The central role of the chemokine receptor, CXCR4, in haemopoietic stem cell transplantation: will CXCR4 antagonists contribute to the treatment of blood disorders?

Recent clinical trials have used CXCR4 antagonists for the rapid mobilization of CD34(+) haemopoietic stem/progenitor cells (HSC/HPC) from the bone marrow to the blood in patients refractory to granulocyte-colony-stimulating factor (G-CSF). These antagonists not only mobilize non-cycling cells with a higher proportion of repopulating cells, but also enhance CD34(+) cell mobilization when used in combination with G-CSF. Here, we review the importance of CXCR4 and its ligand CXCL12 in haemopoiesis, and the potential roles of CXCR4 antagonists in the clinical HSC transplant setting.

Prevalence of depression in a 12-month consecutive sample of patients with ALS.

There is an impression both in clinical practice and in research literature that patients with amyotrophic lateral sclerosis (ALS) possess 'heroic stoicism with a low frequency of depression'. Reliance on specific interview methods may have contributed to differing estimates of mood disorder in people with ALS. The objective of the current study was to compare prevalence rates of depression and anxiety in ALS using different assessment tools. The Beck Depression Inventory (BDI), The Hospital Anxiety and Depression Scale (HADS) and the Spielberger State-Trait Anxiety Inventory (STAI) were sent to a 12-month consecutive sample of 190 patients with ALS attending a tertiary referral clinic in the UK. Data were collected from 104 patients with ALS. Using BDI scores, 44% were categorized as not depressed, 37% were mild-moderately depressed, 13% were moderately-severely depressed, and 6% were severely depressed. In contrast, the HADS depression subscale identified 75% as not depressed, 13% were in the borderline range, and 13% were categorized as meeting 'caseness' for depression. Twenty-five percent of the patients were using antidepressant medication. The estimated prevalence of mood disorder amongst patients with ALS may vary significantly depending on the measure used.

Ultrasound-guided percutaneous drainage of meniscal cysts: preliminary clinical experience.

AIM: To evaluate the efficacy of ultrasound-guided percutaneous drainage of symptomatic meniscal cysts. MATERIALS AND METHODS: Patients with lateral knee joint tenderness and swelling and confirmed meniscal cyst on magnetic resonance imaging (MRI) were consecutively enrolled for ultrasound-guided percutaneous cyst aspiration. Cysts were injected with local anaesthetic and steroid before completion of procedure. All 18 patients (all male, average age 33 years) were subsequently followed up (average time 10 months) and meniscal cyst symptoms assessed by questionnaire. Fischer's exact test used to analyse the data. RESULTS: In every case the procedure was well tolerated, and each patient indicated that they would be willing to have a repeat procedure in the future. Ten patients reported complete resolution of symptoms secondary to therapeutic cyst aspiration and had resumed participation in high-performance sport. Two patients reported a satisfactory sustained response, reporting only occasional "twinges of pain". In the remaining six patients, symptoms returned after an initial pain-free period. The pain-free period ranged from 1-8 weeks. In this study, patient outcome did not significantly correlate with any meniscal cyst characteristic. CONCLUSION: Ultrasound-guided percutaneous aspiration of meniscal cysts is a well-tolerated, simple, and safe procedure. In this small patient series, it was associated with positive early results with favourable outcomes in the mid to long-term. It should be considered in patients unsuitable for surgical debridement or as an interim therapy if surgery is delayed or postponed.

Safety and immunogenicity of UBI HIV-1MN octameric V3 peptide vaccine administered by subcutaneous injection.

Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously using a standard 0-, 1-, 6-month intramuscular schedule and was found to stimulate neutralizing antibody in 60-90% of volunteers. Participants were randomized to receive either 500 micrograms (n = 10; high dose) or 100 micrograms (n = 10; low dose) of immunogen or placebo (alum alone; n = 4) at 0, 1, and 6 months by subcutaneous injection. Responses to the immunogen were evaluated by enzyme-linked immunosorbent assay (ELISA)-detectable antibody and by proliferative responses. Safety was monitored by both clinical assessment and regular review with a clinical psychologist. No serious adverse experiences were observed following administration of the assigned medication. One individual (placebo) seroconverted while on study, following exposure to HIV. After the vaccination course only four individuals (three high dose and one low dose) had ELISA-detectable antibody against the immunogen. In the evaluable samples, from 19 volunteers, only 7 vaccine recipients (3 high dose and 4 low dose) had demonstrable lymphoproliferative responses to preparations of the immunogen. Subcutaneous administration of its candidate vaccine was safe but did not result in uniform or robust immunological responses.

Changes in biologic phenotype of human immunodeficiency virus during treatment of patients with didanosine.

Progression to AIDS in patients harboring human immunodeficiency virus type-1 (HIV-1) isolates expressing a syncytium-inducing (SI) phenotype is faster than in those in whom the virus expresses a non-SI (NSI) phenotype. Zidovudine monotherapy does not appear to alter this outcome. To examine the role of didanosine (ddI) monotherapy in phenotype expression, HIV-1 isolates from 73 patients receiving ddI for up to 72 weeks were analyzed. After 12 weeks, the number of isolates expressing an NSI phenotype was 29% higher than at the start of treatment. Patients receiving high-dose ddI (375 mg twice daily) were significantly more likely to express the NSI phenotype at 12 weeks than patients who received low-dose ddI (100 mg twice daily), even after adjustment for phenotype and CD4 cell count at baseline, suggesting that ddI may be selective against the faster-replicating virus. ddI at 375 mg twice daily significantly increases the probability of an NSI phenotype over the short term in patients with advanced HIV disease.

Ramsey county day treatment services:.

Ramsey County Extended Day Treatment is designed for persons with a serious and persistent mental illness such as major depression, schizophrenia, bipolar disorder or personality disorder. The uniqueness of the model is the combination of an intake and referral group with six levels of group psychotherapy. Additionally, single issue groups provide a concentrated focus on employment or community contribution, anger management, and peer relationships. The result is a well-structured, non-residential program where a client can work in a treatment environment based on one's ability to participate. This article describes the intake and referral group, outlines the six separate programs, and describes the use of occupational therapy and cognitive behavioral therapy throughout the model.

Effects of two formats of informed consent on knowledge amongst persons with advanced HIV disease in a clinical trial of didanosine.

To determine subjects' perception of the purpose of informed consent, 113 subjects were recruited from a dose-controlled clinical trial of didanosine (ddI). Subjects were surveyed regarding how they made decisions regarding their medical care in general, about how they obtained information about this trial in particular, and several aspects of the informed consent procedure. Subjects were then randomly allocated to receive information about the trial by either a written only format or a written and verbal format 1 week before commencement of the trial. An eight-item instrument assessed knowledge of ddI prior to and subsequent to receiving information. Most subjects obtained information about HIV-related issues from their specialist (70%) or general (51%) medical practitioner. A large proportion of subjects (88%) reported that they believed their specialist medical practitioner always acted in their best interest. The majority of subjects (79%) believed that subjects should be allowed the choice between participating in the clinical trial and receiving the drug outside the trial mechanism. Of the subjects, 96% believed that informed consent was necessary in clinical trials; however, their opinions of the purpose of informed consent varied widely. Although they signed the informed consent, 44% of the subjects stated that they did not understand 'all' of the information that was provided. We found that the provision of information by written mode alone, or written and verbal modes were both associated with significant increases in knowledge levels and that there was a significant interaction in the degree of change between the two methods, with the written plus verbal method showing the most improvement over time. There was an interaction between degree of improvement in knowledge of didanosine in subjects who received written information versus those who received written and verbal knowledge and time (pre- versus post-consent) and a significant main effect for time. All subjects were relatively well-informed about the drug and stated that specialist and general medical practitioners were their major source of knowledge for all aspects of their HIV health care.

Strain differentiation of barley yellow dwarf virus isolates using specific monoclonal antibodies in immunosorbent electron microscopy.

Three strain-specific monoclonal antibodies, MAC. 91, MAC. 92 and MAb. MAFF2, were compared with two polyclonal antisera for the diagnosis of barley yellow dwarf virus (BYDV) strains in immunosorbent electron microscopy (ISEM). Used at 1 micrograms ml-1, the three monoclonal antibodies specifically trapped the Rothamsted PAV, RPV and MAV-like type isolates respectively, unlike the polyclonal antisera, which showed considerable heterologous reaction. The efficiency of the monoclonal and polyclonal antibodies in trapping and detecting these isolates of BYDV were compared quantitatively using ISEM and enzyme-linked immunosorbent assay (ELISA) techniques. The test provides a simple and sensitive diagnostic method for BYDV, suitable for small numbers of samples and is useful in confirming doubtful ELISA results.