FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

Reduction in LBNP tolerance following prolonged endurance exercise training.

Eight young men underwent an 8-month endurance exercise training program. Prior to and following the training program, the subjects' maximal oxygen uptake (VO2max), total blood volume (TBV) and plasma volume (PV), tolerance to lower body negative pressure (LBNP) assessed by the cumulative stress index (CSI) to presyncope, and their hemodynamic responses to 0 to -45 torr LBNP was determined. Hemodynamic measures included rebreathe carbon dioxide cardiac output (Qc), heart rate (HR), directly measured arterial blood pressures (ABP), and strain gauge determination of forearm blood flow (FBF) and leg volume changes (delta LgV). Calculated values of stroke volume (SV), forearm, vascular resistance (FVR), and peripheral vascular resistance (PVR) were made. Following training, each subject had an increased VO2max (mean = +27.4%, P < 0.001), TBV (mean = +15.8%, P < 0.02), and PV (mean = +16.5%, P < 0.02) and each subject had a decreased tolerance to LBNP (mean CSI = -24%, P < 0.001). Stepwise linear regression identified that the major factors to significantly predict the decreased CSI pre- to post-training were a reduced response of PVR to LBNP from -15 to -45 torr (Model R2 = 0.853), the delta TBV (model R2 = 0.981), and the greater post-training reduction in SBP to LBNP of 0 to -45 torr (model R2 = 1.0). These data suggest that physiologic adaptations associated with the increased VO2max and TBV resulting from a prolonged endurance exercise training program can alter the reflex control of vasomotion and cardiac output during LBNP and reduce the LBNP tolerance.     

Effects of exercise training on men seropositive for the human immunodeficiency virus-1.

We examined the effects of chronic exercise on fitness and immune status in Caucasian males (34.9 +/- 5.6 yr) diagnosed by Western blot as seropositive for the HIV-1 virus. The exercise regimen involved 12 wk of 1 h sessions 3 d.wk: 20 min of cycle exercise at 60-80% HRreserve was followed by 35 min of strength and flexibility training. After matching subjects on health status (modified Walter Reed criteria), subjects (N = 37) were randomly assigned to exercise or a counseling control condition. Changes in strength, responses to the YMCA cycle test, and serum lymphocytes were tested by MANOVA in a condition (exercise or counseling)-by-time (pretest, posttest) design with repeated measures on time. Results indicated significant (P less than 0.001) group-by-time interactions for strength (N.m) (chest press and leg extension) and for HR (beats.min-1) and total time (TT) on the cycle test at 150 W. Strength and TT increased and HR decreased in the exercise condition, while control subjects did not change. Total leukocyte, lymphocyte, CD4+, and CD8+ cell counts, and the CD4+/CD8+ ratio were statistically unchanged for each condition. We conclude that HIV-1+ men, including those symptomatic for AIDS-related complex, can experience significant increases in neuromuscular strength and cardiorespiratory fitness without changes in lymphocyte phenotypes or clinical diagnosis when the exercise regimen is prescribed and monitored in accordance with ACSM guidelines for healthy adults.     

Carotid baroreflex function ceases during vasovagal syncope

Abstract. Despite the arterial baroreflex control of heart rate and blood pressure, vasovagal syncope is a common cause of loss of consciousness in people exposed to stimuli that reduce the central blood volume, such as head-up tilt. Carotid baroreflex function was evaluated using a rapid pulse train of neck pressure and neck suction in three conscious volunteers who developed a vasovagal episode during head-up tilt. The maximal gain of the carotid-heart rate and carotid-blood pressure baroreflex function curves were identified as measures of carotid baroreceptor responsiveness. When presyncopal symptoms developed, one further baroreflex assessment was obtained before the subjects were returned to the supine position. The bradycardia and hypotension exhibited during pre-syncope and syncope reflected a leftward and downward relocation of both the cardiac and vasomotor stimulusresponse curves. In addition, during the vasovagal syncope, baroreflex control was suppressed as blood pressure remained low during neck pressure stimuli. In conclusion, arterial baroreflex function ceases during vasovagal syncope.     

Cardiovascular responses to lower body negative pressure in endurance and static exercise-trained men

The cardiovascular responses to lower body negative pressure (LBNP) (to -50 torr) were examined in 8 sedentary control (UT), 8 endurance-trained (ET), and 8 weight-trained (WT) human subjects. The results were used to compare and contrast the blood pressure control system of the three subject groups. The primary differences in response included a more effective maintenance of blood pressure, by reason of greater stroke volume and cardiac indices of the WT subjects during LBNP (P less than 0.05). Peripheral vascular resistances were not different (P greater than 0.05) throughout LBN P between the three groups. Therefore, the improved blood pressure maintenance of the WT subjects was attributed to a cardiac effect. The ET subjects were less effective in maintaining blood pressure than UT or WT subjects. This finding was apparently due to an attenuated baroreflex sensitivity, as evidenced by a significantly (P less than 0.05) lower delta heart rate/delta systemic blood pressure ratio, 0.99 for ET vs 1.51 and 1.38 or the UT and WT groups respectively, calculated from the responses observed from 0 to -50 torr of LBNP.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Capsaicin-sensitive afferents are involved in signalling transneuronal effects between cutaneous sensory nerves

The aim of the present study was to investigate changes in contralateral nerves associated with peripheral nerve injuries. Transection and subsequent regeneration of the saphenous nerve on one side caused a suppression of the ability of the contralateral saphenous nerve to produce a neurogenic plasma extravasation response. This effect was transient, and was first evident two weeks after injury, reaching its maximum at four weeks, but was no longer detectable at eight weeks. This change was paralleled by a decrease in the content of substance P, a neuropeptide involved in neurogenic plasma extravasation, in the contralateral nerve. The neurotoxin capsaicin was used to deplete the nerve of a subclass of C-fibres, namely the polymodal nociceptor afferents. Pretreatment of the nerve to be lesioned with capsaicin was sufficient to significantly attenuate the changes in the plasma extravasation response and substance P content observed on the contralateral side. The effectiveness of the capsaicin treatment was confirmed by histological examination. These results strongly suggest that changes observed at a site distant from the location of the nerve injury are dependent on the integrity of capsaicin-sensitive C-fibre afferents within the injured nerve. Furthermore, given that the contralateral nerve has commonly been used as the control for an injury conducted on the homologous nerve or muscle on the opposite side of the body, the underlying assumption being that the contralateral nerve remained unchanged, the present findings emphasize the need for separate groups of control animals which have undergone no surgical procedures.     

Affective modulation of the startle response in depression: influence of the severity of depression, anhedonia, and anxiety

BACKGROUND: The amplitude of the startle reflex response is known to be influenced by the concomitant presentation of affect-toned material--if it is positive affect-toned, the reflex is inhibited, and if it is negative affect-toned, the reflex is augmented. Abundant evidence demonstrates the utility of the affect-startle paradigm as a significant tool for measuring both positive and negative emotions. We applied this paradigm to study emotional reactivity in depression, particularly in relation to symptoms of depression, anhedonia, and anxiety. METHODS: Depressed patients (22) and controls (22) were shown a series of film clips, consisting of two clips with positive valence, two with negative valence, and two with relatively neutral valence. The startle response was measured in reaction to the acoustic startle-eliciting stimuli presented three times binaurally during each clip. RESULTS: Highly depressed and anhedonic patients, relative to controls, showed a reduced mood (self-ratings) and a lack of startle modulation in response to affective film clips whereas patients relatively low on depression/anhedonia displayed a reduced mood only with pleasant clips and a normal pattern of affective startle modulation. Anhedonia and depression were highly positively correlated but neither correlated with anxiety. Anxious patients displayed larger reflexes across all clips and showed a reduced mood modulation with pleasant, but not unpleasant, clips. LIMITATIONS: The large majority of patients was medicated with antidepressants which may have influenced the results. CONCLUSIONS. Reactivity to pleasant stimuli is diminished in patients suffering from low levels of depression and/or anhedonia, but reactivity even to unpleasant stimuli seems compromised at high levels of depression and/or anhedonia. Anxiety is associated with hyperstartle responding.