Stable and metastable hard-sphere crystals in fundamental measure theory.

Using fully minimized fundamental measure functionals, we investigate free energies, vacancy concentrations, and density distributions for bcc, fcc, and hcp hard-sphere crystals. Results are complemented by an approach due to Stillinger, which is based on expanding the crystal partition function in terms of the number n of free particles while the remaining particles are frozen at their ideal lattice positions. The free energies of fcc and hcp and one branch of bcc agree well with Stillinger's approach truncated at n=2. A second branch of bcc solutions features rather spread-out density distributions around lattice sites and large equilibrium vacancy concentrations and is presumably linked to the shear instability of the bcc phase. Within fundamental measure theory and the Stillinger approach (n=2), hcp is more stable than fcc by a free energy per particle of about 0.001k(B)T. In previous simulation work, the reverse situation has been found, which can be rationalized in terms of effects due to a correlated motion of at least five particles in the Stillinger picture.

Sensitization to indigenous pollen and molds and other outdoor and indoor allergens in allergic patients from saudi arabia, United arab emirates, and Sudan.

BACKGROUND: : Airborne allergens vary from one climatic region to another. Therefore, it is important to analyze the environment of the region to select the most prevalent allergens for the diagnosis and treatment of allergic patients. OBJECTIVE: : To evaluate the prevalence of positive skin tests to pollen and fungal allergens collected from local indigenous plants or isolated molds, as well as other outdoor and indoor allergens in allergic patients in 6 different geographical areas in the Kingdom of Saudi Arabia (KSA), the United Arab Emirates, and Sudan. MATERIAL AND METHODS: : Four hundred ninety-two consecutive patients evaluated at different Allergy Clinics (276 women and 256 men; mean age, 30 years) participated in this study. The selection of indigenous allergens was based on research findings in different areas from Riyadh and adjoining areas. Indigenous raw material for pollen grains was collected from the desert near the capital city of Riyadh, KSA. The following plants were included: Chenopodium murale, Salsola imbricata, Rumex vesicarius, Ricinus communis, Artiplex nummularia, Amaranthus viridis, Artemisia monosperma, Plantago boissieri, and Prosopis juliflora. Indigenous molds were isolated from air sampling in Riyadh and grown to obtain the raw material. These included the following: Ulocladium spp., Penicillium spp., Aspergillus fumigatus, Cladosporium spp., and Alternaria spp. The raw material was processed under Good Manufacturing Practices for skin testing. Other commercially available outdoor (grass and tree pollens) and indoor (mites, cockroach, and cat dander) allergens were also tested. RESULTS: : The highest sensitization to indigenous pollens was detected to C. murale (32%) in Khartoum (Sudan) and S. imbricata (30%) and P. juliflora (24%) in the Riyadh region. The highest sensitization to molds was detected in Khartoum, especially to Cladosporium spp. (42%), Aspergillus (40%), and Alternaria spp. (38%). Sensitization to mites was also very prevalent in Khartoum (72%), as well as in Abu Dhabi (United Arab Emirates) (46%) and Jeddah (KSA) (30%). CONCLUSIONS: : The allergenicity of several indigenous pollens and molds derived from autochthonous sources was demonstrated. Prevalence studies in different regions of KSA and neighbor countries indicate different sensitization rates to these and other outdoor and indoor allergens.

Conversion to sirolimus with calcineurin inhibitor elimination vs. dose minimization and renal outcome in heart and lung transplant recipients.

Sirolimus (SRL) has been used as an alternative immunosuppressant strategy to allow either dose minimization or complete withdrawal of calcineurin inhibitors (CNI) therapy to improve renal outcome. One hundred thirty-one heart and 55 lung transplant patients were converted from a CNI to SRL based immunosuppression, with CNI elimination in 25 patients, and dose reduction in 161 patients. Fifty-six (28%) patients died and 65 (33%) patients had a 25% or more decline in estimated glomerular filtration rate (eGFR) during a median follow-up of 18 months. The three groups (SRL only group n = 25; SRL + tacrolimus n = 94; SRL + cyclosporine n = 67) had an initial improvement in estimated glomerular filtration rate (p = 0.05), with subsequent similar slow decline in mean eGFR (repeated measures ANOVA, p = 0.96). After controlling for important potential confounding variables, the three groups had similar renal outcome (p = 0.40) and overall survival (p = 0.45). In conclusion, the benefits of CNI withdrawal vs. minimization as part of SRL-based regimens are similar with regard to renal outcomes and patient survival.

Intestinal parasitosis and use of untreated wastewater for agriculture in Settat, Morocco.

An evaluation was made of the risk of contamination by faecal parasites in the population from the use of wastewater in agriculture. The study was based in 3 rural clusters in the northern region of Settat city, Morocco: 2 rural clusters exposed to untreated wastewater in agriculture and 1 not exposed. The sample comprised 333 people aged 3-60+ years: 214 exposed and 119 non-exposed. Stool samples were collected and examined for intestinal parasites. The results showed that the prevalence of intestinal parasitosis (i.e. evidence of at least 1 type of parasite) in the exposed group was significantly higher that the non-exposed group (66.4% versus 31.9%; relative risk 2.1). The household crowding index was also higher in the exposed group.

Intestinal parasitosis and use of untreated wastewater for agriculture in Settat, Morocco

An evaluation was made of the risk of contamination by faecal parasites in the population from the use of wastewater in agriculture. The study was based in 3 rural clusters in the northern region of Settat city, Morocco: 2 rural clusters exposed to untreated wastewater in agriculture and 1 not exposed. The sample comprised 333 people aged 3-60+ years: 214 exposed and 119 non-exposed. Stool samples were collected and examined for intestinal parasites. The results showed that the prevalence of intestinal parasitosis [i.e. evidence of at least 1 type of parasite] in the exposed group was significantly higher that the non-exposed group [66.4% versus 31.9%; relative risk 2.1]. The household crowding index was also higher in the exposed group

Bioequivalence evaluation of 320 mg gemifloxacin tablets in healthy volunteers.

This study was done to compare the bioavailability of a new tablet formulation of gemifloxacin (gemifloxacin 320 mg/tablet) with that of the reference product (factive 320 mg/tablet). The bioequivalence of a single dose (320 mg) was assessed for gemifloxacin included in the test and reference products by comparing the pharmacokinetic parameters derived from the plasma concentration-time profiles following administration to 24 healthy male volunteers in a balanced, 2-period, 2-sequence, 2-way crossover design. Plasma concentrations of gemifloxacin were analyzed by a validated and sensitive HPLC assay developed in-house. The mean plasma concentration-time profiles are almost superimposable. 18 ANOVAs were performed to compare gemifloxacin plasma levels of the two formulations at each sampling time and there were no statistical differences between the two formulations. The parameters used to measure bioavailability were AUC0-t, AUC0-infinity and Cmax and they were calculated by a model-independent method. The parametric 90% confidence intervals of the mean values for the test/reference ratio were in each case well within the bioequivalence acceptable boundaries of 80-125% for AUCo-t, AUC0-infinity and Cmax. Data obtained in this study prove, by appropriate statistical methods, the essential similarity of plasma levels of gemifloxacin from the test product with those from the reference product suggesting equal clinical efficacy of these two products.

Hydroxyapatite-coated tibial implants compared with cemented tibial fixation in primary total knee arthroplasty. A randomized trial of outcomes at five years.

BACKGROUND: Although excellent long-term results have been reported with cemented tibial fixation, cementless fixation as a means to improve the longevity of total knee prostheses continues to be of interest to clinicians. The purpose of this study was to compare outcomes between cementless tibial fixation with hydroxyapatite and cemented tibial fixation in the first five years following primary total knee arthroplasty. METHODS: We performed a prospective, randomized clinical trial that included eighty-one patients with noninflammatory knee arthritis who underwent primary total knee arthroplasty when they were less than seventy years of age. The subjects were randomized at the time of surgery to be treated with either cementless tibial fixation with hydroxyapatite or cemented tibial fixation. Evaluations were performed preoperatively and at six months, one year, and five years postoperatively by a physical therapist who was blinded to group allocation. Self-reported pain and function, the primary outcomes, were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the RAND 36-Item Health Survey (RAND-36). Complications and revision rates were determined through a review of hospital records and at each patient evaluation. The Knee Society radiographic score was used to evaluate plain radiographs at each assessment. RESULTS: Seventy subjects (86%) completed the five-year assessment. Slightly more pain was reported in the hydroxyapatite group at six months as measured with both the WOMAC and the RAND-36, a difference that disappeared by one year postoperatively. No differences were seen in function, radiographic findings, or complications. No subject required revision of the tibial prosthesis during the study. CONCLUSIONS: At five years postoperatively, there is no difference between cementless tibial fixation with hydroxyapatite and cemented tibial fixation in terms of self-reported pain, function, health-related quality of life, postoperative complications, or radiographic scores.

Post-transplant ischemic injury is associated with up-regulated AlloMap gene expression.

BACKGROUND: The AlloMap gene expression test is used for the non-invasive detection of rejection. However, the impact of early post-transplant ischemic injury on subsequent AlloMap gene expression analysis has not been evaluated before. METHODS: Sixty seven heart transplant recipients, mean age 53 years, were evaluated at a mean 34 months post-transplant. AlloMap score was determined on the same day of heart biopsies. Nineteen patients had evidence of early post-transplant ischemic injury (Injury group). These were compared with the remaining 48 patients, Control group. RESULTS: Using multiple regression model with a backward selection method, post-transplant ischemic injury was found to be associated with significant increased AlloMap score compared with controls (31.5 +/- 4.6 vs. 26 +/- 6.2, p < 0.001). The Injury group had increased transplant vasculopathy (KM 5-year freedom from vasculopathy: 34% vs. 52%, p = 0.015), than Controls. CONCLUSIONS: Post-transplant ischemic injury is associated with up-regulated AlloMap gene expression, and hence, may provide another explanation for a high score in the absence of rejection.

Attrition from heart transplant waiting list for patients on ventricular assist devices is not affected by desensitization strategies.

BACKGROUND: Ventricular assist device (VAD) patients, who are commonly sensitized, can be successfully transplanted using strategies aimed at diminishing antibody burden. However, the impact of these therapies on outcomes for VAD patients on the waiting list is ill-defined. The following study was conducted to ascertain the relationship between desensitization therapies and attrition rate from the waiting list for VAD patients. METHODS: The VAD patients listed between July 1996 and June 2002 were used for this report. Transplant and inpatient pharmacy databases were queried for demographics, date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, and specific causes of death. RESULTS: Among 232 patients listed for heart transplantation who required bridging to transplantation with a VAD, 79 (34%) died while on the waiting list. Common causes of death included multisystem organ failure in 32 (40.5%), sepsis in 19 (24.0%), and stroke in 10 (12.6%) patients. While nearly 50% of these patients were sensitized at listing, only 5 (6.3%) patients received desensitization therapy following VAD implantation. Therapies included mycophenolate mofetil in 3 (3.7%) and IVIG in 2 (2.5%) patients. Not a single patient underwent plasmapheresis or OKT3 therapy. CONCLUSION: For patients bridged to heart transplantation with a VAD, attrition from the waiting list was associated with factors other than desensitization or induction regimens.

Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers.

This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.

Survival beyond 10 years following heart transplantation: The Cleveland Clinic Foundation experience.

BACKGROUND: Long-term survival after heart transplantation is a desirable although challenging goal. METHODS: We analyzed clinical outcomes in the cohort of 170 patients who have undergone heart transplantation at The Cleveland Clinic Foundation and survived >10 years. RESULTS: We found 10-year and 15-year survival rates of 54% and 41%, respectively, in these patients, but there was also a high incidence of complications, such as hypertension, renal dysfunction, transplant vasculopathy, and malignancy. CONCLUSIONS: Long-term survival following cardiac transplantation is possible although complications are frequent. Beyond 10 years, malignancy is a major cause of death.

Donor intracranial bleeding is associated with advanced transplant coronary vasculopathy: evidence from intravascular ultrasound.

OBJECTIVES: We evaluated the impact of spontaneous intracranial bleeding (ICB) in the donor on transplant coronary vasculopathy using serial intravascular ultrasound examinations. MATERIALS AND METHODS: Between January 1995 and December 2000, 72 recipients underwent cardiac transplantation from donors who had experienced spontaneous ICB (ICB group). Their findings using serial intravascular ultrasound analysis at baseline (within 1 month) and 1 year after transplantation were compared with 90 recipients who had undergone transplantation from trauma donors (trauma group). RESULTS: Compared with the Trauma group, the ICB group showed increased coronary intimal thickness (0.55 +/- 0.33 vs 0.39 +/- 0.3 mm; P = .034), plaque volume (3.84 +/- 2.5 vs 2.28 +/- 1.65 mm(3); P = .015) and plaque burden (7.4 vs 2%) at 1 year after transplantation. CONCLUSIONS: Donor spontaneous ICB is associated with significantly increased coronary vasculopathy.

Comparative bioavailability study of doxycycline hyclate (equivalent to 100 mg doxycycline) capsules (doxycin vs vibramycin) for bioequivalence evaluation in healthy adult volunteers.

This investigation was carried out to evaluate the bioavailability of a new capsule formulation of doxycycline (100 mg), doxycin, relative to the reference product, vibramycin (100 mg) capsules. The bioavailability was carried out in 24 healthy male volunteers who received a single dose (100 mg) of the test (A) and the reference (B) products after an overnight fast of at least 10 hours on 2 treatment days. The treatment periods were separated by a 2-week washout period. A randomized, balanced 2-way cross-over design was used. After dosing, serial blood samples were collected for a period of 48 hours. Plasma concentrations of doxycycline were analyzed by a sensitive and validated high-performance liquid chromatography assay. The pharmacokinetic parameters for doxycycline were determined using standard noncompartmental methods. The parameters AUC(0-t), AUC(0-infinity), Cmax, K(el), t(1/2) and Cmax/AUC(0-infinity) were analyzed statistically using log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pharmacokinetic parameters: AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were within the range 80-125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis of the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were 95.98-109.56%, 92.21 to 107.66%, 93.90-112.56%, and 96.0 to 106.91% respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) by the Schuirmann's two 1-sided t-tests. Therefore, the 2 formulations were considered to be bioequivalent.

The influence of donor gender on allograft vasculopathy: evidence from intravascular ultrasound.

BACKGROUND: Allograft vasculopathy is a major risk factor for mortality following cardiac transplantation. Several immune and nonimmune factors have been evaluated as risk factors for the development of coronary vasculopathy. OBJECTIVE: We evaluated the influence of donor gender on the progression of coronary vasculopathy in heart transplant recipients. METHODS: Eighty-nine heart transplant recipients (67 men, 22 women of mean age: 56 +/- 12 years) underwent serial volumetric intravascular ultrasound analysis (IVUS) at baseline (within 1 month) and at 1 year after transplantation. Patients were divided into four groups in relation to the donor-recipient gender status: female-female, n=17; female-male, n=28; male-female, n=5; male-male, n=39. Ultrasound images were recorded during an automated pullback and with an equal number of slices (average=22 per coronary vessel). The measured IVUS indices for the left anterior descending artery were: change in maximal intimal thickness, average intimal area, total plaque volume, and intimal index. RESULTS: Patients were similar in baseline characteristics. At 1 year after transplantation, IVUS indices of coronary vasculopathy were significantly increased among recipients of female allografts (P <.05). CONCLUSION: Heart transplant recipients of female allografts display increased coronary vasculopathy progression.

Severe renal dysfunction complicating cardiogenic shock is not a contraindication to mechanical support as a bridge to cardiac transplantation.

OBJECTIVES: This study investigated outcomes in patients with cardiogenic shock and severe renal dysfunction treated with ventricular assist devices (VAD) as a bridge to cardiac transplantation. BACKGROUND: Previous reports have documented poor survival in patients with cardiogenic shock and severe renal dysfunction treated with VAD. METHODS: We surveyed 215 consecutive patients who received a VAD from 1992 to 2000 and selected patients who had a serum creatinine > or =3.0 mg/dl at the time of VAD placement. Demographic, laboratory, and clinical outcome data were collected. RESULTS: Eighteen patients met the inclusion criteria. Mean serum creatinine at the time of VAD placement was 4.0 +/- 0.7 mg/dl (range 3.0 to 5.2 mg/dl). Seven patients required temporary renal support with continuous venovenous hemodialysis (CVVHD). Eleven patients underwent cardiac transplantation. At six months post-transplantation, mean serum creatinine was 2.0 +/- 0.6 mg/dl (range 1.3 to 3.5 mg/dl). None of the transplanted patients required subsequent renal support. Seven patients died with a VAD before transplantation. Three died early (<1 month) after VAD placement, and all three required CVVHD until death. Four patients survived for >1 month after VAD placement; all four had resolution of renal dysfunction with mean serum creatinine of 1.9 +/- 1.2 mg/dl (range 0.8 to 3.6 mg/dl) without the need for renal support. Overall 30-day and six-month survival after VAD placement, survival to transplantation, and survival one year post-transplantation were similar to patients without severe renal dysfunction. CONCLUSIONS: Contemporary use of VAD leads to resolution of severe renal dysfunction in most cardiogenic shock patients and comparable long-term outcomes to patients without renal dysfunction.

Urinary N-acetyl-beta-D-glucosaminidase in children with diabetes as an early marker of diabetic nephropathy.

We investigated urinary N-acetyl-beta-D-glucosaminidase (NAG) levels in children with type 1 diabetes as an early marker of tubular damage and studied its correlation with microalbuminuria and glycaemic control. The study group comprised 42 children with type 1 diabetes and 20 healthy children as control. Urinary NAG to urinary creatinine ratio, microalbuminuria, glycated haemoglobin (Hb A1c), blood urea and serum creatinine were estimated. Urinary NAG levels in the children with diabetes were significantly higher than those of controls. There were positive correlations between urinary NAG levels and microalbuminuria, Hb A1c and systolic and diastolic blood pressure values. We found that 59.5% of diabetic children were positive for urinary NAG, while 38.1% of them were positive for microalbuminuria.

Urinary N-acetyl-beta-D-glucosaminidase in children with diabetes as an early marker of diabetic nephropathy

We investigated urinary N-acetyl-beta-D-glucosaminidase [NAG] levels in children with type 1 diabetes as an early marker of tubular damage and studied its correlation with microalbuminuria and glycaemic control. The study group comprised 42 children with type 1 diabetes and 20 healthy children as control. Urinary NAG to urinary creatinine ratio, microalbuminuria, glycated haemoglobin [Hb A1c], blood urea and serum creatinine were estimated. Urinary NAG levels in the children with diabetes were significantly higher than those of controls. There were positive correlations between urinary NAG levels and microalbuminuria, Hb A1c and systolic and diastolic blood pressure values. We found that 59.5% of diabetic children were positive for urinary NAG, while 38.1% of them were positive for microalbuminuria

Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact.

BACKGROUND: The use of parenteral positive inotropic agents still remains a major component of therapy for patients with advanced decompensated congestive heart failure (CHF). However, no consensus guidelines have been developed for the appropriate selection of a first-line inotropic therapy. We sought to compare the clinical outcome and economic cost of dobutamine-based and milrinone-based therapy in patients with acute exacerbation of CHF. METHODS AND RESULTS: We retrospectively analyzed the outcome of 329 patients admitted to the heart failure unit with acute exacerbation of CHF. More patients were treated with dobutamine-based therapy (269/329, 81.7%) than with milrinone-based therapy (60/329, 18.3%). Both groups had similar baseline characteristics and similar hemodynamic profiles at baseline, with the exception of higher mean pulmonary arterial pressure in the milrinone group (47 mm Hg vs 42 mm Hg, P <.001). One hundred nine patients (40%) of the dobutamine group required parenteral nitroprusside for hemodynamic optimization compared with 11 patients (18%) in the milrinone group (P <.001). The use of parenteral nitroglycerin and dopamine was similar in both groups. There was no significant difference in the in-hospital mortality rate (dobutamine 7.8% vs milrinone 10%) or clinical outcome between the 2 groups. However, the average direct drug cost per patient was significantly reduced in the dobutamine group compared with the milrinone group ($45 +/- $10 vs $1855 +/- $350, P <.0001). CONCLUSION: Dobutamine-based therapy is an attractive approach for the treatment of decompensated advanced heart failure, achieving comparable clinical efficacy to milrinone with a significantly reduced economic cost.