Synchrotron Radiation Fourier Transform Infrared (SR-FTIR) spectroscopy in exploring ancient human hair from Roman period Juliopolis: Preservation status and alterations of organic compounds.

We explore the preservation status and alterations of organic compounds in Roman period human hairstrandsfrom a specific individual (M196) excavated at Juliopolis (JP). How do these organic compounds present in this c. 2000-year-old human hair compare to those present in modern hair? Alterations to organic compounds in archaeological human hair are caused by biological degradative processes dependent on multifactorial processes acting on the hair since the deposition of a body in a mortuary context. We investigate the type of organic compounds present using Synchrotron Radiation Fourier Transform Infrared (SR-FTIR). Juliopolis (Iuliopolis) is an ancient multiperiod city, located in the Çayirhan district of Nallihan, northwest of Ankara. The Juliopolis necropolis from which M196 was recovered was in use throughout the Hellenistic, Roman, and Byzantine periods, and yielded over 700 tombs with numerous human remains. One tomb (M196) contained human remains of exceptional preservation status, including substantial amounts of hair. Human hair from archaeological contexts is not only extremely rare, but importantly, has high analytical value, with potential for analysis of diet, geographical origins, ancient DNA, metal exposure, and other aspects of life in a time-resolved manner. These data make significant contributions to the life history of the individual (osteobiography), as well as contribute towards key archaeological questions. As these analyses are in their majority destructive, prior evaluation of the preservation of sufficient amounts of the organic compounds on which many such analyses rely upon is crucial, to avoid unnecessary loss of precious ancient samples. The results of our SR-FTIR analyses at SESAME synchrotron show that keratin in the JP M196 is more degraded in comparison to the modern reference sample. However, the results also point to clear potential for further analyses with techniques relying on organic compound preservation, such as C and N isotopic analyses for diet, and aDNA.

Use of CPAP in patients with obstructive sleep apnea admitted to the general ward: effect on length of stay and readmission rate.

BACKGROUND: Obstructive sleep apnea (OSA) has been associated with multiple cardiovascular comorbidities. Despite increased awareness of OSA and its treatments, the management of OSA in the hospital setting remains below expectations. METHODS: We retrospectively reviewed the demographics, clinical characteristics, and hospital course on 413 consecutive patients with a history of OSA on domiciliary CPAP therapy admitted to the general medical ward and analyzed the prevalence of CPAP use and its effect on length of stay (LOS), 30-day readmission rate, and time-to-readmission in our tertiary care teaching hospital. RESULTS: Of the 413 study participants, 264 (64.0 %) patients were receiving CPAP during their hospital admission. Patients who were receiving CPAP therapy during their hospitalization had a significantly higher body mass index (BMI) (41.4 vs. 36.8 kg/m(2), p < 0.001) and were more likely to be African-American (p = 0.01) and have congestive heart failure (CHF) (42.0 vs. 31.0 %, p = 0.038) peripheral vascular disease (PVD) (26.0 vs. 15.0 %, p = 0.013), and uncomplicated diabetes mellitus (p = 0.001) than those who were not. CPAP therapy in the hospital setting did not affect LOS (4.7 vs. 4.0 days, p = 0.291), readmission rate (11.0 % for both groups), or time-to-readmission (20.8 vs. 22.3 days, p = 0.762). CONCLUSION: The majority of patients who are on domiciliary CPAP therapy were receiving CPAP therapy while admitted to the general medical ward of a tertiary care academic hospital. Presence of comorbid conditions such as obesity and certain cardiovascular diseases may have increased the likelihood of prescribing CPAP therapy while in the hospital. In-hospital CPAP therapy did not appear to significantly influence short-term outcomes such as hospital LOS, readmission rate, or time-to-readmission.

[Retroprostatic cyst draining ejaculatory ducts with secondary obstructive azoospermia]. / Kyste rétroprostatique drainant les canaux éjaculateurs avec azoospermie obstructive secondaire.

Obstructive azoospermia constitutes 35 to 40% of azoospermia. Etiologies may be acquired or rarely congenital. Congenital utricular or Mullerian duct cyst may result in compression of ejaculatory ducts. However, they must be differentiated from exceptional wolffian or urogenital cysts, which are located at the same site but in which ejaculatory ducts may drain inside. We report a case of retroprostatic duct cyst diagnosed during work up of male infertility where magnetic resonance imaging (MRI) showed the drainage of both ejaculatory ducts inside and the presence of a thin canal ended blindly in the wall of prostatic urethra. Transurethral resection guided by MRI has been performed resulting in urethral drainage of the cyst, relieving of obstruction and normalization of spermogramm.

[Fournier's gangrene: a review of the recent literature]. / Gangrène de Fournier : revue de la littérature récente.

Fournier's gangrene is a rapidly progressive necrotizing fasciitis of the perineum and external-genital organs. It is secondary to polymicrobial infection by aerobic and anaerobic bacteria with a synergistic action. The aetiology is identified in 95% of cases. The source of infection is either cutaneous, urogenital or colorectal. Predisposing factors, such as age, diabetes and immunodepression, are often present in affected patients. Urgent and aggressive treatment is essential to ensure the patient's survival. Treatment consists of restoration of the fluid and electrolyte balance and broad-spectrum antibiotic therapy rapidly followed by surgical debridement. However, the mortality remains high, about 20 to 80%, frequently, due to delayed diagnosis and management. Patients who survive the infection require reconstructive surgery with sometimes marked sequelae related to the extent of fasciitis and debridement.

An assay for the determination of sirolimus levels in the lymphocyte of transplant patients.

UNLABELLED: Both tacrolimus (TAC) and sirolimus (SRL) bind to the same immunophilin FKBP12; however, their mechanisms of action are distinct. SRL inhibits mammalian target of rapamycin (TOR), which is an enzyme critical to the immune function. TOR inhibition blocks the signal that mediates T-cell proliferation by preventing cell-cycle progression from G1 to S phase. Moreover, TOR inhibition results in a decrease in antibody production by blocking B-cell proliferation and maturation into antibody producing cells. The use of SRL has resulted in a decrease in the number of rejection episodes. As with other immunosuppressive agents, SRL can cause dose-related side effects, the most notable of which are hypercholesterolemia, hyperlipidemia, anemia, and thrombocytopenia. Thus, therapeutic drug monitoring to assess efficacy and toxicity has became a necessity. SRL blood levels do not correlate with its bioactivity and are affected by the concomitant use of other immunosuppressive drugs. To determine the bioactivity of SRL we have developed an assay to determine the level of Sirolimus per lymphocyte of transplant patients. The levels were correlated with lymphocyte count. METHODS: Whole blood samples from patients on SRL were collected in Ethylene Diamine Tetra-acetic acid (EDTA) vacutainer tubes. Immediately the lymphocytes from 2 mL of blood were separated using 1.5 mL of Ficoll gradient, by centrifugation for 30 minutes at 2500 RPM. The lymphocytes were washed three times with phosphate-bufferd saline and the pellet suspended in 150 microL of Middle East research institute (MERI) drug extraction solution (Beirut, Lebanon), which was then added to 300 microL of IMx solublizing reagent. The cytoplasmic SRL concentrations in lymphocytes were measured using kits supplied from Abbott diagnostics or by high-performance liquid tomography. A corresponding whole blood sample from each patient was used to measure blood levels. To determine the level per lymphocyte, the value obtained was divided by the number of lymphocytes and expressed as Pg/cell. A pharmacokinetic profile for both blood and lymphocytes was constructed for each patient using data corresponding to predose C(0), 1 hour (C(1)) and 2 hours (C(2)) after the dose. The lymphocyte enumeration for C(0), C(1), and C(2) was performed using the FACS Calibur Flow Cytometer from Becton Dickinson. The average dose was 2.86 +/- 1.27 mg/d with a C(0) = 8.05 +/- 4.24, C(1) = 21.9 +/- 8.9 ng/mL, and C(2) = 23 +/- 0.03 ng/mL. Although there was a significant correlation (P=.0975) between the dose and C(0), there was no correlation between the dose and C(0) level on the lymphocyte count P=.897. However, there was a strong correlation between SRL lymphocyte levels (pg/cell) and the lymphocyte count (r(2)=.6.06). The higher the concentration of the drug the lower the lymphocyte counts. The assay is sensitive to within 0.45 pg/cell, reproducible with a coefficient of variance (CV) of 6.4% within assay and 7.5% for intraassay.

Cyclosporine lymphocyte maximum level monitoring in de novo kidney transplant patients: a prospective study.

OBJECTIVES: To determine prospectively the temporal variations of cyclosporine-A lymphocyte maximum level, whole blood maximum concentration, and total lymphocyte count in patients with de novo kidney transplantation. MATERIALS AND METHODS: Lymphocyte maximum level, whole blood maximum concentration, and total lymphocyte count were prospectively measured in 35 patients at 1, 2, and 3 months after kidney transplantation. Two groups--a biopsy-proven acute rejection group (REJ+) and a rejection-free group (REJ-)--were compared. RESULTS: Both groups had similar lymphocyte maximum levels, whole blood maximum concentrations, and total lymphocyte counts at the first month after transplantation. REJ+ patients had significantly lower lymphocyte maximum levels at 2 and 3 months (59+/-34 and 33+/-9 pg/Lc) and higher total lymphocyte counts (0.00204+/-0.00078x10(9)/L and 0.00203+/-0.00022x10(9)/L) when compared with their REJ- counterparts (87+/-56 and 63+/-30 pg/Lc, P<.05 and P<.007) and (0.00137+/-0.00074x10(9)/L and 0.0015+/-0.0006x10(9)/L, P<.02 and P<.003) respectively. Whole blood maximum concentrations were significantly higher in patients in the REJ+ group (2050+/-623 vs 1414+/-536 ng/mL, P<.02) at 2 months. At 3 months, the 2 groups were comparable (1158+/-340 vs 1365+/-525 ng/mL, P=NS). CONCLUSIONS: These results suggest that acute rejection is associated with a relatively low cyclosporine- A lymphocyte maximum level and high total lymphocyte count in the early posttransplant period. Cyclosporine-A whole blood maximum concentration failed to correlate with clinical outcome. Cyclosporine-A lymphocyte maximum level seems to offer a more reliable alternative than does whole blood maximum concentration for cyclosporine-A monitoring in patients with kidney transplantation.

Switchability of neoral and equoral according to Food and Drug Administration rules and regulations.

According to the US Food and Drug Administration (FDA), if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the FDA rules (FDA 21 CFR 320, 24) are (1) pharmacokinetic (PK) studies in healthy volunteers, (2) comparative clinical trials, and (3) pharmacodynamic (PD) studies (bioactivity). We evaluated the switchability of Equoral (IVAX-USA) with Neoral (Novartis Switzerland using all FDA rules. In a single oral dose, we undertook a comparative bioavailability study of Equoral (IVAX, USA) Neoral (Novartis, USA), and Neoral (Novartis UK). The pharmacokinetics of Equoral and Neoral were determined with blood levels at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 42, and 48 hours. The area under curve (AUC), AUC extrapolated to infinity (AUC0-inf), rate of absorption (Tmax), extent of absorption (Cmax), half time (t1/2) of Equoral and Neoral were all within the 90% confidence interval of 80% to 125% boundaries. A comparative multinational multicenter clinical trial in stable renal transplant patients included 70 patients (22 women and 48 men) of mean age of 33 years (range, 26 to 43) was performed in Turkey, Lebanon, and Pakistan. In this study the ratios of LSM and the 90% confidence intervals for the Nontransformed/Parameters (AUC0-t, AUCinf, Tmax, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, which are within the 80% to 125% FDA acceptance range. For immunosuppressive drugs, the site of action is the lymphocyte and the measurable response is the decrease in lymphocyte count caused by the relative concentration of the drug in the lymphocyte. In a controlled switch, fixed-dose study, both Equoral and Neoral achieved the same concentration in the lymphocytes and caused the same degree of lymphocyte count reduction. The results of the testing (bioavailability-bioequivalence, clinical studies, and pharmacodynamic-bioactivity) required by FDA for interchangeability ("switchability") of immunosuppressive agents suggests that Neoral and Equoral are switchable.

Mycophenolic acid plasma trough level: correlation with clinical outcome.

OBJECTIVES: Assess the relationship between clinical diagnosis, state of immunosuppression, mycophenolic acid (MPA) plasma trough levels (MPACmin), and mycophenolate mofetil (MMF) dosage in renal transplant recipients. MATERIALS AND METHODS: MPACmin were determined in 30 kidney transplant patients, of whom 7 exhibited biopsy-proven acute rejection. The remaining 23 had normal graft function. Graft outcome, defined by clinical diagnosis and serum creatinine level, was compared according to MPACmin, MMF dosage, and total lymphocyte count (LC). RESULTS: Patients with acute rejection had similar MPACmin (2.4 +/- 1.7 microg/mL), MMF dosages (1.7 +/- 0.5 g), and LCs (0.001165 +/- 0.0040 x 10(9)/L) when compared with normal patients (2.2 +/- 0.7 microg/mL, 1.7 +/- 0.4 g and 0.001160 +/- 0.00527 x 10(9)/L) respectively. Rejection rates were comparable irrespective of MPACmin)ranges and higher in those receiving the 1-g dose (30%) when compared with those receiving 1.5-g and 2-g doses (12.5% and 11.7%). No relationship was observed between MPACmin and MMF doses, and neither parameter correlated with LC. CONCLUSIONS: These results suggest that MPACmin is a poor correlate of clinical outcome and state of immunosuppression. Although the usually recommended dosage of MMF (2 g) may be associated with acute rejection, low-dose MMF (1 g) seems to constitute a higher risk.

The pharmacokinetics of equoral versus neoral in stable renal transplant patients: a multinational multicenter study.

We studied the pharmacokinetics (PKs) of the new generic cyclosporine formulation, Equoral capsules, after the switch from original formulation Neoral capsules in stable renal transplant patients. The study was carried out in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles of the Declaration of Helsinki. The study included clinically stable first renal transplant patients maintained on cyclosporine with no rejection episode during the past 6 months. Hematology, biochemistry, and urine chemistry were determined on day 7, and day 21. The patients were all switched to Neoral (lot number 416MFD0601) on day 0 when the first sparse sampling PK was performed. On day 14 a 12-hour PK profile included predose, 30 minutes; 1 hour; 1 hour 30 minutes; 2 hours; 3 hours; 4 hours; 5 hours; 6 hours; 8 hours; 10-hours and 12-hour samples. Cyclosporine levels were determined using a CYA kit (Abbott TDx). On day 15 the patients were switched from Neoral capsules to Equoral capsules (lot 5T111014) at an equivalent dosage (mg/mg). The second sparse sampling PK was performed on day 21 and a 12-hour PK was performed on day 28. On the morning of day 29 patients were switched from Equoral capsules to Neoral capsules at an equivalent dosage (mg/mg). Additional concentrations were measured on days -7, 18, and 35. Safety parameters were monitored at each visit. The pharmacokinetics of both formulations were equivalent. The mean AUC for Neoral and Equoral was 2856 and 2892, respectively. The ratios of LSM and the 90% confidence intervals for the in-transformed parameters (AUC o-t, AUC inf, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, suggesting that Equoral and Neoral SGC are bioequivalent.