Therapeutics and delivery vehicles for local treatment of osteomyelitis

Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long-term, systemic antibiotic administration, which contributes to the development of antibiotic-resistant bacteria and has limited ability to eradicate challenging biofilm-forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm-forming, antibiotic-resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.     

A controlled trial of scheduled replacement of central venous and pulmonary-artery catheters.

BACKGROUND. The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection, It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site. METHODS. We conducted a controlled trial in adult patients in intensive care units who required central venous or pulmonary-artery catheters for more than three days. Patients were assigned randomly to undergo one of four methods of catheter exchange: replacement every three days either by insertion at a new site (group 1) or by exchange over a guide wire (group 2), or replacement when clinically indicated either by insertion at a new site (group 3) or by exchange over a guide wire (group 4). RESULTS. Of the 160 patients, 5 percent had catheter-related bloodstream infections, 16 percent had catheters that became colonized, and 9 percent had major mechanical complications. The incidence rates (per 1000 days of catheter use) of bloodstream infection were 3 in group 1, 6 in group 2, 2 in group 3, and 3 in group 4; the incidence rates of mechanical complications were 14, 4, 8, and 3, respectively. Patients randomly assigned to guide-wire-assisted exchange were more likely to have bloodstream infection after the first three days of catheterization (6 percent vs. 0, P = 0.06). Insertions at new sites were associated with more mechanical complications (5 percent vs. 1 percent, P = 0.005). CONCLUSIONS. Routine replacement of central vascular catheters every three days does not prevent infection. Exchanging catheters with the use of a guide wire increases the risk of bloodstream infection, but replacement involving insertion of catheters at new sites increases the risk of mechanical complications.     

CPR training for patients' families: do physicians recommend it?

All Seattle-area cardiologists and 25 per cent of selected other physicians were queried by mail to determine whether they recommended CPR (cardiopulmonary resuscitation) training for families of their patients. Two-thirds reported that they advocated training for some patients' families, but only 52 per cent of cardiologists and 37 per cent of the others did so for families of at least half of the patients considered at risk. Physicians who had performed out-of-hospital CPR or had received advanced or recent training were more likely to recommend instruction.     

Combined open and laparoscopic approach to chronic pain following open inguinal hernia repair

Introduction: Chronic groin pain is the most common long-term complication after open inguinal hernia repair. Traditional surgical management of the associated neuralgia consists of injection therapy followed by groin exploration, mesh removal, and nerve transection. The resultant hernia defect may be difficult to repair from an anterior approach. We evaluate the outcomes of a combined laparoscopic and open approach for the treatment of chronic groin pain following open inguinal herniorrhaphy. Methods: All patients who underwent groin exploration for chronic neuralgia after a prior open inguinal hernia repair were prospectively analyzed. Patient demographics, type of prior hernia repair, and prior nonoperative therapies were recorded. The operation consisted of a standard three trocar laparoscopic transabdominal preperitoneal hernia repair, followed by groin exploration, mesh removal, and nerve transection. Outcome measures included recurrent groin pain, numbness, hernia recurrence, and complications. Results: Twelve patients (11 male and 1 female) with a mean age of 41 years (range 29–51) underwent combined laparoscopic and open treatment for chronic groin pain. Ten patients complained of unilateral neuralgia, one patient had bilateral complaints, and one patient complained of orchalgia. All patients failed at least two attempted percutaneous nerve blocks. Prior repairs included Lichtenstein (n=9), McVay (n=1), plug and patch (n=1), and Shouldice (n=1). There were no intraoperative complications or wound infections. With a minimum of 6 weeks follow up, all patients were significantly improved. One patient complained of intermittent minor discomfort that required no further therapy. Two patients had persistent numbness in the ilioinguinal nerve distribution but remained satisfied with the procedure. Conclusions: A combined laparoscopic and open approach for postherniorrhaphy groin pain results in good to excellent patient satisfaction with no perioperative morbidity. It may be the preferred technique for the definitive management of chronic neuralgia after prior open hernia repair.     

The meaning of spirituality: a literature review

This paper presents a literature review in relation to the meaning of spirituality. It is proposed that meeting the spiritual needs of patients is a fundamental part of providing holistic nursing care, but that the assessment and meeting of those needs is impeded by inadequate definitions and conceptual frameworks. It should not be assumed that spirituality is either synonymous, or coterminous, with religion, and it is suggested that to adopt this restrictive view is unhelpful in the provision of individualized care. Reflection on the literature reveals that the self, others and 'God' provide the key elements within a definition of spirituality, and that other emerging themes namely meaning, hope, relatedness/connectedness, beliefs/belief systems and expressions of spirituality, can be articulated in the context of those three key elements. In particular, it is proposed that the nature of 'God' may take many forms and, essentially, is whatever an individual takes to be of highest value in his/her life. It is suggested that the themes emerging from the literature can be utilized as a framework to give practitioners and researchers a direction for future exploration of the concept of spirituality.     

The relationship between cytotoxicity and prognostically significant histologic changes in lymph nodes from patients with cancer of the breast.

Axillary lymph nodes obtained from 37 patients with cancer of the breast were used in a microcytotoxicity assay against a human mammary cancer cell line, ALAB. Cell suspensions made from 60 individual lymph nodes and 51 lymph node pools were tested. Each lymph node was graded for the extent of the histologic changes of sinus histiocytosis (SH), paracortical hyperplasia (PCH), and germinal center hyperplasia (GCH). High levels of cytotoxicity correlated significantly with the presence of SH and PCH. When multiple lymph nodes of individual patients were pooled and tested, a high intensity of GCH correlated with a low degree of cytototoxicity. The cytotoxic activity of pooled lymph nodes from different axillary regions was studied in 20 patients. In 7 of these patients, low axillary lymph node cells were more cytotoxic than high axillary node cells. The reverse was found for 7 patients, and there was no difference in cytotoxicity between axillary regions in 6. Cytotoxic lymph node pools had high SH and low GCH whether they were obtained from the low or high region. Noncytotoxic lymph node pools from the high axillary region had a low intensity of all three histologic reactions. In contrast, noncytotoxic lymph node pools from the low axillary regions had high intensities of SH, PCH, and GCH. These results suggest that germinal center hyperplasia in the lymph nodes nearest an advancing tumor is associated with a local suppression of cytotoxic cell activity.     

Bordetella bronchiseptica flagellin is a proinflammatory determinant for airway epithelial cells

Motility is an important virulence phenotype for many bacteria, and flagellin, the monomeric component of flagella, is a potent proinflammatory factor. Of the three Bordetella species, Bordetella pertussis and Bordetella parapertussis are nonmotile human pathogens, while Bordetella bronchiseptica expresses flagellin and causes disease in animals and immunocompromised human hosts. The BvgAS two-component signal transduction system regulates phenotypic-phase transition (Bvg+, Bvg-, and Bvg(i)) in bordetellae. The Bvg- phase of B. bronchiseptica is characterized by the expression of flagellin and the repression of adhesins and toxins necessary for the colonization of the respiratory tract. B. bronchiseptica naturally infects a variety of animal hosts and constitutes an excellent model to study Bordetella pathogenesis. Using in vitro coculture models of bacteria and human lung epithelial cells, we studied the effects of B. bronchiseptica flagellin on host defense responses. Our results show that B. bronchiseptica flagellin is a potent proinflammatory factor that induces chemokine, cytokine, and host defense gene expression. Furthermore, we investigated receptor specificity in the response to B. bronchiseptica flagellin. Our results show that B. bronchiseptica flagellin is able to signal effectively through both human and mouse Toll-like receptor 5.