Therapeutic challenges in hepatitis C-infected injection drug using patients

Hepatitis C Viral (HCV) infection in the injection drug user (IDU) population is a major medical concern. Concurrent substance abuse, co-morbid mental health conditions, poor socioeconomic status and a complex treatment protocol that is often incompatible with the life styles of IDUs combine to account for poor uptake and completion of HCV treatment. This article discusses HCV antiviral treatment issues relevant to IDUs chronically infected with this virus. The effect of non-injected substances of abuse on treatment outcome is considered. Priority issues requiring research are discussed.     

Psychiatric morbidity in policemen and the effect of brief psychotherapeutic intervention — a pilot study

The level of psychiatric morbidity and perceived sources of stress among police officers were investigated using the General Health Questionnaire (GHQ) and a stress situation questionnaire, which were sent to 171 officers. Half of the responders were invited to attend group counselling sessions weekly for 12 weeks. Outcome measures studied were a second GHQ completed at the end of the treatment period and the amounts of sick leave taken in the 12-week period before, during and after the treatment period. The results were that 61 people returned the first GHQ of whom 59 were male and of whom 14 were classed as ‘cases’. Of the 31 assigned to the treatment group, 22 attended at least one session. Responses to the stress situation questionnaire and the content of counselling sessions tended to confirm the impression that internal aspects of the organization were viewed as prime sources of stress and dissatisfaction. There were no significant changes in GHQ score within or between groups, nor were there significant differences in the amount of sick leave taken. Nevertheless the sessions appeared to be valued and we conclude that this sort of intervention is at least feasible. We recommend that similar studies measure psychiatric morbidity during treatment and at follow-up, rather than immediately after finishing, when reactions to this termination are prominent.     

Binding and hydrodynamic properties of muscarinic receptor subtypes solubilized in 3-(3-cholamidopropyl)dimethylammonio-2-hydroxy-1-propanesulfonate

The muscarinic receptor from the cerebral cortex, heart, and lacrimal gland can be solubilized in the zwitterionic detergent 3-(3-cholamidopropyl)dimethylammonio-2-hydroxy-1-propane sulfonate (CHAPSO) with retention of high affinity [3H]N-methyls-copolamine binding. However, in this detergent there are significant differences in the binding properties of the receptors, compared with those observed in membranes and digitonin solution. Some agents retain a degree of selectivity. In the heart and cortex, agonists can bind with high affinity to a receptor-GTP-binding protein complex. A second, lower affinity, agonist binding state is also present, which resembles a class of sites seen in membranes but not in digitonin solution. The high affinity agonist binding state has been resolved from the lower affinity state on sucrose density gradient centrifugation. Hydrodynamic analysis suggests that the high affinity state is approximately 110,000 Da larger than the lower affinity state. The binding properties of the receptor in CHAPSO can be altered to those seen in digitonin by exchanging detergents after CHAPSO solubilization.     

Self-inflicted orbital and intracranial injury with a retained foreign body, associated with psychotic depression: Case report and review

Reports of intracranial self-multilation by psychotic individuals are associated with severe mental disorders, criminality, or both. We describe a psychotically depressed male who drove a ballpoint pen through his right medial canthus and into his intracranial compartment. The patient developed a cavernous sinus syndrome and a traumatic dissection of the cavernous portion of the carotid artery. The pen was removed intraoperatively. Postoperatively, the patient was placed on a course of broad-spectrum antibiotics, antidepressants, and antipsychotic medications, and he has received long-term psychiatric follow-up. The literature related to these unusual cases is reviewed, and relevant surgical, medical, and psychiatric aspects of treatment are discussed.     

Macroglossia and amyloidoma of the buttock: evidence of systemic involvement in dialysis amyloid

A 48-year-old male on cuprophane haemodialysis for 18 years, with a history of dialysis arthropathy and recurrent carpal tunnel syndrome developed macroglossia and bilateral buttock tumoral masses. The tongue and buttock masses were biopsied. Histology of both biopsies showed amyloid deposits of the beta 2-microglobulin (B2M) variety. Amyloidomas in the gluteal region and macroglossia have not been previously described in amyloid derived from B2M. These findings suggest that systemic B2M amyloidosis can have a similar tissue distribution to AL amyloidosis. This case also stresses the importance of inspection of the tongue, and palpation of the gluteal region for masses, in the assessment of patients with dialysis arthropathy.     

Excitatory amino acid agonists. Enzymic resolution, X-ray structure, and enantioselective activities of (R)- and (S)-bromohomoibotenic acid

The enantiomers of alpha-amino-4-bromo-3-hydroxy-5-isoxazolepropionic acid (4-bromohomoibotenic acid, Br-HIBO, 1) a selective and potent agonist at one class of the central (S)-glutamic acid receptors, were prepared with an enantiomeric excess higher than 98.8% via stereoselective enzymic hydrolysis of (RS)-alpha-(acetylamino)-4-bromo-3-methoxy-5-isoxazolepropionic acid (4) using immobilized aminoacylase. The absolute configuration of the enantiomers of Br-HIBO was established by X-ray crystallographic analysis, which confirmed the expected preference of the enzyme for the S form of the substrate 4. (S)- and (RS)-Br-HIBO were potent neuroexcitants on cat spinal neurones in vivo, while (R)-Br-HIBO was a very weak excitant. Correspondingly, the S enantiomer of Br-HIBO (IC50 = 0.34 microM) was considerably more potent than the R form (IC50 = 32 microM) as an inhibitor of [3H]-(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([ 3H]AMPA) binding to rat brain synaptic membranes in vitro. In contrast, (S)- and (R)-Br-HIBO were approximately equipotent (IC50 values of 0.22 and 0.15 microM, respectively) as inhibitors of [3H]-(S)-glutamic acid binding in the presence of CaCl2. The enantiomers of Br-HIBO showed no significant affinity for those binding sites on rat brain membranes which are labeled by [3H]kainic acid or [3H]-(R)-aspartic acid.