Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT₂ receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence. Received: 30 April 1996/Final version: 3 July 1996     

Sleeping position and rectal temperature.

The effects of sleeping position upon body temperature were assessed by continuous monitoring of rectal temperature in 137 babies sleeping at home under conditions chosen by their parents. There were three groups of subjects: (1) normal babies aged 12-22 weeks whose temperature rhythms were developed, (2) normal babies aged 6-12 weeks who were developing their night time temperature rhythms, and (3) babies the night after diphtheria, pertussis, and tetanus immunisation, whose temperature rhythms were disturbed. Sleeping in the prone position was not associated with higher rectal temperatures at any time of night in young babies, nor did it exaggerate the disturbance of rectal temperature rhythm after immunisation. In older normal babies the prone position did not disturb rectal temperature in the first part of the night, though prone sleepers warmed a little faster prior to walking, especially in warm conditions. Prone sleepers were, however, born earlier in gestation and tended to be of lower birth weight. Normal babies can therefore thermoregulate effectively whatever their sleeping posture, even in warm conditions, though the prone position may make it slightly more difficult to lose heat. It is difficult to see how the prone position, even interacting with warm conditions, could induce lethal hyperthermia in otherwise normal babies. Perhaps the prone position is associated with other risk factors for sudden infant death syndrome.     

The development of whole cell biosensors for on-line screening of herbicide pollution of surface waters

The use of mediator assisted amperometric whole-cell biosensors, monitoring microbial photosynthetic electron transfer, to screen for herbicides in intake protection by the water industry is described. Cells harvested from axenic cultures are loaded onto bacteriological filters and held against a working carbon electrode polarised against the silver chloride reference. Redox mediators are reduced by the microorganisms and then reoxidised at the working electrode resulting in a flow of current. For on-line applications the sensors are controlled by a programmable electrochemical analyser (Artek) and housed in specially designed perspex flow cells which incorporate light emitting diodes (LEDs) for photosynthetic stimulation. A range of cyanobacteria and algae have been tested, but biosensors incorporating unicellular cyanobacteria have proven the most successful. Results obtained using the cyanobacterium Synechococcus show detection levels of less than 200 ppb with response times of less than ten minutes for selected herbicides. Sensor stability in the absence of pollutant poisoning has been found to be greatly influenced by the choice of mediator. Membrane penetrating mediators such as -benzoquinone reduce sensor life to about 24 hours, while a sensor life of up to six days has been achieved with ferricyanide.     

Shoulder instability: impact of glenohumeral arthrotomography on treatment

We used arthrotomography to study the glenoid labrum in 114 patients. Sixty-nine of the patients had anatomic instability of the shoulder (including recurrent dislocation and subluxation of the shoulder), and 45 patients had functional instability of the shoulder (denoted by chronic pain, clicking of the joint, and the sensation that an unstable condition exists without the objective signs of it). Labral tears were revealed arthrotomographically in 86% of the patients with anatomic instability, while only 40% of the patients with functional instability had labral abnormalities, and these were primarily of minor severity. Fifty-six patients (44 of whom had anatomic instability; 12, functional instability) required surgery. The surgical findings were correlated with the arthrotomographic findings, and no false-positive results were revealed. However, arthrotomography demonstrated only part of the pathologic condition of two patients. These results confirm that there is a strong correlation between labral pathologic conditions and anatomic instability of the shoulder. Arthrotomographic studies have a great impact on the selection of therapy in cases of both anatomic and functional instability of the shoulder.     

The relationship between monkey dentate cerebellar nucleus activity and kinematic parameters of wrist movement

Extracellular single-unit recordings were made from cerebellar dentate neurones in two conscious monkeys trained to perform wrist flexion and extension movement tasks that produced a range of static joint positions and dynamic velocities. The experiment was designed to establish whether there is a relationship between the discharge of dentate neurones and movement kinematics. The discharge patterns of 58 “wrist-related” neurones were correlated with joint position, duration of unidirectional movement (referred to as duration of velocity) and amplitude of velocity (peak velocity). Significant (P<0.05) correlations were found between the level of tonic discharge and static joint position in 21 of 58 (36%) neurones. Correlations between phasic discharge and at least one of the velocity variables were found in 17 of 43 (40%) neurones [7 of 43 (16%) showed a correlation between the duration of phasic excitation associated with movement and duration of velocity, 5 of 43 (12%) between the peak rate of phasic excitation and peak velocity and 10 of 43 (23%) between the number of discharges in the period of phasic excitation and peak velocity]. We conclude (for reasons outlined in the Discussion) that there is not a strong relationship between neuronal discharge and kinematic parameters of wrist movement in the dentate nucleus. Received: 21 October 1996 / Accepted: 14 August 1997     

Respiratory airway changes in response to suggestion in normal individuals

Thirty normal individuals were told they were inhaling a substance that would either cause breathing difficulty (N = 15) or not affect breathing (N = 15). Total respiratory resistance was measured prior to and during inhalation. In reality, the subjects inhaled no substance; inhalation consisted of breathing normally into a respiratory resistance recorder. Individuals who received the former suggestion exhibited increased total respiratory resistance during inhalation, whereas individuals who received the latter suggestion did not. These observations demonstrated that the ability of suggestion to affect the respiratory airway is not limited to asthmatic individuals.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.