Biomedical subjects
Publications and source records attributed to A Norman.
Spontaneous brain tumors in 25 pet dogs were diagnosed and treated with a modified CT scanner. Five or more weekly 9-Gy fractions resulted in marked clinical improvement in most dogs and a significant decrease in tumor size in many dogs without adverse effects from the radiotherapy.
The effect of an intensive aluminum-magnesium hydroxide antacid regimen (Maalox TC) on the disposition of intravenous enoxacin was studied in six male and six female volunteers. A single 400-mg dose of enoxacin was administered intravenously over 30 min on two occasions separated by a 1-week washout period. Thirty milliliters of Maalox TC was administered at -8, -2.5, -0.5, 1.5, 3.5, 5.5, 7.5, 9.5, 11.5, 13.5, and 15.5 h relative to the start of one enoxacin infusion. The enoxacin dose in which antacid was coadministered was randomly selected. Fourteen plasma samples were collected over 24 h, and urine was collected in two divided intervals over 48 h. Enoxacin concentrations in plasma and urine samples were determined by high-performance liquid chromatographic assays. The intensive antacid regimen did not change the total clearance (P = 0.058) or steady-state volume of distribution (P = 0.516) for enoxacin. However, the nonrenal clearance and half-life were significantly altered (P < 0.05). The mean nonrenal clearance increased from 13.27 +/- 3.33 to 15.68 +/- 2.35 liters/h (18.2%) following the antacid regimen. This effect of antacid is unlikely to be of clinical significance. Enoxacin may be administered intravenously, but not orally, without regard to antacid treatment.
Urinary excretion of lactulose and mannitol, determined by gas-liquid chromatography, was compared with that of 51Cr-ethylenediaminetetraacetic acid (EDTA) and 14C-mannitol for measurement of intestinal permeability in 28 healthy humans. The 0- to 6-h excretion values for unlabelled and labelled mannitol (marker of transcellular permeability) were normally distributed, whereas excretion values for lactulose and 51Cr-EDTA (markers of paracellular permeability) were skewly distributed, as were the lactulose to mannitol and 51Cr-EDTA to 14C-mannitol ratios. Excretion of the transcellular markers but not of the paracellular markers was significantly correlated to urinary volume; correction for urinary volume resulted in decreased test variability. Significant correlation was found between lactulose and 51Cr-EDTA excretion (p < 0.01) and between mannitol and 14C-mannitol excretion (p < 0.001) but not between the lactulose to mannitol and 51Cr-EDTA to 14C-mannitol ratios (p = 0.11). Inter- and intraindividual test variability was greater for each chemically determined marker than for the corresponding isotope-labelled marker. Similarly, variability was greater for each paracellular marker than for the corresponding transcellular marker and for each paracellular/transcellular marker ratio than for the transcellular marker alone. Variability of mannitol excretion was increased by the frequent presence of food-derived mannitol in the urine.
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.
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.
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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.
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.
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.
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.
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)
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.
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.
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.
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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?
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.