Review of local extravascular delivery systems for chemotherapeutic agents in small animals and horses.

Background: Tumors of various sizes and locations can create a treatment dilemma in achieving adequate surgical margins when sufficient free tissue is not available for closure. Extravascular local adjunctive chemotherapy has been investigated clinically to aid in achieving local tumor control in animals with naturally occurring neoplastic disease. Local chemotherapy can be an alternative primary or a local adjunctive treatment. Objectives and procedures: This is a summary of relevant findings of in vitro and in vivo studies on local chemotherapeutic delivery through carrier media, together with a summary of outcomes of clinical use of local delivery of chemotherapeutic agents in small animals and Equidae. Literature from 1990 to 2022 was evaluated via searches of PubMed, Google Scholar, and CAB Abstracts databases for studies of local extravascular delivery of chemotherapeutic agents and chemotherapeutic-impregnated delivery systems in research and clinical settings in veterinary medicine. Results: Chemotherapeutic-impregnated calcium sulfate hemihydrate beads with carboplatin are currently favored for extravascular delivery and are associated with minimal wound complications. The ideal delivery system may vary depending on the chemotherapeutic agent used, commercial availability, targeted tumor type, and location. Conclusion and clinical relevance: Future investigations might focus on the required dose, the rate of sustained release, and enhancing nodal uptake.

Examen des systèmes d'administration extravasculaire locaux d'agents chimiothérapeutiques chez les petits animaux et les chevaux. Contexte: Des tumeurs de tailles et emplacements différents peuvent créer un dilemme thérapeutique pour obtenir des marges chirurgicales adéquates lorsqu'il n'y a pas suffisamment de tissu libre disponible pour la fermeture. La chimiothérapie d'appoint extravasculaire locale a été étudiée cliniquement pour aider à obtenir une limitation locale de la tumeur chez les animaux atteints d'une maladie néoplasique naturelle. La chimiothérapie locale peut être une alternative primaire ou un traitement local d'appoint. Objectifs et procédures: Il s'agit d'un résumé des résultats pertinents d'études in vitro et in vivo sur l'administration locale de chimiothérapie par le biais de transporteurs, ainsi que d'un résumé des résultats de l'utilisation clinique de l'administration locale d'agents chimiothérapeutiques chez les petits animaux et les équidés. La littérature de 1990 à 2022 a été évaluée via des recherches dans les bases de données PubMed, Google Scholar et CAB Abstracts pour des études sur l'administration extravasculaire locale d'agents chimiothérapeutiques et de systèmes d'administration chimiothérapeutiques imprégnés dans des contextes de recherche et cliniques en médecine vétérinaire. Résultats: Les billes de sulfate de calcium hémihydratée chimiothérapeutique imprégnées de carboplatine sont actuellement privilégiées pour l'administration extravasculaire et sont associées à des complications minimes des plaies. Le système d'administration idéal peut varier en fonction de l'agent chimiothérapeutique utilisé, de la disponibilité commerciale, du type de tumeur ciblé et de l'emplacement. Conclusion et pertinence clinique: Les recherches futures pourraient se concentrer sur la dose requise, le taux de libération prolongée et l'amélioration de l'absorption nodale.(Traduit par Dr Serge Messier).

Repeatability of in vitro carboplatin elution from carboplatin-impregnated calcium sulfate hemihydrate beads made in a clinic setting.

OBJECTIVE: To evaluate the intra-lot and inter-lot consistency and total carboplatin elution over 25 days from carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads manufactured in a clinic setting. STUDY DESIGN: In vitro elution study. METHODS: Two volumes of carboplatin were mixed with CSH to yield 4 mg and 8 mg C-I CSH doses. Two lots of beads were made for each concentration and split into five doses (n = 10 per concentration). Beads hardened in molds and were placed in a covered six-well plate, submerged in phosphate-buffered saline, and incubated with samples collected at 12 time points (0, 6, 12, and 24 hours and 2, 3, 5, 7, 10, 14, 18, and 25 days). The amount of carboplatin in each sample was evaluated by high-performance liquid chromatography/mass spectrometry. Correction for carboplatin degradation and dilution was applied, and eluted carboplatin was calculated. Intra-lot and inter-lot coefficient of variation (CV) was calculated for each concentration. RESULTS: The intra-lot CV ranged between 7.9% and 23.1%, and the inter-lot CV ranged from 3.5% to 10.3%, with improvement noted in each successive lot of beads. Mean peak eluted carboplatin was 2.45 ± 0.43 mg (61%) and 3.68 ± 0.41 mg (45.9%) for the 4-mg and 8-mg C-I CSH beads, respectively, with both occurring at the 12-hour timepoint. CONCLUSION: Progressive improvement in variability with successive lots of beads indicated a learning curve with bead manufacturing with a low variation both within and between lots of C-I CSH beads. CLINICAL SIGNIFICANCE: On-site mixing of carboplatin with commercial CSH bead powder leads to a low variation of carboplatin per bead dose.

Risk factors for temporary tracheostomy tube placement following surgery to alleviate signs of brachycephalic obstructive airway syndrome in dogs.

OBJECTIVE To identify risk factors for temporary tracheostomy tube placement (TTTP) following surgery for alleviation of signs associated with brachycephalic obstructive airway syndrome (BOAS) in dogs. DESIGN Retrospective case-control study. ANIMALS 122 client-owned dogs with BOAS that underwent surgery to alleviate clinical signs (BOAS surgery). PROCEDURES The medical records database of a veterinary teaching hospital was searched to identify dogs that underwent BOAS surgery from January 2007 through March 2016. Of the 198 dogs identified, 12 required postoperative TTTP (cases); 110 of the remaining 186 dogs were randomly selected as controls. Data regarding signalment and select preoperative, intraoperative, and postoperative variables were extracted from the medical record of each dog. Variables were compared between cases and controls and evaluated for an association with the odds of postoperative TTTP. RESULTS Body condition score, tracheal diameter-to-thoracic inlet ratio, staphylectomy technique, and mortality rate did not differ significantly between cases and controls. The odds of postoperative TTTP increased approximately 30% (OR, 1.3) for each 1-year increase in patient age. Postoperative administration of corticosteroids and presence of pneumonia were also positively associated with the odds of postoperative TTTP. Median duration of hospitalization was significantly longer for cases than controls. CONCLUSIONS AND CLINICAL RELEVANCE Age was positively associated with the odds of TTTP in dogs after BOAS surgery, and TTTP led to prolonged hospitalization. Thus, early identification and intervention may be beneficial for dogs with BOAS. The associations between TTTP and postoperative corticosteroid use or pneumonia were likely not causal, but reflective of patient disease severity.

Type, duration, and incidence of pathologic findings after retroorbital bleeding of mice by experienced and novice personnel.

Retroorbital blood collection is a common technique in laboratory rodents due to the ease with which it can be performed and the sample volumes obtained for subsequent blood analyses. However, its use has been discouraged recently due to aesthetic discomfort and anecdotal reports of potential for ocular injury during blood collection. We hypothesized that a single standardized session of in-person training would be sufficient to learn the appropriate technique and minimize the likelihood for adverse outcomes. Experienced instructors (n = 2) conducted hands-on training classes to teach novice personnel (n = 40) to perform this procedure. Blood was collected from anesthetized mice (n = 40) via a capillary tube first placed at the medial canthus of the right eye and then advanced into the retroorbital space; the left retroorbital spaces served as unmanipulated controls. For comparison, the experienced instructors similarly collected blood from 40 additional mice. The tube could be inserted only once in each mouse, with the goal of obtaining 50 to 100 µL blood. Overall, 79 of 80 mice (98.8%) showed normal body condition, posture, and behavior throughout the 14-d study. Thus, any clinical observation scores pertained specifically to ocular lesions, which occurred at least once after sampling in 43 (53.8%) of the mice. Clinical and histopathologic scores of mice after bleeding did not differ between experienced and novice personnel. We conclude that a coordinated hands-on training program can provide consistent and sufficient instruction for research personnel to conduct retroorbital blood collection with competence in anesthetized laboratory mice.

Chiari Malformation Type I, presenting as scapulothoracic pain: a case report.

Patients presenting with recalcitrant symptoms, which are resistant to a range of physical interventions over an extended period of time, need to be examined with care. A 'forensic' approach to the assessment of these patients, with a sensitive approach to the results of the test procedures is required to ensure the practitioner does not miss the more obscure causes. This case report presents a patient who was referred for a clinical assessment for long standing scapular pain, which had been labelled myofascial pain. Through a thorough approach to examination a number of flags appeared which suggested a need for further investigation. These investigations identified that the patient demonstrated a Chiari Malformation Type 1. On review 5 months following neurosurgical intervention her symptoms were significantly reduced. Chiari Malformations Type 1 are often diagnosed in adulthood when symptoms usually first appear. These symptoms may mimic those found with musculoskeletal conditions. Whilst we lack specific clinical tests for this condition, a thorough assessment should identify sufficient 'flags' for referral for further investigations.

Modelling complex biological systems using an agent-based approach.

Many of the complex systems found in biology are comprised of numerous components, where interactions between individual agents result in the emergence of structures and function, typically in a highly dynamic manner. Often these entities have limited lifetimes but their interactions both with each other and their environment can have profound biological consequences. We will demonstrate how modelling these entities, and their interactions, can lead to a new approach to experimental biology bringing new insights and a deeper understanding of biological systems.

Local adaptation along a continuous coastline: prey recruitment drives differentiation in a predatory snail.

Recent work demonstrates that nearshore oceanography can generate strong variation in the delivery of resources (nutrients and larvae) to benthic marine communities over spatial scales of tens to hundreds of kilometers. Moreover, variation in the strength of these bottom-up inputs is often spatially consistent, linked to regional centers of upwelling, coastal topography, and other stable features of the coastline. Whereas the ecological effects of these oceanographic links are increasingly clear, the possibility that these same bottom-up forces might impose spatially varying selection on consumers has not been addressed. Here, we test the hypothesis that a carnivorous snail (Nucella canaliculata) with direct development is locally adapted to persistent differences in prey recruitment within two adjacent oceanographic regions (northern California and Oregon, USA). Previous laboratory studies demonstrated that snails from Oregon rarely drilled the thick-shelled mussel Mytilus californianus, whereas snails from California readily drilled this prey. To test whether these differences reflect local adaptation, snails from two populations in each region were raised through two laboratory generations to minimize the potential influence of nongenetic effects. We then reciprocally outplanted these F2 generation snails to field enclosures at each of the four sites and monitored their growth for 11 months. Recruitment and availability of preferred prey (the acorn barnacle Balanus glandula and blue mussel Mytilus trossulus) at the experimental sites were 1-3 orders of magnitude lower in California than in Oregon. At the California sites, snails that originated from Oregon sources failed to drill larger M. californianus, encountered few alternative prey, and showed almost no growth. In contrast, snails from California drilled M. californianus and showed substantial growth. These results strongly suggest that the capacity of California snails to drill M. californianus allows these snails to succeed in an oceanographic region where the recruitment of alternative, preferred prey is low. More broadly, our results suggest that persistent spatial variation in recruitment and other oceanographically mediated processes may lead to adaptive differentiation among populations of consumers in adjacent coastal regions.

Genetic differences among populations of a marine snail drive geographic variation in predation.

The extent to which community processes can be generalized from local field studies to larger spatial scales remains a contentious issue. The search for broad generality can be hampered when species interactions vary geographically, a common phenomenon attributed to a wide range of underlying ecological factors. Less attention has been directed toward understanding the additional role that evolutionary processes may play in modifying the way that pairs of species interact over large spatial scales. Here we examine whether marked geographic variation in the interaction between a predatory snail (Nucella canaliculata) and an intertidal mussel (Mytilus californianus) arises from phenotypic plasticity or fixed genetic differences among snail populations. Over a three-year period, we reared snails from eight populations in California and Oregon, USA, through two laboratory generations and tested whether family lines differed in their ability to drill M. californianus. Remarkably, F2 generation snails from Oregon sources were generally unable to drill mid-sized Mytilus californianus (5-7 cm long), whereas snails from California readily drilled this prey. Because snails were raised through two generations on a common diet (Mytilus trossulus), these differences among populations likely have a genetic basis. Snails from California and Oregon readily interbred and produced viable offspring in the laboratory, suggesting that populations belong to a single biological species. Field surveys of mussel beds revealed striking geographic variation in predation that closely matched the observed differences in the drilling capacity of N. canaliculata. Drilled M. californianus were common at all sites in California and included many large mussels (> 10 cm long). In contrast, drilled M. californianus were rare on the central Oregon coast and consisted mostly of small mussels (< 3 cm). We hypothesize that persistent variation in prey recruitment along the coast has selected for interpopulation differences in the drilling capacity of this direct-developing snail, with potential consequences for the size structure of mussel beds. Combined with growing evidence of restricted gene flow and low connectivity among many marine populations, this study highlights the importance of considering the contribution of evolutionary processes to geographic variation in species interactions.

Rhodococcus equi infection during treatment of a c-ANCA positive vasculitis: a case report.

Rhodococcus equi is a rare form of opportunistic infection in humans, more common in the immunocompromised. We present a case of pulmonary infection and subsequent cerebral abscess secondary to R. equi in a patient receiving immunosuppression for a c-ANCA positive vasculitis. Heightened awareness of R. equi infection is important when considering immunocompromised patients presenting with sepsis, especially those with cavitating pulmonary lesions and normal respiratory commensals on culture. Delays in diagnosis and treatment can cause increased patient morbidity and mortality.

Brain cyclosporin A levels are determined by ontogenic regulation of mdr1a expression.

Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant patients. We hypothesized that reduced mdr1a expression in newborn and developing mice would affect CyA accumulation within organs and/or toxicity. For functional studies, CyA was administered (5 mg kg(-1) i.p.) to 1-, 12-, and 19-day, and adult male and female mdr1a+/+ and mdr1a-/- mice. Peak blood CyA was lower in 1-, 12-, and 19-day-old (1000 ng ml(-1)) versus adult (1500 ng ml(-1)) mice but was similar in mdr1a+/+ and mdr1a-/- mice. Kidney mdr1a expression (measured by quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and female mice and increased another 4-fold in adult females compared with adult males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal mice. Thereafter, maintenance of hepatic mdr1a expression in females and a reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold) and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and were not dependent on maturational changes in mdr1a mRNA levels. Adults had higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was similar in newborn and adult mice. A similar pattern was observed for the brain accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for central nervous system drug toxicity could be higher in neonates or young children as a consequence of underdeveloped P-glycoprotein.

Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and 11-hydroxy-delta9-THC: cannabinoid metabolites to creatinine ratio study IV.

The objective of this study was to compare urinary excretion patterns of two cannabinoid metabolites in subjects with a history of chronic marijuana use. The first metabolite analyzed was nor-9-carboxy-delta9-tetrahydrocannabinol (delta9-THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically inactive. The second metabolite 11-OH-delta9-THC is an active cannabinoid metabolite and is not routinely measured. Urine specimens were collected from four subjects on 12-20 occasions > or = 96 h apart in an uncontrolled clinical setting. Creatinine was analyzed in each urine specimen by the colorimetric modified Jaffé reaction on a SYVA 30R biochemical analyzer. All urine specimens analyzed for 11-OH-delta9-THC had screened positive for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and submitted for delta9-THC-COOH confirmation by GC-MS (cut-off concentration 15 ng/mL). Eleven-OH-delta9-THC was measured by GC-MS with a cut-off concentration of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated internal standards for quantitative analysis. The mean (range) of urinary delta9-THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The mean (range) of delta9-THC-COOH/creatinine ratios (ng/mL delta9-THC-COOH/mmol/L creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-delta9-THC concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean (range) of 11-OH-delta9-THC/creatinine ratio (ng/mL 11-OH-delta9-THC/mmol/L creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for delta9-THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for delta9 -THC-COOH and 51/63 (81%) were positive for 11-OH-delta9-THC. Overall, the concentrations of 11-OH-delta9-THC in urine specimens collected > or = 96 h apart were lower than delta9-THC-COOH concentrations in 50/51 of the urine specimens in this population. Further urinary cannabinoid excretion studies are needed to assess whether 11-OH-delta9-THC analyses have a role when assessing previous marijuana or hashish use in chronic users whose urine specimens remain positive for delta9-THC-COOH for an extended period of time after last drug use.

Urinary excretion profiles of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol. Study III. A Delta9-THC-COOH to creatinine ratio study.

Huestis and Cone reported in [J. Anal. Toxicol. 22 (1998) 445] that serial monitoring of Delta9-THC-COOH/creatinine ratios in paired urine specimens collected at least 24h apart could differentiate new drug use from residual Delta(9)-THC-COOH excretion following acute marijuana use in a controlled setting. The best accuracy (85.4%) for predicting new marijuana use was for a Delta(9)-THC-COOH/creatinine ratio > or = 0.5 (dividing the Delta9-THC-COOH/creatinine ratio of specimen no. 2 by the specimen no. 1 ratio). In previous studies in this laboratory [J. Anal. Toxicol. 23 (1999) 531 and Forensic Sci. Int. 133 (2003) 26], urine specimens were collected from chronic marijuana users > or = 24 h or > = 48 h apart in an uncontrolled setting. Subjects with a history of chronic marijuana use were screened for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/ml) followed by confirmation for Delta9-THC-COOH by GC-MS (cut-off 15 ng/ml). Creatinine was analyzed as an index of dilution. The objective of the present study was to evaluate whether creatinine corrected specimens could differentiate new marijuana or hashish use from the excretion of residual Delta(9)-THC-COOH in chronic marijuana users based on the Huestis 0.5 ratio. Urine specimens (N=376) were collected from 29 individuals > or = 96 h between urine collections. The mean urinary Delta9-THC-COOH concentration was 464.4 ng/ml, mean Delta9-THC-COOH/creatinine ratio (ng/(ml Delta9-THC-COOH mmoll creatinine)) was 36.8 and the overall mean Delta9-THC-COOH/creatinine ratio of specimen 2/mean Delta9-THC-COOH/creatinine ratio of specimen 1 was 1.37. The Huestis ratio calculation indicated new drug use in 83% of all sequentially paired urine specimens. The data were sub-divided into three groups (Groups A-C) based on mean Delta9-THC-COOH/creatinine values. Interindividual mean Delta9-THC-COOH/creatinine values ranged from 4.7 to 13.4 in Group A where 80% of paired specimens indicated new drug use (N=10) and 20.4-39.6 in Group B where 83.6% of paired specimens indicated new drug use (N=7). Individual mean Delta9-THC-COOH/creatinine values ranged from 44.2 to 120.2 in Group C where 84.5% of paired urine specimens indicated new marijuana use (N=12). Correcting Delta9-THC-COOH excretion for urinary dilution and comparing Delta9-THC-COOH/creatinine concentration ratios of sequentially paired specimens (collected > or = 96 h apart) may provide an objective indicator of ongoing marijuana or hashish use in this population.

Urinary excretion profiles of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol: a Delta9-THC-COOH to creatinine ratio study #2.

Subjects with a history of chronic marijuana use were screened for cannabinoids in urine specimens with the EMIT((R)) II Plus cannabinoids assay with a cut-off value of 50 ng/ml. All presumptively positive specimens were submitted for confirmatory analysis for the major urinary cannabinoid metabolite (Delta(9)-THC-COOH) by GC-MS with a cut-off value of 15 ng/ml. Creatinine was analyzed in each specimen as an index of dilution. Huestis and Cone [J. Anal. Toxicol. 22 (1998) 445] reported that serial monitoring of Delta(9)-THC-COOH to creatinine ratios in paired urine specimens collected at least 24h apart could differentiate new drug use from residual Delta(9)-THC-COOH excretion. The best accuracy (85.4%) for predicting new marijuana use was a Delta(9)-THC-COOH/creatinine ratio > or =0.5 (dividing the Delta(9)-THC-COOH to creatinine ratio of specimen 2 by the specimen 1 ratio). In a previous study in this laboratory [J. Anal. Toxicol. 23 (1999) 531], urine specimens were collected from chronic marijuana users at least 24h apart and dilute urine specimens (creatinine values <2.2 micromol/l) were excluded from the data analysis. The objective of the present study was to determine whether creatinine corrected urine specimens positive for cannabinoids could differentiate new marijuana use from the excretion of residual Delta(9)-THC-COOH in chronic users of marijuana based on the Huestis 0.5 ratio. Urine specimens (N=946) were collected from 37 individuals with at least 48h between collections. All urine specimens were included in the data review irrespective of creatinine concentration. The mean urinary Delta(9)-THC-COOH concentration was 302.4 ng/ml, mean Delta(9)-THC-COOH/creatinine ratio (ng/ml Delta(9)-THC-COOH/(mmol/l) creatinine) was 29.3 and the Huestis ratio calculation indicated new drug use in 83% of all sequentially paired urine specimens. The data were sub-divided into three groups (A-C) based on the mean Delta(9)-THC-COOH/creatinine values. Interindividual Delta(9)-THC-COOH/creatinine mean values ranged from 2.2 to 13.8 in group A (264 specimens, N=15 subjects) where 80.7% of paired specimens indicated new drug use. In group B, mean Delta(9)-THC-COOH/creatinine values ranged from 15.3 to 37.8 in 444 specimens (N=14 subjects) and 83.3% of paired specimens indicated new drug use. In group C, individual mean Delta(9)-THC-COOH/creatinine values were >40.1 (41.3-132.5) in 238 urine specimens (N=8 subjects) and 85.3% of paired urine specimens indicated new marijuana use. Correcting Delta(9)-THC-COOH excretion for urinary dilution and comparing Delta(9)-THC-COOH/creatinine concentration ratios of sequentially paired specimens (collected at least 48h apart) provided an objective indicator of new marijuana use in this population.

Drug and chemical metabolites in clinical toxicology investigations: the importance of ethylene glycol, methanol and cannabinoid metabolite analyses.

Metabolic pathways in humans have been elucidated for most therapeutic drugs, drugs of abuse, and various chemical/solvents. In most drug overdose cases and chemical exposures, laboratory analysis is directed toward identification and quantitation of the unchanged drug or chemical in a biologic fluid such as serum or whole blood. Specifically, most clinical laboratories routinely screen and quantitate unchanged methanol and/or ethylene glycol in suspected poisonings without toxic metabolite analysis. Martin-Amat established in 1978 that methanol associated toxicity to the optic nerve in human poisonings was due to the toxic metabolite formic acid found in methanol poisonings and not due to the direct action by unchanged methanol. Jacobsen reported in 1981 that ethylene glycol central nervous system and renal toxicity were primarily due to one acidic metabolite (glycolic acid) and not due to unchanged ethylene glycol. The first objective of this review is to describe clinical experience with formic acid and glycolic acid analysis in methanol and ethylene glycol human poisonings. Drug metabolite analysis also provides useful information in the assessment and monitoring of drug use in psychiatry and substance abusing populations. Drug analysis in substance abuse monitoring is focused on urine analysis of one or more major metabolites, and less frequently on the unchanged drug(s). Serial monitoring of the major urinary cannabinoid metabolite (delta(9)-THC-COOH) to creatinine ratios in paired urine specimens (collected at least 24 h apart) could differentiate new marijuana or hashish use from residual cannabinoid metabolite excretion in urine after drug use according to Huestis. The second objective is to demonstrate that creatinine corrected urine specimens positive for cannabinoids may help differentiate new marijuana use from the excretion of residual delta(9) -THC-COOH in chronic users of marijuana or hashish. Analysis of toxic chemical metabolites are helpful in the assessment and treatment of chemical poisoning whereas serial monitoring of urinary cannabinoid metabolites are predictive of illicit drug use in the substance abusing population.

Monitoring urinary excretion of cannabinoids by fluorescence-polarization immunoassay: a cannabinoid-to-creatinine ratio study.

Drug testing in substance abuse treatment programs is focused on urine analysis of parent drugs and major metabolites. Huestis reported that serial monitoring of the major urinary cannabinoid metabolite (delta9-THC-COOH)-to-creatinine ratios in paired urine specimens (collected at least 24 hours apart) could differentiate new marijuana or hashish use from residual cannabinoid metabolite excretion in urine after previous drug use. Subjects with a history of chronic marijuana use were screened for cannabinoids in urine over several months by an enzyme immunoassay (EMIT) with a cut-off value of 50 ng/mL. Presumptive positive specimens were confirmed by gas chromatography-mass spectrometry (GC-MS) for delta9-THC-COOH with a cut-off value of 15 ng/mL. The objective of this study was to determine whether a semiquantitative cannabinoids immunoassay (corrected for creatinine concentration) could differentiate new marijuana use from residual cannabinoid excretion in chronic users of marijuana or hashish compared with GC-MS. The criterion for new marijuana use was a cannabinoid-to-creatinine ratio > or =0.5 (dividing the immunoassay quantitative result to creatinine ratio of specimen 2 by the specimen 1 ratio, specimen 3 by the specimen 2 ratio, etc.). Urine specimens were analyzed by fluorescence-polarization immunoassay (FPIA) on an Abbott TDxFLx analyzer after analysis by GC-MS. In 90 urine specimens (group A) with delta9-THC-COOH values determined by GC-MS, the mean delta9-THC-COOH concentration was 44.4 ng/mL (range, 16-100), and the mean FPIA total cannabinoids value was 91.7 ng/mL (range, 21-204 ng/mL) with a correlation coefficient of 0.993 (group A). In 111 specimens (group B), the mean delta9-THC-COOH concentration was 361 ng/mL (range, 101-960 ng/mL). The mean FPIA value was 657 ng/mL (range, 211-1,270 ng/mL), and the correlation coefficient of the B series was 0.975. Percent cross-reactivity for delta9-THC-COOH standards prepared in drug-free urine by FPIA was 82% at 25 ng/mL, 45% at 50 ng/mL, and 50% at 100 ng/mL. Overall, there was 89% agreement (132 of 148 specimens) between FPIA and GC-MS. In 16 of 148 specimens, however, the FPIA and GC-MS paired urine data did not agree. The sensitivity of the FPIA assay was 95.3%, and the specificity was 44.4%. The authors conclude that FPIA cannabinoid analysis should be further evaluated as an alternative to GC-MS quantitation to help distinguish new marijuana use from residual marijuana metabolite excretion in clinical drug treatment programs.

The relationship between serum albumin and hydration status in hemodialysis patients.

OBJECTIVE: A decreased serum albumin level predicts poor survival in end-stage renal failure. Hypoalbuminemia is multifactorial and related to poor nutrition, inflammation, and comorbid disease. Overhydration is also common in renal replacement therapy patients, and hemodilution may also contribute to a low serum albumin level. DESIGN: Crosssectional observational study. SETTING: Outpatient hemodialysis unit of a district general hospital. SUBJECTS: We investigated the relationship of serum albumin to C-reactive protein (CRP) and hydration state in 49 unselected hemodialysis patients (28 men). METHODS: Patients were assessed predialysis and postdialysis at their clinical dry weight. Extracellular fluid volume (Vecf) and total body water (Vtbw) were estimated by whole-body bioelectric impedance. Vecf was expressed as a percentage of Vtbw (Vecf%Vtbw). Predialysis CRP, predialysis and postdialysis serum albumin, and body weight were measured. Normalized protein catabolic rate (nPCR) and KT/V urea were calculated. RESULTS: Predialysis and postdialysis serum albumin levels were 36.9 g/L (95% CI, 35.7 and 38.1) and 41.4 g/L (95% CI, 39.7 and 43.3), respectively (P <.0001). Mean weight change was 2.0 +/- 1.2 kg. Predialysis and postdialysis serum albumin levels were negatively correlated with CRP (before: r = -0.393, P <.005; after: r = -0.445, P =.001) and positively with nPCR (before: r = 0.336, P =.018; after: r = 0.353, P =.013). Predialysis serum albumin level correlated with predialysis Vecf%Vtbw (r = -0.384, P =.006) and postdialysis serum albumin level with postdialysis Vecf%Vtbw (r = -0.654, P <.0001). In multivariate analysis, predialysis albumin was dependent on nPCR (P =.04), CRP (P <.0001), and predialysis Vecf%Vtbw (P =.002), and postdialysis albumin was dependent on nPCR (P =.01), CRP (P =.002), and postdialysis Vecf%Vtbw (both P <.0001). The increase in albumin was strongly correlated with both change in actual weight (r = -0.651, P <.0001) and change in Vecf%Vtbw (r = -0.684, P <.0001). CONCLUSION: In unselected hemodialysis patients, serum albumin level is dependent on nPCR, CRP, and extracellular fluid volume. This relationship persists after dialysis, suggesting that many patients remain fluid overloaded at their postdialysis dry weight.