A review of the mesotheliogenic potency of cleavage fragments found in talc.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management.

This review is intended to provide risk assessors and risk managers with a better understanding of issues associated with total exposures of human populations to ethylene oxide from endogenous and exogenous pathways. Biomonitoring of human populations and lab animals exposed to ethylene oxide has relied upon the detection of hemoglobin adducts such as 2-hydroxyethylvaline (HEV), which provides a useful measure of total exposure to ethylene oxide from all pathways. Recent biomonitoring data from CDC provide an excellent characterization of total exposure to ethylene oxide to the general U.S. population by demographic factors such as age, gender, and race as well as smoking habit, which might be comparable to previous measurements reported for humans and lab animals. The biochemical pathways including gastrointestinal (production by bacteria) and systemic (enzymatic production) pathways by which endogenous ethylene is generated and converted to ethylene oxide are described. The relative importance of endogenous pathways and exogenous pathways via ambient air or tobacco smoke was quantified based upon available data to characterize their relative importance to total exposure. Considerable variation was noted for HEV measurements in human populations, and important sources of variation for all pathways are discussed. Issues related to risk assessment and risk management of human populations exposed to ethylene oxide are provided within the context of characterizing total exposure, and data needs for supporting future risk assessment identified.

Polymorphisms in the prostate-specific antigen gene promoter do not predict serum prostate-specific antigen levels in African-American men.

A major problem with the use of serum prostate-specific antigen (PSA) in predicting prostate cancer risk is the considerable variability of such measurements. Cramer et al. identified a set of single-nucleotide polymorphisms (SNPs) in the upstream regulatory region of the PSA gene that were each associated with increased promoter activity and serum PSA, further suggesting that genotyping these SNPs could be useful in improving the predictive value of PSA screening. In order to replicate this finding, DNA samples from 475 African-American men were genotyped for the same SNPs and no association was observed with either serum PSA level or prostate cancer diagnosis.

Rifabutin absorption in humans: relative bioavailability and food effect.

The relative bioavailability of the capsule dose form (150 mg) and the effect of high-fat food were assessed in a randomized, three-way crossover trial of rifabutin in 12 healthy male volunteers. Each subject received a single 150 mg dose as a solution (treatment A, fasted) or a capsule with food (treatment B) and without food (treatment C), with a 2-week washout period. Serial plasma and urine samples were obtained for 168 and 48 hours, respectively, and rifabutin and its active metabolite, 25-O-deacetyl-rifabutin, quantitated by a validated HPLC procedure. The mean +/- SD maximum concentration for rifabutin in plasma was 238 +/- 65, 156 +/- 52, and 188 +/- 50 ng/ml, time to reach peak concentration was 2.5 +/- 0.4, 5.4 +/- 1.6, and 3.0 +/- 1.1 hours, and the area under the plasma concentration-time curve from zero to infinity [AUC(0-infinity)] was 2989 +/- 726, 2640 +/- 891, and 2516 +/- 601 ng.hr/ml for the solution and the capsule during the fed and fasted states, respectively. Percentage of dose excreted in the urine as unchanged rifabutin was 11.0% +/- 2.4%, 11.4% +/- 4.9%, and 9.1% +/- 2.1% for treatments A, B, and C, respectively. The corresponding AUC(0-infinity) values for the equiactive metabolite 25-O-deacetyl-rifabutin, were 400 +/- 184, 361 +/- 187, and 298 +/- 102 ng.hr/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase I dose-ranging safety and pharmacokinetics study of a novel oral thromboxane synthase inhibitor, FCE 22, 178.

A 100- to 3200-mg dose range of FCE 22,178 was studied in this phase I single-dose escalation safety/kinetics study. After oral administration, a rapid drug absorptive phase and a biexponential disposition profile were observed. Mean estimates of the terminal elimination half-life of FCE 22,178, over the doses studied, ranged from 7.6 to 14.4 hours. A disproportionate increase in both maximum peak plasma concentration (Cmax) and area under the curve (AUC0-infinity) was noticed for doses higher than 400 mg. Mean estimates of systemic clearance (CLs/F) over the 100- to 400-mg doses were 0.053 to 0.064 L/hour/kg, and were significantly higher for the three higher dose levels. This nonlinearity appears to be related to the changes in oral bioavailability. Estimates of distribution volume (Vd, lambda z/F) for FCE 22,178 increased from 0.75 L/kg at the 100-mg dose to 3.00 L/kg at the 3200-mg dose, and renal clearance (CLr) also increased with dose. Both observations may be related to an increase in free fraction of FCE 22,178 at higher doses. Urinary excretion of unchanged drug averaged < 10% for all dose levels. The urinary excretion of the glucuronide metabolite (M1) averaged 41 to 70% for doses up to 400 mg, but diminished to 13% at the 3200-mg dose. The disposition of M1 appeared to be formation-rate limited. In addition, the ratio of the formation to the disposition clearance for M1 was relatively stable and apparently dose independent. No drug-related adverse experiences were observed over the studied dose range after single doses at FCE 22,178.

Cerebellar astrocytoma invading the musculature and soft tissues of the neck. Case report.

A case of cerebellar astrocytoma with unusual growth pattern in an 8-year-old boy is reported. The tumor had some histological hallmarks of malignancy (focally high cellularity, mitotic figures, necroses, and calcifications) and, 17 months after subtotal removal, recurred as a nuchal mass in the area of the incision, infiltrating first the skeletal musculature and later other soft tissues of the neck, including lymph nodes. Although cerebellar astrocytomas may recur locally and some may even seed through the cerebrospinal fluid, this is the first reported case of a tumor of this group to infiltrate skeletal muscle and other soft tissues of the neck. The patient underwent five operations to relieve the cervical organs from pressure.

Digital nerve-grafting for traumatic defects. Use of the lateral antebrachial cutaneous nerve.

We used segments of the lateral antebrachial cutaneous nerve to graft defects in forty-two digital nerves in thirty-five patients. Age was a more important prognostic indicator for functional sensibility than either the length of the nerve graft or the time-interval from injury to grafting. The younger patients did better. A battery of eight tests was used to determine functional sensibility scores. All patients improved and 40 per cent had completely normal sensibility.

Injuries of the cervical spine in high school wrestling.

Severe injuries to the cervical spine and spinal cord have been widely reported from many causes: automobile accidents, diving mishaps, falls, and contact sports. This paper concerns three young men who sustained severe trauma to the cervical spine and spinal cord during high school wrestling. Certain head-holds are prone to cause such injuries. Their tetraparesis and tetraplegia were reversed by reducing the fracture-dislocation and internal stabilization, in one case by decompressive laminectomy when no bony disruption was encountered. Their recoveries were satisfactory, but prevention of these cervical injuries may be accomplished by elimination of the more dangerous holds in wrestling.

Infections of the hand.

The unique anatomic arrangements in the hand make possible rapid extension of infections through synovial-lined spaces if abscesses are not drained and pressure is allowed to build up. Adequate knowledge of these anatomic features and of routes for surgical drainage is mandatory if one is to give adequate management of hand infections. Localized processes, such as paronychia, felon, and human bite infections also require special insight for adequate treatment.

High-compression injection injuries to the hand.

The importance of a specific effect of various agents injected into the hand cannot be overemphasized, since the outpouring of inflammatory edema fluid as a response to the more sclerotic solutions leads to tamponade and occlusion of digital vessels. Moreover, it has been shown that the vascular insufficiency is further increased by actual necrosis of small vessel walls caused by these solutions, which coagulate the protein of the arteriolar and arterial wall. The pathologic physiology is described, which indicates that the usual case of high-compression injection of foreign material into the hand develops severe and sometimes catastrophic consequences related to the tamponade effect occurring from the compression force, the quantity of material injected, and the subsequent outpouring of inflammatory edema fluid occasioned by the chemical irritation of these substances within the tissues. Based upon these findings, it has been pointed out that early treatment of these injuries is mandatory, with adequate incision along diagonal lines on the palmar surface of the hand made with the idea of decompressing the tamponade effect on the digital vessels as well as evacuation of the foreign material. Careful cleansing of the surrounding tissues to remove extensions of the material from the central mass is important. Finally, the postoperative measures, the late treatment procedures, and the rehabilitative surgical procedures have been described.

Treatment of upper extremity reflex sympathetic dystrophy with joint stiffness using sympatholytic Bier blocks and manipulation.

Twenty patients with reflex sympathetic dystrophy involving the upper extremity with associated joint stiffness were treated by manipulation under Bier blocks composed of lidocaine, methylprednisolone, and reserpine or guanethidine. Depending on the patients' response, repeat blocks were performed at 48- to 72-hour intervals. Range of motion in the affected joints (primarily the hand and wrist) improved from a pre-block mean of 46% to 81% of normal following the blocks. Patients also reported an 80% mean improvement in their pain. The treatment of advanced reflex sympathetic dystrophy using joint manipulation under sympatholytic Bier blocks appears to be a safe and effective method of treatment.

Determination of nicorandil in plasma using high-performance liquid chromatography with photoconductivity and ultraviolet detection. Application to pre-clinical pharmacokinetics in beagle dogs.

A sensitive and precise method for the determination of nicorandil, a new anti-anginal medication, is reported. The method involves solid-phase extraction of the drug and internal standard using Bond-Elut C18 extraction columns, reversed-phase high-performance liquid chromatography on a Zorbax-Phenyl column and detection with photoconductivity and ultraviolet detection in series. Photoconductivity, performed with the Tracor 965 photoconductivity detector, provided a limit of detection of 2 ng/ml in plasma (between-day coefficient of variation of 15%) but the linear range of response was limited to only about 100 ng/ml. Ultraviolet detection in series with the photoconductivity detector extended the linear range of the analytical system to 1000 ng/ml (coefficient of variation 4.4%). The utility of the method is demonstrated in a dog pharmacokinetic study in which a 5-mg intravenous dose was compared to a 10-mg oral solution dose in six beagle dogs. The oral solution was absorbed rapidly, achieving an average maximum concentration of 857 ng/ml in 11.2 min. The absolute bioavailability of nicorandil in dogs in this study was determined to be 84.2%.

Scapholunate instability following ganglion cyst excision. A case report.

Complications following ganglion cyst excision include a 3%-50% recurrence rate, wrist stiffness, infection, neuroma formation, and keloid formation. Scapholunate instability is almost never seen as a complication of ganglion excision. Scapholunate instability occurred following excision of a dorsal ganglion in the wrist of a 38-year-old man.

Transfer of sensibility in the hand: a new method to restore sensibility in ulnar nerve palsy with use of microsurgical digital nerve translocation.

We describe a technique of translocation of a functioning proximal digital nerve into a non-functional distal digital nerve. Seventeen cases of digital nerve translocation have been done, thirteen were done for treatment of ulnar nerve palsy. Three patients were less than six months after operation and one had died, leaving thirteen available for follow-up. The average length of follow-up is seventy-eight months. Outcome was assessed objectively by functional sensory testing and subjectively by questionnaire. Ten (85%) of twelve of those tested had return of two-point discrimination. In all cases proprioception and protective sensibility were restored to the affected digit.

Median nerve compression caused by a synovial cyst.

A case of median nerve compression at the wrist by a synovial cyst is described. Precise localization of the source of the synovial cyst was determined by surgical exploration and visualization of the carpal tunnel space.

The tenon method of small joint arthrodesis in the hand.

A technique for arthrodesis of small joints of the hand is described that uses a tenon to secure apposition that has good intrinsic stability as well as a large surface area of cancellous bony contact. A minimum of postoperative immobilization is required. The tenon arthrodesis method has been employed in 85 joints. The literature shows pseudoarthrosis rates of 0 to 33%. This technique had a 2.3% failure rate that compares favorably with those in other published series.

The reliability of interpretation of photoscreening results with the off PS-100 in Headstart preschool children.

BACKGROUND: Photoscreening has emerged as one of the newest means of screening children to detect amblyogenic factors. In the preschool population, it is important to reliably screen children who are at risk for developing amblyopia. This research was undertaken to determine the reliability of the interpretation of photoscreening results in a Headstart preschool population. METHODS: Fifty-four African-American children aged 3 to 5 years of age were examined using the MTI PS-100 photorefractor. Five health care professionals with no prior knowledge of photoscreening techniques were asked to perform independent, masked interpretations of a set of 54 Polaroid snapshots. Their interpretations followed a training session by a company consultant. RESULTS: The kappa coefficient for reliability of interpretation between observers was 0.55. This kappa value indicates that there was moderate agreement between the observers when identifying amblyogenic conditions in a child. CONCLUSIONS: Non-vision professionals using this device for the assessment of children will probably achieve only moderate levels of agreement on pass-fail decisions at first. Higher reliability reported previously by more experienced photoscreeners indicates that agreement could improve with advanced training, feedback regarding diagnostic findings, and experience. Methods to improve the technique, the device, or the training of the examiners are discussed.

A sensitive method for quantitation of rifabutin and its desacetyl metabolite in human biological fluids by high-performance liquid chromatography (HPLC).

Sensitive HPLC-UV methodology has been developed and validated for quantitating rifabutin, an antimycobacterial, and its 25-desacetyl metabolite, LM-565, in human plasma and urine. The HPLC separation for both plasma and urine samples was performed on an ODS, 5-microns, reverse-phase column (25 cm x 4.6-cm ID) using a mobile phase of acetonitrile/0.05 M potassium phosphate, pH 4.2, with triethylamine, (38:61.5:0.5, v/v), at a flow rate of 1.0 ml/min. The separation eluate was monitored by absorbance at 275 nm. Plasma samples (1 ml) were spiked with an internal standard (medazepam), buffered at pH 7.4 and extracted with 80:20 (v/v) hexane:ethyl acetate, and then back extracted with acidified water (0.05 M H3PO4). Linearity was established between 5.0-800 and 2.5-400 ng/ml for rifabutin and LM-565, respectively. Intraday imprecision for rifabutin and LM-565 plasma quality controls prepared at 7.3 and 3.2 ng/ml, respectively, was less than 15% relative standard deviation (RSD). Absolute recovery for parent drug and metabolite, from plasma, was greater than 90% throughout the respective dynamic ranges and greater than 70% for medazepam. Urine samples (1 ml) were acidified with 50 microliters of 3.6 M H2SO4 and diluted with 0.1 M ammonium acetate. Linearity was established between 100 and 5000 ng/ml for both rifabutin and LM-565. Intraday imprecision for a urine control at 200 ng/ml was less than or equal to 12% RSD for either component. The method is currently being used to support Phase I kinetics program for rifabutin in prophylaxis of MAC infection of AIDS patients. Application of this method to a bioavailability assessment is presented.

Miniature Kinematic Mirror Mount for UHV Service.

A miniature kinematic mount allows adjustment of mirror pointing inside ultrahigh vacuum (UHV) by rotating finely threaded screws outside of vacuum. The mount assembly is less than 0.620 in. in diameter, so it fits through the standard tubing used with miniature conflat flanges. The mount is a point-iine-plane device with a sapphire ball at the point position, so that no lubrication is required in vacuum.