent blocking effects on either GABA or glycine responses. Neither GABA nor glycine showed outward rectification in their current-voltage relationships. The functional role of glycine in the rat hippocampal CA1 region is discussed.

Phorbol diacetate differentially regulates the N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated components of the rat hippocampal excitatory postsynaptic currents.

The effects of phorbol 12,13-diacetate (PDAc) on evoked excitatory transmission were studied in neurons of the CA1 area of hippocampal slices of rats, using whole-cell voltage clamp of pyramidal neurons in situ and stimulation of the Schaffer collaterals. The application of PDAc (10 microM) increased the amplitude of the excitatory postsynaptic current (EPSC) and caused a lengthening of its decay, due to an increase in the contribution of the N-methyl-D-aspartate (NMDA) component to the total EPSC. The latter effect was depend upon the concentration of calcium in the extracellular medium. Experiments in which we separated the two components of the EPSCs by 6-cyano-7-nitroquinoxaline-2,3-dione and by 2-amino-5-phosphonopentanoic acid also demonstrated a more pronounced increase in the NMDA receptor-mediated current under PDAc. The effects of PDAc were markedly attenuated by the extracellular application of the protein kinase C inhibitor H-7 (300 microM), but not by intracellular perfusion with 20 mM of the same drug.

Differences in baclofen-sensitivity between CA3 neurons and granule cells of the guinea pig hippocampus in vitro.

In the slice preparation of the guinea pig hippocampus, the effects of (+/-) baclofen added to the Krebs-Ringer solution on dentate granule cells and CA3 pyramidal cells were investigated by means of intracellular recording techniques. In a 10-25 microM concentration, baclofen reduces the inhibitory postsynaptic potentials of the granule cells evoked by electrical stimulation of the perforant path and hyperpolarizes the granule cell membrane slightly. The reduction of both, the excitatory and inhibitory postsynaptic potentials of CA3 pyramidal cells evoked by mossy fiber stimulation, however, is accompanied by a strong hyperpolarization and conductance increase. Further, repetitive discharges of granule cells elicited in the presence of the convulsant bicuculline (25 microM) are hardly affected by baclofen (50 microM), whereas those of CA3 neurons are blocked.

Intra-arterial perfusion therapy with 5-fluorouracil in patients with metastatic colorectal carcinoma and intractable pelvic pain.

In a phase-II trial, 18 patients with intractable pelvic and perineal pain caused by local recurrent and/or metastatic colorectal carcinoma resistant to combinations of analgesics, systemic cytostatic chemotherapy and/or radiation were treated with intra-arterial perfusion therapy using 15-30 mg 5-FU/kg body wt./day for 1-5 days. Of 18 patients, ten achieved complete pain relief for 3-32 weeks (mean, 15.7 weeks); after the perfusion therapy eight used less than 50% of the amount of analgesics required before treatment; one patient had only a minor response; two patients were treated unsuccessfully. Side effects were mild and controllable. One patient died subsequent to arterial embolism in the leg where the catheter was placed; pelvic perfusion therefore appears risky in patients with severe arteriosclerosis.