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L Davidson

Publications and source records attributed to L Davidson.

At least 127 records · Page 7Linked to original sources

Effect of variation in infusion time and macrophage blockade on organ uptake of amphotericin B-deoxycholate.

Amphotericin B is administered as a colloidal suspension due to its insolubility in water. Macrophages, particularly those in the liver, have been implicated as the predominant cell type responsible for the uptake of colloidal amphotericin B. We examined the effect of infusion time and macrophage function to confirm the role of the macrophage in the uptake of amphotericin B. Prolonged infusion time (24 h compared to 6 h) resulted in significantly less hepatic and splenic accumulation of amphotericin B. Blockade of macrophage function with methylpalmitate also resulted in significantly decreased hepatic and splenic uptake of amphotericin B. Uptake of amphotericin B by lung macrophages was not significantly affected by methylpalmitate. The area under the serum concentration versus time curve was significantly higher in the group that received methylpalmitate compared to either the 6 or 24 h amphotericin B infusion groups. These results suggest that fixed macrophages play an important part in the pharmacokinetics of amphotericin B, and that increasing drug solubility may alter the pharmacokinetics of amphotericin B.

Amphotericin B↗

Idiopathic gastroparesis is associated with a multiplicity of severe dietary deficiencies.

UNLABELLED: Idiopathic gastroparesis (IG), a disorder characterized by abnormally delayed emptying of food from the stomach, is associated with many symptoms that could have an impact on dietary intake. The intake of dietary protein, carbohydrate, fat, fiber, vitamins, and minerals was prospectively evaluated in patients with symptomatic IG and compared with asymptomatic controls. Twenty-four patients and 24 age- and sex-matched controls completed a detailed 7-day diet record while consuming a self-selected diet. Dietary information was entered into a computer and analyzed using the Nutranal program. Results were expressed as daily intake and percent recommended dietary allowance (%RDA) when applicable. Patients consumed a diet containing fewer calories than would have been predicted based on age, height, sex, frame, and weight (85% of calculated energy expenditure vs 100%) for controls. Although patients with IG consumed significantly fewer calories than controls (1112 kcal vs 1431 kcal), the proportion of fat (32% vs 34%), carbohydrate (49% vs 48%), and protein (17% vs 16%) was similar in the two groups. Intake of vitamins B6, vitamin C, folate, niacin, riboflavin, thiamine, calcium, copper, iron, magnesium, phosphorus, and zinc were below the %RDA. Intake of vitamin B12, vitamin C, folate, thiamine, niacin, magnesium, phosphorus, and zinc were significantly less than controls. Vitamin A intake was above the RDA and not different from that of controls. Prolonged t1/2 of solids correlated with diminished intake of protein, iron, niacin, and potassium. They correlated inversely with serum albumin in patients with idiopathic gastroparesis. CONCLUSION: Although eating less, patients with IG do not consistently alter the proportion of fat, carbohydrate, and protein in their diets. Because their diet is markedly deficient in a number of essential vitamins and minerals, dietary evaluation and counseling is suggested for all patients with idiopathic gastroparesis.

Adult↗

Solubility and stability of amphotericin B in human serum.

The solubility and stability of amphotericin B in human serum in vitro was assessed using a sensitive high performance liquid chromatographic technique. The solubility of amphotericin B at concentrations ranging from 0.5 micrograms/ml to 10 micrograms/ml in human serum at pH 7.4, at 37 degrees C, and in 5% CO2 (simulated in vivo conditions) showed no significant difference compared with the solubility at 23 degrees C in room air after a 1 h incubation period. Dissolution of the colloidal suspension at a concentration of 2 micrograms/ml reached 81% in 3 min with a small increase in solubility by 60 min. Amphotericin B was very stable (less than 5% loss) in human serum at -20 degrees C for up to 14 days with only a 10% loss of drug at 6 months. In dimethylsulfoxide, however, losses at 6 months were greater than 60%. We conclude that amphotericin B solubilizes, but not completely, from a colloidal form in human serum under simulated in vivo conditions at 37 degrees C and at 23 degrees C in room air over 1 hour. Additionally, amphotericin B is stable in frozen serum for 6 months.

Amphotericin B↗

Trabecular and cortical bone in the radii of women with parathyroid adenomata: a greater trabecular deficit, with a preliminary assessment of recovery after parathyroidectomy.

Radial bone mineral content (BMC) has been reported to be lower than normal in patients with hyperparathyroidism, but those measurements have been made with techniques which do not discriminate between trabecular and cortical bone. We have used a low radiation dose computed tomography technique to make differential measurements of trabecular and cortical bone in the radii of 18 out of 27 eligible female patients with surgically proven adenomata. Prior to parathyroidectomy there was a mean deficit of 40% (P less than 0.001) in trabecular bone density in the distal radius, and a deficit of 16% in cortical bone in the radius mid-shaft compared to normal values. Seventeen months after parathyroidectomy there was a small but significant increase in trabecular bone density in the distal radius in 13 of these patients, and no significant change in cortical bone. If these results represented the situation throughout the skeleton, it is possible that parathyroidectomy may provide some reduction in future risk of fracture in women with primary hyperparathyroidism.

Adult↗

Clinical significance and etiology of infected catheters used for total parenteral nutrition.

Catheter related sepsis (CRS) is the most serious complication of total parenteral nutrition. Frequently, however, low rates of CRS are associated with a high incidence of infection of the catheter tip, the clinical significance of which is unclear. The relationships between CRS, infection of the catheter tip and infection at the site of catheter insertion have been investigated in 283 catheters of 257 patients receiving total parenteral nutrition. CRS occurred in only ten patients (3.5 per cent) whereas organisms were isolated from 108 catheter tips (38.2 per cent). The most common organism isolated was Staphylococcus epidermidis (66.7 per cent). Eight catheter tips were colonized from a distant septic focus. Organisms were isolated from 90 catheter tips which were removed electively from patients who displayed no clinical evidence of sepsis. There was a poor correlation between infected catheter tips and infected catheter insertion sites. Asymptomatic infection of the catheter tip appears to be of little clinical relevance, resulting in no patient morbidity. Contamination of the catheter tip during or after removal seems to account for a significant proportion of these infections.

Bacteria↗

Comparative accuracy of computerized spatial vectorcardiography and standard electrocardiography for detection of myocardial infarction.

New computerized spatial vectorcardiographic variables were analyzed by discriminant analyses for group classification of 94 patients with acute myocardial infarction and 79 normal subjects. Using the integral of the sequential magnitudes of the spatial vectors during the period of initial abnormal depolarization (IAD) of the QRS at a discriminating value of 3 mv X msec., 87% of the subjects were correctly classified with a sensitivity of 85%; specificity of 88%; and an overall predictive accuracy of 87%, p less than .00001. The period of initial abnormal depolarization in which the vectors were integrated was determined by the first derivative of the sequential magnitudes of the spatial vectors of the QRS waveform (dm/dt). The mean value of dm/dt during the period of abnormal depolarization was a poor discriminating variable. The predictive accuracy of this new electrocardiographic criterion for diagnosis of myocardial infarction compared favorably with other computerized methods such as vectorcardiography, polarcardiography, Aitoff spatial trajectory, the 12-lead ECG derived by the Frank XYZ leads as well as the standard 12-lead ECG.

Computers↗

Sulphate conjugation limits fluctuations in free catecholamines in phaeochromocytoma.

More than 80% of total noradrenaline (NA) and adrenaline (A) and nearly 100% of dopamine (DA) circulate in blood as sulphates, and it has been proposed that sulphate conjugation contributes to the inactivation of catecholamines (CA). Sulphate conjugation rapidly responds to changes in sympathetic activity and may buffer the haemodynamic and metabolic consequences of wide fluctuations in CA release in phaeochromocytoma. This hypothesis was tested in seven patients with phaeochromocytoma by consecutive measurements of plasma-free and conjugated NA, under resting conditions, before operation and at least 4 weeks after tumour removal. Free and total (free + sulphates) NA were markedly elevated before compared with 1-4 months after surgery. Similar elevations were seen in free and total A and free DA. Before surgery consecutive measurements of total NA, 5 min apart, were markedly different (17 +/- 4.1 and 13.7 +/- 4.4 ng/ml, respectively), whereas only small differences in free NA levels were present (4.1 +/- 1.5 and 4.3 +/- 1.8 ng/ml). These differences between total and free levels were also apparent for A and DA, but to a lesser degree. In three patients, fluctuations in total NA concentration greater than 12 ng/ml were associated with either no change (one patient) or changes of 0.6 and 2.8 ng/ml in free levels for the other two patients, respectively. Mean blood pressure (BP) varied less than 8 mmHg in these patients. These findings suggest that sulphate conjugation is a dynamic process which may limit wide fluctuations in free CA concentration during episodic secretory activity in phaeochromocytoma.

Adrenal Gland Neoplasms↗

A new human ovarian carcinoma cell line: establishment and analysis of tumor-associated markers.

In the present study we describe the establishment and characteristics of a new human tumor cell line (OV-1063) positive for carcinoembryonic antigen (CEA) originating from ovarian metastatic tumor cells. Analysis of the cultured cells during their in vitro adaptation period revealed while the primary culture exhibited a low proportion of CEA-positive cells, this proportion increased with culture passages and eventually more than 90% of the cells in the established line were CEA-positive. Thus, during the period of adaptation to in vitro growth, a selection for CEA-positive cells took place but the amount of CEA secreted per each positive cell seemed to be constant. Several tumor-associated characteristics were found positive on the established OV-1063 cell line. The in vitro growing cell line exhibited an abnormal chromosome pattern with a near-trisomy karyotype for some chromosomes, colony formation in soft agar as well as positive staining with a monoclonal antibody B38.1. Culture supernatants of the OV-1063 cells contained significant amounts of CEA as well as CA-125 antigen which is an ovarian-carcinoma-associated antigen.

Agar↗

Total and free plasma neuroleptic levels in schizophrenic patients.

Nineteen male patients, under 35 years of age, newly admitted with a diagnosis of schizophrenia, were treated with either chlorpromazine or haloperidol at a fixed dosage for 25 days. Both total and free plasma neuroleptic levels were measured using a radioreceptor assay. Clinical response was measured by the Brief Psychiatric Rating Scale (BPRS). On day 25, nonresponders (those with a decrease of less than 8 points on the BPRS) had both total and free plasma neuroleptic levels within the range observed in responders. It is therefore concluded that lack of therapeutic response is generally not due to inadequate plasma drug levels.

Adult↗

Acute effects of moderate alcohol consumption on blood pressure and plasma catecholamines.

This study examines the response of blood pressure, plasma catecholamines and cortisol to acute alcohol intake in young men with light to moderate drinking habits. Ingestion of alcohol was associated with a highly significant increase in systolic blood pressure and heart rate which occurred before blood alcohol reached its peak concentration of 16.9 +/- 1.1 mmol/l (80 mg/100 ml). After an initial non-specific rise, diastolic pressure fell below values observed after drinking water only. This predominant effect of alcohol on systolic blood pressure is also seen with chronic alcohol consumption. Drinking water and non-alcoholic cold liquids caused a marked fall in plasma adrenaline and a transient rise in noradrenaline concentration. In contrast, drinking alcohol resulted in a relative rise in adrenaline and a delayed increase in noradrenaline concentration. Blood glucose increased after alcohol, supporting a physiological effect of adrenaline on liver glycogenolysis. Plasma cortisol concentration was also significantly higher after drinking alcohol. It is proposed that the relative rise in adrenaline together with higher cortisol levels, repeated over a variable period in susceptible individuals, are implicated in the elevation of blood pressure associated with long term alcohol consumption. It concurs with observations in man and experimental animals of a slow pressor mechanism mediated by adrenaline.

Adult↗

Sex-related differences in resting and stimulated plasma noradrenaline and adrenaline.

Resting and stimulated plasma noradrenaline and adrenaline concentration were compared in 45 females and 45 males of similar age who did not smoke, drink alcohol or caffeine-containing beverages. At rest plasma noradrenaline levels were consistently higher in females and adrenaline levels higher in males. These sex-related differences were maintained after isometric exercise, mental arithmetic and cold pressor testing. Resting noradrenaline concentration was negatively correlated with Quetelet index in males and positively correlated with age in females. These findings, based on precise catecholamine measurements under standardized conditions in subjects of similar age, reveal important sex-related differences which need to be taken into account in assessing sympatho-adrenal activity, particularly in relation to mechanisms in essential hypertension.

Adult↗