Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

OBJECTIVE: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.     

Discoid meniscus in children and adolescents. Our experience in the treatment and follow-up

The purpose of this study was to review the clinical results of partially external meniscectomy performed on 33 arthroscopies in paediatric patients with a minimum follow-up of 24 months. In this retrospective cases series, a partial meniscectomy was performed in all patients. Patients age ranged between 4 and 14 years with an average of 9 years. We used the Watanabe classification for the morphological study of the discoid menisci. Clinical results were determined according to a modified Ikeuchi scale. The results were 25 excellent, two good and one poor. Complications were presented in four patients who developed osteochondritis of the external condyle and external tibial plateau. The arthroscopy is considered a diagnostic and treatment method in symptomatic external discoid meniscus.     

Cerebral Effects in Superior Vena Caval Cannula Obstruction: The Role of Brain Monitoring

A pediatric cardiac case of transient obstruction of the superior vena cava by the venous cannula before cardiopulmonary bypass is presented. With venous obstruction and increase in central venous pressure, reduced cerebral blood flow velocities and absence of diastolic Doppler flow were detected. This was followed by regional cerebral venous oxygen desaturation and global electroencephalographic slowing. Reposition of the venous cannula led to the recovery of these physiologic indicators and a noncomplicated clinical outcome.     

Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors.

PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics. EXPERIMENTAL DESIGN: An initial i.v. bolus was administered to assess the bioavailability of diflomotecan. Fourteen days later, diflomotecan was administered p.o. once daily for 5 days to adult patients with solid malignant tumors and repeated every 3 weeks. BN80915 and its open lactone form BN80942 were measured. RESULTS: Twenty-two patients entered the study and received a total of 57 cycles of oral diflomotecan at flat dose levels of 0.10, 0.20, 0.27, and 0.35 mg. The main toxicity was hematological, but some patients experienced alopecia, mild gastrointestinal toxicity, and fatigue. At the 0.35-mg dose level, 2 of 4 patients experienced dose-limiting toxicity comprising grade 3 thrombocytopenia with epistaxis and febrile neutropenia in 1 patient and uncomplicated grade 4 neutropenia lasting for >7 days in another. Toxicity was acceptable at the 0.27-mg dose level at which dose-limiting toxicities were observed in 3 of 12 patients (grade 4 neutropenia > 7 days, complicated by fever in 1 patient but without other signs of infection). After two cycles of diflomotecan, 6 patients had disease stabilization, which was maintained in 2 patients for 9 months and >1 year, respectively. Diflomotecan pharmacokinetics were linear over the dose range studied. Systemic exposure correlated with the fall in WBC counts. The mean oral bioavailability (+/-SD) was 72.24 +/- 59.2% across all dose levels. Urinary excretion of BN80915 was very low. CONCLUSIONS: The recommended oral diflomotecan dose for Phase II studies is 0.27 mg/day x 5 every 3 weeks. This regimen is convenient and generally well tolerated with a favorable pharmacokinetic profile and high but variable bioavailability.     

Pressão arterial periférica por Dinamap e pressão arterial central por tonometria planar de absorção no ambulatório de Medicina Geral e Familiar

IntroductionCentral blood pressure (CBP) is the pressure exerted by the blood column at any given moment on the aortic and carotid artery walls, which is a close proxy for the blood pressure inside the brain and the heart, and is thus a better marker of cardiovascular morbidity and mortality than peripheral blood pressure (PBP).ObjectiveTo assess how the augmentation index (AI), peripheral pulse pressure (pPP), central pulse pressure (cPP) and subendocardial viability ratio (SEVR) vary in hypertensive patients according to level of control of CBP and PBP.MethodsWe performed an observational, cross-sectional study in a convenience sample from a general practice in Central Portugal over a period of four days in May 2010. Measurements were taken after a four-minute resting period. The following values were considered to reflect controlled pressures: PBP <140/90 mmHg, CBP <130/80 mmHg, pPP <55 mmHg and cPP <45 mmHg.ResultsThe sample included 92 patients, 38 male (41.3%), mean age 62.3±11.1 years, with no significant difference in gender distribution. PBP was controlled in 55 (59.8%), and CBP in 53 (57.6%). Both PBP and CBP were controlled in 50 patients (54.3%) and neither was controlled in 34 (37.9%). pPP and cPP were significantly lower in those with controlled PBP (p<0.001) and CBP (p<0.001). AI was non-significantly lower in those with controlled PBP (78±9 vs. 80.7) and those with controlled CBP (78±9 vs.81±7) (p=0.02). SEVR was within the desirable range in 92 patients (92.2%). 78.4% of individuals were taking drugs acting on the renin angiotensin aldosterone system (RAAS).ConclusionsIn a convenience sample of 92 patients, PBP and CBP were controlled in 59.8% and 57.6%, respectively. Those with controlled PBP had significantly better peripheral systolic and diastolic blood pressure, CBP, pPP and cPP; the same was true of those with controlled CBP, who also had a significantly better AI. The percentage of the cardiac cycle in diastole had a desirable value for 92,2% of the subjects.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Effect of 200 μG/day of vitamin k1 on the variability of anticoagulation control in patients on warfarin: A randomized controlled trial

Background

Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin.

Methods

Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient’s INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability.

Results

Fifty out of 54 patients were analyzed (intervention: n = 26; placebo: n = 24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259 ± 0.307 with the intervention and -0.046 ± 0.345 with placebo (p = 0.026). There was no effect on the change scores of the (%) TTR (p = 0.98), the number of INRs out-of-range (p = 0.58) and the number of dose changes (p = 0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p = 0.017), dosing errors (p = 0.0009) and missed INR appointments (p = 0.035).

Conclusion

Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.     

Non-invasive expandable prosthesis in musculoskeletal oncology paediatric patients for the distal and proximal femur. First results

Purpose

The non-invasive expandable prosthesis for skeletally immature patients is used after limb salvage surgery following tumor resection. The aim of the study was to assess the effectiveness of this treatment.

Methods

Seven paediatric patients with femoral tumors had resection and limb salvage with an uncemented non-invasive growing prosthesis. Mean age at the time of surgery was 9.8 (range 8–12) years. There were six distal femur osteosarcomas and one proximal femur Ewing sarcoma. Six total knee prosthesis were implanted at the time of primary tumor resection and one bipolar hip prosthesis was a revision from a failed osteoarticular hip allograft. Functional outcomes and emotional acceptance were assessed using the MSTS score.

Results

The mean follow-up was 65.3 months (range 29–91) months. Two patients died of pulmonary metastasis and there was no local recurrence. The mean femoral resection was 18 cm (range 17–19) on the knee, and 24 cm on the hip. Mean total expansion was 36.4 mm (range 12.3–63.5). The mean MSTS score after rehabilitation was 26.3 (range 21–29). There was one lengthening device failure, one late infection and one patient who required iliofemoral bypass grafting surgery for a pelvic metastasis. No local recurrence occurred.

Conclusions

The non-invasive expandable prosthesis reduces the final limb-length discrepancy in growing patients with an acceptable function and appears to have an advantage as compared to invasive expandable prostheses which require multiple surgical procedures, but the complications rate is still high.

     

Studies on new cyclic imides obtained from aminophenazone with analgesic properties. Potent effects of a 3,4-dichloromaleimide derivative

This paper describes the synthesis of new cyclic imides obtained by reaction with aminophenazone (CAS 58-15-1, 4-aminoantipyrine) and different anhydrides with further cyclization with acetic acid under reflux. Their structures were confirmed by spectral data (IR and NMR) and elemental analysis. The analgesic activity of the synthesized compounds was investigated initially with the writhing test in mice and the most promising compound, a 3,4-dichloromaleimide derivative (3), was analyzed using other models of nociception. The results indicated that compound 3 exerts potent analgesic activity in mice, being more active than some reference drugs. The analgesia caused by this compound was not reversed by naloxone in the writhing test. In the hotplate test, compound 3 did not increase the latency period of pain induced by thermal stimuli, confirming that it does not interact with opioid systems.     

Use of acetylcholinesterase inhibitors and memantine in Alzheimer-type dementia

BACKGROUND: The therapeutic options to treat Alzheimer-type dementia (ATD) in recent years, have made it increasingly necessary to become familiar with the employment pattern of these new medicinal products. METHODS: A cross-sectional observational study of the population with ATD treated with acetylcholinesterase inhibitors and/or memantine in the Gallician Health Service. Databases were compiled with the demographic variables and use data during April 2005 of the medicinal products studied. RESULTS: Of the 5110 patients with ATD, 70.47% were women. The mean age of the women was 80.12 and of the men was 78.61 years old, with standard deviations of 6.66 and 7.03, respectively. The female sex was one of the factors associated with presenting ATD to pharmacological treatment (OR: 1.932 [CI 95%: 1.819-2.052]). The medication used most was donepezyl (44.46% of patients). Significant differences were found in that memantine was used to treat more patients in the group of patients < or =64 years (19.7% in < or =64 years vs. 14% in >64 years [p < 0.05]), and donepezyl was preferentially used in patients > or =95 years (75% in > or =95 years vs. 46.9% in <95 years [p < 0.03]). No significant differences were observed in the use of anti-dementia therapy, expressed in DDD/patient/day between the sexes, age groups, or in the age groups separated according to sex. CONCLUSIONS: The use of memantine (in monotherapy or in combination) is more frequent in patients under 64 years old. Female sex was found to be a factor associated with presenting ATD to pharmacological treatment.