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.     

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

Effect of endotoxin and a burn injury on lung and liver lipid peroxidation and catalase activity

Both endotoxin and a burn alone produce oxidant-induced tissue lipid peroxidation. The endotoxin response is due in large part to hydrogen peroxide. The combination of endotoxin after a burn results in an increased liver, but not lung, oxidant injury. Our purpose was to determine whether the burn oxidant injury inactivated endogenous liver tissue catalase, thereby amplifying a subsequent H2O2 insult. Twenty-six adult sheep were studied. Twelve sheep had a 15% TBS burn. Tissue catalase activity, measured in lung and liver 3 days postburn, was significantly decreased from a control of 3.58 +/- 1.8 and 193 +/- 63, respectively, to 1.72 +/- 0.63 and 148 +/- 33 k(sec-1)/0.5 gram tissue. The addition of endotoxin 3 days postburn resulted in an increase in liver malondialdehyde, MDA, a measure of lipid peroxidation, from a control of 110 +/- 80 to 450 +/- 54 nmol/gram tissue. This value was significantly greater than the 210 +/- 80 nmol/gram tissue seen after endotoxin alone. Lung tissue MDA with burn and endotoxin was 65 +/- 8 compared to 42 +/- 7 for control and 80 +/- 6 nmol/gram for endotoxin alone. We conclude that a decrease in liver catalase activity occurs after a burn. The decrease corresponds to an accentuated oxidant-induced lipid peroxidation after an added endotoxin insult where H2O2 is known to be an etiologic agent. The catalase activity also decreases in postburn lung, but accentuated lung damage was not seen, indicating a variable tissue response from the burn-induced decrease in antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

FACTORS RELATED TO PERINEAL TRAUMA IN CHILDBIRTH

We conducted an observational cohort study in three nurse-midwifery services to identify patient characteristics and clinical care measures related to perineal trauma at birth. Data were collected on all women who began care with a nurse-midwife in labor, using an adaptation of the Nurse-Midwifery Clinical Data Set (n = 3,049). Study variables included demographics, perineal management techniques and position for birth, and other intrapartum care and events. Univariate and multivariate analyses showed that episiotomy was strongly related to fetal bradycardia, prolonged second stage, ethnic status, and maternal education level. Warm compresses and flexion/counterpressure to slow delivery were protective. Spontaneous lacerations were influenced by these factors as well. The lateral position for birth was protective, and use of oils or lubricants and the lithotomy position increased lacerations. Multisite studies in nurse-midwifery practices may provide an ideal means of determining effective care measures in healthy populations.     

Moderate smoke inhalation produces decreased oxygen delivery, increased oxygen demands, and systemic but not lung parenchymal lipid peroxidation

We studied the first 24-hour lung and systemic physiologic response to a moderate smoke inhalation injury. In addition, we monitored oxidant-induced lipid peroxidation (LP), using malondialdehyde and conjugated dienes. Sixteen adult sheep with lung and soft tissue lymph fistulas were given 20 breaths of smoke while under anesthesia. Eight sheep were given a tidal volume of 5 ml/kg smoke, confining the inflammatory injury to airways only. Eight sheep were given 10 ml/kg smoke after which focal alveolar collapse and a carboxyhemoglobin level of 28% +/- 5% were noted in addition to airways injury. No significant lung or systemic physiologic changes were noted in the 5 ml/kg smoke exposure. However, plasma levels of malondialdehyde increased significantly, indicating that LP had occurred. With the 10 ml/kg smoke exposure, a 50% early decrease in oxygen consumption was noted. At 12 hours, oxygen consumption was then significantly increased by 30% over baseline. Fluid requirements to maintain filling pressures were also significantly increased, comparable to that seen after a 20% total body surface burn. A change in soft tissue permeability was noted with a twofold increase in systemic lymph, which could in part explain the fluid requirements. Lung lymph flow increased by only twofold, and lung water was not increased, whereas arterial partial oxygen pressure decreased from a baseline of 95 +/- 4 mm Hg to 60 +/- 5 mm Hg. Systemic LP was evident when both plasma malondialdehyde and conjugated dienes increased significantly. Liver tissue malondialdehyde at postmortem examination was double the normal level. However, lung parenchymal malondialdehyde was not increased.(ABSTRACT TRUNCATED AT 250 WORDS)