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Biomedical subjects

J A Smith

Publications and source records attributed to J A Smith.

At least 37 records · Page 2Linked to original sources
PubMed2003

Identification of risk factors for future fracture in patients following distal forearm fracture.

The challenge for healthcare systems around the world is delivering timely preventative strategies to subjects most likely to develop fragility fractures. The success or failure of national campaigns will be determined at local level, and many studies to date have found under-utilization of osteoporosis treatment strategies due to reduced public and healthcare professional awareness. An important link between the at-risk patients and their appropriate therapy is their identification and assessment. In the context of a medium sized secondary care provider, this study examined the efficiency of a nurse-led service for assessing women following distal forearm fracture, looking for additional risk factors for future fracture and also looking at uptake of the assessment programme among the target population. Two hundred and two women, median (range) age 69 (50-91) years presented with distal forearm fracture over a 9-month period. Fifty-four subjects did not participate in the study: they were significantly older than those who did ( P<0.002). One hundred and forty-eight subjects underwent assessment of falls risk, future hip fracture risk and calcaneal ultrasound attenuation measurement: 107 attended for assessment at the hospital and 41 required a health professional to visit at their place of residence-the latter group were significantly older ( P<0.0002). Of 148 subjects assessed, 76 (51%) had one or more risk factors for a fall: these subjects were significantly older ( P<0.0002) and more likely to have required a home visit ( P<0.002). Twenty-seven (18%) were considered at risk of a future hip fracture: again they were older and more likely to have required a home visit ( P<0.0005). Ninety-one subjects (61%) had a calcaneal ultrasound attenuation T-score below -2.0, and were referred for bone densitometry: again, they were older ( P<0.0002) and more likely to have required a home visit ( P<0.05). Bone densitometry demonstrated osteoporosis in 47 (52%) of those with low attenuation, osteopenia in 31 and normal bone density in 13. Of 76 subjects deemed to be at risk of falls, 31 (41%) had osteoporosis demonstrated on bone densitometry and of those at risk of future hip fracture, 12 (44%) had osteoporosis. Only nine (22%) subjects who received home visits had no risk factors for falls or hip fracture and normal bone density, compared to 45 (42%) of those who attended hospital. This study has demonstrated that the efficiency of a program to assess additional risk of future fracture in a population who have already fractured may be influenced by where the assessment is delivered: it may be that the patients at greatest risk did not avail of the service.

Accidental Falls↗
PubMed2003

Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer.

BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors involved in genetic control of many cellular processes. PPAR and PPAR have been implicated in colonic malignancy. Here we provide three lines of evidence suggesting an inhibitory role for PPAR in colorectal cancer development. METHODS: Levels of PPAR mRNA and protein in human colorectal cancers were compared with matched non-malignant mucosa using RNAse protection and western blotting. APC(Min)/+ mice were randomised to receive the PPAR activator methylclofenapate 25 mg/kg or vehicle for up to 16 weeks, and small and large intestinal polyps were quantified by image analysis. The effect of methylclofenapate on serum stimulated mitogenesis (thymidine incorporation), linear cell growth, and annexin V and propidium iodide staining were assessed in human colonic epithelial cells. RESULTS: PPAR (mRNA and protein) expression levels were significantly depressed in colorectal cancer compared with matched non-malignant tissue. Methylclofenapate reduced polyp area in the small intestine from 18.7 mm(2) (median (interquartile range 11.1, 26.8)) to 9.90 (4.88, 13.21) mm(2) (p=0.003) and in the colon from 9.15 (6.31, 10.5) mm(2) to 3.71 (2.71, 5.99) mm(2) (p=0.009). Methylclofenapate significantly reduced thymidine incorporation and linear cell growth with no effect on annexin V or propidium iodide staining. CONCLUSIONS: PPAR may inhibit colorectal tumour progression, possibly via inhibition of proliferation, and may be an important therapeutic target.

Animals↗
PubMed2002

The neurogenetics of mucolipidosis type IV.

BACKGROUND: Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. OBJECTIVE: To comprehensively characterize the clinical and genetic abnormalities of MLIV. METHODS: Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for follow-up every 1 to 2 years for up to 5 years. Standard clinical, neuroimaging, neurophysiologic, and genetic techniques were used. RESULTS: All patients had varying degrees of corneal clouding, with progressive optic atrophy and retinal dystrophy. Twenty-three patients had severe motor and mental impairment. Motor function deteriorated in three patients and remained stable in the rest. All had a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron deficiency or anemia. Head MRI showed consistent characteristic findings of a thin corpus callosum and remained unchanged during the follow-up period. Prominent abnormalities of speech, hand usage, and swallowing were also noted. Mutations in the MCOLN1 gene were present in all patients. Correlation of the genotype with the neurologic handicap and corpus callosum dysplasia was found. CONCLUSIONS: MLIV is both a developmental and a degenerative disorder. The presentation as a cerebral palsy-like encephalopathy may delay diagnosis.

Adolescent↗
PubMed2002

Footstrike is the major cause of hemolysis during running.

There is a wide body of literature reporting red cell hemolysis as occurring after various forms of exercise. Whereas the trauma associated with footstrike is thought to be the major cause of hemolysis after running, its significance compared with hemolysis that results from other circulatory stresses on the red blood cell has not been thoroughly addressed. To investigate the significance of footstrike, we measured the degree of hemolysis after 1 h of running. To control for the potential effects of oxidative and circulatory stresses on the red blood cell, the same subjects cycled for 1 h at equivalent oxygen uptake. Our subjects were 10 male triathletes, who each completed two separate 1-h sessions of running and cycling at 75% peak oxygen uptake, which were performed in random order 1 wk apart. Plasma free hemoglobin and serum haptoglobin concentrations were measured as indicators of hemolysis. We also measured methemoglobin as a percentage of total hemoglobin immediately postexercise as an indicator of red cell oxidative stress. Plasma free hemoglobin increased after both running (P < 0.01) and cycling (P < 0.01), but the increase was fourfold greater after running (P < 0.01). This was reflected by a significant fall in haptoglobin 1 h after the running trials, whereas no significant changes occurred after cycling at any sample point. Methemoglobin increased twofold after both running and cycling (P < 0.01), with no significant differences between modes of exercise. The present data indicate that, whereas general circulatory trauma to the red blood cells associated with 1 h of exercise at 75% maximal oxygen uptake may result in some exercise-induced hemolysis, footstrike is the major contributor to hemolysis during running.

Adult↗
PubMed2002

Estimating the prevalence of inbreeding from incomplete pedigrees.

A previous review of inbreeding in natural populations suggested that close inbreeding (inbreeding coefficient f = 0.25) is generally rare in wild birds and mammals. However, the review did not assess rates of moderate inbreeding (f = 0.125), which may make a rather larger contribution to overall inbreeding in a population. Furthermore, previous studies may have underestimated the prevalence of inbreeding in wild populations with incomplete pedigrees. By categorizing inbreeding events by the relationship of the parental pair, we suggest a simple method for estimating rates of close and moderate inbreeding from incomplete pedigree data. We applied this method to three wild populations of ruminants: red deer on Rum, Scotland, Soay sheep on Hirta, Scotland and reintroduced Arabian oryx on the Jiddat-al-Harasis, Oman. Although paternal half-sib pairs were the most common category of inbreeding in all three populations, there was considerable variation among populations in the frequencies of the various categories of inbreeding. This variation may be largely explained by differences in population size and dynamics, in maternal and paternal sibship size and in the overlap of reproductive lifespan of consecutive generations. Close and moderate inbreeding appear to be a routine part of breeding behaviour in these ruminant populations.

Animals↗
PubMed2002

Characterization of specific IgE response in vitro against protein and drug allergens using atopic and normal donors.

BACKGROUND: As the incidence of allergy to different compounds increases in society, the need to understand and characterize specific IgE responses becomes obvious. Different cell culture systems have been evaluated for their ability to support such IgE secretion. METHODS: One system employed human peripheral lymphocytes (PBL) from normal donors stimulated with anti-CD3 activated T cells with or without the presence of allergens like benzylpenicillin (BP) and Phlenum pratense (PP). Secretion of IgE was analyzed in ELISA and compared to the IgG response to the nonallergenic antigen tetanus toxoid (TT). Another system employed stimulation of T and B cells with a heterotope, consisting of a T helper cell epitope derived from TT, and a B cell allergen epitope derived from BP. The specific IgE secretion was compared, using lymphocytes from normal as well as BP-allergic donors. RESULTS: Anti-CD3 stimulated T cells supported BP-specific IgE secretion in six of 11 normal donors. This response was inhibited in four donors and enhanced in two donors by the addition of the BP-allergen to the culture. In contrast, addition of the protein allergen (PP) or antigen (TT) to the same culture system inhibited both IgE and IgG synthesis in all experiments. Cells from the majority (10/16) of the BP-allergic donors failed to produce BP-specific IgE in vitro, when cultured in the presence of allergen. CONCLUSIONS: An allergen specific immune response is readily generated in vitro. The differential response against benzylpenicillin between different donor categories most probably reflects the level of pre-exposure to this allergen in vivo.

Allergens↗
PubMed2002

The pollination ecology of Grevillea beadleana McGillivray, an endangered shrub from northern New South Wales, Australia.

Grevillea beadleana (Proteaceae) is an endangered species known from five populations in northern New South Wales, Australia. The reproductive ecology of G. beadleana was compared in two populations with a ten-fold difference in the number of plants. Grevillea beadleana was found to be self-compatible in both populations and an examination of pollen viability and stigma maturation revealed that the species is protandrous. Flowering within inflorescences is acropetallous. In the first season plants in the largest population produced approx. ten-fold more inflorescences than those in the smaller population and, although the number of flowers per inflorescence did not vary significantly between populations the first season, the larger population produced more fruit per inflorescence than the smaller population. However, fruit to flower ratios were less than 0.2 in both seasons and populations. In both populations the number of fruit was significantly greater at the proximal end of the inflorescence, where flowers open first, compared with medial and distal positions. Several bird species were observed visiting flowers, although few birds were recorded foraging at plants in the smaller population. Within both populations, birds tended to make more within- than between-plant visits. Self-compatibility, acropetally and proximal fruit-set, combined with the predominantly within-plant movement of honeyeaters, suggests inbreeding may be common within both populations of G. beadleana. Pollination and fruiting success are discussed for G. beadleana and breeding systems among rare and common taxa in Grevillea are reviewed.

Animals↗
PubMed2001

Novel engagement of CD14 and multiple toll-like receptors by group B streptococci.

Group B streptococcus (GBS) imposes a major health threat to newborn infants. Little is known about the molecular basis of GBS-induced sepsis. Both heat-inactivated whole GBS bacteria and a heat-labile soluble factor released by GBS during growth (GBS-F) induce nuclear translocation of NF-kappaB, the secretion of TNF-alpha, and the formation of NO in mouse macrophages. Macrophages from mice with a targeted disruption of MyD88 failed to secrete TNF-alpha in response to both heat-inactivated whole bacteria and GBS-F, suggesting that Toll-like receptors (TLRs) are involved in different aspects of GBS recognition. Immune cell activation by whole bacteria differed profoundly from that by secreted GBS-F. Whole GBS activated macrophages independently of TLR2 and TLR6, whereas a response to the secreted GBS-F was not observed in macrophages from TLR2-deficient animals. In addition to TLR2, TLR6 and CD14 expression were essential for GBS-F responses, whereas TLR1 and TLR4 or MD-2 did not appear to be involved. Heat lability distinguished GBS-F from peptidoglycan and lipoproteins. GBS mutants deficient in capsular polysaccharide or beta-hemolysin had GBS-F activity comparable to that of wild-type streptococci. We suggest that CD14 and TLR2 and TLR6 function as coreceptors for secreted microbial products derived from GBS and that cell wall components of GBS are recognized by TLRs distinct from TLR1, 2, 4, or 6.

Animals↗
PubMed2001

Comparison of three techniques to measure unsaturated-zone air permeability at Picatinny Arsenal, NJ.

The purpose of this study is to compare three techniques to measure the air permeability of the unsaturated zone at Picatinny Arsenal, NJ and to examine the effects of moisture content and soil heterogeneity on air permeability. Air permeability was measured in three ways: laboratory experiments on intact soil cores, field-scale air pump tests and calibration of air permeability to air pressures measured in the field under natural air pressure conditions using a numerical airflow model. The results obtained from these three methods were compared and found to be similar. Laboratory experiments performed on intact cores measured air permeability values on the order of 10(-14) to 10(-9) m2. Low-permeability cores were found between land surface and a depth of 0.6 m. The soil core data were divided into two layers with composite vertical permeability values of 1.3 x 10(-13) m2 from land surface to a 0.6-m depth and 3.8 x 10(-10) m2 for the lower layer. Analyses of the field-scale pump tests were performed for two scenarios: one in which the entire unsaturated zone was open to the atmosphere and one assuming a cap of low permeability extending 0.6 m below land surface. The vertical air permeability values obtained for the open scenario ranged from 1.2 x 10(-9) to 1.5 x 10(-9) m2, and ranged from 3.6 x 10(-9) to 6.8 x 10(-9) m2 in the lower layer, assuming an upper cap permeability of 6.0 x 10(-14) m2. The results from the open scenario are much higher than expected and the possible reasons for this ambiguity are discussed. The results from the capped scenario matched closely with those from the other methods and indicated that it is important to have background information on the study site to correctly analyze the pump test data. The optimized fit of the natural subsurface air pressure was achieved with an intrinsic permeability value of 3.3 x 10(-14) m2. When the data were refitted to the model assuming two distinct layers of the unsaturated zone, the optimized fit was achieved with intrinsic air permeabilities of 1.6 x 10(-14) m2 for the upper, low-permeability region and 8.4 x 10(-9) m2 for the lower region. Vertical air-permeability predictions from the three methods are similar provided that soil cores are collected from all representative depths to account for heterogeneous layers and that the correct assumptions are made when analyzing field-scale pump test data.

Air↗
PubMed2001

Acute biomechanical and histological effects of intradiscal electrothermal therapy on human lumbar discs.

STUDY DESIGN: Human cadaver lumbar spines were used to assess the acute effects of intradiscal electrothermal therapy in vitro. OBJECTIVE: To determine whether intradiscal electrothermal therapy produces acute changes in disc histology and motion segment stability. SUMMARY OF BACKGROUND DATA: Intradiscal electrothermal therapy has been introduced as an alternative for the treatment of discogenic low back pain. Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested including shrinkage of the nucleus or sealing of the anulus fibrosus by contraction of collagen fibers, and thermal ablation of sensitive nerve fibers in the outer anulus. METHODS: Intradiscal electrothermal therapy was performed with the Spinecath by Oratec on 19 fresh, frozen human lumbar cadaver specimens. In a separate study, eight specimens were tested biomechanically and instrumented to map the thermal distribution, whereas five specimens were tested only biomechanically, both before and after intradiscal electrothermal therapy. Six additional specimens were heated with intradiscal electrothermal therapy, and the resulting canal was backfilled with a silicone rubber compound to allow colocalization of the catheter and anular architecture. RESULTS: A consistent pattern of increased motion and decreased stiffness was observed. For the specimens in which only biomechanical measurements were taken, a 10% increase in the motion, on the average, at 5 Nm torque was observed after intradiscal electrothermal therapy. No apparent alteration of the anular architecture was observed around the catheter site in the intradiscal electrothermal therapy-treated discs. CONCLUSION: The data from this study suggest that the temperatures developed during intradiscal electrothermal therapy are insufficient to alter collagen architecture or stiffen the treated motion segment acutely.

Adult↗
PubMed2001

Clinical outcome of trans-sacral interbody fusion after partial reduction for high-grade l5-s1 spondylolisthesis.

STUDY DESIGN: A clinical retrospective study was conducted. OBJECTIVE: To evaluate the clinical and radiographic outcome of reduction followed by trans-sacral interbody fusion for high-grade spondylolisthesis. SUMMARY OF BACKGROUND DATA: In situ posterior interbody fusion with fibula allograft has improved the fusion rates for patients with high-grade spondylolisthesis. The use of this technique in conjunction with partial reduction has not been reported. METHODS: Nine consecutive patients underwent treatment of high-grade (Grade 3 or 4) spondylolisthesis with partial reduction followed by posterior interbody fusion using cortical allograft. The average age at the time of surgery was 27 years (range, 8-51 years), and the average follow-up period was 43 months (range, 24-72 months). Before surgery, eight patients had low back pain, seven patients had radiating leg pain, and five patients had hamstring tightness. The average grade of spondylolisthesis by Meyerding grading was 3.9 (range, 3-5). Charts and radiographs were evaluated, and outcomes were collected by use of the modified SRS outcomes instrument. RESULTS: Radiographic indexes demonstrated significant improvement with partial reduction and fusion. The slip angle, as measured from the inferior endplate of L5, improved from 41.2 degrees (range, 24-82 degrees ) before surgery to 21 degrees (range, 5-40 degrees ) after surgery. All the patients were extremely or somewhat satisfied with surgery. The two patients who underwent this operation without initial instrumentation experienced fractures of their interbody grafts. Both of these patients underwent repair of the pseudarthrosis with placement of trans-sacral pedicle screw instrumentation and subsequent fusion. CONCLUSIONS: Partial reduction followed by posterior interbody fusion is an effective technique for the management of high-grade spondylolisthesis in pediatric and adult patient populations, as assessed by radiographic and clinical criteria. Pedicle screw instrumentation with the sacral screws capturing L5 is recommended when this technique is used for the treatment of high-grade spondylolisthesis. According to the clinical and radiographic results from this study, partial reduction and posterior fibula interbody fusion supplemented with pedicle screw instrumentation is an effective technique for select patients with high-grade spondylolisthesis at L5-S1.

Adolescent↗
PubMed2001

Management of fixed sagittal plane deformity: results of the transpedicular wedge resection osteotomy.

STUDY DESIGN: Retrospective review of a consecutive clinical series. OBJECTIVES: To evaluate the efficacy of the transpedicular wedge resection osteotomy as a technique for correction of sagittal and coronal deformity and to assess the clinical value of the procedure as assessed by patient satisfaction. SUMMARY OF BACKGROUND DATA: The transpedicular wedge resection osteotomy is a well-established procedure for management of fixed sagittal deformity in ankylosing spondylitis. The utility of the procedure for applications in fixed deformity other than ankylosing spondylitis has not been demonstrated, and the efficacy of the procedure in the correction of coronal deformity has not been reported. METHODS: A total of 13 consecutive cases undergoing transpedicular wedge resection osteotomy for the management of sagittal deformity of any etiology were reviewed. Radiographic studies, complications, and satisfaction assessment using the modified Scoliosis Research Society instrument were the outcome parameters measured. RESULTS: Etiologies of deformity included postsurgical, ankylosing spondylitis, idiopathic, and infectious. Measurement of C7 sagittal plumb line to sacrum improved 63% at the most recent follow-up. Lumbar lordosis increased from -15.5 degrees to -45.4 degrees. Coronal balance was improved in all patients who had preoperative imbalance, with an average improvement of 60% maintained at follow-up. Patient satisfaction was high in all patients and not dependent on the etiology of deformity. CONCLUSIONS: The transpedicular wedge resection osteotomy is an effective procedure for the management of fixed sagittal deformity and is generalizable for multiple etiologies. Simultaneous correction of coronal deformity is possible. The clinical value of the procedure is demonstrated in high rates of patient satisfaction.

Adult↗
PubMed2001

Development of a simplified, sensitive high-performance liquid chromatographic method using fluorescence detection to determine the concentration of UCN-01 in human plasma.

UCN-01 is a naturally derived anticancer agent isolated in the culture broth of actinomyces streptomyces. We have developed a sensitive high-performance liquid chromatographic method for the determination of UCN-01 in human plasma. UCN-01 was isolated from human plasma after intravenous administration, by using 100% ice-cold acetonitrile liquid-liquid phase extraction. Liquid chromatographic separation was achieved by isocratic elution on a phenyl analytical column. The mobile phase consisted of acetonitrile-0.5 M ammonium acetate (45:55) with 0.2% triethylamine added as a modifier. The UCN-01 peak was identified from other peaks using fluorescence excitation energy and emission energy wavelengths of 310 and 410 nm, respectively. Retention time for UCN-01 was 4.2 +/- 0.5 min. The UCN-01 peak was baseline resolved, with nearest peak at 2.6 min distance. No interfering peaks were observed at the retention time of UCN-01. Peak area amounts from extracted samples were proportional over the dynamic concentration range used: 0.2 to 30 microg/ml. Mean recoveries of UCN-01 at concentrations of 0.5 and 25 microg/ml were 89 and 90.2%, respectively. Relative standard deviations for UCN-01 calibration standards ranged from 1.89 to 2.31%, with relative errors ranging from 0.3 to 11.6%. Assay precision for UCN-01 based on quality control samples of 0.50 microg/ml was +/- 4.86% with an accuracy of +/-5.7%. For drug extracted from plasma the lowest limit of detection was 0.1 microg/ml, with the lowest limit of quantitation being 0.2 microg/ml. This method is suitable for routine analysis of UCN-01 in human plasma at concentration from 0.2 to 30 microg/ml.

Alkaloids↗
PubMed2001

Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin.

Anvirzel is an extract of Nerium oleander currently undergoing Phase I clinical evaluation as a potential treatment for cancer. Two of the active components of Anvirzel are the cardiac glycosides oleandrin and oleandrigenin. Previous studies have demonstrated that, in vitro, cardiac glycosides may inhibit fibroblast growth factor-2 (FGF-2) export through membrane interaction with the Na(+),K(+)-ATPase pump. In continuing research on the antitumor activity of this novel plant extract, the relative abilities of oleandrin and oleandrigenin to inhibit FGF-2 export from two human prostate cancer cell lines, DU145 and PC3, were examined. An ELISA assay was utilized to determine the FGF-2 concentration in the cell culture medium before and after exposure to cardiac glycosides or the parent extract material Anvirzel. Both cell lines were exposed to non-cytotoxic concentrations of oleandrin (0.05 and 0.1 ng/mL) for up to 72 hr. Studies also were conducted with Anvirzel and ouabain. Oleandrin (0.1 ng/mL) produced a 45.7% inhibition of FGF-2 release from PC3 cells and a 49.9% inhibition from DU145 cells. Non-cytotoxic concentrations (100 ng/mL) of Anvirzel produced a 51.9 and 30.8% inhibition of FGF-2 release, respectively, in the two cell lines. The decrease in FGF-2 release from cells required continuous incubation for 48--72 hr; shorter incubation times were not effective. These results demonstrate that Anvirzel, like oleandrin, inhibited FGF-2 export in vitro from PC3 and DU145 prostate cancer cells in a concentration- and time-dependent fashion and may, therefore, contribute to the antitumor activity of this novel treatment for cancer.

Biological Transport↗
PubMed2001

Development of a high-performance liquid chromatographic method to determine the concentration of karenitecin, a novel highly lipophilic camptothecin derivative, in human plasma and urine.

Karenitecin is a novel, highly lipophilic camptothecin derivative with potent anticancer potential. We have developed a sensitive high-performance liquid chromatographic method for the determination of karenitecin concentration in human plasma and urine. Karenitecin was isolated from human plasma and urine using solid-phase extraction. Separation was achieved by gradient elution, using a water and acetonitrile mobile phase, on an ODS analytical column. Karenitecin was detected using fluorescence detection at excitation and emission wavelengths of 370 and 490 nm, respectively. Retention time for karenitecin was 16.2 +/- 0.5 min and 8.0 +/- 0.2 min for camptothecin, the internal standard. The karenitecin peak was baseline resolved, with the nearest peak at 3.1 min distance. Using normal volunteer plasma and urine from multiple individuals, as well as samples from the 50 patients analyzed to date, no interfering peaks were detected. Inter- and intra-day coefficients of variance were <4.4 and 7.1% for plasma and <4.9 and 11.6% for urine. Assay precision, based on an extracted karenitecin standard plasma sample of 2.5 ng/ml, was +4.46% with a mean accuracy of 92.4%. For extracted karenitecin standard urine samples of 2.5 ng/ml assay precision was +2.35% with a mean accuracy of 99.5%. The mean recovery of karenitecin, at plasma concentrations of 1.0 and 50 ng/ml, was 81.9 and 87.8% respectively. In urine, at concentrations of 1.5 and 50 ng/ml, the mean recoveries were 90.3 and 78.4% respectively. The lower limit of detection (LLD) for karenitecin was 0.5 ng/ml in plasma and 1.0 ng/ml in urine. The lower limit of quantification (LLQ) for karenitecin was 1 ng/ml and 1.5 ng/ml for plasma and urine, respectively. Stability studies indicate that when frozen at -70 degrees C, karenitecin is stable in human plasma for up to 3 months and in human urine for up to 1 month. This method is useful for the quantification of karenitecin in plasma and urine samples for clinical pharmacology studies in patients receiving this agent in clinical trials.

Antineoplastic Agents↗