Taking heroin maintenance seriously: the politics of tolerance.
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Biomedical subjects
Publications and source records attributed to A Parry.
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Potential morbidity remains substantial in aortic root replacement. The tissues are often fragile, contributing to the risk of haemorrhage and postoperative complications. In the past surgery has been directed towards minimising haemorrhage by wraparound techniques and the right atrial fistula method of Cabrol. However, recent use of aortic homografts, collagen-impregnated grafts and tissue glues have reduced bleeding and simplified operative technique. Profound hypothermia and total circulatory arrest allows aneurysm resection to extend into the aortic arch. Between 1986 and 1991 25 aortic root replacements were carried out at the Oxford Heart Centre in 21- to 76-year-olds, 13 for aorto-annular ectasia (4 due to Marfan's syndrome), 7 for aortic dissection (2 Marfan's syndrome) and 2 for complications of previous aortic valve replacement. Three patients had homograft root replacement for aortic root endocarditis. We implanted 14 Medtronic composite grafts, 1 St Jude conduit and 7 collagen-coated Dacron grafts (Hemashield, Meadox) into which a Starr-Edwards valve was sewn, as well as 3 homografts. One patient with a massive chronic dissection following previous aortic valve replacement required an interposition graft to the coronary ostia. In the others, the coronary ostia were mobilised from the native aorta and directly implanted into the conduit. In dissections a ring of pericardium or GoreTex was used to buttress the coronary anastomoses. Six patients also required coronary artery grafting. Native aorta was excised and not wrapped around the conduit. Coagulation defects were corrected aggressively with platelets, fresh frozen plasma and cryoprecipitate.(ABSTRACT TRUNCATED AT 250 WORDS)
Eight patients underwent both cardiac operation and repair of abdominal aortic aneurysm. All had respiratory impairment and significant impairment of left ventricular function, whereas six patients had severe diffuse distal coronary disease. In all patients the cardiac procedure was performed first, and the patients continued to receive cardiopulmonary bypass. Rewarming was not commenced until the abdominal repair was well under way, to protect the vital organs. There were no problems in weaning the patients from bypass, and six of the patients were extubated within 24 hours; one required ventilation for 36 hours. One patient died of colonic infarction complicated by kidney failure without being extubated. Another patient who was initially extubated in 11 hours required reintubation because of poor lung function and eventually died of multisystem organ failure caused by bilateral lower limb ischemia that persisted despite embolectomies. All survivors are well and in New York Heart Association functional class I or II between 3 and 18 months postoperatively. We conclude that for patients considered unfit for abdominal aortic aneurysm operations because of the nature of the cardiac disease, the combined operation with cardiopulmonary bypass is both safe and effective.
We studied all patients with postinfarction ventricular septal rupture referred to the Oxford Heart Centre for operation over a 4 1/2-year period. Twenty one women and 8 men were admitted to the Centre, 13 of whom had received streptokinase and 16 of whom had not. The median interval between symptomatic onset of myocardial infarction and the development of septal rupture was 24 hours for those treated by early thrombolysis (all streptokinase) and six days for those who were not. Of the 26 patients who underwent surgical repair, three were operated on less than 36 hours after streptokinase infusion, in one case within 12 hours of thrombolytic treatment. Macroscopic observation of the disintegrating myocardium showed muscle bundles dissected by blood rendered incoagulable by thrombolytic treatment, together with the histologic features of reperfusion injury. The overall surgical mortality rate for the streptokinase group was 33% and for the others 21%. The patient operated on within 12 hours of thrombolytic treatment recovered uneventfully. Six of seven surgical deaths were caused by left ventricular or biventricular failure and one by gastrointestinal hemorrhage. All survivors were in New York Heart Association classes II or III between 2 weeks and 4 1/2 years after operation. We conclude that thrombolysis leads to early breakdown of the interventricular septum after acute myocardial infarction but does not preclude early repair.
The complete adoption of a narrative paradigm for therapy is proposed and its implications and possibilities spelled out, especially for life in a post-modern world that lacks any objective frame of reference. In the post-modern sensibility, the story is set free to perform as simply a story that allows for re-invention as the story-teller finds a voice rooted in the person's own experience and in the connection of her story to those of others, and to larger stories of culture and humanity. The realization that we are all characters in each other's stories as well as our own reminds us that our stories only go forward as we act in ways that also forward the stories of others. A hermeneutics for such therapy validates and questions all points of view so that they do not harden into stories that are assumed to be objectively true.
Tandem mass spectrometric techniques have been developed for analysing alkylated purines in human urine. These techniques are designed with the objectives firstly of identifying unknown adducts derived from mixed exposures to alkylating agents, and secondly of quantifying these adducts with minimal sample purification.
The effects of azelaic acid (AZA) on the epidermis of 47 individuals (12 with normal skin, 15 with seborrheic skin and 20 suffering from acne) and on in vitro cultured keratinocytes are reported. Topical application of a 20% AZA cream significantly improved the lesions of acne patients, but failed to induce clinically detectable changes in normal or seborrheic epidermis. Complementary investigations clearly showed that AZA treatment failed to induce specific changes in sebum composition, excretion rate, or in the size of sebaceous glands, but modified epidermal keratinization. Keratohyalin granules and tonofilament bundles were reduced in size and number, mitochondria were swollen and the rough endoplasmic reticulum of malpighian keratinocytes enlarged. The infundibular epidermis of acne individuals showed marked reduction of the horny layer thickness, widening of the horny cell cytoplasm, transitional corneal cells, normalization of filaggrin distribution, and the comedo contained few bacteria and spores. In vitro, AZA exerted marked time- and dose-dependent antiproliferative cytostatic effects on cultured keratinocytes, with a 50% inhibitory dose of 20 mM, decreased some keratinocyte proteins (highly soluble fractions S2, keratohyalin macroaggregate R2, and non-cross-linked fibrous protein S4) and a 95 kD and a 35 kD protein of the cytosolic fraction. Mitochondria were frequently damaged and the rough endoplasmic reticulum enlarged. Our results indicate that AZA is an antikeratinizing agent, displaying antiproliferative cytostatic effects on keratinocytes and modulating the early and terminal phases of epidermal differentiation.
It is known that in vitro incubation of the expectorant drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) with nitrite yields methylcyclohexyl nitrosamine (NMCA). NMCA is capable of methylating DNA when administered to rats. In vivo tests with bromhexine have also demonstrated that the drug methylates DNA when it is orally administered in the presence of sodium nitrite, presumably due to the intragastric formation of NMCA. In this study the potential of bromhexine to methylate nucleic acids in man, under physiological conditions, has been investigated. 20 volunteers were orally administered on each of three successive days 48 mg of bromhexine hydrochloride, labelled with three deuterium atoms in the N-methyl group. Urine was collected before treatment and subsequent to the last dose, and analysed by GC-MS for d0- and d3-7-methylguanine. 7-Methylguanine is naturally occurring in urine owing to the turnover of t-RNA of which it is a minor constituent. It is also a repair product from nucleic acids methylated by carcinogens, which is known to be excreted unmetabolised largely within 24 h of the methylation process. Unlabelled 7-methylguanine was present at levels of 7.36 +/- 2.43 mg/d in control urine and 6.12 +/- 2.36 mg/d in treated urine, in accord with previously published values. The excretion of isotopically labelled 7-methylguanine averaged 0.43 +/- 0.077% of the unlabelled concentration for control urines and 0.44 +/- 0.066% for treated urines, i.e. no d3-7-methylguanine could be detected following the drug treatment. The observed signals were largely accounted for by the naturally occurring isotopes 13C and 15N.(ABSTRACT TRUNCATED AT 250 WORDS)
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The determination of urinary 3-methyladenine has been explored as a potential monitor of exposure to methylating carcinogens. A method based on the use of high resolution gas chromatography--mass spectrometry has been developed for measuring this methylated base in human urine. Urine is extracted by XAD-2 column chromatography and the extract purified by reverse phase C18 h.p.l.c. Derivatization with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide yields the mono-tert-butyldimethylsilyl derivative of 3-methyladenine which has good gas chromatographic properties and is stable towards hydrolysis. The gas chromatographic separation was carried out using an SE-52 capillary column and quantitation made by electron impact selective ion monitoring mass spectrometry employing deuterium-labelled 3-methyladenine added initially to the urine as internal standard. Measurable levels (4.50-16.07 micrograms/24 h) of the methylated base have been found in control (i.e. nominally unexposed) human urines.
Human gingival organ culture was used to test the hypothesis that gamma interferon (gamma-IFN), which induces HLA-DR and HLA-DQ antigens on Langerhans cells, modulates CD4 antigen expression on these same cells. Before culture, the density of CD4+ cells in the gingival epithelium was 12.7% +/- 3.8% of the density of CD1+ cells. gamma-IFN (200 IU/ml) enhanced CD4 expression such that at 24 h, all CD1+ cells also expressed CD4. Prostaglandin E2, which in isolation had no effect, partially abrogated the stimulatory effect of gamma-IFN on CD4 expression. These results imply that gamma-IFN and prostaglandin E2 are two signals which regulate CD4 expression on gingival Langerhans cells.
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