Challenges associated with vascular access through the common carotid artery during embalming procedures in humans: A technical note.

BACKGROUND: The teaching of anatomy is a key component in the training of physicians, and the foundation of this teaching is the human body, which must be properly prepared to be used as a teaching aid. Due to a lack of modern literature on this topic, we decided to write a technical note discussing access to the carotid artery. MATERIALS AND METHODS: We pre-qualified 43 donor bodies for the study. The bodies had to meet standards such as no signs of post-mortem decomposition, preservation of body integrity, and the absence of known infections. Carotid artery access was performed based on descriptions of the types of vascular access performed in surgery and our own observations. RESULTS: We consider carotid artery access to be a convenient option due to its ease of location. When performed correctly and with attention to the surrounding structures, it is relatively low in tissue trauma, which translates into a higher quality of preparation. Data analysis has revealed several factors that can have a significant impact on the success of the embalming procedure. CONCLUSIONS: Proper execution of minimally invasive access to the common carotid artery minimizes tissue damage and ensures a high success rate of the procedure. Knowledge of the types of vascular access is essential for preparing the highest quality specimens.

Effect of Endurance Cardiovascular Training Intensity on Erectile Dysfunction Severity in Men With Ischemic Heart Disease.

The protective effect of physical activity on arteries is not limited to coronary vessels, but extends to the whole arterial system, including arteries, in which endothelial dysfunction and atherosclerotic changes are one of the key factors affecting erectile dysfunction development. The objective of this study was to report whether the endurance training intensity and training-induced chronotropic response are linked with a change in erectile dysfunction intensity in men with ischemic heart disease. A total of 150 men treated for ischemic heart disease, who suffered from erectile dysfunction, were analyzed. The study group consisted of 115 patients who were subjected to a cardiac rehabilitation program. The control group consisted of 35 patients who were not subjected to any cardiac rehabilitation. An IIEF-5 (International Index of Erectile Function) questionnaire was used for determining erectile dysfunction before and after cardiac rehabilitation. Cardiac training intensity was objectified by parameters describing work of endurance training. The mean initial intensity of erectile dysfunction in the study group was 12.46 ± 6.01 (95% confidence interval [CI] = 11.35-13.57). Final erectile dysfunction intensity (EDI) assessed after the cardiac rehabilitation program in the study group was 14.35 ± 6.88 (95% CI = 13.08-15.62), and it was statistically significantly greater from initial EDI. Mean final training work was statistically significantly greater than mean initial training work. From among the parameters describing training work, none were related significantly to reduction of EDI. In conclusion, cardiac rehabilitation program-induced improvement in erection severity is not correlated with endurance training intensity. Chronotropic response during exercise may be used for initial assessment of change in cardiac rehabilitation program-induced erection severity.

A comparative, randomized trial of concentration-controlled sirolimus combined with reduced-dose tacrolimus or standard-dose tacrolimus in renal allograft recipients.

BACKGROUND: The clinical safety and efficacy of sirolimus plus reduced-dose tacrolimus was evaluated in de novo renal allograft recipients enrolled in a comparative, open-label study. METHODS: One hundred twenty-eight renal allograft recipients were randomly assigned (1:1) to receive reduced-dose tacrolimus plus sirolimus (rTAC) or standard-dose tacrolimus and sirolimus (sTAC) for 6 months. The primary efficacy endpoint was calculated creatinine clearance values at 6 months. RESULTS: Demographic variables were similar between groups. At 6 months, mean (± standard deviation) calculated creatinine clearance was significantly improved in the rTAC group (63.8 vs 52.7 mL/min, P = .005), although mean serum creatinine values were not significantly different. Patient survival (95.2% and 96.9%) and graft survival (93.7% and 98.5%) were similar between the rTAC and sTAC groups, respectively. Acute rejection rates were 17.5% with rTAC and 7.7% with sTAC (P = .095). CONCLUSIONS: The rTAC regimen provided effective immunosuppression and was associated with improved creatinine clearance. Adequate immunosuppressant exposure must be achieved in the early postoperative period to minimize the risk of acute rejection.

Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle.

Action potentials and whole cell sodium current were recorded in canine epicardial, midmyocardial, and endocardial myocytes in normal sodium at 37 degrees C. Tetrodotoxin (TTX) reduced the action potential duration of midmyocardial cells to a greater degree than either epicardial or endocardial cells. Whole cell recordings in potassium-free and very-low-chloride solutions revealed a slowly decaying current that was completely inhibited by 5 microM TTX or replacement of external and internal sodium with the impermeant cation N-methyl-D-glucamine. Late sodium current density at 0 mV was 47% greater in midmyocardial cells and averaged -0.532 +/- 0.058 pA/pF in endocardial, -0.463 +/- 0.068 pA/pF in epicardial, and -0.785 +/- 0.070 pA/pF in midmyocardial cells. Neither the frequency dependence of late sodium current nor its recovery from inactivation exhibited transmural differences. After a 4.5-s pulse to -30 mV, late sodium current recovered with a single time constant of 140 ms. We conclude that a larger late sodium conductance in midmyocardial cells will favor longer action potentials in these cells. More importantly, drugs that slow inactivation of sodium channels will produce a nonuniform response across the ventricular wall that is proarrhythmic.

Conception and pregnancy during interferon-alpha therapy for chronic hepatitis C.

We report a case of a patient who became pregnant while on interferon-alpha therapy for chronic hepatitis C. To date, there have been 23 reported cases of interferon administration during pregnancy; only one was in a patient with hepatitis C. We report our case and review the literature regarding the effects of interferon on pregnancy.

Interaction of the retinoblastoma protein (pRb) with the catalytic subunit of DNA polymerase delta (p125).

The retinoblastoma gene product (pRb) interacts with many cellular proteins to function in the control of cell division, differentiation, and apoptosis. Several pRb binding proteins complex with pRb through an amino acid sequence called the LXCXE motif. The catalytic subunit of DNA polymerase delta (p125) contains a LXCXE motif. To further study the biochemical function of this polymerase, we sought to determine if p125 interacts with pRb. Experiments using GST-pRb fusion proteins showed that p125 from breast epithelial (MCF10A) cell extracts associates with pRb. In addition, GST-p125 fusion proteins bound pRb from the same cell extracts. The pRb that associated with GST-p125 was largely unphosphorylated. Coimmunoprecipitation experiments using cell cycle synchronized cells revealed that p125 and pRb form a complex predominantly during G1 phase, the phase during which pRb is mostly unphosphorylated. In vitro phosphorylation of GST-pRb by the cyclin dependent kinases reduced the ability of p125 to associate with GST-pRh. Addition of the LXCXE containing protein SV40 large T antigen to GST-pRb blocks the ability of p125 to associate with pRb, suggesting that it may be through a LXCXE sequence by which p125 interacts with pRb. Finally, in vitro polymerase assays demonstrate that GST-pRb fusion protein stimulates DNA polymerase delta activity.

I(NaCa) contributes to electrical heterogeneity within the canine ventricle.

This study examines the amplitude of sodium-calcium exchange current (I(NaCa)) in epicardial, midmyocardial, and endocardial canine ventricular myocytes. Whole cell currents were recorded at 37( degrees )C using standard or perforated-patch voltage-clamp techniques in the absence of potassium, calcium-activated chloride, and sodium-pump currents. I(NaCa) was triggered by release of calcium from the sarcoplasmic reticulum or by rapid removal of external sodium. I(NaCa) was large in midmyocardial myocytes and significantly smaller in endocardial myocytes, regardless of the method used to activate I(NaCa). I(NaCa) at -80 mV was -0.316 +/- 0. 013, -0.293 +/- 0.016, and -0.210 +/- 0.007 pC/pF, respectively, in midmyocardial, epicardial, and endocardial myocytes when activated by the calcium transient. When triggered by sodium removal, peak I(NaCa) was 0.74 +/- 0.04, 0.57 +/- 0.04, and 0.50 +/- 0.03 pA/pF, respectively, in midmyocardial, epicardial, and endocardial myocytes. Epicardial I(NaCa) was smaller than midmyocardial I(NaCa) when activated by removal of external sodium but was comparable to epicardial and midmyocardial I(NaCa) when activated by the normal calcium transient, implying possible transmural differences in excitation-contraction coupling. Our results suggest that I(NaCa) differences contribute to transmural electrical heterogeneity under normal and pathological states. A large midmyocardial I(NaCa) may contribute to the prolonged action potential of these cells as well as to the development of triggered activity under calcium-loading conditions.

Estimation of the usefulness of neoplastic markers TPS and CA 125 in diagnosis and monitoring of ovarian cancer.

PURPOSE: We have undertaken an attempt to compare the suitability of tumor markers TPS (tissue polypeptide specific antigen) and CA125 for diagnosis and monitoring of ovarian cancer patients. METHODS AND MATERIAL: The studies were performed on 33 patients treated for ovarian cancer in the Department of Oncology, Karol Marcinkowski School of Medicine, Poznan from 1995-1996, Serum levels of TPS and CA125 were determined before surgery and at each chemotherapy course. CONCLUSION: Estimation of the neoplastic markers TPS and CA125 is suitable for diagnosis of ovarian cancer. Parallel use of TPS and CA125 in ovarian cancer patients increases sensitivity of the diagnosis. Estimation of TPS is highly suitable and estimation of CA125 is of low value in detection of mucinous ovarian cancer. Serum levels of the neoplastic markers TPS and CA125 decrease after total or debulking surgery for ovarian cancer. Serum TPS and CA125 levels reflect the course of the neoplastic process during chemotherapy.

The antifungal antibiotic clotrimazole potently inhibits L-type calcium current in guinea-pig ventricular myocytes.

The antimycotic agent clotrimazole (CLT) is a promising potential therapeutic agent for a variety of diseases including cancer. Although it is known that CLT alters calcium homeostasis in many cell types, its cardiac effects are virtually unknown. We investigated the effects of CLT on L-type calcium current (ICa,L) and action potentials in guinea-pig ventricular myocytes. CLT (5, 25 and 50 microM) inhibited basal ICa,L by 16, 59 and 93%, respectively. The inhibitory effect of CLT was rapid and the peak effect was attained within 3 min. At a concentration of 25 microM, the inhibitory effect of CLT was partially reversible whereas the response to 50 microM CLT persisted following drug withdrawal. CLT abbreviated action potential duration at 50 and 90% of repolarization and suppressed the plateau significantly. These results indicate that CLT may have important cardiac effects at concentrations used to induce the antiproliferative action of the drug.

Significance of tissue polypeptide specific antigen (TPS) in diagnosis and monitoring of treatment in ovarian cancer.

Tissue polypeptide specific antigen (TPS) finds increasingly broad application in diagnosis and monitoring of treatment in ovarian cancer. Its sensitivity increases in parallel to clinical advancement of the tumor and to the grade of cellular differentiation. TPS may represent valuable supplementation of conventional markers in diagnosis of mucous carcinoma. Improved sensitivity and specificity of the technique for detection of ovarian cancer occur when two or more additional tumour markers are used in parallel. TPS has been found to represent a dependable index of surgical completeness. Determination of TPS in the sera of patients with ovarian cancer in the course of chemical treatment provides important information on the course of the neoplastic process and defines the response of the host to the applied treatment.

Long-term considerations after switching antipsychotics.

The so-called "atypical" antipsychotics are rapidly becoming the de facto standard pharmacologic treatment of schizophrenia. This article reviews some common psychopharmacologic and psychological issues that may arise after an outpatient with schizophrenia is switched to one of the newer antipsychotics. Important issues to consider in the first few months after switching include assessment of response to the new medication, dealing with subsequent psychological reactions, and management of an unsatisfactory response. Once the response is established, there are other pharmacologic and psychological issues that arise during the next year or two. Pharmacologic issues that emerge later on include the role of long-term combination antipsychotics, management of new side effects, and deciding whether and when to switch again. Some of the long-term psychological issues include changes in self-image that arise from being less visibly ill, sexuality and intimacy concerns, and recovery issues.

INaCa and ICl(Ca) contribute to isoproterenol-induced delayed after depolarizations in midmyocardial cells.

The contributions of electrogenic sodium/calcium exchange current (INaCa), calcium-activated chloride conductance [ICl(Ca)], and calcium-activated nonselective cation conductance to delayed afterdepolarizations (DAD) were examined. Nonselective cation channels were absent in canine M cells, since inhibition of INaCa and ICl(Ca) eliminated all calcium-activated currents without abolishing cell shortening. After the cells were treated with isoproterenol and ouabain to increase calcium loading, INaCa was 168 +/- 30 x 10(-3) pC/pF and ICl(Ca) was 114 +/- 24 x 10(-3) pC/pF. Transient overlapping inward and outward currents were evoked positive to the chloride reversal potential (ECl). Outward current was chloride sensitive, and inward current was blocked by replacement of external sodium with lithium. When ECl was -50 mV, triggered activity occurred in normal external sodium and persisted after inhibition of INaCa. Steps to -80 mV revealed oscillating inward currents in normal sodium and chloride, which persisted after inhibition of INaCa. When ECl was equal to -113 mV, ICl(Ca) opposed INaCa at the resting potential. DAD occurred in normal sodium, and inhibition of outward ICl(Ca) provoked triggered activity. We conclude that INaCa represents approximately 60% of the total calcium-activated current at resting potentials but that both INaCa and ICl(Ca) work in concert to cause DAD in calcium-overloaded cells.

Ito1 dictates behavior of ICl(Ca) during early repolarization of canine ventricle.

The contributions of the 4-aminopyridine (4-AP)-sensitive transient outward potassium conductance (Ito1) and the calcium-activated chloride conductance (ICl(Ca)] to cardiac action potentials were investigated in canine ventricular myocytes. Action potentials or currents were recorded at 37 degrees C using standard whole cell or amphotericin B perforated-patch-clamp techniques. Inhibition of Ito1 by 1 mM 4-AP prolonged phase 1 repolarization, elevated the action potential notch, and depressed the plateau. Action potential voltage clamp revealed that 4-AP blocked a rapidly decaying outward current during phase 1 without affecting plateau or diastolic currents. These results suggested that depression of the plateau was not a direct result of Ito1 inhibition but followed from delayed phase 1 repolarization. Calcium current (ICa) at the peak of the action potential dome was reduced 60 +/- 4% when the rate of phase 1 repolarization was reduced. ICl(Ca) measured by action potential clamp reversed over the course of the action potential. Chloride fluxes associated with outward and inward components of the 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid-sensitive current were +130 +/- 17 and -184 +/- 20 (pA.ms)/pF, respectively. The effects of selective inhibition of ICl(Ca) on the action potential were dependent on the rate of early repolarization and the prominence of the notch. Inhibition of ICl(Ca) elevated the plateau and slightly abbreviated action potential duration when the notch was prominent. When repolarization was prolonged and the notch was shallow, inhibition of ICl(Ca) elevated the notch and the plateau and abbreviated duration. We have shown that Ito1 and ICl(Ca) contribute to canine ventricular action potentials. The extent of overlap between Ito1 and ICl(Ca) during the action potential is largely determined by the amplitude of Ito1 and the depth of the notch. Regional differences in the density of Ito1, or interventions that moderate phase 1 repolarization by reducing this current, will have considerable effect on the time course of ICa and calcium-dependent conductances.

Sodium effects on 4-aminopyridine-sensitive transient outward current in canine ventricular cells.

Tetrodotoxin (TTX) or substitution of external Na+ reduces the 4-aminopyridine-sensitive transient outward current (Ito1) in rat ventricular myocytes. We investigated the outcome of reducing external sodium on the kinetics, gating, and selectivity of Ito1 with a dual-patch electrode technique to record whole cell currents and transmembrane potentials independently of the voltage clamp in canine midmyocardial cells. Steps from -80 to 0 mV produced overlapping inward sodium and outward potassium currents, accompanied by a loss of voltage control associated with activation of INa. Substitution of external Na+ or application of TTX abolished INa, restored voltage control, and reduced Ito1. Inactivation of INa with a 10-ms prestep to -45 mV decreased Ito1 to the same extent as external Na+ substitution. The kinetics, gating, and selectivity of Ito1 recorded after inactivation of INa were unaffected by drastic reductions in external Na+. Our findings suggest that a larger Ito1 in the presence of normal external Na+ is due to 1) transient loss of voltage control and concomitant changes in activation of Ito1 and/or 2) facilitation of an outward current by intracellular Na+. We conclude that reduction of external sodium has no direct effect on the kinetics or gating of Ito1, non does Na+ contribute to current flow through Ito1 channels in canine midmyocardial cells.

Postdischarge medication compliance of inpatients converted from an oral to a depot neuroleptic regimen.

OBJECTIVE: This preliminary study assessed the effects on outpatient medication compliance of converting inpatients with schizophrenia from oral to depot neuroleptic medication. METHODS: Subjects consisted of 93 neuroleptic-responsive inpatients with schizophrenia from three New York City hospitals who were part of a one-year prospective longitudinal study of medication compliance. Forty patients were converted to depot neuroleptic medication while hospitalized; the other 53 remained on oral medication. Symptoms, side effects, and medication compliance of the two groups were compared at one, six, and 12 months postdischarge. RESULTS: Inpatients converted to depot medication had significantly better compliance at one month postdischarge. Differences in demographic characteristics, symptoms, hospital site, and baseline attitudes toward medication did not account for this finding. The initial positive effect on compliance waned, and no significant between-group differences in compliance were found at six and 12 months postdischarge. CONCLUSIONS: Conversion to depot medication before hospital discharge may facilitate medication compliance during transition to outpatient treatment, but other interventions are needed to maintain compliance over time.

Polarization control of a Q-switched, diode-pumped Nd:YAG laser.

We describe control of the polarization state of a diode-pumped Nd:YAG laser that is Q switched with an acousto-optic modulator (AOM). One of two orthogonal linear polarization states can be made dominant, depending on the amount of loss introduced by the AOM. Heterodyne beating indicates that the two polarization states are of slightly different frequencies.

Intracellular calcium activates a chloride current in canine ventricular myocytes.

The contribution of chloride and potassium to the 4-aminopyridine (4-AP)-resistant transient outward current was investigated in dog cardiac myocytes. Whole cell currents were recorded at 37 degrees C in single cells dissociated from epicardial and midmyocardial regions of the canine ventricle. Sodium-calcium exchange current and voltage-dependent transient outward potassium current (IA) were blocked in sodium-free solutions containing 2 mM 4-AP; sodium channels were inactivated by the -50-mV holding potential. When patch pipettes contained 0.4-0.8 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, voltage-clamp steps over the range -20 to +50 mV activated an inward calcium current (ICa) and a Ca(2+)-activated chloride current [ICl(Ca)]. ICl(Ca) was blocked by 200 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), or reduction of external chloride. Independent of the presence of potassium, the reversal potential of the SITS-sensitive current varied with extracellular chloride, as predicted for a chloride-selective conductance. The bell-shaped current-voltage relation of ICl(Ca) has a threshold of -20 mV and a peak at +40 mV. No evidence could be found for a Ca(2+)-activated potassium current or a Ca(2+)-activated nonspecific cation current under these conditions. ICl(Ca) contributed to oscillatory inward currents at diastolic potentials in cells superfused by isoproterenol and high Ca2+, suggesting a role for this current in triggered arrhythmias associated with delayed afterdepolarizations. In the normal heart, ICl(Ca) is likely to contribute to rate- and rhythm-dependent repolarization of the cardiac action potential.

Rating of medication influences (ROMI) scale in schizophrenia.

Noncompliance with neuroleptic treatment is a major barrier to delivery of effective treatment for schizophrenia outpatients. This article describes the development of a standardized measure for the assessment of attitudinal and behavioral factors influencing patient compliance with neuroleptic treatment. The Rating of Medication Influences (ROMI) scale was developed as part of a longitudinal study of neuroleptic noncompliance in schizophrenia and administered to 115 discharged schizophrenia outpatients. Analyses of the following were conducted to assess the scale's psychometric properties: (1) interrater reliability, (2) internal consistency, (3) principal components, (4) correlation with other subjective measures, and (5) correlation with independent family reports. Most (95%) of the ROMI patient-report items were reliable, whereas rater-judgment items were not reliable. The rater section was dropped. A principal components analysis of the reliable patient-report items yielded three subscales related to compliance (Prevention, Influence of Others, and Medication Affinity) and five subscales related to noncompliance (Denial/Dysphoria, Logistical Problems, Rejection of Label, Family Influence, and Negative Therapeutic Alliance). There were significant correlations between these subscales, and independently obtained family-report ROMI items were significant. The Denial/Dysphoria subscale correlated strongly with two other published measures of dysphoric response to neuroleptics, whereas the other noncompliance subscales did not. The ROMI is a reliable and valid instrument that can be used to assess the patient's subjective reasons for medication compliance and non-compliance. The subscale findings suggest that the ROMI provides a more comprehensive data base for patient-reported compliance attitudes than the other available subjective measures. Indications for use of the ROMI and other subjective measures of neuroleptic response are reviewed.

Loss of differentiation control in transformed 3T3 T proadipocytes.

Nontransformed 3T3 T mesenchymal/proadipocyte stem cells can be readily induced to differentiate, yet previous work has shown that 3T3 T cells that are spontaneously or virally transformed not only lose their normal growth control mechanisms but also lose the ability to differentiate. Loss of growth control can be due to autocrine mechanisms in some transformed cells, but the mechanisms involved in disrupting differentiation control are poorly understood. Our goal is to further define the growth and differentiation defects that arise in neoplastically transformed cells and the mechanisms underlying those defects. For example, exogenous transforming growth factor beta and tumor necrosis factor, both of which are secreted aberrantly by some tumor cells, are known inhibitors of different steps of the normal 3T3 T adipocyte differentiation process, suggesting a potential role as autocrine factors in disrupting differentiation of transformed 3T3 T cells. In the current study we transformed 3T3 T cells in vitro with chemical or UV irradiation treatment in order to determine if the acquisition of the transformed phenotype after these treatments is also associated with loss of differentiation control as it is with spontaneously or virally transformed cells. Four chemically and two UV-treated 3T3 T cell lines were isolated from type III foci and all have been found to be tumorigenic in syngeneic animals and to have lost the ability to differentiate. Relative to the parental cell line the differentiation abilities of the transformed clones ranged from 0 to less than 5%. In this regard, we also analyzed the normal and aberrant expression of three growth factors and differentiation inhibitors in transformed cells. Both transforming growth factor alpha and beta were found to be expressed in non-transformed 3T3 T cells as determined by Northern blot analyses. In addition, both were found to be down-regulated during differentiation of 3T3 T cells. Transformed/differentiation-defective 3T3 T cells expressed varied levels of transforming growth factor alpha and beta. Three of the new transformed clones expressed particularly high levels of transforming growth factor alpha. Very low levels of tumor necrosis factor expression were found in the normal cells and the transformed cells appeared to express tumor necrosis factor at similar levels. In contrast, none of the transformed cells expressed any of the differentiation-specific genes tested (lipoprotein lipase, glycerol-3-phosphate dehydrogenase, etc.). Even a transformed clone which could undergo growth arrest but not morphological differentiation expressed no differentiation-specific genes. Together, these data suggest that neoplastic transformation in general disrupts differentiation control.(ABSTRACT TRUNCATED AT 400 WORDS)