Hypertriglyceridaemia-induced pancreatitis: a contributory role of capecitabine?

Capecitabine is an orally administered pro-drug of 5-fluorouracil that confers superior disease-free survival and presumably has a more favourable side-effect profile. Here we report on a patient who developed acute necrotising pancreatitis and very high triglyceride levels as well as hand-foot syndrome after receiving capecitabine for colonic cancer. Increased awareness of this potential side-effect and close monitoring of lipid levels may be warranted, especially in patients who have other conditions predisposing them to severe secondary hyperlipidaemia when using this drug.

The Chinese version of the pelvic pain and urgency/frequency symptom scale: a useful assessment tool for street-ketamine abusers with lower urinary tract symptoms.

OBJECTIVE: To investigate the use of a translated Chinese version of the pelvic pain and urgency/frequency symptom scale as an assessment and prognostic tool to evaluate the severity of street-ketamine-associated lower urinary tract symptoms and their reversibility after abstinence. DESIGN: Cross-sectional study. SETTING: A special designated out-patient clinic in a regional hospital in Hong Kong. PARTICIPANTS: There were 50 patients with street-ketamine-associated lower urinary tract symptoms and 20 healthy individuals. MAIN OUTCOME MEASURES: Reliability and validity of the questionnaire; frequency of individual lower urinary tract symptoms, cystoscopic, urodynamic and radiological abnormalities, and their correlation with pelvic pain and the urgency/frequency score. RESULTS: The test-retest reliability coefficient was 0.755 (P<0.001). Cronbach's alpha was 0.974. Mann-Whitney U test proved the discriminatory ability of the questionnaire (P<0.001). Patients with specific lower urinary tract symptoms had a higher mean pelvic pain and urgency/frequency total score compared to those without them: frequency (23.8 vs 17.3), nocturia (22.4 vs 14.0), urgency (22.5 vs 15.1), dysuria (22.7 vs 13.3), and haematuria (24.8 vs 16.2). The number of daytime voids and nocturia episodes correlated well with pelvic pain and urgency/frequency scores. With an increasing score, the likelihood of having cystitis changes, urodynamic abnormalities and hydronephrosis increased, while the cystometrically determined bladder capacity decreased. None of the patients with a score of 16 or below had urodynamic abnormality or hydronephrosis. The mean score change in the abstinence group was -4.33, versus +3.33 in their counterparts. CONCLUSIONS: The Chinese version of the pelvic pain and urgency/frequency questionnaire is reliable and valid for assessment in patients with street-ketamine-associated lower urinary tract symptoms. The pelvic pain and urgency/frequency score correlates well with symptom severity as well as endoscopic, urodynamic and radiological abnormalities in patients with street-ketamine-associated lower urinary tract symptoms. A cut-off total pelvic pain and urgency/frequency score of 17 may suggest more serious urological sequelae from ketamine abuse. Abstinence from ketamine reduced lower urinary tract symptoms, but the extent of reversibility of urinary tract damage is yet to be evaluated.

Fragmentation of alpha-radical cations of arginine-containing peptides.

Fragmentation pathways of peptide radical cations, M(+*), with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of Co(III)(salen)-peptide complexes [salen = N,N'-ethylenebis (salicylideneiminato)]. Subsequent hydrogen abstraction from the beta-carbon of the side-chain followed by C(alpha)-C(beta) bond cleavage results in the loss of a neutral side chain and formation of an alpha-radical cation with the radical site localized on the alpha-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of arginine-containing alpha-radicals, suggesting that for these systems radical migration precedes fragmentation. In contrast, proton-driven fragmentation dominates CID spectra of alpha-radicals produced via the loss of the arginine side chain. Radical-driven fragmentation of large M(+*) peptide radical cations is dominated by side-chain losses, formation of even-electron a-ions and odd-electron x-ions resulting from C(alpha)-C bond cleavages, formation of odd-electron z-ions, and loss of the N-terminal residue. In contrast, charge-driven fragmentation produces even-electron y-ions and odd-electron b-ions.

Methionine, alpha-methylmethionine and S-methylcysteine radical cations: generations and dissociations in the gas phase.

Methionine, alpha-methylmethionine and S-methylcysteine radical cations have been formed by oxidative dissociations of [CuII(M)(CH3CN)2]*2+ complexes. The radical cations M*+ were trapped, and CID spectra (MS3) of these ions are presented. Fragmentations of the methionine and S-methylcysteine radical cations, initiated by migration of the alpha-carbon hydrogen atom to the sulfur, trigger the losses of water and thiomethanol from methionine and thiomethanol from S-methylcysteine. Deuterium labeling experiments show that considerable H-D scrambling and rearrangements involving N-H and S-H hydrogens occur in the methionine radical cation prior to fragmentation. An additional channel for S-methylcysteine is the loss of ammonia following beta-hydrogen migration. Methylation at the alpha-carbon of methionine results in a radical cation that fragments differently. Two neutral losses from alpha-methylmethionine, NH3 and methyl vinyl sulfide, CH2=CH-S-CH3, are initiated by gamma-hydrogen migration; a third channel is the loss of *COOH. DFT computations at the B3LYP/6-311+ +G(d,p) level have been used to test aspects of the proposed fragmentation mechanisms of the radical cations.

Bilateral epidural extension of thoracic capillary vertebral (intraosseous) hemangioma mimicking spinal meningioma.

We describe a rare case of vertebra (intraosseous) hemangioma with bilateral and symmetrical epidural extension causing cord compression in a 24-year-old woman. The epidural component was isointense to cord on both T1 and T2 sequences, and enhanced markedly and homogenously following gadolinium administration. The gradual in onset and progressive nature with the typical enhancing pattern lead the neurosurgeon to the more common diagnosis of spinal meningioma. Epidural extension of vertebral hemangiomas causing cord compression is rarely reported. Review of literatures reveal that cases that have been reported are of unilateral extension into epidural space and of cavernous type. This is the first case report of capillary vertebral (intraossous) hemangioma with bilateral extension through both intervetebral foramen into the epidural space causing myelopathy.

Use of lithium in the treatment of thyrotoxicosis.

OBJECTIVES: To evaluate the efficacy and safety of lithium in the treatment of thyrotoxicosis, and to study the dose and serum levels at which therapeutic response occurs. DESIGN: Retrospective study. SETTING: Thyroid clinic of a regional hospital in Hong Kong. PATIENTS: Thirteen patients with thyrotoxicosis pending therapy with radioiodine or surgery, in whom thionamides were contra-indicated due to adverse reactions or failure of treatment. MAIN OUTCOME MEASURES: Free thyroxine levels, time to euthyroidism, and side-effects of lithium. RESULTS: A satisfactory response, defined as a fall by 40% or more in free thyroxine levels and clinical improvement, was achieved in eight patients within 1 to 2 weeks of lithium therapy. In four others, response occurred in 3 to 5 weeks. Response was slow and inadequate in one patient due to 'escape'. The median dosage of lithium was 750 mg daily, with a range of 500 to 1500 mg daily. The median serum lithium level was 0.63 mmol/L. Lithium toxicity was observed in one patient. CONCLUSIONS: A relatively low dose of lithium offers a safe and effective alternative means of controlling thyrotoxicosis in patients who cannot tolerate or do not respond to thionamides.

Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study.

OBJECTIVE: To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy. DESIGN: Single-blind randomised prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003. MAIN OUTCOME MEASURES: NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans. RESULTS: The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy. CONCLUSION: A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity.

HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

HLA-C locus alleles in patients with psoriatic arthritis (PsA).

The aim of this investigation was to compare the frequency of alleles at the HLA-C locus in patients with psoriatic arthritis to that in the disease free population and to relate the HLA genes to disease phenotype in psoriatic arthritis (PsA). Ninety-four consecutive patients seen in the (PsA) clinic between April and July 1996 and 100 disease-free controls had HLA typing performed by both serologic and molecular techniques. Patients' disease was assessed according to a standard protocol. Fisher's exact test was used to compare the frequency of HLA alleles in the patients and controls. HLA-C determined by PCR-SSP decreased the frequency of non-identified, that is, "blank" (or null) alleles to 6% in patients and controls. HLA-Cw*0602 was present in 32 patients and 18 controls: allele frequency of 17% in the patients versus 9% in the controls (p < 0.01). Amongst patients with psoriatic arthritis, those who carried the HLA-Cw*0602 allele had a significantly earlier mean age of onset of their psoriasis (p = 0.003). This study confirms that molecular DNA techniques improve detection of C-locus alleles. The HLA-Cw*0602 is increased amongst patients with psoriatic arthritis compared to controls. The HLA-Cw*0602 is associated with an earlier age of onset of psoriasis.

Acute intestinal graft-versus-host disease in a syngeneic bone marrow transplant recipient.

BACKGROUND: We report a case of intestinal graft-versus-host disease (GVHD) in a syngeneic bone marrow transplant patient. METHODS: Several days after receiving a bone marrow transplant from his identical twin for treatment of non-Hodgkin's lymphoma, a 47-year-old man developed a skin rash and diarrhea. RESULTS: A colonic biopsy on day +15 revealed characteristic changes of acute intestinal GVHD. Molecular studies (microsatellite DNA and HLA sequence-specific primer polymerase chain reaction analyses) confirmed the genotypic identity of donor and host and the improbability of transfusion-associated GVHD. CONCLUSION: This case illustrates that pathological evidence of GVHD does not absolutely require the presence of genetic differences between host and donor and questions existing concepts about the nature of cyclosporine-induced GVHD.

Microsecond rotational dynamics of F-actin in ActoS1 filaments during ATP hydrolysis.

Rabbit skeletal muscle F-actin labeled at Cys374 with the triplet probe erythrosin-5-iodoacetamide had a steady-state phosphorescence anisotropy (rp) of 0.090 +/- 0.005 at 20 degrees C in 100 mM KCl, pH 7.0, buffer. Titration with skeletal muscle S1 fragment increased rp to 0.138 +/- 0.006 at a mole ratio of 1:1. In the presence of ATP, the anisotropy of the actoS1 complex initially decreased to 0.050 +/- 0.005, a value significantly smaller than the anisotropy of pure F-actin; rp subsequently increased to 0.126 +/- 0.002. The time course of the increase matched that expected from the measured actin-activated ATPase of S1. The plateau value at long time, 0.126, was identical to that of actoS1 in the presence of exogenous ADP or ADP plus phosphate. Characterization of the spectroscopic properties of the erythrosin probe indicated that the changes in rp were not due to changes in fast probe motions on the surface of the filament or the phosphorescence emission lifetime, or in the orientation of the probe on the surface of F-actin, suggesting that they reflect large-scale changes in the microsecond rotational dynamics of actin. ATP hydrolysis by actoS1 thus appeared to induce rotational motions of or within F-actin on the phosphorescence time scale (approximately 300 microseconds). Although the precise physical origin of the induced rotational motions is unknown, this study provides direct evidence that large-scale conformational fluctuations of the actin filament are associated with the force-generating event in actomyosin.