Paravertebral blocks reduce the risk of postoperative urinary retention in inguinal hernia repair.

PURPOSE: Inguinal hernia repair and general anesthesia (GA) are known risk factors for urinary retention. Paravertebral blocks (PVBs) have been utilized to facilitate enhanced recovery after surgery. We evaluate the benefit of incorporating PVBs into our anesthetic technique in a large cohort of ambulatory patients undergoing inguinal hernia repair. METHODS: Records of 619 adults scheduled for ambulatory inguinal hernia repair between 2010 and 2015 were reviewed and categorized based on anesthetic and surgical approach [GA and open (GAO), GA and laparoscopic (GAL), PVB and open (PVBO), and GA/PVB and open (GA/PVBO)]. Patients were excluded for missing data, self-catheterization, chronic opioid tolerance, and additional surgical procedures coinciding with hernia repair. Risk factors associated with the primary outcome of urinary retention were examined using logistic regression. RESULTS: PVBO (n = 136) had significantly lower odds than GAO of experiencing urinary retention (odds ratio 0.16; 95% CI 0.05-0.51); overall (P < .01), with 4.4% (n = 6) of the patients in the PVBO group having urinary retention versus 22.6% (n = 7) with GAO. Expressed as intravenous morphine equivalences, the PVBO group had the lowest median opioid use (5 mg), followed by GA, PVB, and open (7.5 mg); GAO 25 mg; and GAL 25 mg. Also, 30% (n = 41) of the PVBO group required no opioid analgesia in the postanesthesia care unit. CONCLUSIONS: PVBs as the primary anesthetic or an adjunct to GA is the preferred anesthetic technique for open inguinal hernia repair as it facilitates enhanced recovery after surgery by decreasing risk of urinary retention, opioid requirements, and length of stay.

Detection and characterization of enterovirus associated with herpangina and hand, foot, and mouth disease in Seoul, Korea.

BACKGROUND: Human enteroviruses (HEVs) are a major cause of herpangina, HFMD (hand, foot, and mouth disease), and other neurological diseases in Seoul, Korea. METHODS: A total of 56 specimens from hospitalized patients collected from February to December 2009 (37 females and 19 males) in Seoul were tested for HEV from stool, throat swab, and vesicle swab samples taken from patients with herpangina or HFMD using cell culture and RT-PCR in 2009. By the 1D gene, encoding the VP1 capsid protein, seven different HEV genotypes were detected with Coxsackievirus A2, A4, A5, A9, A16 (CA), Coxsackievirus B1 (CB), and Enterovirus 71 (EV71). The most prevalent genotype was CA16 (6, 10.7%), followed by CA2 (4, 7.1%), CA5 (4, 7.1%), EV71 (2, 3.6%), CA4 (1, 1.8%), CA9 (1, 1.8%), and CB1 (1, 1.8%). The 1D gene sequences of two EV71 strains were closely related with one another (98.5% nucleotide similarity) and belonged to the C4 genotype. CONCLUSIONS: It is important to continuously survey the genetic characteristics of EV71 and CA16 from patients, which will provide useful data that aids in our understanding of HFMD infections in Seoul, Korea and may contribute to future control.

The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies.

Since the recognition of human acquired immune deficiency syndrome, numerous classes of pharmacologic therapeutics have been developed to manage the disease. Current therapy includes co-administration of combinations of drugs classified by their mechanism of action as 'transcriptase inhibitors', 'protease inhibitors', 'integrase inhibitors' and the more recent 'fusion inhibitors'. This review focuses on the chemokine system and the recognition of chemokine receptors as targets for anti-human immunodeficiency virus (HIV) therapy. The FDA-approved chemokine (C-C motif) receptor 5 (CCR5) antagonist maraviroc (Selzentry) is discussed in detail, along with another compound vicriviroc, currently in clinical trials. The mechanism of action, pharmacokinetics, toxicity and current status of research on CCR5 antagonists is described. Further, potential therapeutic uses of these agents other than anti-HIV therapy are discussed.

AT(1) receptor blockade with losartan during gestation in Wistar rats leads to an increase in thirst and sodium appetite in their adult female offspring.

We studied the effects of angiotensin II receptor blockade with losartan on thirst and sodium appetite in pregnant Wistar rats and on their adult female offspring. During maternal adaptation to pregnancy, average daily total water intake increased by 63% (P<0.01); NaCl intake by 214% (P<0.001). These changes were not blocked by daily s.c. injections of losartan (50 mg/kg bw i.p.) from gestation day (GD) 2 until GD 19 which implied that maternal AT(1) receptors were not involved in the up regulation of thirst and sodium appetite during pregnancy. Losartan blockade during gestation led to a significant and continued increase in thirst and sodium appetite in the adult female offspring. Daily water intakes were greater in the losartan (LO) group than in the vehicle-injected control group (CO), leading to a total water intake of 1114 +/- 80.6 ml/kg bw compared with 738 +/- 56.7 ml/kg bw (P<0.05) during the 8-day period of observation. Daily sodium intakes were usually 2-3 times greater in the LO group compared with the CO group, amounting to a final cumulative intake of 232 +/- 33 mmol/kg bw compared with 93.8 +/- 16.5 mmol/kg bw (P<0.05) in 8 days. These elevated sodium and water intakes were nearly counterbalanced by the increased renal excretion of water and sodium by fully functional kidneys that were not injured by the drug. Body weights were 10% lower in the LO group at the start but remained unchanged relative to the CO group during the entire 8-day period of observation. Plasma electrolytes, blood hematocrit and carotid MABP in the LO group did not differ from the CO group.

In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis.

A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide- specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.

Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by central nervous system inflammation and demyelination. Retinoids regulate cell differentiation and growth by binding to and activating retinoic acid receptors, which seem to be nuclear transcription factors. The effect of retinoids on chronic relapsing EAE produced by the transfer of myelin basic protein (MBP)-specific lymph node cells (LNC) was studied. All-trans-retinoic acid (tRA) inhibited the proliferation of MBP-specific LNC in vitro. However, the capacity of these cells to transfer EAE was markedly reduced by concentrations of tRA that only mildly inhibited T cell proliferation. The presence of tRA during in vitro MBP-specific LNC activation resulted in a considerable increase in IL-4 mRNA, whereas mRNA for IL-2, TNF-alpha, and IFN-gamma was decreased. Increased IL-4 also was detected in culture supernatants. However, the presence of a neutralizing Ab to IL-4 (11B11) during MBP-specific LNC activation in vitro did not reverse the inhibition of encephalitogenicity caused by tRA. The administration of retinoids in vivo resulted in an improved clinical course, even when given after disease onset. These findings suggest that T cell activation in the presence of tRA results in the development of T cells of the Th2 phenotype, which, in turn, might be responsible for the decrease in the encephalitogenicity of MBP-specific T cells. The modulation by retinoids of an immune response dominated by Th1-like T cells to one in which the protective cytokines of Th2-like cells predominate may have potential relevance for human demyelinating diseases such as multiple sclerosis.