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Biomedical subjects

A Norman

Publications and source records attributed to A Norman.

At least 19 recordsLinked to original sources

Linoleate produces remission in canine mycosis fungoides.

Linoleic acid (LA) administered orally as safflower oil (SFO), which is 76% LA, produced remission in 6 out of 8 dogs with mycosis fungoides (MF). Following each feeding of SFO on 5 successive days to a normal dog peak plasma levels of non-esterified (free) LA in excess of 200 microM were observed. No clinical toxicity was observed from the SFO feedings in the normal or MF animals at the levels of SFO (3 ml/kg) used in these studies. However, a marked rise in white blood cells (WBC) and lymphocytes and a marked transient drop in the serum glutamine transaminases SGOT and SGPT was noted both in the normal and MF animals. These effects of LA may be significant for the remission of MF.

Alanine Transaminase

Myositis ossificans with atypical clinical, radiographic, or pathologic findings: a review of 23 cases.

Myositis ossificans is a relatively rare, well-defined entity. The 23 cases sent for consultation to two of us (L.V.A. and A.N.) were reviewed. Clinical, radiologic, and microscopic information was reexamined, and special attention was given to features infrequently seen in typical myositis ossificans. Average age at presentation was 23 years, but 1 patient was younger than 2 years, and 2 were younger than 10 years. Due to the uncommon location of 15 lesions and an unusual presentation in 5, the correct diagnosis was not obvious in these cases. A history of trauma was elicited in 8 patients, denied by 7, and was not queried in the remainder. Radiologic studies raised the possibility of a malignant bone-forming tumor in at least three instances; myositis ossificans was originally diagnosed in 6 cases radiologically. In 8 cases, histologic evidence suggested malignancy, including osteosarcoma, either parosteal or extraosseous, in 6. Other diagnoses included epithelioid sarcoma and callus formation. Presentation of these variations from the norm highlights the importance of recognizing the evolution of a nonneoplastic fibro-osseous and cartilaginous entity in which conservative treatment is curative.

Adolescent

Serum concentrations and excretion of bile acids in cirrhosis.

Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (= synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients.

Adult

Calculation of radiation dose enhancement factors for dose enhancement therapy of brain tumours.

When brain tumours are loaded with iodinated contrast media (CM) and exposed to x-rays, the photoelectrons, Auger electrons and fluorescent x-rays from the iodine enhance the radiation dose absorbed by the tumour. A modified CT scanner, the CTX, can be used to localize the tumour and to deliver the dose enhancement therapy. Monte Carlo calculations are presented here of the central-axis radiation depth dose in a brain containing a tumour loaded with an iodine concentration of 5 mg ml-1 and irradiated with the CTX operated at various kV settings. The dose enhancement factor (DEF) is also calculated for various field sizes and for 5 mg ml-1 of gadolinium in the tumour when the CTX is operated at 140 kV. The calculated values of the DEF are close to published experimental results.

Animals

Rapid destructive osteoarthritis: clinical, radiographic, and pathologic features.

Twenty-seven cases of an unusual, poorly recognized destructive hip arthropathy with radiographic findings of rapid severe joint destruction are presented. Radiographic findings mimicked those of other disorders such as septic arthritis, rheumatoid and seronegative arthritis, primary osteonecrosis with secondary osteoarthritis, or neuropathic osteoarthropathy, but none of the patients had clinical, pathologic, or laboratory evidence of these entities. All patients underwent hip arthroplasty, and osteoarthritis was confirmed at pathologic examination. Rapid progression of hip pain and disability was a consistent clinical feature. The average duration of symptoms was 1.4 years. Radiographs obtained at various intervals before surgery (average, 18 months) in nine patients documented rapid hip destruction. Involvement was unilateral in 89% (24 of 27 cases). Twenty patients (83%) were elderly women. The authors postulate that these cases represent an uncommon, rapidly destructive subset of osteoarthritis.

Aged

Dose-ranging pharmacokinetic study of ciprofloxacin after 200-, 300-, and 400-mg intravenous doses.

OBJECTIVE: To assess the pharmacokinetics and tolerance of ciprofloxacin after the administration of single intravenous doses of 200, 300, and 400 mg. DESIGN: Double-blind, three-period, randomized, crossover trial. SETTING: Private, university-affiliated, hospital-based, clinical research center. PATIENTS: Normal healthy male volunteers, 18-40 years of age. INTERVENTIONS: Subjects received 200-, 300-, and 400-mg single intravenous doses of ciprofloxacin via 30-minute infusions in random sequence. MAIN OUTCOME MEASURES: Serum ciprofloxacin concentrations were determined by HPLC after each dose and the results were used to derive pharmacokinetic parameters. Tolerance was assessed by reported and observed adverse events, urine microscopic examinations for crystals, and examination of intravenous infusion sites. RESULTS: The mean area under the time curve (AUC) values displayed linearity with respect to the administered dose. No statistical differences were observed in total body clearance, steady-state volume of distribution, or elimination half-life with respect to dose administered. The mean total body clearance, steady-state volume of distribution, or elimination half-life ranged from 36 to 41 L/h, 146 to 169 L, and 3.5 to 3.7 h for the 200-, 300-, and 400-mg doses, respectively. Adverse effects, including venous irritation (four subjects) and crystalluria (two subjects), were mild and did not require withdrawal of any subject from the study. CONCLUSIONS: Intravenous ciprofloxacin in doses ranging from 200 to 400 mg demonstrated linear pharmacokinetics. These single doses were well tolerated, although cases of transient venous irritation and crystalluria were observed.

Adolescent

Production of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 by growth zone and resting zone chondrocytes is dependent on cell maturation and is regulated by hormones and growth factors.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and 24,25-(OH)2D3 have been shown to promote chondrocyte proliferation and differentiation; resting zone chondrocytes respond primarily to 24,25-(OH)2D3, whereas growth zone chondrocytes respond primarily to 1,25-(OH)2D3. This study determined whether resting zone and growth zone cells produce 24,25-(OH)2D3 or 1,25-(OH)2D3; whether this production is regulated by 1,25-(OH)2D3 (10(-8) M), 24,25-(OH)2D3 (10(-7) M), dexamethasone (10(-7) M), or recombinant human transforming growth factor-beta 1 (11 ng/ml); and whether the metabolites produced are biologically active. Confluent fourth passage rat costochondral growth zone or resting zone chondrocytes were cultured in Dulbecco's Modified Eagle's Medium containing [3H]25-hydroxyvitamin D3 ([3H]25OHD3), 2% fetal bovine serum, and antibiotics. Metabolism of [3H]25OHD3 was measured by analyzing the lipid extracts of the conditioned medium and the cell layer for [3H]1,25OHD3, [3H]1,25-(OH)2D3, and [3H]24,25-(OH)2D3 using flow-through scintillation spectroscopy of HPLC eluates. Chemically synthesized radioinert vitamin D3 metabolites were used as standards, and their migration was determined by absorbance at 254 nm. To ensure that the radioactive peaks were 1,25-(OH)2D3 and 24,25-(OH)2D3, the fractions were rechromatographed into three other HPLC solvent systems. Biological activity was confirmed; the addition of HPLC-purified 1,25-(OH)2D3 produced by growth zone chondrocytes elicited a dose-dependent stimulation of alkaline phosphatase specific activity in growth zone cell cultures, but had no effect on the resting zone cells. There was a time-dependent increase in both [3H]1,25-(OH)2D3 and [3H]24,25-(OH)2D3 in the conditioned medium of both types of cultures. At 24 h, the percent conversion of [3H]25OHD3 to [3H]1,25-(OH)2D3 was 5.3 +/- 1.2, and the percent conversion to [3H]24,25-(OH)2D3 was 1.8 +/- 0.4 in growth zone chondrocyte cultures. No such effect was found in cultures freeze-thawed five times or without cells. When resting zone cells were cultured with [3H]25OHD3, the percent conversion to 1,25-(OH)2D3 and 24,25-(OH)2D3 was 4.5 +/- 1.0 and 1.7 +/- 0.4, respectively. The addition of dexamethasone significantly increased the percent production of 1,25-(OH)2D3 at 6 and 24 h and at 6 h by resting zone and growth zone cells, respectively, compared to the control values. Recombinant human transforming growth factor-beta 1 increased the percent production of 1,25-(OH)2D3 after 1 h in resting zone cells and, after 24 h, the production of 24,25-(OH)2D3 in growth zone cells. Radiolabeled 1,25-(OH)2D3 and 24,25-(OH)2D3 were not detected in the cell layer.(ABSTRACT TRUNCATED AT 400 WORDS)

24,25-Dihydroxyvitamin D 3

Presence of bile acid metabolites in serum, urine, and faeces in cirrhosis.

Studies have been made of the presence of bile acid metabolites in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, indicating only mild impairment of liver function, whereas the remaining two patients comprised Child group C. A complex mixture of bile acids was isolated from serum, urine, and faeces, and 26 bile acids were identified by gas-liquid chromatography coupled to mass spectrometry. Identification was made of the primary bile acids, cholic (C) and chenodeoxycholic (CDC) acid, and metabolites of these bile acids converted through 7-dehydroxylation, keto-formation, 6-hydroxylation, 1 beta-hydroxylation, allo-formation or nor-formation. All of the bile acids have previously been described either in healthy humans or patients with hepatobiliary disease. With the exception of C, CDC, and deoxycholic acid, all of the bile acids were present only infrequently, and none of the bile acids was pathognomonic for liver cirrhosis. The proportion of metabolites of the primary bile acids C and CDC was similar to that previously reported in healthy humans, the lowest proportion being recorded in the Child group C patients. Repeated determinations of the metabolite pattern in two patients showed large variations, indicating that the bile acid metabolism varies from time to time. We conclude that in mild cirrhosis, no significant alterations in microbial or hepatic transformation of bile acids seem to occur.

Bacteria

Predicting normal tissue injury in radiation therapy.

We tested three radiobiologic models, the nominal standard dose (NSD), the biologic index of reaction (BIR), and the linear quadratic (LQ) models to determine which best predicts normal tissue injury in radiation therapy. Clinical data for radiation myelopathy, rib fracture and pericardial effusion were used for all three models to predict injury. We assumed that on the average injuries occurred at higher equivalent doses of radiation than were received by patients who were not injured. We used a t-test to determine whether there were in fact significant differences in the mean values of the equivalent doses among the injured and non-injured. The means were calculated for the four sets of injury by the three models. For the LQ model it was necessary to choose a value for the parameter alpha/beta; the results were not sensitive to the choice over the range of 1/2 to 12 Gy. None of these models showed a significant difference between injured and non-injured patients for all four sets of data. The BIR model showed significant differences in three sets, the LQ model was significant in two and marginally significant in one set, and the NSD was significant in two sets. This analysis illustrates therefore, that the linear quadratic model can be adopted for analysis of clinical data with results that are no worse and possibly better than the NSD model.

Humans

Equilibration of labelled and endogenous bile acids in patients with liver cirrhosis after administration of (24-14C)cholic and chenodeoxycholic acids.

On separate occasions (24-14C)cholic acid and (24-14C)chenodeoxycholic acid were administered intravenously to patients with liver cirrhosis and the isotope excretion in urine and faeces monitored. Bile acids in serum, urine and faeces were extracted and separated into unconjugated bile acids, glycine- and taurine conjugates, glucuronides and sulphates. Individual bile acid conjugates were separated by high-performance liquid chromatography (HPLC) and the unconjugated bile acids were separated by gas-liquid chromatography (GLC) and identified by gas chromatography-mass spectrometry (GC-MS). Individual bile acid conjugates were quantified and their isotope contents determined. In serum, isotope contents declined rapidly during the first day, followed by a markedly slow rate of reduction. In accordance with this, the excretion of isotope from the patients was found to be very slow and the routes of bile acid excretion were changed, which resulted in an increased ratio of urine/faeces isotope excretion. Studies of the ratio of labelled to endogenous bile acid conjugates indicated that a continuous transformation of the labelled compounds occurred during the period of study. As judged from serum bile acids, conjugation to glycine- or taurine conjugates was rapid. The specific activities of labelled sulphate esters were consistently lower than for other conjugates during the 300-min observation period. During the first day, the urinary bile acids contained a high proportion of unconjugated labelled bile acids, which gradually disappeared. Labelled primary bile acids were slowly converted into microbial products, mainly 7-alpha dehydroxylated derivatives. The observed slow transformations resulted in a much delayed equilibration of labelled and endogenous bile acid derivatives, which invalidates isotope techniques for calculation of kinetic data of bile acid turnover. However, the observed very slow turnover of labelled bile acids in cirrhosis, owing to the persistent high rate of intestinal absorption and low capacity for urinary excretion, makes it possible for the intestinal flora to markedly change the composition of the bile acids in the pool. Studies of endogenous urinary and faecal bile acid excretion revealed the changed route of bile acid excretion with a high urinary/faeces ratio and the decreased synthesis of bile acids in cirrhosis.

Bile Acids and Salts

Swabs: the forgotten item of nursing care?

Swabs are items used every day in every operating room where invasive procedures are performed. How often do scrub nurses hand surgeons swabs, and how often is thought given to their shape, size and composition and their suitability for use inside our patients?

Evaluation Studies as Topic

Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis.

Ataxia-telangiectasia is a syndrome with many facets, involving a progressive cerebellar ataxia, immunodeficiency, cancer susceptibility, radiosensitivity, defects in DNA repair/processing, chromosomal breakage and rearrangements, elevated serum alphafetoprotein, and premature aging. Ataxia-telangiectasia is an autosomal recessive disorder, rare in outbred populations; carriers of the ataxia-telangiectasia gene may be as common as 1 in 60 and have subclinical radiosensitivity and cancer susceptibility. One estimate suggests that 8.8% of patients with breast cancer could be carriers of ataxia-telangiectasia. These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. The genes for the 3 most common ataxia-telangiectasia complementation groups, which include 97% of tested families, have recently been localized to the long arm of chromosome 11.

Ataxia Telangiectasia

Effect of reactive pharmacy intervention on quality of hospital prescribing.

OBJECTIVE: To evaluate the medical impact of reactive pharmacy intervention. DESIGN: Analysis of all interventions during 28 days by all 35 pharmacists in hospitals in Nottingham. SETTING: All (six) hospitals in the Nottingham health authority (a teaching district), representing 2530 mainly acute beds, 781 mental illness beds, and 633 mainly health care of the elderly beds. PATIENTS: Hospital inpatients and outpatients. INTERVENTIONS: Recording of every important intervention made by pharmacists to prescriptions for both inpatients and outpatients when they perceived inadequacies of drug prescription or administration, including characterisation of the problem, coding of outcome, recording of time taken to initiate and resolve intervention, and grade of prescribing doctor. The problems were independently assessed for their potential to cause medical harm. RESULTS: 769 Interventions (about 2.9% of prescriptions) were made, of which 60 concerned prescriptions rated as having a major potential for medical harm. The commonest problems concerned dosage, which was wrong in 280 prescriptions (102 for antibiotics) and not stated in 50 (one for antibiotics), especially those associated with a major potential for medical harm (32 prescriptions). These concerned sedatives; analgesics; cardiovascular drugs or diuretics; and iron, vitamin, or mineral preparations. Also common were overprolonged prescription of antibiotics (48 prescriptions), confusion of drug names (nine), and inadvertent coprescription of excessive quantities of aspirin or paracetamol in plain and compound preparations (seven). The pharmacist's recommendation was accepted in 639 instances (86%), and the prescription was altered in 575, leading to an appreciable (246 cases) or minor (231 cases) improvement. Interventions had little effect on costs; 427/646 had no effect and 130 produced savings less than 50p. Pharmacy intervention (730/769 interventions) occupied on average 41 minutes per pharmacist per week. CONCLUSIONS: Most reactive pharmacy interventions concerned prescribing errors with a limited potential for medical harm, but a small number of detected errors with a major potential for medical harm; cost savings were not appreciable.

Decision Making

The CT scanner as a therapy machine.

Many tumors in the brain and in other tissues can be delineated precisely in images obtained with a CT scanner. After the scan is obtained the patient is taken to another room for radiation therapy and is positioned in the beam with the aid of external markers, simulators or stereotactic devices. This procedure is time consuming and subject to error when precise localization of the beam is desired. The CT scanner itself, with the addition of a collimator, is capable of delivering radiation therapy with great precision without the need for external markers. The patient can be scanned and treated on the same table, the isocenter of the beam can be placed precisely in the center of the lesion, the beam can be restricted to just those planes in which the lesion appears several arcs can be obtained by simply tilting the gantry, and the position of the patient in the beam can be monitored continuously during therapy. We describe here the properties of the CTX, the CT scanner modified for therapy.

Animals