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Biomedical subjects

J Morton

Publications and source records attributed to J Morton.

At least 127 records · Page 7Linked to original sources

Isolation of a novel morphinan 3-O-diglucuronide metabolite from dog urine.

Following oral administration of the narcotic antagonist nalmefene [17-(cyclopropylmethyl)-4,5 alpha-epoxy-6-methylenemorphinan-3,14-diol] labeled with 14C to the dog, approximately 50% of the dose was excreted in the urine as a highly polar water-soluble conjugate. Although this major metabolite could be hydrolyzed with beta-glucuronidase to yield nalmefene, the intact conjugate was chromatographically more polar on reversed-phase high-performance liquid chromatography (HPLC) than authentic nalmefene 3-O-glucuronide. Milligram quantities of the metabolite were subsequently isolated and subjected to fast atom bombardment (FAB) mass spectral and nuclear magnetic resonance (NMR) analyses. The conjugate was identified as nalmefene 3-O-beta-diglucuronide with a 1,2-beta linkage between the two glucuronic acids. It is unlikely that this novel form of conjugate is unique to nalmefene and it is probably a metabolite of other morphinans and/or similar drugs in the dog. Nalmefene 3-O-diglucuronide is not a metabolite of nalmefene in man.

Animals↗

Secretion of antidiuretic hormone in neurosurgical patients: appropriate or inappropriate?

In neurosurgical patients with hyponatraemia (plasma sodium less than 130 mmol/l) and natriuresis, increased antidiuretic hormone (ADH) secretion may be appropriate rather than inappropriate. Ten such patients were studied prospectively to assess circulating ADH concentration and body fluid volumes. Compared with a control group, the mean plasma ADH level was significantly elevated (0.9 pmol/l (s.e.m. = 0.2) versus 0.2 pmol/l (s.e.m. = 0.1], the total body water was normal (101% (s.e.m. = 3) versus 100% (s.e.m. = 6], while the blood volume was significantly reduced (89% (s.e.m. = 3) versus 104% (s.e.m. = 5]. The elevated ADH level was therefore appropriate to a reduced blood volume. This suggests that, in neurosurgical patients with hyponatraemia, fluid restriction could be dangerous. Serial observations in this small group of patients showed that salt replacement and normal fluid intake resulted in a fall in the elevated ADH levels.

Acute Disease↗

Are fixed-dose oestrogen/progestogen combinations ideal for all HRT users?

Although progestogens protect the endometrium against excessive oestrogen-induced stimulation, they can cause adverse symptomatic and psychological effects and may have undesirable metabolic consequences. Thus, the minimum progestogen dose which results in consistent endometrial transformation should be prescribed. To define this dose for norethisterone and dl-norgestrel, 197 endometrial samples obtained from postmenopausal women receiving conjugated equine oestrogens (0.625 mg or 1.25 mg daily) with one of six doses of norethisterone (or the acetate), or one of three doses of dl-norgestrel added for the first 12 days of each calendar month were examined with the light microscope; 109 samples were also assessed by transmission electron microscopy. There was an inverse relation between the percentage of samples showing proliferative features and the progestogen dose. However, proliferative endometrium was observed in 6% of samples with the highest dose of dl-norgestrel (500 micrograms) and in 3% of samples with 2.5 mg norethisterone. Conversely, complete secretory transformation was observed in 25% of samples with the lowest dose of norethisterone (0.1 mg) and in 40% of samples with 75 micrograms dl-norgestrel. Mild atypical hyperplasia was diagnosed in four samples. There was a wide inter-patient variation in response and none of the nine progestogen dose regimens induced secretory change in every patient.

Cell Division↗

Bulimia: symptoms and syndromes in an urban population.

The widely used DSM-III criteria for the diagnosis of bulimia essentially define bulimia as a syndrome of guilty, secretive and subjectively hard to control binge over-eating. A self-report questionnaire for bulimic behavior was administered to three community and two hospital populations in South Australia. 13% of females in the community samples could be categorized as bulimic according to the DSM-III criteria. Those criteria did not adequately define the behaviour of patients in treatment for bulimia in a Weight Disorders Unit, 85% of whom not only binged, but induced vomiting afterwards. When diagnostic criteria were more closely aligned to clinical experience, the prevalence of bulimia in the community appeared closer to 1-2%. New DSM criteria (DSM-III-R) have been proposed and prevalence rates using them fell within the 1-2% range.

Adolescent↗

Relative biological effectiveness of 241Am relative to 192Ir for continuous low-dose-rate irradiation of BA1112 rat sarcomas.

Sealed sources of 241Am have been developed for intracavitary irradiation of gynecological cancers. Relative to conventional isotopes (that is, 226Ra, 137Cs, 192Ir), 241Am allows for better shielding of dose-limiting normal tissues in the patient. In addition, the long half-life of 241Am (432 years) makes it an attractive isotope both for clinical use and for long-term radiobiology studies. Using a previously developed in vivo applicator system, BA1112 sarcomas on WAG/Rij Y rats were irradiated using 241Am or 192Ir at three different dose rates. Following in vivo treatment of the sarcomas with graded doses of radiation, cell survival curves were determined using an in vitro colony formation assay. The slopes of the resulting cell survival curves were observed to increase significantly as the dose rate increased from 0.30 to 0.60 Gy/h, then to decrease slightly as the dose rate increased from 0.60 to 0.95 Gy/h. The relative biological effectiveness (RBE) of 241Am relative to 192Ir was observed to increase linearly with increasing dose rate; the RBEs were 0.96 +/- 0.009, 1.09 +/- 0.12, and 1.17 +/- 0.11 at dose rates of 0.30, 0.60, and 0.95 Gy/h, respectively.

Americium↗

Assessment of power spectral edge for monitoring depth of anaesthesia using low methohexitone infusion.

The study describes an attempt to determine the minimal sleep infusion rate for the intravenous anaesthetic, methohexitone using EEG power spectral edge (PSE) as an index of anaesthetic depth. PSE was found to remain stable during a continuous infusion at declining rates, with decreasing plasma concentration. We were unable to define a sleep infusion rate using PSE as an index of anaesthetic depth. PSE was found to be unsuitable for monitoring anaesthetic depth.

Adult↗

Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU.

Sedation was studied in 30 patients requiring overnight ventilation in the intensive therapy unit (ITU). Patients received an infusion of either alfentanil or pethidine, supplemented with midazolam. The infusion rates were adjusted to provide optimal sedation as judged by a nurse, and measurements were made of quality of sedation, recovery and serum cortisol concentration. In addition, blood concentrations of alfentanil were measured to permit pharmacokinetic and pharmacodynamic analysis. Satisfactory sedation was achieved in both groups. The required infusion rate for alfentanil was between 0.4 and 0.5 micrograms kg-1 min-1. Recovery was good in both groups, apart from one patient in the alfentanil group, in whom recovery was greatly prolonged and alfentanil pharmacokinetics were abnormal. A difference was found in the metabolic response to surgery between the two groups, the response in the alfentanil group being significantly less marked.

Aged↗

Disorganisation of intermediate filament structure in alcoholic and other liver diseases.

The distribution of Mallory body antigens JMB1 and 2 was examined in 82 human fresh diagnostic needle liver biopsies and 28 necropsies by the indirect immunoperoxidase technique using 2 monoclonal antibodies (anti-JMB1 and 2) against Mallory bodies. The JMB1 antigen was detectable in bile duct epithelium and in hepatocytes of histologically normal livers. It was also found in all Mallory bodies in various hepatic disorders. This antigen was markedly increased in the cytoplasm of all liver cells in acute alcoholic hepatitis superimposed on alcoholic cirrhosis, in most cases of acute alcoholic hepatitis, and in severe fatty infiltration of the liver with or without Mallory body formation. Mallory bodies contained this antigen but the cytoplasm of Mallory body containing cells lacked JMB1. In normal liver the JMB2 antigen was localised on the cytoplasmic intermediate filament network of hepatocytes and bile duct epithelium; and almost all Mallory bodies also contained this antigen but the adjacent cytoplasm of these cells lacked JMB2. In severe alcoholic liver disease these antigens could not be detected in large zones of hepatocytes even when these hepatocytes did not contain Mallory bodies. It is evident that there is disorganisation of intermediate filament constituents in severe alcoholic liver disease.

Antibodies, Monoclonal↗

An evaluation of the Sequoia-Turner Cell Dyn 900.

A formal evaluation of the Sequoia-Turner Cell Dyn 900, a compact eight-parameter semi-automated blood cell counter, was carried out in a small paediatric haematology laboratory. The instrument's precision, linearity and carry-over were adequate. Comparison with a Coulter ZF6 system plus visual platelet count showed good agreement, and results in the UK National External Quality Assessment Scheme also compared well with 'all methods' values. Throughput was assessed at 54 eight-parameter counts per hour. The machine proved to be reasonably economical, highly reliable and easy to operate. It was popular with staff and can be recommended, particularly for the smaller laboratory.

Autoanalysis↗

Treatment of word retrieval deficits in aphasia. A comparison of two therapy methods.

The effects of two therapy methods in the treatment of picture naming problems are compared, using a within-patient design with 12 adult patients with chronic acquired aphasia. We contrast techniques that require the patient to process the meaning corresponding to the picture name (semantic treatment) with those that provide the patients with information about the phonological form of the name (phonological treatment). With each method, patients either had 4 sessions of treatment over one week, or 8 sessions over two weeks. Both methods caused day-by-day improvement that was specific to the actual items treated. Both methods resulted in significant improvement in naming when this was measured one week after the end of treatment, with a small, but significant advantage for the semantic treatment; this is mainly due to improvement that generalizes to untreated items. We conclude that specific and theoretically motivated treatment methods can cause significant improvement in the word retrieval ability of patients with chronic aphasia.

Adult↗

Headaches after childbirth.

71 women were examined daily for the presence of headache in their first post partum week. Post natal headache (PNH) occurred in 27, (39%) of the women and was most frequent on days 4-6 post partum. PNH was significantly associated with a previous or family history of migraine and pre-menstrual migraine. Although 83% of those with PNH had a migraine diathesis, they did not describe their headache as one of their usual migraines as it was considerably milder. Headaches were more frequent among multigravida but as rather more multigravida had a previous migraine diathesis this may reflect a sampling bias. PNH subjects had significantly more tension and depression suggesting that at least some PNH may be tension headache. Around 3 or 4 days post partum, women began to lose weight and the onset of headache often coincided with the start of this weight loss. 12 women with, and 12 without PNH took part in a metabolic study, and collected sequential 24 h urine samples from days 2-7 post partum. Potassium and oestrogen excretion were increased on day 3, and progesterone on days 3, 4 and 5. Differences in the excretion pattern of these hormones might reflect small changes in renal function and further work measuring plasma hormone levels could help to clarify this. PNH, like pre-menstrual headache and pill withdrawal headache may represent a further example of the triggering effect that a fall in sex hormone level has on the migraine diathesis.

Adolescent↗