Primary orthostatic tremor is an exaggeration of a physiological response to instability.

Primary orthostatic tremor (POT) is a rare disorder characterised by an intense sense of unsteadiness upon standing and a 16-Hz tremor in which the timing between tremor bursts in different muscles (unilateral and bilateral) remains constant. Hitherto, similar EMG activity has not been described in healthy subjects and it has been postulated that the oscillations seen in POT are primarily pathological. In this study, EMG was recorded from tibialis anterior in healthy subjects who were made unsteady through vestibular galvanic stimulation or leaning backwards. Under these conditions, a peak at approximately 16 Hz was seen in the coherence between the left and right tibialis anterior. This bilateral coherence was absent when the subjects activated the same muscles when not unsteady. These data indicate the existence of a physiological system involved in organising postural responses under circumstances of imbalance and characterised by a highly synchronised output at approximately 16 Hz. In addition, the results suggest that the core abnormality in POT may be an exaggerated sense of unsteadiness when standing still, which then elicits activity from a 16-Hz oscillator normally engaged in postural responses.     

Localization of striatal and nigral tachykinin receptors in the rat

The effects of lesioning mesostriatal dopamine projections or striatal neurons on tachykinin binding in the basal ganglia were assessed in the rat. 6-Hydroxydopamine lesions of the medial forebrain bundle destroyed striatal dopamine terminals as assessed by [³H]mazindol autoradiography, but did not significantly affect the binding of NK-1 ([³H][Sar⁹, Met(O₂)¹¹]substance P) or NK-3 ([³H]senktide) tachykinin ligands in the striatum. 6-Hydroxydopamine lesions significantly reduced NK-3 binding in the substantia nigra pars compacta, but not the ventral tegmental area. In contrast, striatal quinolinic acid lesions reduced both NK-1 and NK-3 binding in the striatum, but failed to affect NK-3 binding in the substantia nigra. These findings suggest that both NK-1 and NK-3 receptors within the striatum are predominantly post-synaptic with respect to dopamine neurons, whereas nigral NK-3 receptors are located on dopaminergic neurons.     

Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons

OBJECTIVE: To evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. DESIGN: Nested case-control study. SETTING: Tennessee Medicaid program. PARTICIPANTS: Medicaid enrollees 65 years of age or older were included in the study. The 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986. The 7063 control persons represented a stratified random sample of other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs, compared with that among nonusers, was 4.1 (95% CI, 3.5 to 4.7). For current users, the risk increased with increasing dose, from a relative risk of 2.8 (CI, 1.8 to 4.3) for the lowest to a relative risk of 8.0 (CI, 4.4 to 14.8) for the highest dose category. The risk was greatest in the first month of use (relative risk, 7.2; CI, 4.9 to 10.5). If the association is fully causal, 29% of peptic ulcers in the study sample resulted from the use of these drugs, and the excess risk associated with such use was 17.4 hospitalizations for ulcer disease per 1000 person-years of exposure. CONCLUSIONS: These data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons.     

Long-term use of depot-norethisterone enanthate: effect on blood lipid fractions.

This is the third report of a metabolic study on 56 long-term users (24 for 2-5 yr; 32 for over 5 yr) of the injectable contraceptive norethisterone enanthate (Net-En) and deals with the effects on the blood levels of lipoprotein fractions. There was no significant difference between this group and a group of 30 non-users in serum concentrations of triglycerides, total cholesterol, low density and very low density lipoproteins. There was a significant reduction in mean high density lipoprotein levels between the controls and the user groups (16% for the intermediate duration and 12% for the longer duration). Age, ethnic group, body-mass index and a close family history of cardiovascular disease were taken into account, as were various lifestyle factors: diet, exercise, alcohol consumption and smoking. In a smaller group, levels of apoproteins A and B were also assayed. There was a significant reduction in apoprotein A between controls and all users, but the significance was lost on adjusting for confounding variables. Consideration was given to the ratio of total cholesterol to high density lipoprotein cholesterol as an index of coronary risk. There were no significant differences in the total cholesterol:HDL-C ratio between controls and user groups. There was a significant interaction with ethnic group (Caucasian or Afro-Caribbean) in the response to duration of use.     

Drug-Induced Antibodies: Interaction of the Drug with a Polymorphic Platelet-Antigen

Preincubation of donor platelets with ticarcillin will prevent the reactivity of a platelet antibody against these platelets, whereas no influence was observed on antisera against HLA, 5A, 5b and ZWa. The implications for the mechanism of drug-induced antibodies with restricted specificity will be discussed.     

In vivo microdialysis and conditioned place preference studies in rats are consistent with abuse potential of tramadol.

The abuse potential of tramadol was investigated using both in vivo microdialysis measures of dopamine (DA) release within the nucleus accumbens (NAc) shell and the conditioned place preference (CPP) paradigm in rats. Tramadol (75 mg/kg, i.p.) induced a statistically significant increase (starting 80 min posttreatment) in DA release within the NAc shell, which was maintained for at least 120 min posttreatment. Tramadol (18.75, 37.5, and 75 mg/kg i.p.) produced a statistically significant CPP, with the effects of the two highest doses comparable to those induced by morphine (5 mg/kg, s.c.). The release of DA within the NAc shell may be responsible for the rewarding properties of tramadol and, together with the CPP results, provide evidence that tramadol may possess greater abuse potential than originally believed.     

Adopting an information management approach to the design and implementation of information systems.

As the NHS adopts an information management approach to coordinated handling of total information resources, methods of systems analysis and design require assessment to ensure that they are appropriate. Mandatory use of Structured Systems Analysis and Design Methodology (SSADM) may be encouraging a damagingly narrow view of information systems. Research is described in which an holistic view of information systems is applied, allowing the needs of information users to play a stronger role in determining how information will be supplied to them. The techniques may also assist the training activities associated with implementing new systems.