Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38

Excessive neutrophil activation causes posttraumatic complications, which may be reduced with hypertonic saline (HS) resuscitation. We tested if this is because of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25 mM) suppressed degranulation and superoxide formation in response to fMLP and blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in response to phorbol myristate acetate (PMA). This indicates that HS suppresses neutrophil function by intercepting signal pathways upstream of or apart from PKC. HS activated p38 by itself and enhanced degranulation in response to PKC activation. This enhancement was reduced by inhibition of p38 with SB203580, suggesting that p38 up-regulation participates in HS-induced enhancements of degranulation. HS had similar effects on the degranulation of cells that were previously stimulated with fMLP, but had no effect on its own, suggesting that HS enhancement of degranulation requires another signal. We conclude that depending on other stimuli, HS can suppress neutrophil activation by intercepting multiple receptor signals or augment degranulation by enhancing p38 signaling. In patients HS resuscitation may reduce posttraumatic complications by preventing neutrophil activation via chemotactic factors released during reperfusion.     

Treatment of vancomycin-resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases

OBJECTIVE: Previous studies of surgical treatment for acromegaly have used varied criteria for 'cure', but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN: We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew's Hospital between 1985 and 1993. PATIENTS: One hundred consecutive patients (53 male, mean age 46 years, range 18-68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5-8 years) after operation. MEASUREMENTS: GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900 h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS: Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5 mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission post-operatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5-8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS: The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.     

Determination of peptidoglycan-associated protein in Escherichia coli NCIB 8545 by capillary zone electrophoresis

An efficient reliable and sensitive capillary zone electrophoresis assay for the six major bacterial peptidoglycan-associated proteins of Escherichia coli NCIB 8545 is described. The method provides the facility to determine quantitatively the effect of antibacterials on bacterial peptidoglycan-associated protein synthesis and thus to further elucidate the mechanism of antibacterial action of such drugs as the antifolates which recently have been shown to adversely affect peptidoglycan synthesis.     

The radiographic and imaging characteristics of porous tantalum implants within the human cervical spine

STUDY DESIGN: Seven cadaveric cervical spines were implanted with a porous tantalum spacer and a titanium alloy spacer, and their radiographic and imaging characteristics were evaluated. OBJECTIVE: To determine the radiographic characteristics of porous tantalum and titanium implants used as spacers in the cervical spine. SUMMARY OF BACKGROUND DATA: Anterior decompressive surgery of the disc space or the vertebral body creates a defect that frequently is repaired with autologous bone grafts to promote spinal fusion. Donor site morbidity, insufficient donor material, and additional surgical time have spurred the development of biomaterials to replace or supplement existing spinal reconstruction techniques. Although the promotion of a solid bony fusion is critical, the implanted biomaterial should be compatible with modern imaging techniques, should allow visualization of the spinal canal and neural foramina, and should permit radiographic assessment of bony ingrowth. METHODS: Cadaveric spines containing the implants were imaged with plain radiography, computerized tomography, and magnetic resonance imaging. The image distortion produced by the implants was determined qualitatively and quantitatively. RESULTS: The tantalum and titanium spacers were opaque on plain radiographic films. On computed tomographic scans, more streak artifact was associated with the tantalum implants than with the titanium. On magnetic resonance imaging, the porous tantalum implant demonstrated less artifact than did the titanium spacer on T1- and T2-weighted spin echo and on T2*-weighted gradient-echo magnetic resonance images. Overall, the tantalum implant produced less artifact on magnetic resonance imaging than did the titanium spacer and therefore allowed for better visualization of the surrounding bony and neural structures. CONCLUSION: The material properties of titanium and porous tantalum cervical interbody implants contribute to their differential appearance in different imaging methods. The titanium implant appears to image best with computed tomography, whereas the porous tantalum implant produces less artifact than does the titanium implant on several magnetic resonance imaging sequences.     

Microjet impingement followed by scanning electron microscopy as a qualitative technique to compare cellular adhesion to various biomaterials

Adhesion of cells to biomaterial surfaces is one of the major factors which mediates their biocompatibility. Quantitative or qualitative cell adhesion measurements would be useful for screening new implant materials. Microjet impingement has been evaluated by scanning electron microscopy, to determine to what extent it measures cell adhesion. The shear forces of the impingement, on the materials tested here, are seen to be greater than the cohesive strength of the cells in the impinged area, causing their rupture. The cell bodies are removed during impingement, leaving the sites of adhesion and other cellular material behind. Thus the method is shown not to provide quantification of cell adhesion forces for the metals and culture plastic tested. It is suggested that with highly adherent biomaterials, the distribution and patterns of these adhesion sites could be used for qualitative comparisons for screening of implant surfaces.     

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.     

Anthropology, tooth wear, and occlusion ab origine

The purpose of this essay is to emphasize that anthropology, the study of man in his environments, is a potent tool for scientific discovery and inspiration in dental science. It attempts to capture flashes of creative anthropological insight which have illuminated studies of tooth wear and occlusion in the past. While it documents contributions, understandings, and misunderstandings from Australian and New Zealand dentists, it is not a hagiography. The real saint of this essay is the Australian aborigine. For when men and women are understood in their environments, much is learned from them which challenges preconceptions of our dental science culture. The essay concludes that new, contemporary Australian culture needs to be studied by anthropological approaches if we are to understand how dental erosion is exacerbating tooth wear and damaging the occlusions of contemporary Australians. Much remains to be discovered about contemporary lifestyles, habits, and diets that lead to dental erosion, the principal cause of contemporary tooth wear in this part of the world.     

Mutation analyses of KRAS exon 1 comparing three different techniques: temporal temperature gradient electrophoresis, constant denaturant capillary electrophoresis and allele specific polymerase chain reaction

Pefloxacin plus metronidazole versus netilmicin plus metronidazole in the prevention of nosocomial infections during contaminated surgery. Surgical prophylaxis is widely used in contaminated surgery, especially colorectal surgery. In this clinical trial the efficacy of pefloxacin 800 mg i.v. slow infusion associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then metronidazole alone after 6 and 12 hours versus netilmicin 200 mg i.m. associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then both after 6 and 12 hours were evaluated in 97 patients suffering by colorectal surgery. Efficacy of prophylaxis in patients was evaluated in terms of appearance of post-surgical infections (abdominal, urinary, respiratory and wound infections). In pefloxacin + metronidazole group (53 patients), two cases of wound infections (3.8%) and three cases of respiratory infections (5.8%) were observed. In netilmicin + metronidazole group (44 patients), two cases of wound infections (4.9%), three cases of urinary infections (7%), three cases of respiratory infections (7.5%) and one case of intra-abdominal infection were observed. Our data confirmed that in colorectal surgery, the association pefloxacin, drug with microbiological and pharmacokinetics characteristics suitable for prophylaxis + metronidazole, active against anaerobes pathogens, prevents post-surgical infections as well as a reference association (netilmicin + metronidazole), with the advantage of a single administration.