Millijoule laser pulse delivery for spark ignition through kagome hollow-core fiber.

We report on power handling oriented design of kagome lattice hollow-core fiber and demonstrate through it for the first time nanosecond laser pulses induced spark ignition in a friendly manner. Two different core designs and transmission bands are investigated and evaluated. The energy threshold damage was measured to be in excess of the 10 mJ level and the output power density is approaching the TW/cm2 after focusing; demonstrating the outstanding ability of such fiber for high power delivery.

Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant.

A nonspecific opsonin function has been ascribed to human alpha 2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the products obtained in the course of the preparation of the protein. To date, no definitive agreement existed with regard to a molecular homogeneous entity of alpha 2 HS glycoprotein (Ba-alpha 2 glycoproteins). The purpose of the current work was to study the variations in serum level of alpha 2 HS in patients suffering from an acute inflammatory process of bacterial etiology and to determine whether a decrease in alpha 2 HS was accompanied by the appearance of fragments of this protein in the serum. A method of preparing alpha 2 HS was thus developed, using an immune absorbent as a final purification step. In an intermediary step of the preparation, alpha 2 HS was found to bind zinc when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha 2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to less than 10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha 2 HS and alpha 1 antitrypsin (AT)was determined in 23 patients. When the acute-phase (AP-)reactant alpha 1 AT was increased (difference with normal mean greater than +2 or +3 SD), the sera showed a large decrease in alpha 2 HS (difference with normal mean less than -2 or -3 SD). The serum level of alpha 2 HS, albumin, alpha 2 macroglobulin, and of positive AP-reactants, orosomucoidinal study of seven patients. The results were submitted to a principal components analysis. Alpha 2 HS showed a negative correlation with the AP-reactants alpha 1 AT, orosomucoid, and haptoglobin (P less than 0.05) and a positive correlation with albumin (P less than 0.05); these findings indicate that alpha 2 HS is a negative AP-reactant. In addition, analysis of the principal components confirms thestrong analogy between alpha 2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.

A new paradigm for staging pedicle screw-based spinal procedures: rationale, feasibility, safety, and efficacy.

OBJECT: The aims of this study were to present the rationale for and the evolution of a staged, two-procedure paradigm for spinal surgery requiring pedicle screw instrumentation, and to evaluate the feasibility, safety, and efficacy of the technique. METHODS: The rationale for the new algorithm is presented for consideration in the form of unproven hypotheses subject to verification by subsequent studies. The first stage of the two-staged algorithm, performed in an interventional radiology (IR) setting, involves percutaneous placement of either headless pedicle screws or K-wire fragment placeholders of the trajectory for pedicle screws. The second stage, performed days or weeks later, involves open surgical completion of instrumentation placement and other surgical objectives. The techniques for IR percutaneous K-wire fragment and percutaneous screw placement evolved over the duration of the study. Instrumentation was placed in 126 pedicles in 25 patients. Efficacy was equated to the accuracy of screw placement, which was evaluated using computed tomography (CT). Algorithms incorporating correction for metal artifact were developed to determine deviation of the screws and K-wire fragments from proper position. Over 1500 measurements were made to evaluate K-wire fragment and screw position in the 116 instrumented pedicles for which CT data were available. RESULTS: Accuracy of placement (relative to both cortical and pedicle breaches or to only pedicle breaches) was 98 to 100% for K-wire fragments, 96 to 98% for screws following K-wire fragments, and 100% for percutaneous screws. The only adverse consequence of pedicle screw placement by this method was one infection that occurred 8 months postoperatively. CONCLUSIONS: The staged, two-procedure paradigm for pedicle screw placement proved, within the limits of this study, to be feasible, safe, and effective; therefore, the unproven rationale behind the new paradigm merits further evaluation in a larger cohort of patients with randomized, matched controls.

Supercontinuum generation system for optical coherence tomography based on tapered photonic crystal fibre.

We report smooth and broad continuum generation using a compact femtosecond Ti:Sapphire laser as a pump source and a tapered photonic crystal fibre as a nonlinear element. Spectral output is optimized for use in optical coherence tomography, providing a maximum longitudinal resolution of 1.5 microm in free space at 809 nm centre wavelength without use of additional spectral filtering.

An institutional approach to maintenance of excellent outcomes for carotid endarterectomy in a setting with moderate-to-low procedure volume.

BACKGROUND: Institutions and surgeons with high procedure volumes have been reported to have lower morbidity and mortality rates for patients undergoing carotid endarterectomy. Demonstrating comparable results is essential for centers with moderate or low volume. If comparable results cannot be demonstrated, a low- to moderate-volume center should not perform the procedure. STUDY DESIGN: A prospective study of a program to achieve and sustain excellent outcomes after carotid endarterectomy was conducted at a single institution with low-to-moderate volumes. Results of this effort from January 1997 through December 2005 are reported. Key features of our approach include institutional control over which and how many surgeons can perform carotid endarterectomy. Surgeons must be experienced carotid surgeons and consistently perform more than 12 procedures annually and be continuously monitored. Surgical outcomes were independently audited through a mandated institutional carotid endarterectomy data registry. Surgeons with poor outcomes are barred from doing carotid endarterectomies; and annually updated outcomes data are posted on the Internet. RESULTS: This approach was used for 555 carotid endarterectomies in 503 patients. Our outcomes-with total death and disabling stroke rate of 1.6%-compare favorably with, and are not statistically different from, published benchmarks, despite volumes at our institution ranging from 44 to 81 patients annually and the participation of 8 surgeons during the study period. CONCLUSIONS: Surgeons should perform carotid endarterectomies only if excellent outcomes can be demonstrated. We conclude that by using an approach like ours, even institutions with moderate-to-low carotid endarterectomy volumes can achieve excellent outcomes. We propose that all institutions should assume responsibility for ensuring excellent carotid endarterectomy outcomes using a comprehensive outcomes-based approach with independent auditing similar to that presented here.

Effect of approach side during anterior cervical discectomy and fusion on the incidence of recurrent laryngeal nerve injury.

OBJECT: This retrospective study was designed to determine whether side of approach during instrumented, one- or two-level primary anterior cervical discectomy and fusion (ACDF) affects the incidence of recurrent laryngeal nerve (RLN) injury diagnosed by observation of the vocal cords (OVC). METHODS: Records of all patients who underwent one- or two-level instrumented primary ACDF (418 patients) between January 1995 and February 2004 were reviewed. Data collected from these charts included surgeon, patient demographics, preoperative diagnosis, side of exposure, number of vertebral levels fused, and presence of RLN injury diagnosed by OVC after referral for persistent dysphonia. Time from surgery to OVC for patients with right-sided exposures was not statistically different from that for patients with left-sided exposures. Of 418 patients, 278 (66.5%) had right-sided exposures and 140 (33.5%) had left-sided exposures. Eight RLN injuries (1.9%) were noted-five in patients with right-sided exposures (1.8%) and three in patients with left-sided exposures (2.1%). The difference between right- and left-sided injury rates was shown to be nonsignificant using Fisher exact tests. CONCLUSIONS: Results indicate that, given the study's sample size, side of approach during instrumented, one- or two-level primary ACDF has no significant effect on RLN injury incidence in patients with persistent dysphonia referred for OVC. The definitive answer regarding the true incidence of RLN injury relative to approach side awaits a prospective study with preoperative, immediate postoperative, and periodic OVC in a large, homogeneous population with sufficient numbers of patients with right- and left-sided approaches.

Role of the O-phosphoserine clusters in the interaction of the bovine milk alpha s1-, beta-, kappa-caseins and the PP3 component with immobilized iron (III) ions.

alpha s1- and beta-Caseins have a sequence cluster -Ser(P)-Ser(P)-Ser(P)-Glu-Glu- which is not present in kappa-casein and the whey PP3 component. The affinity of these phosphoproteins for the iron(III)-iminodiacetic acid (IDA) complex immobilized on Sepharose was studied as a function of pH, urea concentration, calcium ion concentration, enzymatic dephosphorylation and temperature. The affinity of the three polyphosphorylated proteins (alpha s1- and beta-caseins, PP3) was similar. The sequence cluster was not a specific recognition pattern of the iron(III) ion. These three proteins presented a site of high affinity and a site of weak affinity. kappa-Casein, which had only one Ser(P) residue, presented only the site of weak affinity. Their primary site which was absent after dephosphorylation or calcium ion addition required the presence of at least two Ser(P) residues close in space. Their secondary site was sensitive to the presence of urea. It was sensitive to pH variation for PP3 and kappa-casein. The study of the affinity of a few free amino acids towards iron(III)-IDA showed that the secondary site involved tryptophan and tyrosine residues for alpha s1- and beta-caseins, histidine residues for PP3 and cysteine residues for kappa-casein.

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Sulfinpyrazone kinetics after intravenous and oral administration.

Sulfinpyrazone kinetics has been investigated after intravenous and oral doses. They may be described by a 3-compartment open model. In the body about half the drug is in the plasma or in interstitial fluids, which equilibrated with plasma. Most of the rest is in an extravascular compartment, from which it easily diffuses back to the plasma. About 3% of the dose is still in the body after 24 hr and is located mainly in a deep compartment. After oral administration, sulfinpyrazone is quickly absorbed, largely from the stomach.

Influence of rifampin on the pharmacokinetics of pefloxacin.

Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.

Metronidazole kinetics in patients with acute renal failure on dialysis: a cumulative study.

Nine patients with acute renal failure who were undergoing dialysis at intervals depending on clinical state were injected with metronidazole, 7.5 mg . kg-1 iv every 8 hr. Plasma samples were drawn during the 8 hr after the first infusion, during the first dialysis session, and during the course of the fourth infusion after the first three dialysis sessions. Metronidazole and its two main metabolites (alcohol [M1] and acid [M2]) were assayed by HPLC. The plasma t 1/2 of metronidazole (6.8 hr) is of the same order as that in healthy subjects. M1 and M2 plasma levels increased continuously until the next infusion. Dialysis clearances of metronidazole and its metabolites were about 60 ml . min-1; 25% of metronidazole in the body at the beginning of hemodialysis was eliminated. The corresponding apparent t 1/2 s are 3.3 hr (metronidazole), 8.0 hr (M1), and 7.9 hr (M2). In patients with acute renal disease under hemodialysis, there was no cumulation of metronidazole and its metabolites; hence there is no need for change in dosage regimen.

Characterization of atypical cells in the juvenile rat organ of corti after aminoglycoside ototoxicity.

Hair cell regeneration is well documented in the inner ear sensory epithelia of lower vertebrates and birds and may occur in the vestibular organs of mammals. By contrast, hair cell loss in the mature mammalian cochlea is considered irreversible. However, recent reports have suggested that an attempt at hair cell regeneration could occur in vivo in aminoglycoside-lesioned cochleas from neonatal rats. After amikacin treatment, atypical cells with apical specialization reminiscent of early differentiating stereocilia are transiently present at the apex of the intoxicated cochleas but fail to differentiate as hair cells in later stages. In the present study, we used electronic microscopy, histochemistry, and confocal microscopy to investigate the cellular rearrangements in the amikacin-lesioned organ of Corti of rat pups. In addition, we used 5-bromo-2'-deoxyuridine immunocytochemistry to determine whether mitotic processes are involved in the formation of the atypical cells. The morphologic and molecular data suggest that atypical cells are not recovering hair cells, but share characteristics of immature hair cells and supporting cells. Proliferative cells were absent from the region occupied by atypical cells, suggesting that the latter did not arise through mitotic processes. Altogether, the present results support the hypothesis that atypical cells arise through direct transformation of some of the supporting cells that reorganize during hair cell degeneration.

Penetration of lomefloxacin into human prostatic tissue.

Serum and prostatic tissue concentrations of lomefloxacin were measured in 12 elderly patients who underwent transurethral resection of the prostate after receiving a single oral dose of 400 mg. The peak serum concentration of lomefloxacin was 2.5-10.0 micrograms/mL (mean, 5.2 +/- 1.9 micrograms/mL). During surgery, serum and tissue concentrations averaged 4.6 +/- 2.2 micrograms/mL and 6.5 +/- 2.7 micrograms/g, respectively. The ratio of tissue to serum concentrations was 1.53 +/- 0.54. The levels of lomefloxacin in serum and prostatic tissue were found to be higher than the minimum inhibitory concentration (MIC) values for most urinary tract pathogens.

Pharmacokinetic study of cefmenoxime (SCE 1365-CMX) in healthy adults.

Cefmenoxime pharmacokinetics were investigated in six healthy volunteers after intravenous and intramuscular administration of 0.5, 1, and 2 g. Blood and urine samples were analyzed by reversed-phase high-pressure liquid chromatography using ultraviolet detection at 275 nm. The assay is precise and linear up to 200 micrograms/ml-1, with 0.02 micrograms/ml-1 as the limit of detection. Linearity of cefmenoxime kinetics was demonstrated because the area under the plasma concentrations is proportional to studied doses. Eight hours after 1 g of cefmenoxime intramuscularly, mean plasma concentrations are, respectively, 0.6 +/- 0.1 and 0.3 +/- 0.1 microgram/ml-1. Intramuscular cefmenoxime is rapidly absorbed (Ka = 7.28 hours-1) with complete bioavailability (F = 0.99); apparent volume of distribution is 0.35 liters/kg-1 and elimination half-life 1.5 hours. The fraction of cefmenoxime excreted unchanged in the urine after intramuscular administration is 0.72, indicating a major contribution of renal clearance in total clearance. Experimental data after intramuscular administration were well fitted with a two-compartment model.

Is presentation of bacteremia in the elderly the same as in younger patients?

OBJECTIVE: To compare the presentation of bacteremia in young and elderly patients. PATIENTS AND METHODS: Seventy-one elderly (mean age 80.4 years) and 34 younger inpatients (mean age 45.7 years) with bacteremia were prospectively studied. These were compared with a control group of 187 geriatric patients (mean age 81.3 years) with clinical signs of bacteremia but in whom blood cultures were negative. Bacteremia was defined as one or more positive blood cultures showing a pathogenic bacteria in patients with clinical signs of bacteremia. In all 105 patients with bacteremia, 16 common clinical or biological signs of the disease were immediately investigated after blood culture. Patients were classified into three groups: elder patients and young patients with bacteremia and elderly patients without bacteremia. RESULTS: Only three clinical findings of the 16 studied were found in at least 70% of the bacteremic elderly patients: fever, increased erythrocyte sedimentation rate, and a clinical indication of the source of infection. These three signs were found statistically more often in bacteremic elderly compared with nonbacteremic elderly patients (P < 0.01). Seven other signs (hypothermia, altered mental state, leukopenia, and lymphopenia) had a specificity above 80%. On a logistic regression analysis, four variables were significantly and independently associated with bacteremia in the elderly: rapid onset of infection (defined as a period < or = 48 hours between the earliest manifestation of bacteremia and the time of blood blood sample), fever, altered general state, and clinical indication of the source of infection. Younger infected patients had more chills, sweating, alter general state, altered mental state or lymphopenia than did the bacteremic elderly patients. Bacteremic elderly patients had statistically few symptoms than the young infected patients (P < 0.001). CONCLUSIONS: In elderly patients with early stage bacteremia, most of the signs or symptoms that are considered typical in the literature appear irregularly. None appeared pathognomonic. Elderly patients with bacteremia had fewer signs or symptoms than younger infected patients.

Pharmacokinetics of aztreonam in patients with chronic renal failure.

The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given.

Amikacin intoxication induces apoptosis and cell proliferation in rat organ of Corti.

Recently, an attempt at cochlear hair cell neodifferentiation has been reported in amikacin-treated rats. In the present study, we aimed to ascertain whether hair cell losses are mediated by apoptosis and whether cell proliferation occurs in damaged intoxicated cochleas. The results show that apoptosis is responsible for hair cell losses and that cell proliferation occurs in the region of the outer spiral sulcus but not in the region of Deiters cells and pre-existing hair cells. We suggest that cell proliferation maintains a certain homeostasis in the number of non-sensory cells and participates in epithelial scar formation. Neodifferentiated cells therefore probably arise from direct transdifferentiation, which could be triggered by phagocytosis of apoptotic bodies.

Attempt at hair cell neodifferentiation in developing and adult amikacin intoxicated rat cochleae.

Recent studies have shown that an attempt at auditory hair cell neodifferentiation occurs in vivo in the rat organ of Corti after amikacin intoxication during the last stages of cochlear maturation. Atypical cells, with morphological characteristics reminiscent of very immature sensory hair cells, were transiently observed after outer hair cell losses. The aim of the present study was to assess (i) if this attempt at hair cell neodifferentiation was related to the degree of maturity of the organ of Corti and (ii) to characterise morphological and molecular changes in the scarring epithelium. We therefore investigated, using electron and confocal microscopy, morphological and molecular changes in cochleae from rats treated with amikacin at two different periods: from post natal day (PND) 1 to PND 8, when the organ of Corti is very immature; and from PND 30 to 37, when the organ of Corti is morphologically and functionally mature. In both groups, transient atypical cells were observed, attesting that the attempt at hair cell neodifferentiation is not strictly related to the immaturity of the cochlea. The results also suggest that Deiters cells are involved in the appearance of atypical cells, possibly through a transdifferentiation process. Finally, it appears that non-sensory epithelial cells from the outer spiral sulcus progressively colonize the region of pre-existing outer hair cells.

Sequential changes in anti-GAL-1 staining of the rat organ of Corti following amikacin exposure.

Hair cell loss and a non-functional epithelial reorganization appeared in the organ of Corti after acoustic or toxic damage. Moreover, in the drug damaged organ of Corti, transient atypical cells were recently described with characteristics of both immature hair cells and/or non-sensory epithelial cells. The phenotype of these atypical cells has been now investigated by using the galectine 1 (GAL-1) antibody. In the normal organ of Corti, this antibody recognizes all the epithelial cells except the sensory hair cells and their supporting cells. At PD 21, transient atypical cells were not stained by GAL-1 antibody, suggesting that they were originated from hair cells or their supporting cells. Later, the organ of Corti was substituted by an epithelial scare, GAL-1 stained. This study also emphasizes the particular resistance of the cochlear apex to degeneration after antibiotic intoxication.

Neurological manifestations of Lyme disease and treatments.

Lyme disease is a multi-systemic infection due to B. burgdorferi, with neurological manifestations observed in its second and third stages. Except for the suggestive triad meningitis--radiculoneuritis--facial palsies, the diagnosis is often difficult because of the pleiomorphism of neurological manifestations. These can be localized or diffuse, with central involvement, meningitis or peripheral manifestations. Past history, cerebrospinal fluid (CSF) examination, immuno-assays for specific antibodies in serum and especially CSF are helpful in diagnosis. Betalactam antibiotics (penicillin G, amoxicillin, and third generation cephalosporins) are the most effective treatment with good results in the early and acute stages of neurological disease.