Identification of two groups of smoldering multiple myeloma patients who are either high or low producers of interleukin-1.

Interleukin-1beta (IL-1beta) is abnormally expressed by the plasma cells obtained from myeloma patients, and it is a potent inducer of the important myeloma growth factor, IL-6. We investigated whether levels of IL-1beta biologic activity might distinguish different groups of patients with smoldering multiple myeloma (SMM). We measured the ability of IL-6 production by bone marrow stromal cells to serve as a surrogate marker for IL-1beta biologic activity. Using this IL-1beta bioassay, we found that it is sensitive at < 1 pg/ml of recombinant IL-1beta and that IL-1beta biologic activity is detectable with either mature or pro-IL-1beta-transduced myeloma cell lines. Patients with active myeloma induced quantitatively higher levels of stromal cell IL-6 production when compared with those with monoclonal gammopathy of undetermined significance (MGUS). The bioassay distinguished two groups of SMM patients, those who were high producers, similar to patients with active MM, and those who were low producers, comparable to MGUS patients. IL-1 antagonists inhibited the paracrine IL-6 production by > or = 90% in the majority of patients with an elevated IL-6 level. Based on such studies, it may be possible to predict patients that will progress to active MM and to delay or prevent this progression with IL-1 antagonists.     

Epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration

Epithelioid gastrointestinal stromal tumors (GISTs) may cause significant diagnostic confusion on fine-needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and melanoma, particularly when metastatic. This study characterizes the cytologic features of nine cases of epithelioid GISTs that were obtained by computerized tomographic guidance in five, by endoscopic ultrasound in three, and from an excised liver tumor in one. Six cases presented as liver masses, one as a perisplenic mass, one as an abdominal mass, and one as a gastric mass. The aspirates revealed mainly single or small clusters of epithelioid cells with a moderate amount of granular to clear cytoplasm, small uniform nuclei with mild to marked nuclear envelope irregularities. Binucleation and intranuclear inclusions were frequent findings. Collagenous stroma was seen in most cases. In three cases, a neuroendocrine tumor was the initial diagnosis. Immunocytochemical staining for c-kit (CD117) was performed on cellblocks in six cases and was positive in five cases. On the subsequent surgical specimen, CD117 was positive in the c-kit-negative cytology case. The diagnosis of GIST should be considered in aspirates of the gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in making a definitive diagnosis.     

Effects of Lymphocyte Isolation and Timing of Processing on Detection of CD127 Expression on T Cells in Human Immunodeficiency Virus-Infected Patients

Decreases in the detection of CD127 expression on T cells of human immunodeficiency virus-infected patients by flow cytometry can occur by delayed processing or by peripheral blood mononuclear cell isolation and cryopreservation. These observations should be considered in the interpretation of functional studies and the planning of multicenter clinical trials.     

Muscular and postural synergies of the human hand

Because humans have limited ability to independently control the many joints of the hand, a wide variety of hand shapes can be characterized as a weighted combination of just two or three main patterns of covariation in joint rotations, or "postural synergies." The present study sought to align muscle synergies with these main postural synergies and to describe the form of membership of motor units in these postural/muscle synergies. Seventeen joint angles and the electromyographic (EMG) activities of several hand muscles (both intrinsic and extrinsic muscles) were recorded while human subjects held the hand statically in 52 specific shapes (i.e., shaping the hand around 26 commonly grasped objects or forming the 26 letter shapes of a manual alphabet). Principal-components analysis revealed several patterns of muscle synergy, some of which represented either coactivation of all hand muscles, or reciprocal patterns of activity (above and below average levels) in the intrinsic index finger and thumb muscles or (to a lesser extent) in the extrinsic four-tendoned extensor and flexor muscles. Single- and multiunit activity was generally a multimodal function of whole hand shape. This implies that motor-unit activation does not align with a single synergy; instead, motor units participate in multiple muscle synergies. Thus it appears that the organization of the global pattern of hand muscle activation is highly distributed. This organization mirrors the highly fractured somatotopy of cortical hand representations and may provide an ideal substrate for motor learning and recovery from injury.     

Legionella pneumophila NudA Is a Nudix hydrolase and virulence factor

We studied the identity and function of the 528-bp gene immediately upstream of Legionella pneumophila F2310 ptsP (enzyme I(Ntr)). This gene, nudA, encoded for a Nudix hydrolase based on the inferred protein sequence. NudA had hydrolytic activity typical of other Nudix hydrolases, such as Escherichia coli YgdP, in that Ap(n)A's, in particular diadenosine pentaphosphate (Ap(5)A), were the preferred substrates. NudA hydrolyzed Ap(5)A to ATP plus ADP. Both ptsP and nudA were cotranscribed. Bacterial two-hybrid analysis showed no PtsP-NudA interactions. Gene nudA was present in 19 of 20 different L. pneumophila strains tested and in 5 of 10 different Legionella spp. other than L. pneumophila. An in-frame nudA mutation was made in L. pneumophila F2310 to determine the phenotype. The nudA mutant was an auxotroph that grew slowly in liquid and on solid media and had a smaller colony size than its parent. In addition, the mutant was more salt resistant than its parent and grew very poorly at 25 degrees C; all of these characteristics, as well as auxotrophy and slow-growth rate, were reversed by transcomplementation with nudA. The nudA mutant was outcompeted by about fourfold by the parent in competition studies in macrophages; transcomplementation almost completely restored this defect. Competition studies in guinea pigs with L. pneumophila pneumonia showed that the nudA mutant was outcompeted by its parent in both lung and spleen. NudA is of major importance for resisting stress in L. pneumophila and is a virulence factor.     

Virulence Differences in Mice of Type A and B Histoplasma capsulatum Yeasts Grown in Continuous Light and Total Darkness

Type B yeasts were more virulent for mice than type A under most experimental conditions. Mice infected with type B yeasts grown in the light lived significantly longer than those with type B yeasts grown in the dark. Virulence differences of type A yeasts grown in continuous fluorescent light versus total darkness were not statistically significant.     

The variable influence of lifestyle and income on medical students' career specialty choices: data from two U.S. medical schools, 1998-2004.

PURPOSE: Recent reports on medical students' career choices suggest that lifestyle increasingly influences career decisions. The authors addressed the changing influence of lifestyle and income on career choice, how these influences differ by specialty, and the specific careers students identify as lifestyle friendly. METHOD: From 1998 to 2004, 1,334 (73%) fourth-year medical students from Brody School of Medicine at East Carolina University (no. = 485 graduates) and New York Medical College (no. = 1,348 graduates) completed a questionnaire that addressed career specialty preferences, as well as income and lifestyle concerns. Students were asked to rate career choice influences on a four-point scale (1 = no influence, 4 = major influence). Factor analysis of these influences identified seven factors including one each for lifestyle and income. RESULTS: A total of 1,327 students indicated a career preference. Lifestyle (p = .018) and income (p = .011) were found to increasingly influence medical students' career choices during the study period. Overall, the authors found significant differences between specialties in the relative contribution of these factors. Students' perceptions of specialties existed on a continuum of lifestyle friendly (e.g., radiology) to lifestyle unfriendly (e.g., obstetrics-gynecology). Contrary to previous reports, the students' responses indicate they perceived the primary care specialties as lifestyle intermediate compared to other specialties. CONCLUSIONS: Lifestyle and income have become more important to medical students in their career choice, and the relative influence of these factors varies considerably between specialties. This study suggests that previous efforts to dichotomize careers into those with controllable and uncontrollable lifestyles may mask important complexities.     

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.     

Examination of Streptococcus mutans for immunoglobulin G Fc reactivity.

Representative strains of oral streptococci were tested for Fc immunoglobulin G (IgG) reactivity by two different techniques, agglutination of rabbit-IgG sensitized sheep erythrocytes and uptake of human and rabbit 125I-radiolabeled IgG. None of the S. mutans serotypes a through e reacted with the Fc region of either human or rabbit IgG. Additionally, other streptococci such as S. sanguis, S. salivarius, S. faecalis, and S. mitis failed to show appreciable Fc reactivity as assayed by these techniques. The group A, C, and G streptococci, previously shown to possess Fc reactivity, proved to be reactive in these experiments, as did a protein A-containing strain of Staphylococcus aureus.     

Community participation in primary health care (PHC) programmes: lessons from tuberculosis treatment delivery in South Africa

Background

Currently, there is renewed interest in the role community participation can play in Primary Health Care (PHC) programmes such as the delivery of effective anti-TB treatment to patients in high-burden settings.

Objectives

To explore the feasibility of community participation in a high-burden Tuberculosis Control Programme and to establish how supervision of treatment by lay volunteers compares with other methods of tuberculosis treatment delivery in the Northern Cape province of South Africa.

Methods

Prospective study involving 769 patients with confirmed pulmonary TB who were followed-up over a one-year period. Questionnaire interviews were also carried out with 135 lay volunteers participating in the TB programme.

Results

One-third of the TB patients in the study received their treatment from lay volunteers in the community. Treatment outcomes for new patients supervised from the community were found to be equivalent to those who received treatment through other modes of treatment delivery (RR=1.04[0.94–1.16], p=0.435). For the re-treatment patients, community-based treatment was found to be superior (RR=5.89[2.30–15.09], p<0.001), to self-administered therapy.

Conclusions

Health care planners should consider community participation as a viable way of ensuring accessibility and effectiveness in PHC programmes. There is need for more research into ways of achieving sustainability in resource-limited but high disease burden settings.