The treatment of phantom limb pain using immersive virtual reality: three case studies

Purpose. This paper describes the design and implementation of a case study based investigation using immersive virtual reality as a treatment for phantom limb pain.

Method. Three participants who experienced phantom limb pain (two with an upper-limb amputation, and one with a lower-limb amputation) took part in between 2 and 5 immersive virtual reality (IVR) sessions over a 3-week period. The movements of participants' anatomical limbs were transposed into the movements of a virtual limb, presented in the phenomenal space of their phantom limb.

Results. Preliminary qualitative findings are reported here to assess proof of principle for this IVR equipment. All participants reported the transferal of sensations into the muscles and joints of the phantom limb, and all participants reported a decrease in phantom pain during at least one of the sessions.

Conclusion. The authors suggest the need for further research using control trials.     

Inside the Premier/CMS Pay-for-Performance Project

In an H&HN exclusive roundtable discussion, representatives from the five top-performing hospitals describe what they've learned so far from the Premier/CMS Pay-for-Performance Project. For hospitals around the country, so-called value-based ent will soon be the primary way they get paid by both public and commercial insurers. The Premier/CMS participants offer valuable insights--and warnings--about the challenges ahead.     

Influence of caffeine on heart rate variability in patients with long-standing type 1 diabetes

OBJECTIVE: The effect of caffeine on cardiovascular health remains controversial. Patients with long-standing type 1 diabetes are at risk of autonomic failure and sudden cardiac death. We investigated the effects of caffeine on autonomic dysfunction (as assessed by heart rate variability [HRV]) in this high-risk group and in a control population. RESEARCH DESIGN AND METHODS: Using a randomized blinded, placebo-controlled, crossover design trial, we examined 2 weeks of caffeine consumption (250 mg twice daily) on HRV in 20 type 1 diabetic patients and 10 matched healthy volunteers. RESULTS: Baseline HRV was blunted in the diabetic patients (P < 0.0005 vs. control subjects) and markedly increased by caffeine in both groups (+103% in the group with diabetes [P = 0.009] and +38% in control subjects [P = 0.002]). The caffeine-associated increase in HRV was not statistically different between the control and the type 1 diabetes groups (P = 0.16). CONCLUSIONS: Modest amounts of caffeine improved autonomic function in diabetic patients and healthy volunteers. For individuals with abnormal HRV, regular caffeine use may have the potential to reduce the risk of cardiovascular events.     

Loperamide: studies on its mechanism of action.

The effects of loperamide on net solute and water absorption, and prostaglandin E2 (PGE2) and cholera toxin-induced secretion were studied in the rat jejunum using an in vivo steady-state perfusion technique. Loperamide stimulated absorption of fluid, electrolytes, and glucose and reversed PGE2 and cholera toxin-induced secretion to absorption; this opiate analogue had no effect on cholera toxin stimulation of adenylate cyclase activity or the rise of tissue cyclic AMP (cAMP) concentrations. The opiate antagonist, naloxone, reduced the antisecretory effects of loperamide without affecting tissue levels of cAMP. These results indicate that loperamide inhibits PGE2 and cholera toxin-induced secretion, and that this phenomenon is independent of any direct effect that cholera toxin has on the adenylate cyclase system. The action of naloxone suggests, but does not prove, that loperamide exerts its effect via opiate receptors.     

Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells

The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44⁺CD24^-/loSSEA-3⁺ or ESA^hiPROCR^hiSSEA-3⁺ markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44⁺CD24^-/loSSEA-3⁺ formed tumor in mice, compared with more than 100 cells with CD44⁺CD24^-/lo. Suppression of SSEA-3 expression by knockdown of the gene encoding β-1,3-galactosyltransferase 5 (β3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.Cancer stem cells (CSCs), which are rare cells with the ability of self-renewal and tumor initiation, are closely related to cancer progression and specific targets for effective therapy and early diagnosis (1–5). To date, many CSCs have been identified and characterized by protein markers. Breast CSCs (BCSCs) were first discovered in 2003 by Al-Hajj et al. (6); it was demonstrated that breast cancer cells with CD44⁺CD24^-/lo expression have higher level of tumorigenicity than others and can form tumor in animals with ∼100 of such cells. In addition, other proteins such as ALDH-1, CD133, CD326 (ESA), CD201 (PROCR), and their combinations, are also reported as BCSCs biomarkers (7–9). However, the BCSCs obtained from the enrichment process based on these markers still contain a large number of noncancer stem cells, and study of such cells would provide nonspecific characteristics of CSCs. Therefore, new markers are required to enrich and obtain better-defined BCSCs for analysis and study.Glycolipids are known to be altered during cancer development (10–15). In our previous study, the globo-series glycans SSEA-3 (Gb5), SSEA-4 (sialyl-Gb5), and globo-H (fucosyl-Gb5) are found exclusively on the cell surface of many cancers, including breast cancer and BCSCs (16–18). We also reported that BCSCs carrying either ESA^hiPROCR^hi or CD44⁺CD24^-/lo showed high expression of these globo-series epitopes (19). SSEA-3 is synthesized from Gb4 by β3GalT5 (20), and globo-H and SSEA-4 are synthesized from SSEA-3 by fucosyltransferases 1 and 2 (FUT1, FUT2) (21, 22) and ST3 β-galactoside α-2,3-sialyltransferase 2 (ST3Gal2) (23), respectively. These reports prompt us to investigate whether SSEA-3 and the related glycans and enzymes in the globo-series pathway are cancer specific and are BCSC markers.     

Pneumocystis jirovecii pneumonia in African miners at autopsy.

SETTING: Deceased miners from South Africa whose cardio-respiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: 1) To document the incidence of Pneumocystis jirovecii pneumonia (PJP) in autopsied miners; 2) to compare the incidence of PJP over a 5-year period; 3) to record the incidence of concomitant lower respiratory tract infection in a group of PJP-infected deceased miners coming to autopsy from 1996 to 2000; and 4) to describe the accuracy of the in-life diagnosis of PJP in this group. DESIGN: Case series of 328 deceased Black miners with histological evidence of PJP at autopsy. RESULTS: Of the 328 miners with PJP at autopsy, 107 (32.6%) had a concomitant respiratory infection, the most common being cryptococcal pneumonia (46.7%), followed by bacterial pneumonia (34.6%) and pulmonary tuberculosis (13.1%). Overall, Pneumocystis pneumonia was unsuspected prior to death in 89% of cases; however, diagnostic accuracy in life improved from 7% in 1996 to 21% in 2000. CONCLUSION: The high rate of undiagnosed PJP is cause for concern. Clinicians should have a heightened awareness for PJP in Africa, particularly as the disease is treatable at low cost and effective prophylaxis is available.     

Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure

OBJECTIVES: The purpose of this research was to evaluate the therapeutic value of initiating a beta-blocker before an angiotensin-converting enzyme inhibitor (ACEI) in the treatment of heart failure. BACKGROUND: Although ACEI and carvedilol produce benefits in heart failure, whether the order of initiation of therapy determines the impact on left ventricular (LV) function and New York Heart Association functional class (NYHA FC) has not been determined. METHODS: A single-center, prospective, randomized, open-label study was performed. We evaluated whether initiation of therapy with carvedilol either before (n = 38) or after (n = 40) perindopril therapy in newly diagnosed patients in NYHA FC II to III heart failure with idiopathic dilated cardiomyopathy, with the addition of the alternative agent after six months, determined subsequent changes in NYHA FC and LV function (echocardiography and radionuclide ventriculography). Study drugs were titrated to maximum tolerable doses. RESULTS: There were no differences in baseline characteristics between the study groups. After 12 months 11 patients died (6 in the group where the ACEI was initiated). At 12 months the group receiving carvedilol as initial therapy achieved a higher tolerable dose of carvedilol (43 +/- 17 mg vs. 33 +/- 18 mg, p = 0.03); a lower dose of furosemide (p < 0.05); and better improvements in symptoms (NYHA FC, p < 0.002), LV ejection fraction (radionuclide: 15 +/- 16% vs. 6 +/- 13%, p < 0.05; echocardiographic, p < 0.01), and plasma N-terminal pro-brain natriuretic peptide concentrations (p < 0.02). CONCLUSIONS: As opposed to the conventional sequence of drug use in the treatment of heart failure, initiation of therapy with carvedilol before an ACEI results in higher tolerable doses of carvedilol and better improvements in FC and LV function.     

The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy

We have reported previously that despite treatment with angiotensin-converting enzyme inhibitors and beta blockers, the outcome of patients with peripartum cardiomyopathy (PPC) remains unfavorable. Similar to other etiologies of left ventricular dysfunction, we found elevated levels of tumor necrosis factor-alpha (TNF-alpha) in this group of patients. In the present study we sought to evaluate the effects of pentoxifylline, a drug known to inhibit the production of TNF-alpha, on clinical status, left ventricular function, and circulating plasma levels of TNF-alpha, in patients with PPC. We followed prospectively 59 consecutive women with PPC. The first 29 patients (group 1) were treated with diuretics, digoxin, enalapril and carvedilol. The next 30 consecutive patients (group 2) received pentoxifylline 400 mg TID in addition to the previous therapy. Clinical evaluation, echocardiograms and TNF-alpha determinations were performed at baseline and after 6 months of treatment. Patients in the pentoxifylline group were older and had a higher E/A ratio. Nine patients died (eight in group 1, P = 0.009 between groups). A combined end-point of poor outcome defined as either death, failure to improve the left ventricular ejection fraction >10 absolute points or functional class III or IV at latest follow-up, occurred in 52% of patients in group 1 and 27% of patients in group 2 (P = 0.03). Treatment with pentoxifylline (P = 0.04) was the only independent predictor of outcome. In conclusion, the results of this study suggest that the addition of pentoxifylline to conventional treatment, improves outcome in patients with peripartum cardiomyopathy.     

Efficacy of different drug classes used to initiate antihypertensive treatment in black subjects: results of a randomized trial in Johannesburg, South Africa

BACKGROUND: Thiazides are recommended to initiate antihypertensive drug treatment in black subjects. OBJECTIVE: To test the efficacy of this recommendation in a South African black cohort. METHODS: Men and women (N = 409), aged 18 to 70 years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg, were randomized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained-release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5 mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line drugs were titrated up and after 2 months other medications were added to the regimen. RESULTS: While receiving monotherapy (2 months, n = 366), the patients' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide, and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients treated with nifedipine was controlled: 133 (63.3%, P相似文献