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Biomedical subjects

J Fox

Publications and source records attributed to J Fox.

At least 253 records · Page 14Linked to original sources

Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients.

72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients.

Amphotericin B↗

Theophylline blood levels as a guide to intravenous therapy in children.

A retrospective analysis of the records of 56 children admitted in status asthmaticus was done to assess the impact of serum theophylline levels on subsequent therapeutic decisions. In 39% of the cases, levels obtained following the initial theophylline bolus were below therapeutic range and in 6% they were above therapeutic range. In 31% of instances of theophylline levels obtained during the phase of continuous aminophylline infusion, the physician decided to administer additional theophylline. The median hospital stay was 2.65 days. Monitoring serum theophylline levels following intravenous loading and during continuous infusion provides the physician with a valuable clinical tool and may help to shorten the period of hospitalization for patients in status asthmaticus.

Adolescent↗

In vivo stability of nitrite and nitrosamine formation in the dog stomach: effect of nitrite and amine concentration and of ascorbic acid.

Formation of N-nitrosodimethylamine (NDMA) from the precursors nitrate and dimethylamine has been studied in the chronically fistulated dog stomach. Measurements have also been made as a function of time for nitrite stability and gastric pH, and a nonabsorbable marker has been used to correct for gastric emptying and dilution. In the fasting animal NDMA forms within minutes after addition of the reactants if the pH is below 5. The presence of food in the stomach slows the reaction, and the additional presence of ascorbic acid greatly depresses the amount of NDMA formed. The concentration of nitrite in gastric juice declines rapidly after its introduction, but the concentration of NDMA declines even more rapidly than nitrite. This suggests that NDMA is probably rapidly absorbed directly from the dog stomach, in contrast to earlier results in rodent experiments.

Absorption↗

Parathyroid, renal, and skeletal responses to induced hypocalcemia in the dog.

This study was designed to determine 1) whether the plasma immunoreactive parathyroid hormone (IPTH) response to acutely attained, constant (8 h) hypocalcemia is biphasic, and 2) if so, how kidney and bone respond to these changing plasma IPTH levels. We initiated constant hypocalcemia (decrement of Ca, 1.7 mg/dl) in six conscious dogs using the "calcium clamp" technique. Plasma IPTH concentrations increased maximally (fivefold) within 15 min and then decreased gradually over 1 h to a constant, but still elevated level (3.2-fold increase). Urinary excretion of phosphate and hydroxyproline increased more slowly, reaching plateaus at 1.75 h (76% increase) and 5.5 h (70% increase), respectively. The EGTA infusion rate required to maintain constant hypocalcemia was virtually constant (85 +/- 9 mumol.kg-1.h-1) after 20 min and corresponded to skeletal release of about 80 mg Ca.kg-1.day-1. The contribution of the kidney in conserving filtered calcium was relatively minor (2.0 +/- 0.5 mumol.kg-1.h-1). These data demonstrate that the parathyroid response to acute, constant hypocalcemia is biphasic and is temporally divergent from the uniphasic phosphaturic and hydroxyprolinuric responses. The ensuing increased skeletal release of calcium is very high and is maximal within minutes.

Animals↗

FIRST AID: a design philosophy and a program for on-line symptom processing.

A major problem for computer-aided diagnosis systems, particularly those designed for on-line use in clinical settings, is that their operation may be obtrusive or unacceptable within established clinical routine. Criteria for a general approach to the design of the on-line aids in clinical decision-making are presented. An interpreter is described that is designed to be broadly applicable within the area of statistical diagnosis, but which is also designed to encourage the development of congenial clinical systems. The use of the program and its features are illustrated by an application in the diagnosis of 'dyspepsia'.

Computers↗

The "calcium clamp": effect of constant hypocalcemia on parathyroid hormone secretion.

This report describes acute studies of parathyroid hormone (PTH) secretion and metabolism in conscious dogs, performed with a new technique, the "calcium clamp." Bolus injections and graded infusions of either calcium (Ca) or EGTA, respectively, increase or decrease plasma Ca to desired levels in 1-2 min; rapid determination of plasma Ca permits feedback control of the infusion rates to maintain the desired Ca concentration for prolonged periods. Using this technique, we have examined the effect in five dogs of a sustained (1 h) decrease in plasma Ca from 9.6 to 7.6 mg/dl on the secretion of PTH. Plasma immunoreactive PTH (IPTH) concentration in precaval blood increased within 1 min, peaked at 4-10 min (greater than 5 times control), but thereafter declined gradually to 57% of the maximum at 60 min, despite ongoing and constant hypocalcemia. Abrupt restoration of normocalcemia caused IPTH levels to decrease with an apparent half-time of 3.0 +/- 0.3 min (mean +/- SE). Thus, external feedback-regulated control of plasma Ca is possible in experimental animals. IPTH concentrations decline from the maximum during constant hypocalcemia, a new observation that suggests that PTH secretion and/or metabolism are altered progressively by the hypocalcemia.

Animals↗

Episodic secretion of parathyroid hormone in the dog.

This study was designed to determine whether parathyroid hormone (PTH) is secreted episodically, to characterize any such rhythms, and to see whether the rhythms can be altered by stimulating PTH secretion using constant hypocalcemia. We collected blood samples at 1-min intervals for 1 h from the precava or postcava of conscious dogs during normocalcemia or induced, constant hypocalcemia. In two anesthetized normocalcemic dogs we catheterized a caudal thyroid vein and collected all the effluent blood in 1-min fractions. Immunoreactive PTH (IPTH) concentrations were determined in quadruplicate, and the results were subjected to spectral analysis. In both the precava and postcava of normocalcemic dogs, there were regular oscillations in IPTH levels with a period of 12 min (range, 10-15 min) and a +/- 14% variation about the overall mean. Although significant two- to fourfold changes in IPTH levels still occurred during constant hypocalcemia, there was no significant rhythmicity. Significant cycles in IPTH concentration (mean 8.4-min period) were observed in thyroid venous effluent plasma during normocalcemia, confirming that the phenomenon represented episodic secretion that was not affected by pentobarbital anesthesia.

Animals↗

Retarded growth rate caused by glucocorticoid treatment or dietary restriction: associated changes duodenal, jejunal, and ileal calcium absorption in the chick.

Calcium (Ca) absorption is reportedly stimulated in the ileum of glucocorticoid-treated rats. Our study was designed to investigate this phenomenon in the chick; to determine to what extent any stimulation might compensate for inhibition of Ca absorption in the duodenum; and to compare any changes seen with those caused by growth retardation induced by dietary restriction alone. We assessed CA absorption from different sites in the intestine of chicks treated with betamethasone (BM; 25 micrograms/kg . day for 14 days), or diet-restricted to permit growth at the same rate as those treated with BM, using the ligated loop technique in vivo. There was a similar significant inhibition of Ca absorption in both BM-treated and diet-restricted chicks in both duodenum (to 73% and 67% of the control level, respectively) and jejunum (to 74% and 77% of the control level, respectively). Absorption of Ca from the ileum of BM-treated birds equaled that in controls, but diet-restricted chicks unexpectedly showed a 100% stimulation. We conclude that in the chick, BM treatment does not stimulate ileal calcium absorption, but diet-restriction does. The lack of effect of bM in the ileum may reduce the magnitude of the decrease in Ca absorption from the entire small intestine when compared to the duodenum and jejunum alone, but the stimulated absorption seen in the ileum of diet-restricted birds is almost sufficient to restore Ca absorption from the entire small intestine to the control level.

Aging↗

Stimulation by low phosphorus and low calcium diets of duodenal absorption of phosphate in betamethasone-treated chicks.

Although the inhibitory effect of glucocorticoids on the intestinal absorption of calcium is well recognized, their effect on the absorption of phosphate is less well documented. We studied the effect of the oral administration of betamethasone (BM; 25 micrograms/kg per day) on the duodenal absorption of phosphate in chicks fed normal calcium, normal phosphorus (NCaNP), normal calcium, low phosphorus (NCaLP) or low calcium, normal phosphorus (LCaNP) diets using the ligated loop technique in vivo. The daily oral administration of BM for 8 days significantly reduced the absorption of phosphate in chicks fed the NCaNP diet (21% decrease) but had less effect in chicks fed the NCaLP (14% decrease) or LCaNP (9% decrease) diets in which birds the absorption of phosphate was significantly raised (49 and 87% respectively). In one group of chicks, BM was administered for 9 days before the birds were transferred to the NCaLP or LCaNP diets. Adaptation was again unaffected by the treatment. Thirty-four per cent of the absorbed phosphate was retained in the duodenal tissue. Treatment with BM reduced the amount retained but this may have been caused by the lower weight of the duodenal segment in these chicks as BM administration markedly reduced growth rate. We have concluded that the duodenal absorption of phosphate in the chick can be inhibited by treatment with BM, although this may be secondary to the reduced rate of growth, but the increase in the absorption of phosphate caused by feeding NCaLP or LCaNP diets was unaffected by the steroid.

Animals↗

Conditions for albumin dimerisation in hephrotic urines. Dependence on an ultrafilterable factor.

At--14 degrees C the albumin in the urine of some patients with a nephrotic syndrome polymerises into dimer and higher polymers. This occurs at low ionic strengths within 1-3 days and in the pH range 5-10. For polymerisation both an altered albumin molecule and a low molecular weight ultrafilterable fraction in the urine are necessary. The appearance of both is probably related to steroid therapy. The ultrafiltrate fraction has molecular mass < 700, and is not peptide, amino acid, fatty acid or highly charged ion.

Albumins↗

Effect of low calcium and low phosphorus diets on the intestinal absorption of water in intact and parathyroidectomized pigs.

Young pigs, each surgically prepared beforehand with a Thiry-Vella loop of jejunum, were used to study the effect of feeding low calcium and low phosphorus diets on the intestinal absorption of water. Feeding a low phosphorus diet caused a highly significant stimulation in the absorption of water in parathyroid gland-intact and parathyroidectomized pigs; low calcium diets were without effect.

Animals↗

Human relevance: epidemiology and occupational exposure.

This paper reviews briefly some industrial applications which may result in occupational exposure of the workforce to preformed N-nitroso compounds. It considers exposure to nitrate in more detail, discussing epidemiological evidence which lends support to the hypothesis that high nitrate ingestion is related to high mortality from gastric cancer, through the formation in vivo of carcinogenic N-nitroso compounds. It presents the preliminary findings in a census-based mortality study of industrial workers exposed to nitrate-containing dust in the manufacture of fertilizers.

Adult↗

Parathyroid hormone does not increase nephrogenous cyclic AMP excretion by the dog.

The renal excretion of nephrogenous cyclic AMP (NcAMP) increases in response to parathyroid hormone (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH interrelationships in dogs we observed no change in total urinary cAMP (UcAMP) excretion when endogenous plasma PTH levels were increased up to 10-fold. This study was designed to investigate the effects of physiologic and pharmacologic levels of PTH on NcAMP and UcAMP excretion in the dog. Maintaining plasma Ca 2 mg/dl below normal for 40 minutes caused an 8-fold increase in plasma PTH concentration, a 50% increase in the urinary fractional excretion of phosphate (FEP) but no changes in plasma cAMP levels or in UcAMP or NcAMP excretion. Infusion of a pharmacologic amount of parathyroid extract (15 U/min for 20 min) increased plasma cAMP 5-fold, UcAMP excretion 3-fold and FEP by 50% but was without effect on NcAMP excretion. We conclude that NcAMP excretion is not stimulated by PTH in the dog and thus cannot be used as an index of PTH action in vivo. The increase in UcAMP excretion by pharmacologic amounts of PTH results from glomerular filtration of increased plasma cAMP, which may be generated in bone.

Animals↗

Use of electrochemical sensors for on-line monitoring of ionized calcium, potassium, and glucose in whole blood of living dogs.

We report the development and evaluation of electrochemical sensors for continuous on-line measurement of whole-blood ionized calcium, potassium, and glucose in living animals. Ionized calcium and potassium are measured with ion-selective electrodes, by using a unique differential approach. A polarographic sensor coupled with a membrane with bound glucose oxidase is used in the glucose analyzer. The modular concept of instrument design permits one mainframe, computer, and pump system to house any analyzer module or a combination of modules. A small volume of venous blood (about 2 mL/h) is continuously withdrawn from the subject through a double-lumen catheter and pumped through the analyzer(s). Results of in vitro correlation studies and studies in normal dogs (including responses of ionized calcium, potassium, and glucose to various stresses) support the validity of the measurements.

Animals↗