Pre-B cells in peripheral blood of multiple myeloma patients

Although multiple myeloma is a disease of plasma cells, abnormalities have been detected in both B and T lymphocytes in peripheral blood. Although multiple myeloma patients are deficient in surface Ig (sIg)- positive B lymphocytes, analysis of lymphocytes present in blood indicates an abnormally large pool of circulating pre-B cells. These pre-B cells express BA-1, do not bear sIg, and contain cytoplasmic mu chains. High numbers of pre-B cells occur in 88% of individuals with frank myeloma and in 44% of individuals with monoclonal gammopathy of undetermined significance. Pre-B cells bearing BA-1 differ between patients in their expression of HLA-DR and receptors for peanut agglutinin (PNA). Those pre-B cells in myeloma patients are either BA- 1+ PNA- HLA-DR+ (54% of patients) or BA-1+ PNA+ HLA-DR- (30% of patients), or have a mixture of phenotypes (14% of patients). Pre-B cells of the PNA- phenotype are almost always HLA-DR+, and PNA+ pre-B cells are HLA-DR-. Within the same patient, the pre-B cell population varies by both quantitative and qualitative definitions. The number of pre-B cells may increase 460-fold and temporal shifts of surface phenotype from BA-1+ PNA- to BA-1+ PNA+ or vice versa have been detected. These observations indicate an abnormality in the B lymphocyte differentiation pathway leading to pre-B cells in the periphery that vary in number and cell surface phenotype, and that are unable to express sIg.     

Antithrombin Milano: a new variant with monomeric and dimeric inactive antithrombin III

A qualitative defect of antithrombin III (AT III) has been demonstrated over three generations in eight members of an Italian family by the discrepancy between a normal amount of antigen and decreased antithrombin and anti-Xa activity in the presence or in the absence of heparin. By two-dimensional immunoelectrophoresis in the absence of heparin, two peaks of AT III were present in all patients' plasma. AT III was purified from normal and propositus plasma by sulfate dextran precipitation followed by heparin affinity chromatography. The elution profile of the patient's AT III was abnormal and allowed the separation of two populations of AT III, normal and abnormal. The first fraction (normal AT III) contained AT III activity, migrated as a single peak by two-dimensional immunoelectrophoresis and by sodium dodecyl sulfate- polyacrylamide gel electrophoresis (SDS-PAGE), demonstrated a single band with a molecular weight (mol wt) identical to that of normal AT III (60,000). Conversely, the last fraction, devoid of AT III activity, migrated as a single abnormal peak by two-dimensional immunoelectrophoresis in the absence of heparin. By SDS-PAGE, two bands were observed: one with a mol wt of 60,000 and a second one with a mol wt of 120,000. Western blots clearly demonstrated cross-reactivity of the 120,000 and 60,000 mol wt bands with monospecific antisera to human AT III. Reduction of the 120,000 mol wt band converted it to a single 60,000 mol wt band, suggesting the presence of an abnormal dimeric form of AT III. The name AT III Milano is proposed for this new variant.     

Treatment of hairy cell leukemia with recombinant alpha 2 interferon

Nine patients with progressive hairy cell leukemia were treated with subcutaneous injections of recombinant alpha 2 interferon (2 to 10 X 10(6) U/m2) three times weekly. Eight patients completed at least eight weeks of treatment and were evaluable; one patient with refractory thrombocytopenia died of an intracerebral hemorrhage after two doses of interferon. Seven of eight patients responded, with responses occurring as early as two weeks. Four patients also had resolution of their monocytopenia. No complete responses were seen with up to 30 weeks of treatment. Bone marrow biopsies demonstrated improvement in all eight patients. No unforeseen toxicity occurred, but most patients had transient myelosuppression during the first few weeks of treatment. Recombinant alpha 2 interferon is effective in the treatment of hairy cell leukemia, with acceptable toxicity.     

How do healthcare consumers process and evaluate comparative healthcare information? A qualitative study using cognitive interviews

Background  

To date, online public healthcare reports have not been effectively used by consumers. Therefore, we qualitatively examined how healthcare consumers process and evaluate comparative healthcare information on the Internet.     

Journeys to tuberculosis treatment: a qualitative study of patients, families and communities in Jogjakarta, Indonesia

Background  

Many tuberculosis (TB) patients in Indonesia are diagnosed late. We seek to document patient journeys toward TB diagnosis and treatment and factors that influence health care seeking behavior.     

Incarceration experiences among a community-recruited sample of injection drug users in Bangkok, Thailand

Background  

Since 2003 Thailand has waged an aggressive "war on drugs" campaign focused on arresting and incarcerating suspected drug users and dealers. However, little is known about incarceration experiences among IDU in the wake of the recent war on drugs. Therefore, we sought to examine incarceration experiences among IDU in Bangkok, Thailand.     

Dual modulation of urinary bladder activity and urine flow by prostanoid EP3 receptors in the conscious rat

Background and purpose:

Cyclooxygenase inhibitors function to reduce levels of prostaglandin E₂ (PGE₂) and are broadly efficacious in models of bladder overactivity. We therefore investigated a regulation of urinary bladder function in conscious rats by modulation of the EP₃ receptor for PGE₂.

Experimental approach:

The activity of the EP₃ receptor agonist GR63799X, and EP₃ receptor antagonists, CM9 and DG041, at recombinant EP₃ receptors was evaluated in vitro. In vivo, intraduodenal dosing during conscious, continuous-filling cystometry of spontaneously hypertensive rats was utilized to determine the urodynamic effect of EP₃ receptor modulation.

Key results:

GR63799X dose-dependently (0.001–1 mg·kg⁻¹) reduced bladder capacity, as indicated by a reduction in both the micturition interval and volume of urine per void. In contrast, CM9 (10 and 30 mg·kg⁻¹) and DG041 (30 mg·kg⁻¹) enhanced bladder capacity, as indicated by significantly longer micturition intervals and larger void volumes. CM9 and DG041 inhibited the responses to GR63799X supporting the in vivo activity of these pharmacological agents at the EP₃ receptor. In addition to its effect on bladder capacity, GR63799X increased endogenous urine production. Intra-arterial infusion of saline mimicked the enhancement of urine flow observed with GR63799X, and the response was inhibited by CM9.

Conclusions and implications:

These data support the EP₃ receptor as a modulator of urinary bladder activity in the conscious rat, and in addition, indicate a role for EP₃ receptor activity in regulating urine flow.     

Peripheral and central sites of action for the non-selective cannabinoid agonist WIN 55,212-2 in a rat model of post-operative pain

Background and purpose:

Activation of cannabinoid (CB) receptors decreases nociceptive transmission in inflammatory or neuropathic pain states. However, the effects of CB receptor agonists in post-operative pain remain to be investigated. Here, we characterized the anti-allodynic effects of WIN 55,212-2 (WIN) in a rat model of post-operative pain.

Experimental approach:

WIN 55,212-2 was characterized in radioligand binding and in vitro functional assays at rat and human CB₁ and CB₂ receptors. Analgesic activity and site(s) of action of WIN were assessed in the skin incision-induced post-operative pain model in rats; receptor specificity was investigated using selective CB₁ and CB₂ receptor antagonists.

Key results:

WIN 55,212-2 exhibited non-selective affinity and agonist efficacy at human and rat CB₁ versus CB₂ receptors. Systemic administration of WIN decreased injury-induced mechanical allodynia and these effects were reversed by pretreatment with a CB₁ receptor antagonist, but not with a CB₂ receptor antagonist, given by systemic, intrathecal and supraspinal routes. In addition, peripheral administration of both CB₁ and CB₂ antagonists blocked systemic WIN-induced analgesic activity.

Conclusions and implications:

Both CB₁ and CB₂ receptors were involved in the peripheral anti-allodynic effect of systemic WIN in a pre-clinical model of post-operative pain. In contrast, the centrally mediated anti-allodynic activity of systemic WIN is mostly due to the activation of CB₁ but not CB₂ receptors at both the spinal cord and brain levels. However, the increased potency of WIN following i.c.v. administration suggests that its main site of action is at CB₁ receptors in the brain.British Journal of Pharmacology (2009) 157, 645–655; doi:10.1111/j.1476-5381.2009.00184.x; published online 3 April 2009     

Symptomatic and neuroprotective effects following activation of nigral group III metabotropic glutamate receptors in rodent models of Parkinson's disease

Background and purpose:

Increased glutamatergic innervation of the substantia nigra pars reticulata (SNpr) and pars compacta (SNpc) may contribute to the motor deficits and neurodegeneration, respectively, in Parkinson''s disease (PD). This study aimed to establish whether activation of pre-synaptic group III metabotropic glutamate (mGlu) receptors reduced glutamate release in the SN, and provided symptomatic or neuroprotective relief in animal models of PD.

Experimental approach:

Broad-spectrum group III mGlu receptor agonists, O-phospho-l-serine (l-SOP) and l-2-amino-4-phosphonobutyrate (l-AP4), were assessed for their ability to inhibit KCl-evoked [³H]-d-aspartate release in rat nigral prisms or inhibit KCl-evoked endogenous glutamate release in the SNpr in vivo using microdialysis. Reversal of akinesia in reserpine-treated rats was assessed following intranigral injection of l-SOP and l-AP4. Finally, the neuroprotective effect of 7 days'' supra-nigral treatment with l-AP4 was examined in 6-hydroxydopamine (6-OHDA)-lesioned rats.

Key results:

l-SOP and l-AP4 inhibited [³H]-d-aspartate release by 33 and 44% respectively. These effects were blocked by the selective group III mGlu antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG). l-SOP also reduced glutamate release in the SNpr in vivo by 48%. Injection of l-SOP and l-AP4 into the SNpr reversed reserpine-induced akinesia. Following administration above the SNpc, l-AP4 provided neurochemical, histological and functional protection against 6-OHDA lesion of the nigrostriatal tract. Pretreatment with CPPG inhibited these effects.

Conclusions and implications:

These findings highlight group III mGlu receptors in the SN as potential targets for providing both symptomatic and neuroprotective relief in PD, and indicate that inhibition of glutamate release in the SN may underlie these effects.     

A systematic review of musculoskeletal disorders among dental professionals

Abstract:  Musculoskeletal problems have become a significant issue for the profession of dentistry and dental hygiene. This review provides a detailed examination and discussion regarding the prevalence of musculoskeletal disorders (MSD) in dental personnel and possible causative factors. All research studies or literature reviews, which have reported on the prevalence of musculoskeletal symptoms and/or potential risk factors for this problem in dentists, dental hygienists and dental students, were selected for inclusion. Our literature suggests that the prevalence of general musculoskeletal pain ranges between 64% and 93%. The most prevalent regions for pain in dentists have been shown to be the back (36.3–60.1%) and neck (19.8–85%), while the hand and wrist regions were the most prevalent regions for dental hygienists (60–69.5%). Interestingly, we found that studies on MSDs among dental and dental hygiene students are quite limited. Many risk factors have been identified, including static and awkward posture and work practices. Overall, the review suggests that musculoskeletal problems represent a significant burden for the dental profession. More research in the form of larger studies is urgently required, to help more clearly elucidate the development of this important issue for dental hygienists and dental hygiene students.