Insulin resistance in syndrome X.
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Biomedical subjects
Publications and source records attributed to A F Jones.
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Nephrotoxicity is less common than hepatotoxicity in paracetamol overdose but renal tubular damage and acute renal failure occur even in the absence of hepatotoxicity. It is possible that antidotal therapy with agents such as N-acetylcysteine may not prevent renal toxicity and, indeed, on the basis of animal work, may actually potentiate tubular damage. Careful clinical attention should be paid to renal function in patients poisoned with paracetamol.
Alpha 1-antitrypsin was measured in 5-day faecal collections from patients with colorectal cancer or adenomatous polyps and a symptomatic control group. Collections were homogenized and lyophilized prior to measurement of alpha 1-antitrypsin by radial immuno-diffusion. Colorectal cancer dry weight concentrations were significantly higher than the symptomatic control results, with 57% having results greater than 95% normal values of this control group. There was no significant difference between adenomatous polyp dry weight concentrations and symptomatic control results. Wet weight concentrations were calculated from wet/dry ratios. Colorectal cancer wet weight concentrations were significantly higher than symptomatic control results with 48% having results greater than 95% normal values of this control group. Alpha 1-antitrypsin was also measured in non-lyophilized samples from an asymptomatic control group (n = 39). Colorectal cancer wet weight concentrations were significantly higher than asymptomatic control results, with 62% having results greater than 95% normal values of this control group. Faecal alpha 1-antitrypsin measurement deserves further assessment for use in detecting colorectal cancer.
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A 37 year old male presented after the ingestion of paraquat ('Gramoxone', 20% w/v). Plasma paraquat concentrations indicated that he had a greater than 50% probability of death. The patient survived following a period of acute oliguric renal failure and with only mild pulmonary toxicity.
Fluorescence (excitation 360 nm, emission 454 nm) generation in glycated albumin was investigated. Antioxidants and the metal chelator desferrioxamine (DFX) were used to study the mechanism of fluorescence generation. Delipidation studies, reverse phase chromatography and scanning fluorimetry were performed to examine the nature of this fluorescence. The mechanism of action of aminoguanidine, a compound which has been shown to inhibit the formation of visible fluorescence in proteins in vitro and in vivo was investigated in relation to glycation and by comparison with compounds with structural similarities. We conclude that hydrogen peroxide, metal ions and hydroxyl radicals are involved in fluorescence generation in glycated albumin, which is largely lipid in nature, and arises through glycation, amino acid oxidation and changes in bound lipid. Our results suggest that the action of aminoguanidine is not specifically related to blocking of ketoamine groups on glycated proteins as previously suggested.
Transvaginal ultrasonography has provided new anatomic and pathophysiologic information about the female pelvis. Because of probe proximity to the organ of interest and higher insonating frequency, resolution is dramatically improved. Problems previously encountered during transabdominal scanning, such as obesity, bowel gas, and a retroverted uterus, no longer preclude accurate diagnosis. Patient acceptance is nearly universal. Physiologic information concerning the endometrium and ovarian follicles has improved infertility diagnosis and treatment. Hormonal and vascular Doppler changes can be correlated with cyclic endometrial patterns and follicle size. Oocyte retrieval, management of pre-existing inflammatory disease, and treatment of complications of pregnancy are easier and safer with a transvaginal approach. Uterine malformations, leiomyomas, and cancers are more easily detected in premenopausal and postmenopausal women. The documentation of early intrauterine or ectopic pregnancy has decreased maternal morbidity and mortality. Tube-sparing procedures with preservation of reproductive potential are now more commonly employed due to earlier recognition of unruptured tubal pregnancy. Interventional TVS has led to improved recognition and treatment of pelvic cysts and abscesses and multiple pregnancy. Chorionic villous sampling can be performed more easily without the need for anesthesia, with adequate tissue obtained.
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A polymerase chain reaction (PCR) assay has been developed and validated by using allele-specific oligonucleotide (ASO) primers to specifically amplify E3, E2, and E4 polymorphic sequences of the human apolipoprotein E (apo E) genes. Degenerate ASOs containing one or two additional 3' mismatches provided greater specificity than did ASOs containing a single mid-sequence or 3' allele-specific mismatch with plasmid pEB4 or genomic DNA as template. Optimal specificity and efficiency of amplification did not correlate with primer annealing conditions, whether determined theoretically or via oligo-melting experiments. Pre-cycling denaturation times and high cycling denaturation temperatures were also required for optimal amplification, presumably because of the high G:C content (75-85%) of apo E gene sequences. Conditions permissive for amplification and discrimination with plasmid DNA did not transpose favorably to amplification from human genomic DNA from peripheral blood leukocytes; the latter required nested primer reactions. These data may be valuable in predicting PCR assay conditions for other G:C-rich sequences containing polymorphic sequence differences. The assay described is both more accurate and rapid (24 h) than previously described methods for phenotyping or genotyping human apo E from blood specimens.
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Patterns of plasma ACTH and cortisol concentrations were studied in 10 healthy subjects (five male, five female in the early follicular phase, overall age range 21-32 years) by sampling through an indwelling cannula every 15 min for 24 h. The subjects were in hospital, ambulant, and taking normal meals. Plasma ACTH was measured by a two-site immunoradiometric assay with a detection limit of 3.9 ng/l (0.9 pmol/l). Pulses were identified by the method of Clayton et al. (1987) using stringent criteria to minimize false positive peaks. All subjects showed a circadian rhythm of ACTH, the acrophase occurring between 0615 and 0920 h in all but one subject and the mesor value was between 9.2 and 18.6 ng/l (2.0 and 4.1 pmol/l). There were significantly fewer pulses between 1800 and 2400 h compared with the other three 6-h periods. The pattern of ACTH differed between males and females in several respects: more pulses (18 vs 10), greater mean peak amplitude (16.8 vs 10.3 ng/l), greater area under the 24-h profile (350.9 vs 206.6 ng/l h) and higher mean level (14.7 vs 8.6 ng/l) in the males. In contrast, the cortisol pattern did not show statistically different sex differences. The sex differences suggest greater sensitivity to, or availability of, ACTH to the female adrenal cortex, or different set points in cortisol feedback.
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