Patients with thrombolysed stroke in Vietnam have an excellent outcome: results from the Vietnam Thrombolysis Registry

Background and purpose: We present the early experience in thrombolysis in three major centers of Ho Chi Minh city, namely 115 People Hospital, Gia Dinh Hospital, and An Binh Hospital. Methods: A prospective study of consecutive patients treated with intravenous tPA with a treatment protocol similar to that of the National Institute of Neurological Disorders and Stroke (NINDS) trial. National Institutes of Health Stroke Scale (NIHSS) scores on admission and Modified Rankin Scale (MRS) scores at 3 months were measured for all patients. Intracranial and systemic hemorrhagic complications were recorded. Result: A total of 121 of 6171 (2%) patients with acute IS received thrombolysis over 3 years. Mean age was 57 years (range 18–78) and initial median NIHSS score was 12 ( range 5–23). The mean delay between symptom onset and treatment was 143 min (range 50–210). Seventy‐three (60.3%) patients received the standard dose with the remaining 48 patients (36.9%) treated with a lower dose, a mean calculated dose of 0.62 mg/kg (range, 0.6–0.86 mg/kg). Over half (56.3%) of the patients receiving low dose achieved functional independence (mRS score 0–1) at 3 months compared with 34.2% in the standard‐dose group (P = 0.01). The 3‐month mortality rate was also higher in the standard‐dose group (2.1% vs. 12.5% with standard‐dose tPA; P = 0.04). Symptomatic intracranial hemorrhage was noted in four patients of standard‐dose group and one patient of low‐dose group (P = 0.36). Conclusion: Intravenous thrombolysis, particularly in a lower dose, is safe and feasible in the treatment of acute IS in our selected Vietnamese population.     

Correlation of immune activation during late pregnancy and early postpartum with increases in plasma HIV RNA, CD4/CD8 T cells, and serum activation markers

A previously observed rise in the plasma viral load postpartum in both treated and untreated HIV-positive women remains unexplained. Virological and immunological markers were evaluated in HIV-negative controls and HIV-positive pregnant women with and without antiretroviral treatment. Plasma HIV RNA, CD4/CD8 T cells, and serum activation markers were sequentially measured during the third trimester, at delivery, and 2 to 8 weeks postpartum in a cohort of HIV-positive pregnant women (n = 96) enrolled in a maternal-fetal HIV transmission study and a control group of HIV-negative pregnant women (n = 28). Mean plasma HIV RNA (P = 0.003) increased from delivery to postpartum, and mean CD4 T cells (P = 0.002) and serum β2-microglobulin (P < 0.0001) increased from the third trimester through postpartum among the HIV-positive women. Mean CD8 T cells increased from the third trimester through postpartum in women receiving zidovudine (ZDV) and in those not treated (P < 0.05) but remained stable in those on highly active antiretroviral therapy (HAART) and the HIV-negative controls. Increases in serum β2-microglobulin were correlated with increases in HIV RNA (P = 0.01). HIV-positive pregnant women showed postpartum increases in plasma HIV RNA, CD4 T cells, and serum β2-microglobulin regardless of the treatment regimen. The rise in CD4 T cells and β2-microglobulin was also observed in HIV-negative pregnant women, suggesting hormonal changes and/or labor-induced cytokines may contribute to immune activation. Immune activation correlated with increased plasma HIV RNA in postpartum women despite treatment, although HAART appeared to blunt the effect. The observed rise in plasma HIV RNA postpartum, which correlated with markers of immune activation, may have implications for enhanced transmission to infants through early breast-feeding and to sexual partners.     

Are gadolinium-based contrast media nephrotoxic? A renal biopsy study

Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.     

Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: A cross-sectional study

BACKGROUND: Geohelminth infection and poor hygiene may be protective against allergic sensitization. OBJECTIVE: To determine whether current helminth infection is associated with a reduced prevalence of allergen skin test sensitization in a Southeast Asian population of children with a high prevalence of hookworm infection. METHODS: A total of 1742 Vietnamese schoolchildren were invited to take part in a cross-sectional survey. Allergen skin sensitization to house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and American cockroach (Periplaneta americana) were measured and stool samples for qualitative and quantitative geohelminth estimation collected. RESULTS: A total of 1601 children age 6 to 18 participated. Sensitization to dust mites was present in 14.4% and to cockroach in 27.6% of children. In a mutually adjusted model, the risk of sensitization to dust mites was reduced in those with higher hookworm burden (adjusted odds ratio [OR] for 350+ vs no eggs per gram, 0.61; 95% CI, 0.39-0.96) and with Ascaris infection (adjusted OR, 0.28; 0.10-0.78), and increased in those using flush toilets (adjusted OR for flush toilet vs none/bush/pit, 2.51; 1.00-6.28). In contrast, sensitization to cockroach was not independently related to geohelminth infection but was increased in those regularly drinking piped or well water rather than from a stream (adjusted OR, 1.33; 1.02-1.75). CONCLUSION: Geohelminth infection, sanitation, and water supply influence the risk of allergic sensitization in Vietnamese children. This is consistent with a protective effect against allergy by geohelminth or other gastrointestinal infection. CLINICAL IMPLICATIONS: If the inverse relationship between geohelminth infection, poor sanitation, and allergic sensitization proves to be causal, drugs derived from parasite products may help to alleviate clinical allergic disease.     

Osteopontin is involved in Th1-mediated immunity against Plasmodium falciparum infection in a holoendemic malaria region in Vietnam

We examined the role of osteopontin (OPN) in immunity against Plasmodium falciparum infection. We measured the mRNA levels for OPN and several cytokines in RNA preparations extracted from dried blood on filter paper obtained from falciparum malaria patients in Vietnam. Expression of OPN mRNA was detected in 134 of 161 patients. The expression of both interleukin-12 p40 and interferon-gamma mRNAs in the group positive for OPN mRNA was significantly higher than that in the group negative for OPN mRNA. The level of parasitemia in the OPN mRNA-positive group was much lower than that in the negative one. These results suggest that OPN might suppress multiplication of the parasites through T helper 1 cells-mediated immune responses.     

Local down-regulation of myelin-associated glycoprotein permits axonal sprouting with chronic nerve compression injury

Chronic nerve compression (CNC) injuries induce a robust Schwann cell proliferation in a distinct spatial and temporal pattern, which is accompanied by an increase in the number of small un-myelinated axons in the area of the injury. These findings suggest that this local proliferation of Schwann cells may induce local axonal sprouting. Here, we use quantitative electron microscopic techniques to define the nature of this sprouting response, and explore whether the local sprouting is in response to down-regulation of expression of myelin-associated glycoprotein (MAG) by proliferating Schwann cells. Axonal sprouting was observed without evidence of Wallerian degeneration in the outer region of CNC-injured nerves with a noticeable increase in Remak bundles within this region of injury. Immunolabeling of teased nerve fibers and Western blot analysis of nerves from CNC-injured animals revealed a local down-regulation of MAG protein within the zone of injury. Moreover, local delivery of purified MAG protein intraneurally at the time of CNC model creation abrogates the axonal sprouting response. These data demonstrate that CNC injury triggers axonal sprouting and suggests that a local down-regulation of MAG within the peripheral nerve secondary to CNC injury is the critical signal for the sprouting response.     

Botulinum toxin: clinical use

Since its development for the use of blepharospasm and strabismus more than 2.5 decades ago, botulinum neurotoxin (BoNT) has become a versatile drug in various fields of medicine. It is the standard of care in different disorders such as cervical dystonia, hemifacial spasm, focal spasticity, hyperhidrosis, ophthalmological and otolaryngeal disorders. It has also found widespread use in cosmetic applications. Many other indications are currently under investigation, including gastroenterologic and urologic indications, analgesic management and migraine. This paper is an extensive review of the spectrum of BoNT clinical applications.     

R7BP Complexes With RGS9-2 and RGS7 in the Striatum Differentially Control Motor Learning and Locomotor Responses to Cocaine

In the striatum, signaling through G protein-coupled dopamine receptors mediates motor and reward behavior, and underlies the effects of addictive drugs. The extent of receptor responses is determined by RGS9-2/Gβ5 complexes, a striatally enriched regulator that limits the lifetime of activated G proteins. Recent studies suggest that the function of RGS9-2/Gβ5 is controlled by the association with an additional subunit, R7BP, making elucidation of its contribution to striatal signaling essential for understanding molecular mechanisms of behaviors mediated by the striatum. In this study, we report that elimination of R7BP in mice results in motor coordination deficits and greater locomotor response to morphine administration, consistent with the essential role of R7BP in maintaining RGS9-2 expression in the striatum. However, in contrast to previously reported observations with RGS9-2 knockouts, mice lacking R7BP do not show higher sensitivity to locomotor-stimulating effects of cocaine. Using a striatum-specific knockdown approach, we show that the sensitivity of motor stimulation to cocaine is instead dependent on RGS7, whose complex formation with R7BP is dictated by RGS9-2 expression. These results indicate that dopamine signaling in the striatum is controlled by concerted interplay between two RGS proteins, RGS7 and RGS9-2, which are balanced by a common subunit, R7BP.     

Professional and educational initiatives, supports, and opportunities for advanced training in public health

The United States is facing a public health workforce shortage and pharmacists have the opportunity and obligation to address this challenge in health care. There have been initiatives and supports from within and beyond the profession for the pharmacist's role in public health. This article identifies existing professional and educational initiatives for the pharmacist's expanded role in public health, as well as postgraduate and other advanced educational opportunities in public health. Recommendations also are provided on how to further engage pharmacists in public health activities to alleviate the public health workforce challenge.