Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Prediction of plan adaptation in head and neck cancer proton therapy using clinical, radiographic, and dosimetric features.

PURPOSE: Because proton head and neck (HN) treatments are sensitive to anatomical changes, plan adaptation (re-plan) during the treatment course is needed for a significant portion of patients. We aim to predict re-plan at plan review stage for HN proton therapy with a neural network (NN) model trained with patients' dosimetric and clinical features. The model can serve as a valuable tool for planners to assess the probability of needing to revise the current plan. METHODS AND MATERIALS: Mean beam dose heterogeneity index (BHI), defined as the ratio of the maximum beam dose to the prescription dose, plan robustness features (clinical target volume (CTV), V100 changes, and V100 > 95% passing rates in 21 robust evaluation scenarios), as well as clinical features (e.g., age, tumor site, and surgery/chemotherapy status) were gathered from 171 patients treated at our proton center in 2020, with a median age of 64 and stages from I-IVc across 13 HN sites. Statistical analyses of dosimetric parameters and clinical features were conducted between re-plan and no-replan groups. A NN was trained and tested using these features. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the prediction model. A sensitivity analysis was done to determine feature importance. RESULTS: Mean BHI in the re-plan group was significantly higher than the no-replan group (p < .01). Tumor site (p < .01), chemotherapy status (p < .01), and surgery status (p < .01) were significantly correlated to re-plan. The model had sensitivities/specificities of 75.0%/77.4%, respectively, and an area under the ROC curve of .855. CONCLUSION: There are several dosimetric and clinical features that correlate to re-plans, and NNs trained with these features can be used to predict HN re-plans, which can be used to reduce re-plan rate by improving plan quality.

Rates, costs, return to work and reoperation following spinal surgery in a workers' compensation cohort in New South Wales, 2010-2018: a cohort study using administrative data.

BACKGROUND: Internationally, elective spinal surgery rates in workers' compensation populations are high, as are reoperation rates, while return-to-work rates following spinal surgery are low. Little information is available from Australia. The aim of this study was to describe the rates, costs, return to work and reoperation following elective spinal surgery in the workers' compensation population in New South Wales (NSW), Australia. METHODS: This retrospective cohort study used administrative data from the State Insurance Regulatory Authority, the government organisation responsible for regulating and administering workers' compensation insurance in NSW. These data cover all workers' compensation-insured workers in New South Wales (over 3 million workers/year). We identified a cohort of insured workers who underwent elective spinal surgery (fusion or decompression) between January 1, 2010 and December 31, 2018. People who underwent surgery for spinal fracture or dislocation, or who had sustained a traumatic brain injury were excluded. The main outcome measures were annual spinal surgery rates, cost of the surgical episode, cumulative costs (surgical, hospital, medical and physical therapy) to 2 years post-surgery, and reoperation and return-to-work rates 2 years post-surgery. RESULTS: There were 9343 eligible claims (39.1 % fusion; 59.9 % decompression); claimants were predominantly male (75 %) with a mean age of 43 (range 18 to 75) years. Spinal surgery rates ranged from 15 to 29 surgeries per 100,000 workers per year, fell from 2011-12 to 2014-15 and rose thereafter. The average cost in Australian dollars for a surgical episode was $46,000 for a spinal fusion and $20,000 for a decompression. Two years post-fusion, only 19 % of people had returned to work at full capacity; 39 % after decompression. Nineteen percent of patients underwent additional spinal surgery within 2 years of the index surgery, to a maximum of 5 additional surgeries. CONCLUSION: Rates of workers' compensation-funded spinal surgery did not rise significantly during the study period, but reoperation rates are high and return-to-work rates are low in this population at 2 years post- surgery. In the context of the poor evidence base supporting lumbar fusion surgery, the high cost, increasing rates, and the increased likelihood of poor outcomes in the workers' compensation population, we question the value of this procedure in this setting.

Minimal important improvement thresholds for the six-minute walk test in a knee arthroplasty cohort: triangulation of anchor- and distribution-based methods.

BACKGROUND: The 6-minute walk test (6MWT) is a commonly used metric for measuring change in mobility after knee arthroplasty, however, what is considered an improvement after surgery has not been defined. The determination of important change in an outcome assessment tool is controversial and may require more than one approach. This study, nested within a combined randomised and observational trial, aimed to define a minimal important improvement threshold for the 6MWT in a knee arthroplasty cohort through a triangulation of methods including patient-perceived anchor-based thresholds and distribution-based thresholds. METHODS: Individuals with osteoarthritis performed a 6MWT pre-arthroplasty then at 10 and 26 weeks post-surgery. Each rated their perceived improvement in mobility post-surgery on a 7-point transition scale anchored from "much better" to "much worse". Based on these responses the cohort was dichotomised into 'improved' and 'not improved'. The thresholds for patient-perceived improvements were then identified using two receiver operating curve methods producing sensitivity and specificity indices. Distribution-based change thresholds were determined using two methods utilising effect size (ES). Agreement between the anchor- and distribution-based methods was assessed using kappa. RESULTS: One hundred fifty-eight from 166 participants in the randomised cohort and 222 from 243 in the combined randomised and observational cohort were included at 10 and 26 weeks, respectively. The slightly or more patient-perceived improvement threshold at 26 weeks (an absolute improvement of 26 m) was the only one to demonstrate sensitivity and specificity results both better than chance. At 10- and 26-weeks, the ES based on the mean change score divided by the baseline standard deviation (SD), was an absolute change of 24.5 and 37.9 m, respectively. The threshold based on a moderate ES (a 0.5 SD of the baseline score) was a change of 55.0 and 55.4 m at 10- and 26-weeks, respectively. The level of agreement between the 26-week anchor-based and distribution-based minimal absolute changes was very good (k = 0.88 (95 % CI 0.81 0.95)). CONCLUSION: A valid threshold of improvement for the 6MWT can only be proposed for changes identified from baseline to 26 weeks post-surgery. The level of agreement between anchor- and distribution-based methods indicates that a true minimal or more threshold of meaningful improvement following surgery is likely within the ranges proposed by the triangulation of all four methods, that is, 26 to 55 m.

Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.

AIMS: To characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors. MATERIALS AND METHODS: MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP-1 or glucagon receptors, to potentiate glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months. RESULTS: MEDI0382 potently activated rodent, cynomolgus and human GLP-1 and glucagon receptors and exhibited a fivefold bias for activation of GLP-1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP-1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor-mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP-1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys. CONCLUSIONS: Repeated administration of MEDI0382 elicits profound weight loss in DIO mice and non-human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP-1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients.

Interventions to reduce vasovagal reactions in blood donors: a systematic review and meta-analysis.

Vasovagal reactions (VVRs) in blood donors have significant implications for the welfare of donors, donor retention and the management of donor sessions. We present a systematic review of interventions designed to prevent or reduce VVRs in blood donors. Electronic databases were searched for eligible randomised trials to March 2015. Data on study design and outcomes were extracted and pooled using random effects meta-analyses. Sixteen trials met the inclusion criteria: five trials (12 042 participants) of pre-donation water, eight trials (3500 participants) of applied muscle tension (AMT) and one trial each of AMT combined with water, caffeine, audio-visual distraction and/or social support. In donors receiving pre-donation water, the relative risk (RR) compared with controls for VVRs was 0·79 [95% confidence interval (CI) 0·70-0·89, P < 0·0001] and the mean difference (MD) in severity of VVRs measured with the Blood Donation Reactions Inventory (BDRI) score was -0·32 (95% CI -0·51 to -0·12, P < 0·0001). Excluding trials with a high risk of selection bias, the RR for VVRs was 0·70 (95% CI 0·45-1·11, P = 0·13). In donors who received AMT, there was no difference in the risk of chair recline in response to donor distress from controls (RR 0·76, 95% CI 0·53-1·10, P = 0·15), although the MD in BDRI score was -0·07 (95% CI -0·11 to -0·03, P = 0·0005). There was insufficient data to perform meta-analysis for other interventions. Current evidence on interventions to prevent or reduce VVRs in blood donors is indeed limited and does not provide strong support for the administration of pre-donation water or AMT during donation. Further large trials are required to reliably evaluate the effect of these and other interventions in the prevention of VVRs.

An unusual case of anaemia and lymphadenopathy in a soldier on deployment.

We describe the case of a British soldier, originally from southeast Africa, who presented to the British military hospital in Helmand Province, southern Afghanistan, with a history of constitutional upset, profound anaemia and diffuse lymphadenopathy with hepatosplenomegaly. Following evacuation to the UK investigations revealed a rare (and a not so rare) diagnosis. This case raises a number of questions regarding the population at risk, the prevalence of endemic diseases in this population and laboratory capabilities in the deployed setting.

Stereo-selective inhibition of transient receptor potential TRPC5 cation channels by neuroactive steroids.

BACKGROUND AND PURPOSE: Transient receptor potential canonical 5 (TRPC5) channels are widely expressed, including in the CNS, where they potentiate fear responses. They also contribute to other non-selective cation channels that are stimulated by G-protein-coupled receptor agonists and lipid and redox factors. Steroids are known to modulate fear and anxiety states, and we therefore investigated whether TRPC5 exhibited sensitivity to steroids. EXPERIMENTAL APPROACH: Human TRPC5 channels were conditionally expressed in HEK293 cells and studied using intracellular Ca2+ measurement, whole-cell voltage-clamp and excised patch techniques. For comparison, control experiments were performed with cells lacking TRPC5 channels or expressing another TRP channel, TRPM2. Native TRPC channel activity was recorded from vascular smooth muscle cells. KEY RESULTS: Extracellular application of pregnenolone sulphate, pregnanolone sulphate, pregnanolone, progesterone or dihydrotestosterone inhibited TRPC5 activity within 1-2min. Dehydroepiandrosterone sulphate or 17ß-oestradiol had weak inhibitory effects. Pregnenolone, and allopregnanolone, a progesterone metabolite and stereo-isomer of pregnanolone, all had no effects. Progesterone was the most potent of the steroids, especially against TRPC5 channel activity evoked by sphingosine-1-phosphate. In outside-out patch recordings, bath-applied progesterone and dihydrotestosterone had strong and reversible effects, suggesting relatively direct mechanisms of action. Progesterone inhibited native TRPC5-containing channel activity, evoked by oxidized phospholipid. CONCLUSIONS AND IMPLICATIONS: Our data suggest that TRPC5 channels are susceptible to relatively direct and rapid stereo-selective steroid modulation, leading to channel inhibition. The study adds to growing appreciation of TRP channels as non-genomic steroid sensors.

Upregulated TRPC1 channel in vascular injury in vivo and its role in human neointimal hyperplasia.

Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.

Videoendoscopic evaluation of the upper respiratory tract in 93 sport horses during exercise testing on a high-speed treadmill.

REASONS FOR PERFORMING STUDY: Videoendoscopy of the upper respiratory tract (URT) during high-speed treadmill exercise has proved to be invaluable in the assessment of URT dysfunction in racehorses. However, very little information exists regarding dynamic airway collapse in other sport horses used in nonracing equestrian disciplines. OBJECTIVES: To evaluate the videoendoscopic findings at rest and during exercise in a mixed population of sport horses referred for investigation of poor athletic performance and/or abnormal respiratory noise. METHODS: Videoendoscopy of the upper airway was performed at rest and during high-speed treadmill exercise in 93 horses. RESULTS: Dynamic airway obstructions were diagnosed in 77% of horses and were frequently complex in nature. The most common forms of dynamic collapse included soft palate dysfunction (54%), dynamic laryngeal collapse (38%), axial deviation of the aryepiglottic folds (24%) and pharyngeal wall collapse (18%). In the majority of horses, no obvious abnormalities were identified at rest. Enforced poll flexion was found to be a contributing factor in 24% of cases. CONCLUSIONS: Dynamic obstructions of the URT were a common cause of poor performance and/or abnormal respiratory noise in sport horses referred for investigation of performance problems. POTENTIAL RELEVANCE: This study highlights the importance of videoendoscopic evaluation of the URT during exercise in horses utilised for equestrian sports where exercise during competition is submaximal in nature.

Primary distension of the guttural pouch lateral compartment secondary to empyema.

A 6-year-old, 420-kg quarter horse gelding was presented with a 2-month history of difficulty swallowing and dyspnea. The horse was diagnosed with a right guttural pouch empyema with many large chondroids. Two surgeries were required to completely remove all the chondroids from what proved to be a primary distension of the guttural pouch lateral compartment.

Nutrient uptake by viscera drained by the portal vein in neonatal calves during intravenous infusion of glutamine.

OBJECTIVE: To quantify glutamine use by viscera drained by the portal vein in neonatal calves and to determine whether uptake could be stimulated by long-term IV infusion or long-term use of oral supplements. ANIMALS: 4 healthy neonatal calves. PROCEDURE: A femoral artery, jugular vein, and the portal vein were surgically cannulated in each calf. Blood flow in the portal vein was measured, using an ultrasonic transit-time flow probe. Calves were given an IV infusion of glutamine on days 6, 8, and 10 after surgery. Before the first infusion, calves were fed a diet of milk only. The diet was supplemented with glutamine for the second and third infusions. Glutamine was administered via the jugular vein during a 5-hour period. Venous and arterial blood samples were collected every hour for 5 hours. RESULTS: During glutamine infusion, uptake of glutamine by viscera drained by the portal vein increased in association with increased production of ammonia. Glutamine supplementation of the diet did not alter glutamine uptake. Glutamine infusion did not increase viscera uptake of indispensable amino acids. Long-term use of glutamine supplements or infusion of glutamine for periods of more than 1 hour increased glutamine uptake by viscera. Arterial leucine concentration and uptake of leucine by the viscera decreased during glutamine infusion, indicating that leucine became the limiting factor. CONCLUSION: Glutamine administration (supplements or infusions) to calves may require that a mixture of amino acids be provided to improve effectiveness. CLINICAL RELEVANCE: Glutamine may be beneficial in treatments designed to promote intestinal healing in diarrheic calves.

Long-term surgical preparation of portal vein-drained viscera for determination of their nutritional requirements in preruminant calves.

OBJECTIVE: To develop a surgical preparation to study the nutrient concentration difference across the portal vein-drained viscera of preruminant calves over a 2-week period. ANIMALS: 9 healthy preruminant male Holstein calves. PROCEDURE: A bilateral subcostal approach was used to reach the portal area to provide access for proper placement of an ultrasonic transit time flow probe around the portal vein. The umbilical vein was used as an entry point for the portal vein catheter. The femoral artery was also catheterized. Calves were observed daily, and food intake was recorded. Body weight was recorded weekly. The calves were euthanatized, and necropsy was performed 2 weeks after surgery. RESULTS: Of the 9 calves, 7 recovered without surgical complications. Within 24 hours of surgery, 1 calf developed an intestinal hernia at the flank incision that was surgically repaired without further complications. One calf was euthanatized a week after surgery because it developed septicemia secondary to catheter-related infection. CONCLUSION: The bilateral subcostal approach provided access to the portal area, and the umbilical vein was useful as an entry point. Application of an ultrasonic flow probe provided consistent measurements of blood flow over a 2-week period. CLINICAL RELEVANCE: These results may have implications for development of treatment to promote gastrointestinal tract healing in calves with diarrhea.

Affinity and kinetics of the interactions between an alphabeta T-cell receptor and its superantigen and class II-MHC/peptide ligands.

Immune activation is mediated by a specific interaction between the T-cell receptor (TCR) and an antigenic peptide bound to the major histocompatibility complex (MHC). T-cell activation can also be stimulated by superantigens which bind to germline-encoded variable domain sequences of certain TCR beta-chains. We have used a surface plasmon resonance biosensor to characterize the molecular interactions between a class II-restricted alphabeta TCR and its superantigen and MHC/peptide ligands. The extracellular domains of the murine D10 TCR (Valpha2, Vbeta8.2) were expressed in insect cells and secreted as a disulfide-linked heterodimer. In the absence of MHC class II, purified soluble D10 TCR bound to Staphylococcus aureus enterotoxin C2 with an association rate of 1.69+/-0.12 x 10(4)M(-1) sec(-1) and a dissociation rate of 1.9+/-0.47 x 10(-2) sec(-1), giving a dissociation constant of 1.1 microM. Binding of the TCR to S. aureus enterotoxin B was barely detectable and could not be measured accurately due to the rapid dissociation rate. Soluble D10 TCR also bound to a soluble murine MHC class II I-A(k) molecule containing a fused antigenic conalbumin peptide and complementary leucine zipper sequences to facilitate efficient chain pairing. The purified I A(k) chimera specifically stimulated proliferation of the D10 T-cell clone, and bound to immobilized soluble D10 TCR with an association rate of 1.07+/-0.19 x 10(4)M(-1)sec(-1) and a dissociation rate of 2.2+/-0.65 x 10(-2) sec(-1), giving a dissociation constant of 2.1 microM.

Conformational integrity and ligand binding properties of a single chain T-cell receptor expressed in Escherichia coli.

We recently showed that a soluble, heterodimeric murine D10 T-cell receptor (TCR) (Valpha2Calpha, Vbeta8.2Cbeta) expressed in insect cells binds both Vbeta8.2-specific bacterial superantigen staphylococcal enterotoxin C2 (SEC2) and a soluble, heterodimeric major histocompatibility complex class II I-Ak.conalbumin peptide complex with a low micromolar affinity. To define further the structural requirements for the TCR/ligand interactions, we have produced in Escherichia coli a soluble, functional D10 single chain (sc) TCR molecule in which the Valpha and Vbeta domains are connected by a flexible peptide linker. Purified and refolded D10 scTCR bound to SEC2 and murine major histocompatibility complex class II I-Ak.conalbumin peptide complex with thermodynamic and kinetic binding constants similar to those measured for the baculovirus-derived heterodimeric D10 TCR suggesting that neither the TCR constant domains nor potential N- or O-linked carbohydrate moieties are necessary for ligand recognition and for expression and proper folding of the D10 scTCR. Purified D10 scTCR remained soluble at concentrations up to 1 mM. Circular dichroism and NMR spectroscopy indicated that D10 scTCR is stabilized predominantly by beta-sheet secondary structure, consistent with its native-like conformation. Because of its limited size, high solubility, and structural integrity, purified D10 scTCR appears to be suitable for structural studies by multidimensional NMR spectroscopy.

Two chimaeric transcription units result from an inversion breaking intron 1 of the factor VIII gene and a region reportedly affected by reciprocal translocations in T-cell leukaemia.

Analysis of mRNA in two haemophilic monozygotic twins offers novel information on the organisation of expressed sequences distal to the coagulation factor VIII gene. These patients show an inversion that, in contrast to the common inversions responsible for 1/5 of all haemophilia A, affects the first rather than intron 22 of the gene. This displaces the most telomeric of the factor VIII exons (exon 1) by approximately 100 kb towards the telomere, and close to the region of the C6.1A gene. This novel inversion creates two hybrid transcription units: one formed by the promoter and first exon of the factor VIII gene followed by a widely expressed sequence; the other by the promoter and coding region of the C6.1A gene plus most of the factor VIII gene (part of intron 1 and exons 2-26). Investigation of this transcription unit reveals that the C6.1A gene has an unsuspected intron in the region coding for the previously described 3'-untranslated tail of the message. Furthermore, exons located beyond the known C6.1A sequence and present in normal transcripts precede exons 2-26 of the factor VIII gene in the hybrid mRNA of the haemophilic twins. The factor VIII sequences in this hybrid mRNA are not expected to be expressed because they lack the first exon, encoding the prepeptide, and follow a translation stop in the C6.1A gene. Leukaemia-related translocations in the C6.1A region suggest that this region may be somewhat unstable.

cDNA cloning, expression, and chromosomal localization of a human UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase.

Oligonucleotide primers derived from the cDNA encoding a full-length bovine UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase (GalNAc-transferase) [Homa, F. L., Hollander, T., Lehman, D. J., Thomsen, D. R., and Elhammer, A. P. (1993) J. Biol. Chem. 268, 12609-12616], were used for PCR to isolate sequences encoding a homologous enzyme from human salivary gland cDNA. Comparison of the human and bovine nucleotide sequences reveals 94.8% sequence identity in their coding regions and 87% identity in their 3-untranslated regions. The translation of the human GalNAc-transferase coding region predicts an amino acid sequence which is nearly identical (99.6%) to that of the bovine counterpart; there are five conservative and one non-conservative amino acid substitutions between the two enzymes. Expression of the bovine and human cDNAs in the insect cell line, Sf9, resulted in the synthesis of proteins which appeared identical on SDS-PAGE and which had similar enzymatic properties. Screening of a somatic cell human/rodent hybrid panel with a probe derived from the human GaLNAc-transferase cDNA sequence indicated that the human GalNAc-transferase gene is localized to chromosome 18.

Identification and quantification of fluorine-containing metabolites of 1-chloro-2,2,2-trifluoroethane (HCFC133A) in the rat by 19F-NMR spectroscopy.

1-Chloro-2,2,2-trifluorethane (HCFC133a) causes a reduction in testis weight and germinal epithelial cell atrophy in the rat following exposure by inhalation at concentrations of 10,000 ppm and above. Following administration by gavage, an increased incidence of Leydig cell tumors of the testis was seen. The metabolism of HCFC133a has been investigated in respect to the known toxicity of this compound. Male rats were exposed by inhalation to an atmosphere of 50,000 ppm HCFC133a for a period of 6 hr. Analysis of urine, collected during the exposure period and up to 48 hr following exposure, by 19F-NMR spectroscopy identified 2,2,2-trifluoroethanol (TFE; and its beta-glucuronide), trifluoroacetaldehyde (TFAA; as its hydrate and urea adduct), and trifluoroacetic acid (TFA) as fluorine-containing metabolites of HCFC133a. Of the total amount of metabolite eliminated in urine, 83% was excreted within 24 hr postdose, establishing a rapid elimination of metabolites by this route. TFAA, an established testicular toxicant, was the major metabolite accounting for 57% of the total fluorinated metabolites eliminated in urine, whereas TFA and TFE accounted for 29% and 14%, respectively. The presence of these metabolites in urine is consistent with an oxidative route of metabolism of this fluorocarbon.

Analysis of antigen receptor genes in Hodgkin's disease.

AIM: To analyse the configuration of the antigen receptor genes in Hodgkin's disease. METHODS: DNA extracted from 45 samples of Hodgkin's disease was analysed using Southern blotting and DNA hybridisation, using probes to the joining region of the immunoglobulin heavy chain gene, the constant region of kappa immunoglobulin light chain gene, and the constant region of the beta chain of the T cell receptor gene. RESULTS: A single case of nodular sclerosing disease showed clonal rearrangement of the immunoglobulin heavy and light chain genes, all other samples having germline immunoglobulin genes. The nature of the clonal population in the diseased tissue is uncertain, because the intensity of the rearranged bands did not correlate with the percentage of Reed-Sternberg cells present. The T cell receptor genes were in germline configuration in all the samples. CONCLUSIONS: Antigen receptor gene rearrangement is a rare finding in unselected cases of Hodgkin's disease.