Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH (p = 0.001) and occipital DWMH (p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH (p = 0.003), as well as occipital DWMH (p = 0.001) and temporal DWMH (p = 0.002) loads. FRS-CVD was associated with frontal PWMHs (p = 0.003) and frontal DWMHs (p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.     

Alcohol consumption and its relation to risk factors for cardiovascular disease in the north-west of Russia: the Arkhangelsk study

BACKGROUND: To explore indicators and levels of alcohol consumption in a Russian population, and to elaborate these in relation to risk factors for cardiovascular disease. METHODS: A total of 1963 men and 1734 women, aged 18-75 years, consecutively recruited at their compulsory annual medical check-up at the Semashko outpatient clinic, Arkhangelsk, participated in a cross-sectional health survey. The survey comprised a physical examination, a six-page questionnaire on health and lifestyle, and blood tests. RESULTS: Gamma-glutamyltransferase (GGT) levels in both sexes were more than twice as high as found in comparable studies. Elevated GGT-levels were 4-5 times more frequent than found in Norwegian studies. Alcohol Use Disorder Identification Test (AUDIT) identified up to 75% of male workers and 47% of female workers as hazardous or harmful alcohol drinkers. The traditional risk factors for cardiovascular disease were significantly higher in subjects with a high level of GGT. CONCLUSION: The findings indicate an extremely high level of alcohol consumption in this population. Elevation in GGT was significantly associated with increased risk for cardiovascular disease.     

Single-chip mechatronic microsystem for surface imaging and force response studies

We report on a stand-alone single-chip (7 x 10 mm) atomic force microscopy unit including a fully integrated array of cantilevers, each of which has an individual actuation, detection, and control unit so that standard atomic force microscopy operations can be performed by means of the chip only without any external controller. The system offers drastically reduced overall size and costs as well as increased scanning speed and can be fabricated with standard complementary metal oxide semiconductor technology with some subsequent micromachining steps to form the cantilevers. Full integration of microelectronic and micromechanical components on the same chip allows for the controlling and monitoring of all system functions. The on-chip circuitry, which includes analog signal amplification and filtering stages with offset compensation, analog-to-digital converters, a powerful digital signal processor, and an on-chip digital interface for data transmission, notably improves the overall system performance. The microsystem characterization evidenced a vertical resolution of < 1 nm and a force resolution of < 1 nN as shown in the measurement results. The monolithic system represents a paradigm of a mechatronic microsystem that allows for precise and fully controlled mechanical manipulation in the nanoworld.     

Urgent carotid endarterectomy is safe in patients with few comorbid medical conditions

Recent reports from single institutions have confirmed the efficacy of carotid endarterectomy (CEA) performed in the urgent or emergent setting, although with higher perioperative mortality and morbidity. We determined the results of urgently performed CEA in academic and community hospitals and whether patient or hospital factors affected outcome. The records of patients undergoing CEA in all nonfederal hospitals in the state of Connecticut between 1992 and 2002 were reviewed, and symptomatic patients who presented in an urgent or emergent fashion were compared to patients treated electively. Multivariable logistic regression was used to determine the effect of patient risk factors on perioperative mortality, stroke, and cardiac complications. Patients undergoing urgent CEA (n = 764, 6.3%) had higher perioperative mortality (2.0% vs. 0.3%, p < 0.0001) and stroke (2.9% vs. 1.1%, p < 0.0001) but not cardiac complications (3.0% vs. 2.2%, p = 0.14) compared to patients undergoing elective CEA (n = 11,312). Patients undergoing urgent CEA and with high rates of associated comorbidity had a higher risk of perioperative mortality (7.8% vs. 0.4, p = 0.001), stroke (10.9% vs. 0.8%, p = 0.0002), and cardiac complications (14.1% vs. 0.8%, p < 0.0001) compared to patients presenting urgently but with little comorbidity. Perioperative mortality was associated with performance of the procedure in hospitals with low bed capacity (odds ratio [OR] = 4.6, p = 0.01). Perioperative stroke was associated with renal insufficiency (OR = 5.3, p = 0.04). Perioperative cardiac complications were associated with diabetes (OR = 2.6, p = 0.03) and performance in hospitals with low bed capacity (OR = 5.0, p < 0.01). Urgent admission was associated with age >/=80 (OR = 1.2, p = 0.04), renal disease (OR = 1.8, p = 0.05), and cardiac disease (OR = 1.3, p < 0.01). Urgently performed CEA has higher perioperative mortality and stroke compared with electively performed cases. However, the subset of patients with low rates of associated comorbid medical conditions but urgently needing CEA is associated with low rates of perioperative complications. Patients with severe associated comorbid medical conditions who present urgently for CEA may form a high-risk group of patients to be considered for referral to large treatment centers or possibly alternative therapy.     

Dynamic contrast‐enhanced‐MRI of tumor hypoxia

Patients with highly hypoxic primary tumors show increased frequency of locoregional treatment failure and poor survival rates and may benefit from particularly aggressive treatment. The potential of gadolinium diethylene‐triamine penta‐acetic acid‐based dynamic contrast‐enhanced‐MRI in assessing tumor hypoxia was investigated in this preclinical study. Xenografted tumors of eight human melanoma lines were subjected to dynamic contrast‐enhanced‐MRI and measurement of the fraction of radiobiologically hypoxic cells and the fraction of pimonidazole‐positive hypoxic cells. Tumor images of K^trans (the volume transfer constant of gadolinium diethylene‐triamine penta‐acetic acid) and v_e (the fractional distribution volume of gadolinium diethylene‐triamine penta‐acetic acid) were produced by pharmacokinetic analysis of the dynamic contrast‐enhanced‐MRI data, and K^trans and v_e frequency distributions of the non‐necrotic tumor tissue were established and related to the extent of hypoxia. Tumors showing high K^trans values and high v_e values had low fractions of hypoxic cells, whereas tumors showing both low K^trans values and low v_e values had high hypoxic fractions. K^trans differentiated better between tumors with low and high hypoxic fractions than did v_e. This study supports the current attempts to establish dynamic contrast‐enhanced‐MRI as a method for assessing the extent of hypoxia in human tumors, and it provides guidelines for the clinical development of valid assays. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Long-term outcome of surgically and medically treated patients with gastroesophageal reflux disease: a matched-pair follow-up study

OBJECTIVE: A recent randomized study has shown that the long-term effects of continuous medical treatment of gastroesophageal reflux disease (GERD) with a proton-pump inhibitor are comparable to those of open fundoplication. We compared the long-term effects of anti-reflux surgery with those of medical care according to clinical practice. MATERIAL AND METHODS: This is a questionnaire-based 3-10 years follow-up study of 373 patients with GERD operated on in two hospitals with either open or laparoscopic fundoplication, and pair-matched non-operated controls treated medically according to clinical practice. The controls were matched for hospital, age, sex, follow-up time, degree of esophagitis, presence of hiatus hernia and Barrett's esophagus. The questionnaires used for symptoms and health-related quality of life (QoL) were the Gastrointestinal Symptoms Rating Scale and the Psychological General Well-Being Index, respectively. RESULTS: Response rates were about 80%, and 179 pairs of operated patients and controls remained for analysis (102 based on laparoscopic and 77 on open fundoplication). Independently of the surgical technique, the operated patients suffered at the follow-up from significantly (p <0.001) fewer reflux symptoms than the non-operated controls, the mean scores being 1.34 and 2.51, respectively. The operated patients suffered from slightly more symptoms of indigestion (p <0.05). No consistent significant differences between the groups were found for QoL. Significant differences in QoL in favor of the operated patients were found when dealing only with the 43 pairs with no concurrent disease. CONCLUSION: The study shows that in our area anti-reflux surgery is more effective in relieving reflux symptoms than medical care according to clinical practice.     

New Alcohol Markers—How Useful Are They in Population Studies: The Svalbard Study 1988–89

Regular high consumption of alcohol in selected populations have, with high precision, been identified by two new alcohol markers; carbohydrate-deficient transferrin and mitochondrial aspartate aminotransferase. To test these markers in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST) were measured in the Norwegian population, 310 males and 171 females, aged 18 to 60 years, living at Svalbard. Using self-reported alcohol intake as gold standard, sensitivity, specificity, positive predictive value, and likelihood-ratio were estimated according to different cutoff-points for alcohol intake and for the tests. In contrast to earlier studies, the sensitivity was in general low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for any of the tests. Whereas CDT showed its best discriminatory power at lower intake of alcohol, GGT discriminated best at higher levels. Parallel and serial analysis of CDT and GGT indicated a conditional independence between the tests, as well as at higher and at lower levels of alcohol consumption. mAST was judged as not suitable in population studies.     

Prophylactic regimens in colorectal surgery: Comparisons between metronidazole used alone or with ampicillin for one or three days

The purpose of this study was to compare as anti-infectious prophylaxis in elective colorectal cancer surgery the effect of metronidazole alone and in combination with ampicillin, and the effect of a duration of 1 or 3 days of prophylaxis. The prophylactic regimens designated regimens A-D given in randomized order were metronidazole 500 mg used alone or with 2.0 g ampicillin administered every 8 hours as separate but simultaneous infusions. All patients studied received preoperative mechanical evacuation of bowel contents. Eight surgical departments participated in the study. Two hundred thirty-three patients were studied. The distribution of sex, age, and type of operation was similar among the groups of patients receiving each regimen, except that there were more cases of sigmoidectomy, low anterior resection, or rectal amputation in the group receiving regimen D. The duration of the operations was comparable, even for each type of operation considered separately. Samples for bacteriological examination were obtained by abscess punctures when relevant. The pus was taken and transported to the laboratory under anaerobic conditions. Moderate or severe infections were observed in 6 (10.3%) of 58 patients on regimen A, in 2 (3.5%) of 58 patients on regimen B, in 4 (7.0%) of 57 receiving regimen C, and in 2 (3.3%) of 60 given regimen D. The highest incidence of postoperative infections was observed in rectal amputation. The bacteria causing postoperative infections were similar in the regimens A and C receiving only metronidazole for 1 and 3 days, respectively and in regimens B and D in which ampicillin was added. Only one anaerobe, aClostridium perfringens, was recovered from regimen C; twenty-two strains of anaerobic bacteria were recovered from regimen A. The number of aerobic bacteria was 25 in regimen A and 16 in regimen C. The yield of bacteria was much more sparse when metronidazole was combined with ampicillin. Eleven isolates (2 anaerobes) were recovered from regimen B, only one isolate was recovered from patients on regimen D, an indole positiveProteus. In conclusion, th'is study indicates that a combination of metronidazole and ampicillin is particularly useful in rectal surgery. Metronidazole alone may suffice in colonic surgery, but a combination with an agent against aerobes is recommended in rectal surgery. The difference between 1-day prophylaxis and 3-day prophylaxis was insignificant for metronidazole plus ampicillin; a single day of this prophylactic regimen would appear advisable.

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Resumen El propósito de este trabajo ha sido el de comparar, en la profilaxis anti-infecciosa en cirugía colorectal electiva, el efecto de: (a) metronidazol solo y en combinación con ampicilina, y (b) la profilaxis de un día con la de tres días de duración. Los 4 regimenes profilácticos designados como regímenes A-D, y suministrados al azar, fueron metronidazol 500 mg utilizado como agente único o con ampicilina 2.0 g en infusiones simultáneas cada 8 horas iniciadas una hora antes de la operación. Todos los pacientes del estudio también fueron sometidos a evacuación mecánica del contenido intestinal según el procedimiento de rutina en cada hospital. Ocho departamentos quirúrgicos participaron en el estudio, el cual incluyó 233 pacientes. La distribución según sexo, edad y tipo de operación fué similar, excepto que hubo un mayor número de casos de sigmoidectomía, resección baja anterior o amputación rectal en el grupo que recibió el regimen D. La duración de las operaciones fué comparable, aún para cada tipo de operación considerado aisladamente. Se obtuvieron cultivos por punción de abscesos cuando se consideró pertinente, y el pus fué tomado y transportado al laboratorio bajo condiciones anaeróbicas. Infecciones moderadas o severas fueron observadas en 6 de 58 pacientes (10.3%) en el regimen A, en 2 de 58 en el regimen B (3.5%), en 4 de 57 en el regimen C (7.0%) y en 2 de 60 en el regimen D (3.3%). La mayor incidencia de infección postoperatoria se encontró en casos de amputación rectal. Las bacterias causantes de las infecciones postoperatorias fueron similares en los regimenes A y C que recibieron sólo metronidazol por 1 o por 3 días respectivamente, y en los regimenes B y D en que se añadió ampicilina. Sólo un anaerobio, unClostridium perfringens, fué recuperado en el regimen C, y 22 cepas de bacterias anaerobias en el regimen A. El numéro de bacterias aeróbicas fué de 25 en el regimen A y 16 en el regimen C. La proliferación bacteriana fué mucho menor cuando se combinó el metronidazol con la ampicilina. Once cultivos positivos (2 anaerobios) fueron logrados en el regimen B, y sólo uno en el regimen D, unProteus indol-positivo. En conclusión, este estudio indica que la combinación de metronidazol y ampicilina es particularmente útil en cirugía rectal. El metronidazol solo puede ser suficiente en cirugía colónica, pero su combinación con un agente efectivo contra los aerobios es recomendable en cirugía rectal. La diferencia entre la profilaxis de un día y la de 3 días fué insignificante para la combinación de metronidazol y ampicilina; un único día de profilaxis parece ser el regimen recomendable.

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Résumé Le but de l'étude entreprise par les auteurs fut de comparer l'effet prophylactique anti-infectieux du métronidazole employé isolement ou en association avec l'ampicilline pendant 1 ou 3 jours. Quatre protocoles différents désignés par les lettres A.B.C.D. ont été ainsi pris en considération. L'étude a été conduite en série par tirage au sort. Cinq cent (500) mg de métronidazole employé isolement ou en association avec 2 g d'ampicilline ont été injectés séparément 3 fois par 24 heures pendant 1 jour ou 3 jours. L'intestin ayant été évacué par les moyens mécaniques classiques.Huit services de chirurgie ont participé à l'étude qui a groupé 233 malades. Le sexe, l'âge, le type et la durée de l'opération ont été sensiblement identiques pour les 4 groupes avec cependant un nombre plus important de sigmoidectomies, de résections abdominales antérieures du rectum ou d'amputations rectales dans le groupe D.Selon les cas, les spécimens de pus ont été prélevés au tampon au niveau de l'incision pariétale ou par ponction en présence d'abcès collectés. Le pus prélevé a été transporté au laboratoire en milieu anaérobie. Les résultats ont été les suivants: chez 6 des 58 malades (10,3%) soumis au protocole A (500 mg de métronidazole × 3 en 24 heures), chez 2 des 58 sujets (3,5%) soumis au régime B (500 mg de métronidazole et 2 g d'ampicilline × 3 en 24 heures), chez 4 des 57 patients (7%) soumis au régime C (500 mg de métronidazole × 3 en 24 heures pendant 3 jours) et chez 2 des 60 opérés (3,3%) soumis au régime D (500 mg de métronidazole et 2 g d'amicilline × 3 en 24 heures pendant 3 jours) fut observée une infection modérée ou grave. Le taux le plus élevé d'infections postopératoires a été constaté après amputation du rectum.Les bactéries à l'origine de l'infection ont été identiques quel qu'ait été le protocole prophylactique anti-infectieux suivi. L'emploi du métronidazole isolé s'est soldé par la présence de 22 types de bactéries anaérobie pour le protocole A et un type seulement pour le protocole C de 25 types de bactéries aérobies pour le protocole A et de 16 pour le protocole C. L'association métronidazole et ampicilline s'est soldé par un nombre plus clairsemé de types bactériens: 11 dont 2 anaérobies pour le protocole B et un seul (protéus) pour le protocole D.En conclusion, cette étude permet d'affirmer que la combinaison du métronidazole et de l'ampicilline est particulièrement efficace dans la chirurgie rectale.Le métronidazole isolé est suffisant en cas de chirurgie colique mais son association avec un agent exerçant son action sur les germes aérobies est recommandé dans la chirurgie rectale. La différence entre le traitement prophylactique d'une durée d'un jour ou de trois jours ayant été insignifiante lorsque le métronidazole était associé à l'ampicilline. Un traitement prophylactique pendant 24 heures suivant ce protocole apparaît suffisant.