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Background: Proactive consultation-liaison psychiatry improves identification of psychiatric needs and reduces time to psychiatric consultation and length of stay (LOS) among medical inpatients in academic clinical settings., Objective: To evaluate the effect of a proactive model on LOS, consult rate, and consultation latency in a nonacademic community hospital., Methods: We implemented a modified proactive consultation-liaison service (PCS) in a 32-bed acute care medical-surgical unit in a community hospital. We compared outcomes during a 90-day PCS intervention period to preintervention and postintervention cohorts receiving consultation-as-usual in the same unit. During the intervention, a psychiatrist reviewed the electronic medical record of patients admitted to the study unit to guide recommendations and collaborated with existing unit staff. Primary outcomes were LOS, consultation rate, and consultation latency. Secondary outcomes included restraint utilization, 1:1 companion utilization, and a survey completed by unit nursing staff., Results: Half of patients on the study unit had psychiatric comorbidity. Median LOS in the PCS cohort was 3.0 days versus 5.0 days in the preintervention and postintervention cohorts. The consultation rate was higher in the PCS cohort (1.4% before intervention; 33% intervention; 6.5% after intervention), and median consultation latency was also reduced during the intervention (57.6 h before intervention; 19.2 h intervention; 48 h after intervention)., Conclusions: Implementation of a modified PCS model is feasible in a community hospital setting and can reduce LOS, enhance psychiatric service utilization, and reduce consultation latency. This study demonstrates that proactive consultation-liaison may offer the same benefits to nonacademic community hospitals as it does to large academic centers., (Copyright © 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Uric acid (UA) has been identified as one major risk factor for cardiovascular diseases. Lowering of serum UA levels improves endothelial function. The present study investigates for the first time concentration-dependent effects of UA on human aortic endothelial cells (HAEC) and the cellular pathways involved in global proteomic analysis., Methods: The concentration dependent effects of UA on HAEC were investigated by nanoLC-MS/MS and ingenuity pathway analysis to reveal putative cellular pathways. For verification of the identified pathways the abundance or activity of key proteins was measured using ELISA or Western blotting. NO production was quantified by confocal laser microscopy., Results: We identified ubiquitin-proteasome system (UPS) and eIF4 signaling as the major pathways regulated by UA. K-means clustering analysis revealed 11 additional pathways, of which NO, superoxide signaling and hypoxia were further analyzed. A complex regulatory network was detected demonstrating that 500μmol/L UA, which is well above the concentration regarded as pathological in clinical settings, led to diminishing of NO bioavailability. In addition a UA-dependent downregulation of eIF4, an upregulation of UPS and an increase in HIF-1α were detected., Conclusions: Here we show for the first time, that increasing UA levels activate different sets of proteins representing specific cellular pathways important for endothelial function. This indicates that UA may alter far more pathways in HAEC than previously assumed. This regulation occurs in a complex manner depending on UA concentration. Further studies in knockout and overexpression models of the identified proteins are necessary to prove the correlation with endothelial dysfunction., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Serum uric acid (sUA) plays a major role in the development of morbidities associated with obesity, especially cardiovascular diseases. Within the purine pathway, xanthine oxidase (XOD) represents the key enzyme. The aim of this study was to investigate the dynamics of sUA and XOD following sleeve gastrectomy (SG) in a rat model of high-fat-diet (HFD) induced obesity., Patients: Over a period of 11 weeks, 30 rats received a HFD, and 10 rats received a low fat diet (LFD). Thereafter, 10 randomly selected HFD rats and 10 LFD rats were sacrificed. The remaining 20 HFD rats were randomly assigned to either SG or sham operation (SH) and studied 14 days postoperatively., Methods: The white adipose tissues (WAT) from visceral (intestinal and retroperitoneal) and inguinal (subcutaneous) depots were collected. sUA and urine UA (uUA) were measured by high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Abundance and activity of XOD was investigated in the liver, colon, adipose tissue, and skeletal muscle by enzyme-linked immunosorbent assay (ELISA)., Results: HFD led to significant weight gain, elevated sUA levels, increased WAT and increase of XOD activity. Fourteen days postoperatively, SG rats showed a significant decrease of weight and adipose tissue, improved glucose metabolism, and changes of gut hormones. The sUA and uUA levels were significantly decreased following SG. Furthermore, XOD activity was significantly down-regulated in WAT., Conclusion: HFD induces elevated sUA levels by gain of WAT and increase of XOD activity. Following SG, the reduction of WAT as the major source of XOD and the lowering of XOD activity are the basis for the decrease of sUA., (Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: This phase II study was undertaken to define the efficacy and toxicity of pemetrexed in combination with gemcitabine in patients with metastatic breast cancer., Patients and Methods: Patients with measurable metastatic breast cancer who had previously received an anthracycline and a taxane in either the adjuvant or metastatic setting were treated with gemcitabine 1250 mg/m2 (intravenous; days 1 and 8) and pemetrexed 500 mg/m2 (intravenous; day 8) every 21 days., Results: Fifty-nine patients received a median of five cycles (range one to 22) of treatment and were followed until death or for a median of 28 months (range 19.4-36.6) among living patients. Fourteen partial responses for an overall response rate of 24% [95% confidence interval (CI) 16% to 39%] were documented. Nine (15%; CI 5% to 32%) patients had stable disease for >6 months. The median survival time was 10.3 months (95% CI 8.3-18.9) and the 1 year survival rate was 49% (95% CI 38% to 64%). The median time to progression was estimated to be 3.7 months (95% CI 2.3-5.3). The most common grade 3 or 4 toxicities were neutropenia and thrombocytopenia in 83% and 27% of patients, respectively. Fourteen percent of patients experienced febrile neutropenia. Other common grade 3 or 4 non-hematological toxicities included fatigue (17%), dyspnea (15%), rash (7%) and anorexia (5%)., Conclusions: The combination of pemetrexed and gemcitabine is clinically active, with an overall response rate of 24% in patients with metastatic breast cancer who have previously been treated with an anthracycline and a taxane. Myelosuppression (66% grade 4 neutropenia and 14% febrile neutropenia) was the major treatment-related toxicity observed for this combination.

Background: PS-341 is a proteasome inhibitor with preclinical activity in pancreatic cancer tumor models and synergistic activity with gemcitabine. This randomized phase II study determined the tumor response rate (RR) for PS-341 alone and the 6-month survival and RR for the combination of gemcitabine and PS-341 in patients with metastatic pancreatic adenocarcinoma., Patients and Methods: Patients were randomized to receive 3-week cycles of either arm A: PS-341 1.5 mg/m(2) i.v. bolus (over 3--5 s) on days 1, 4, 8 and 11 or arm B: PS-341 1.0 mg/m(2) (same as arm A otherwise) plus gemcitabine 1,000 mg/m(2) i.v. on days 1 and 8. Patients progressing on arm A were allowed to receive arm B treatment., Results: Arm A: 42 evaluable patients were enrolled with a confirmed RR of 0% (95% CI 0% to 8%), median survival of 2.5 months (95% CI 2.0-3.3), and median time to progression (TTP) of 1.2 months (95% CI 1.1--1.3). Twelve of 43 evaluable patients (28%) experienced at least one grade 4+ AE. Arm B: 39 evaluable patients yielded a 6-month survival rate of 41% (16/39, 95% CI 29.8% to 67.0%), median survival of 4.8 months (95% CI 2.4--7.4), median TTP of 2.4 months (95% CI 1.5--3.1), and confirmed RR of 10% (4 partial responses/0 complete responses, 95% CI 3% to 24%). Eleven of 43 evaluable patients (26%) experienced at least one grade 4+ AE. One patient had grade 5 hypotension., Conclusion: The use of PS-341 alone or in combination with gemcitabine did not result in an overall survival and RR better than that expected for gemcitabine alone. Based on the lack of efficacy and the toxicity seen in our trial, there does not appear to be a role for PS-341 in pancreatic adenocarcinoma with either of the schedules used in this trial.

Background: Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease., Patients and Methods: Thirty-three patients were randomized to either docetaxel (100 mg/m(2)) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m(2)) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately., Results: Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35% [95% confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15% to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment., Conclusions: Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.

Sphygmomanometry is the most common technique of blood pressure (BP) determination. In order to study effects of predictability and controllability in sphygmomanometric BP measurements, 72 normotensive healthy subjects were examined. BP was determined continuously and non-invasively using a Finapres device (Penaz-technique) and by sphygmomanometry. Five sphygmomanometric measurements took place, during the fourth the arm cuff was inflated to 300 mmHg, the others were done with a pressure of 175 mmHg. Subjects were randomly assigned to one of three groups: In one group the recordings were unpredictable to the subject, in the second group measurements were announced 1 min before cuff inflation took place, and in the third group, subjects could decide when the sphygmomanometric recordings should occur. With unpredictable measurements systolic and diastolic BP decreased (approx. 5 mmHg). When sphygmomanometric recordings were controllable or predictable to the subject BP remained relatively stable. We would suggest that automatic BP devices (e.g. in ambulatory BP monitoring) should generally work with acoustic signals, making cuff inflation predictable for the subject.

Due to the increasing global HIV prevalence, comprehensive knowledge about clinical HIV transmission risks in health care professionals is essential. Mainly medical and nursing students are at risk, because they are working close to infected patients. By using an anonymous questionnaire, the study analysed the assessments of German medical/dental students (n = 182), Lithuanian medical students (n = 176) and Namibian student nurses (n = 135) on the risk of getting HIV infected in different clinical situations. It became obvious that the Namibian student nurses overestimated the risk of HIV transmission in several situations (eg changing dirty linen, physical examination). In comparison, the Lithuanian students showed the most realistic assessments, while the German students also tended to overestimate the risks of HIV transmission. The results indicate that assessments on the risk of HIV transmission in clinical situations are influenced by the national prevalence and daily contacts with HIV patients. Education of health care students should consider this and focus more on epidemiological aspects and infection control procedures, to avoid endangering students and patients.

Background: Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer., Methods: Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks., Findings: 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group., Interpretation: Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.

Sphygmomanometry is the most common technique of blood pressure (BP) determination. We were interested in the role of anxiety as a predictor of BP changes induced by painful stimuli during sphygmomanometry. We studied 141 normotensive healthy subjects who were asked to complete a State-Trait-Anxiety-Inventory (STAI) prior to the experiment. BP was determined continuously and non-invasively using a Finapres device (Penaz-technique) and by arm sphygmomanometry. Five sphygmomanometric measurements took place, during the fourth the arm cuff was inflated to 300 mmHg (unpredictable to the subject), the others were done with a pressure of 175 mmHg. State and trait anxiety (STAI X1 and X2) correlated positively with diastolic BP changes during inflation of the arm cuff (state anxiety: r = 0.26, P < 0.05; trait anxiety: r = 0.20, P < 0.05). Our results suggest that anxiety may have an impact on cardiovascular responses following painful stimuli.

Background/objectives: Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma., Patients and Methods: Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy., Results: Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively., Conclusion: In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.

This study is based upon 207 examinations for the evaluation of the ability to operate a motor vehicle in persons with transient disturbances of the cerebral function. In 26 persons, the EEG was repeated after sleep deprivation. There was EEG activation with transient disturbances in seven cases (not present in the routine EEG). In five individuals, there were transient disturbances in the routine EEG as well as after sleep deprivation. No abnormalities were recorded in 14 persons. No driver's license could be granted in five patients with unequivocal spike wave complexes or spike wave paroxysms following sleep deprivation. In two patients, however, the permission to drive could be granted. These patients showed spike wave patterns in the routine EEG, but no seizures had occurred for several years and their performance in the experimental-psychological evaluation (with simulator) were superior. In persons with suspected and clinically obscure cerebral attacks, as well as in persons with known seizure disorder but seizure-free for several years, the EEG after sleep deprivation must be regarded as a highly informative test which may crucially influence the decision. The method of activation corresponds with a type of stress with which the motorist must deal frequently. This test can be carried out on an outpatient basis and with negligible iatrogenic damage.

Permanent pacemakers were implanted in 50 children. Indications were symptomatic sinus node dysfunction in 34 (68%), surgical block in 9 (18%), and congenital block in 7 (14%). Twenty-three (68%) of the 34 children with sinus node dysfunction had undergone prior cardiac operations. Only 4 of the 50 patients (8%) had electrode problems after a mean pacing time of 29.5 months (range, 1 to 96 months). All 35 of the mercury-cell pulse generators used in 28 patients ceased to function after an average useful life of 20.8 months (range, 1 to 51 months). The lithium-powered units in the 45 survivors all show satisfactory pacing after 5 to 44 months (mean, 28.1 months). With improved pacemaker technology, longer survival after complex repairs, and better monitoring techniques, the indications for cardiac pacing in children have broadened. Surgical block now is an indication in only a small fraction of the pediatric pacemaker population. Sinus node dysfunction accounts for an ever-increasing majority of the pacemakers we currently implant in children.

Total surgical repair of a Taussig-Bing malformation in an 8-year-old boy was accomplished successfully after previous palliative procedures. The child had undergone a Rashkind septostomy when he was 10 days old, banding of the pulmonary artery and division of a patent ductus arteriosus when he was 2 weeks old, and a Blalock-Hanlon septectomy when he was 1 year old. Complete repair involved patching the ventricular septal defect (VSD), debanding and patching the pulmonary artery, and rerouting the venous return by performing a Mustard procedure. Because of its high location, the VSD could not be reached properly through the tricuspid valve and was approached through the pulmonary arteriotomy. Excellent exposure was obtained by retracting the pulmonary valve, and patch closure of the defect was achieved without difficulties. We believe this approach to the VSD is preferable because no incision is necessary in the right ventricle. This is important since the right ventricle becomes the systemic ventricle after the Mustard operation.

Twenty-five patients (16 male, 9 female) underwent right-sided valve replacement (10 pulmonary valve replacement, 14 tricuspid valve replacement, 3 tricuspid plus pulmonary valve replacement, and 2 replacements of a single atrioventricular valve) at the University of Nebraska Medical Center from June 1977 to December 1986. Twenty-one patients (84%) are long-term survivors with 2,035 months follow-up (range, 41 to 143 months; mean, 96.9 months). Twenty-three Carpentier-Edwards bioprosthetic valves, one Ionescu-Shiley bioprosthetic valve, and nine St. Jude Medical valves were inserted. Follow-up of 17 patients with a Carpentier-Edwards valve ranged from 5 years 9 months to 11 years 9 months (mean, 8 years 11 months). To date there has been one reoperation after 3 years 4 months in this group. One patient who received an Ionescu-Shiley bioprosthesis required re-replacement at 20 months after operation. Three of 4 patients who received St. Jude mechanical valves and are long-term survivors have required replacement after 36 to 56 months. We conclude that the Carpentier-Edwards bioprosthetic valve is a viable option in the right side of the heart in the young age group when annular size is adequate to accommodate an appropriate bioprosthesis.

In a retrospective study involving 680 EEG investigations in 593 patients the effects of various psychopharmaceutical agents were examined by visual interpretation of the EEG. The drugs were given singly in the majority of cases and were combined in others, and special attention was paid to the occurrence of paroxysmal EEG activity. The proportions of abnormal EEGs in the various groups were (in descending order): clozapine 59%, lithium salts 50%, butyrophenone 44%, maprotiline 37%, dibenzepine 32%, laevomepromazine and amitriptyline 31%, imipramine 9% and diazepam 4%. The proportions of paroxysmal discharges (13%) and generalized transient disturbances with groups of slow waves (16%) were also greatest in the clozapine group. During 3.5 years (1973-1974, May 1979-November 1980) we observed drug-induced generalized seizures in 16 inpatients = 0.28% of all inpatients (N = 5785) in that time. The psychotropic drugs given to these patients were either laevomepromazine (Neurocil 4x), perazine (Taxilan 3x), maprotiline (Ludiomil 3x), clozapine (Leponex 2x), lithium carbonate (Quilonum retard 2x) and amitriptyline (Saroten 2x) alone or partly in combination with butyrophenone (3x), fluphenazine (2x) and biperiden (3x). The appearance of paroxysmal EEG activity seems dose dependent and occurs more often during treatment with a combination of psychoactive compounds, than in patients receiving a single drug.

Etomidate was injected i.v. within 10 or 60 s at various doses. After etomidate 0.3 mg kg-1 the plasma concentration was 1.6 micrograms ml-1 at 1 min after the end of injection. For about 7 min a good hypnotic effect (stages C0-D2) was observed on the e.e.g. recording. For surgical procedures, however, a combination with analgesic drugs appeared to be necessary. When the dose of etomidate was increased (0.1-0.4 mg kg-1) a linear increase in plasma concentration and slow e.e.g. activity was observed concomitantly. Anaesthesia could be prolonged with additional injections or with continuous infusion. Each additional injection produced a steep increase in concentration of short duration with marked deepening of hypnosis. The infusion induced only a moderate increase in plasma concentration, whereas the depth of sleep during the period of infusion remained nearly the same. E.e.g. changes induced by etomidate are similar to those after barbiturates and other i.v. anaesthetics.

Three children with a pacemaker sustained similar lead fractures within a two-year period. Each fracture occurred in the corkscrew portion of a Medtronic Model 6917 epicardial lead. All patients were boys. The leads had been in place for 12, 45, and 43 months prior to fracture. None of the patients had sustained major trauma. Fracture of the corkscrew lead has been considered an uncommon complication. However, three lead fractures in the corkscrew area in a population of 60 children followed at this institution indicate that this may be a more common cause of pacemaker-system malfunction than previous data suggest. A plea is made for reporting all pacing failure to the manufacturer.