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S Farley

Publications and source records attributed to S Farley.

9 recordsLinked to original sources

Serum fluoride and serum osteocalcin levels in response to a novel sustained-release monofluorophosphate preparation: comparison with plain monofluorophosphate.

In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.

Aged

Antidiabetic agents.

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Diabetes Complications

Pharmacokinetic profile of a new fluoride preparation: sustained-release monofluorophosphate.

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5-10 microM/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5 +/- 1.6 vs 3.5 +/- 0.8 microM/liter, P < 0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (Cmax MFP-SR: 10.6 +/- 3 vs CmaxMFP: 18.9 +/- 5 microM/liter, P < 0.005) and a significantly longer absorption lag time (TmaxMFP-SR 7.3 +/- 1.6 vs TmaxMFP: 3.0 +/- 0.6 h, P < 0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5-10 microM/liter for 24 hours.

Aged

Interpretation bias in responses to ambiguous cues in pain patients.

Pain patients and control subjects responses to ambiguous cues were compared in two separate investigations. In the first, pain patients, control subjects and physiotherapists were asked to produce a list of spontaneous associations to ambiguous cues (such as terminal and growth). To control for mood effects the experiment was repeated with three more groups: Pain patients, osteopaths and a control group. Measures of anxiety and depression were incorporated in the analysis. Results indicate that pain patients systematically produce more pain related associations than the other groups, and that this effect is independent of anxiety and depression levels. The discussion concentrates on the implications of these findings both for the theory of pain processing and for clinical interventions.

Adult

The effect of fluoride therapy on blood chemistry parameters in osteoporotic females.

To determine the potential adverse effects, if any, of long-term fluoride ingestion in humans, samples were collected from 25 adult females taking daily doses of fluoride (mean, 23 mg elemental F) for the treatment of osteoporosis and from 38 osteoporotic female controls. Patients in the fluoride group had been receiving therapy for approximately 18 months with a mean duration of 4.2 years and had serum fluoride values of at least 10 mumol/l. Laboratory analyses for fluoride were conducted on plasma, urine and drinking water samples collected from each panelist. Blood was also collected for blood chemistry analyses and plasma lymphocytes were examined for the frequency of sister chromatid exchange (SCE). Plasma and urine fluoride levels were significantly different between the two groups, while water fluoride was not. The SCE frequency, a measurement of potential genotoxicity, did not differ between the two groups. Of the blood chemistry parameters measured, albumin, alkaline phosphatase, sodium, chloride, the albumin/globulin (A/G) ratio, indirect bilirubin, lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) were found to be significantly different between the two groups (P < or = 0.05). However, none of the mean group values were outside stated normal ranges for any of these parameters. We conclude that the risk of developing adverse systemic effects from the ingestion of fluoride, at dosages and for a duration comparable with that of our panel, is minimal.

Aged

Evidence that fluoride therapy increases trabecular bone density in a peripheral skeletal site.

We measured the spinal bone density (SBD) and femoral condyle bone density (FCD) in normal and osteoporotic females (n = 219) both before and during fluoride therapy. SBD and FCD in untreated osteoporotics were significantly lower (P < 0.05) than those in the age-matched controls. SBD and FCD were correlated in the untreated (r = 0.62; P < 0.0001) as well as in the fluoride-treated osteoporotics (r = 0.42; P < 0.0001). SBD and FCD were significantly increased (P < 0.05) in response to fluoride therapy. The average rates of increase in FCD and SBD were similar (1.3 +/- 1.3 vs. 1.24 +/- 1.4 mg/cc.month). We conclude that the osteogenic action of fluoride is not limited to the axial skeleton. An increase in trabecular bone density also occurs at peripheral weight-bearing sites such as the femoral condyle.

Aged

Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina).

Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina) were studied in 74 cases at the Washington Regional Primate Research Center. The medical records of monkeys during the 5-year period from 1983 to 1988 were analyzed to determine the age at death, age at first episode of diarrhea, number of episodes of diarrhea, episode and cumulative duration of diarrhea, and etiologies of diarrhea. Univariate analysis, using one control for each case, indicated that only episode duration was related to intestinal amyloidosis. Affected monkeys had significantly longer mean episode durations of diarrhea. None of the etiologies examined--bacteria, protozoa, fungi, and simian retrovirus--were significant risk factors for amyloid deposition in the intestinal tract.

Age Factors