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Biomedical subjects

D H Schweitzer

Publications and source records attributed to D H Schweitzer.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.

Adult↗
PubMed2004

Pharmacokinetic/pharmacodynamic modelling of effects of dexamethasone and prednisolone in combination with endogenous cortisol on lymphocyte counts and systemic markers of bone turn over and inflammation in healthy and asthmatic men.

OBJECTIVE: To compare potency and efficacy of dexamethasone (DEXA) and prednisolone (PRED) in assumed equipotent doses in combination with endogenous cortisol, using lymphocyte counts, plasma osteocalcin (OC), and eosinophilic cationic protein (ECP) as effect variables and to evaluate potential differences between healthy subjects and asthmatic patients. METHODS: Eight healthy subjects and six asthmatic patients who had stopped taking their regular inhaled glucocorticosteroid treatment (ICS) for 1 week, were given an IV bolus of DEXA and PRED in assumed equipotent doses of 2.0 mg and 12.5 mg, respectively, on separate occasions, in combination with subcutaneously injected granulocyte-colony-stimulating factor (G-CSF) as a stimulant for ECP production. Plasma levels of DEXA, PRED, cortisol and effect variables were determined over 25 h and pharmacokinetic-pharmacodynamic (PK-PD) modelling was performed. RESULTS: Baseline cortisol concentration was lower in patients than in healthy subjects. Both of the exogenous glucocorticoids (GCs) diminished cortisol production. In the healthy subjects, the cortisol production remained suppressed for the full duration of the study day after DEXA but not after PRED. In the asthmatic patients though, the reappearance of the endogenous production of cortisol was seen after both DEXA and PRED. The E(max) values for lymphocyte counts and OC showed that cortisol acted as partial, and DEXA and PRED as full agonists. The observed responses of DEXA and PRED suppressing cortisol, OC and lymphocyte counts were all of the same relative order of magnitude, in accordance with the estimated PD parameters. However, cortisol was estimated to have very little effect on ECP and modelling further predicted that DEXA and PRED were only partial agonists for this effect, without a difference between healthy and asthmatic subjects. Yet, in healthy subjects, the area under the concentration-time curves (AUCs) indicated unexpectedly that ECP was only suppressed after PRED and not after DEXA, while in patients it was suppressed after both GCs. The rank order of potency on lymphocyte counts, OC and ECP was DEXA>PRED>cortisol, although the different relative potencies of the three GCs involved were not the same for all of the three effect variables and differences were also found between healthy and asthmatic subjects. CONCLUSION: PK-PD modelling studies of GCs demonstrated not only differences in potency of DEXA and PRED on the measured systemic markers, but also different potencies per target tissue and differences between healthy and asthmatic men. The effects caused by the achieved blood concentrations of DEXA and PRED, expressed as AUCs of the effect variables, were in accordance with their respective E(max) values in case of the lymphocytes and OC but not for ECP.

Adult↗
PubMed2004

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003; these studies were pooled to provide a summary variance-weighted effect size. The antidepressant-induced percentage increase of the intravaginal ejaculation latency time (IELT) was calculated and examined against various methodological items. A significant difference in efficacy between SSRIs was observed. Using daily treatment, paroxetine appeared more effective than the other SSRIs. Retrospective use of a questionnaire, subjective reports, single-blind and open study designs generate far greater variability of ejaculation time both at baseline and during active drug treatment than real time assessment by stopwatch. In conclusion, at daily treatment, the overall efficacy of paroxetine, clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the strongest ejaculation delay. Only eight (18.5%) studies on antidepressant treatment fulfilled all criteria used in evidence-based medicine, for example, randomised, double-blind studies with prospective real time (stopwatch) assessment of the IELT at each intercourse. Single-blind studies, open designs, retrospective reporting, or the use of a questionnaire to assess ejaculation time should be avoided.

Adult↗
PubMed2003

The interaction between Sillence type and BMD in osteogenesis imperfecta.

Clinical studies with bisphosphonates in children with osteogenesis imperfecta (OI) show an increase in BMD and a decrease in fracture rate. Bone strength in children with OI is not only influenced by changes in BMD but also by changes in collagen I structure of the organic bone matrix. Therefore, we studied the interaction between these two factors in a cross-sectional, single center study including 54 children. We assumed that vertebral deformities in OI represent an unbalance between load and bone strength. Body weight was considered to be a well quantifiable load on vertebral bodies. BMD served as a marker, representing the amount of bone tissue available for vertebral load bearing, and the Sillence classification, either type I or III/IV, as a marker representing the quality of the organic bone matrix. Independent associations were observed between the prevalence of vertebral deformities and (1) Sillence type (OR: 5.7, 95%Cl:1.2-26.8), (2) BMD (OR: 0.003, 95%Cl: 0-0.25) and (3) body weight (OR: 1.15, 95%Cl: 1.05-1.25). Regarding the anthropometrical differences among the different types of OI, the BMD/body weight ratio was introduced to evaluate the BMD in relation to body size. Prevalent vertebral deformities were associated with low BMD/body weight ratios (OR: 0.04, 95%Cl: 0.008-0.2) in OI type I, but no association was found in type III/IV. It was concluded that BMD and Sillence type have independent relationships with vertebral deformities. The BMD/body weight ratio correlates with vertebral deformities in children with OI type I. Its meaning in types III/IV needs further research with larger samples because of the relatively high prevalence of vertebral deformities in this group.

Absorptiometry, Photon↗
PubMed2003

Distinct actions of prednisolone and dexamethasone towards osteocalcin and eosinophilic cationic protein in assumed clinically equivalent doses: a study in healthy men.

OBJECTIVE: To study the effects of prednisolone (PRED) and dexamethasone (DEXA) in assumed clinically equivalent doses towards the lowering of cortisol, osteocalcin (OC) and the stimulated rise of eosinophilic cationic protein (ECP) by granulocyte colony stimulating factor (G-CSF). METHODS: At four separate sessions of 25 h each, saline i.v. alone, G-CSF s.c. alone or in combination with either 12.5 mg PRED i.v. or 2.0 mg DEXA i.v., were randomly administered in eight healthy male subjects. RESULTS: All subjects had equal lowering of cortisol after DEXA and PRED at 10 h, whereas a sustained suppression at 25 h persisted only after administration of DEXA. Between 4 h and 10 h after administration of DEXA and PRED, the change in the area under the concentration-time curve (DeltaAUC4-10) of OC became 24.4% and 2.3% lower, respectively ( p<0.0001). After 25 h, this effect persisted for DEXA. DeltaAUC4-10 of the G-CSF-stimulated ECP response decreased by a mean of 76.8% after PRED compared with DEXA and to controls ( p<0.02), and this difference had disappeared at 25 h. DEXA did not elicit any effect towards the G-CSF-stimulated ECP response. CONCLUSION: PRED and DEXA in formerly assumed clinically equivalent doses induced a similar suppression towards cortisol within the first 10 h, but had different actions towards blood concentrations of OC and ECP following G-CSF stimulation in healthy male subjects.

Adult↗
PubMed2003

Lack of relationships between cumulative methylprednisolone dose and bone mineral density in healthy men and postmenopausal women with chronic low back pain.

The medical use of glucocorticoids (GCs) is related to low bone mineral density (BMD). In this study we tested the hypothesis that the cumulative dose of GC is not related to BMD outcome. The study was cross-sectional in design and included healthy individuals with chronic low back pain resistant to conventional treatments. In two steroid-naive subjects cortisol and methylprednisolone (MP) concentrations were serially assessed after a single MP depot injection (160 mg epidurally). Furthermore, in 14 men and 14 postmenopausal women, previously treated with multiple epidural MP depots, endocrine parameters were analysed in relation to BMD outcomes. The minimal cumulative MP dose received by all 28 subjects was 3 g. In the two steroid-naive subjects, cortisol concentrations were completely suppressed for at least 6 days and partly recovered over the course of 30 days. During this period, MP concentrations remained detectable in plasma. In the 28 subjects, the cumulative MP dose received was 7.76+/-4.23 g in the men and 8.50+/-3.13 g in the women (mean+/-1SD). None of the men had osteoporosis, but osteopenia was prevalent in 78.5% according to WHO criteria extrapolated to men. Half of the women had osteoporosis and half of them had osteopenia. The body mass index (BMI) and endogenous oestradiol levels of the men were not related to BMD outcomes. Univariate linear relationships in women were found between BMI and spinal ( r 0.62; P=0.02) and total hip BMD ( r 0.61; P=0.03), but not femoral neck BMD. In women, relationships were also found between the total and, for protein binding-corrected oestradiol levels, and spinal BMD ( r 0.70; P=0.01 and r 0.72; P=0.01, respectively) and total hip BMD ( r 0.53; P=0.08 and r 0.56; P=0.05, respectively). No significance was observed between endogenous oestradiol levels and the BMD of the femoral neck. The administration of a single MP depot injection (160 mg) resembled a systemic low peak dose GC exposure. The administration of multiple MP depots in men and women with chronic low back pain revealed no relationship between cumulative GC dose and BMD. These findings support the hypothesis of a non-existent relationship between cumulative GC dose and BMD outcomes in healthy men and women with a prior GC administration of at least 3 g.

Aged↗
PubMed2003

Low 11-deoxycortisol to cortisol conversion reflects extra-adrenal factors in the majority of women with normo-gonadotrophic normo-estrogenic infertility.

BACKGROUND: Women with normogonadotrophic normo-estrogenic oligomenorrhoea often disclose a variety of clinical symptoms. Many of these individuals are obese with features of pseudo-hypercortisolism. In the current study, 11-deoxycortisol and cortisol concentrations were determined in this group and compared with ovulatory controls. METHODS AND RESULTS: Twenty-six women with clomiphene citrate-resistant infertility, 12 lean and 11 obese ovulatory controls were studied. Women with infertility had the highest 11-deoxycortisol concentrations (mean +/- SD: 4.1 +/- 1.5 ng/ml) compared with obese and lean controls (3.1 +/- 1.4 and 2.4 +/- 0.9 ng/ml) (P < 0.01), but similar morning cortisol concentrations (0.47 +/- 0.15, 0.45 +/- 0.16 and 0.47 +/- 0.18 nmol/l). Baseline 11-deoxycortisol/cortisol ratios (>90th percentile of ovulatory controls) were elevated in 23/26 infertile women (88%), and in 3/26 women (12%) after adrenocorticotrophic hormone (ACTH) stimulation. Three out of six lean infertile women had elevated baseline 11-deoxycortisol/cortisol ratios, but none of these women had elevated ratios after ACTH stimulation. Stepwise regression analysis, after exclusion of testosterone, revealed significant correlations between the groups (lean controls, obese controls, infertility) and ACTH-stimulated 11-deoxycortisol/cortisol ratio (P < 0.05), but not with fasting glucose, insulin, cortisol, 11-deoxycortisol and baseline 11-deoxycortisol/cortisol ratios. CONCLUSIONS: Congenital adrenal hyperplasia was not observed in the majority of infertile women. The data indicate that extra-adrenal factors were involved in most of the infertility syndromes that were studied.

Adrenal Hyperplasia, Congenital↗
PubMed2001

[Ultrasound measurement of calcaneus: a promising method for prediction of osteoporotic fractures].

When carrying out quantitative ultrasound (QUS) measurements of the calcaneus, broadband ultrasound attenuation (BUA, in dB/MHz) and speed of sound (SOS, in m/s) are assessed. From in vitro studies it is known that the mechanical properties of trabecular bone (stiffness and strength) can be better predicted with QUS than with dual energy X-ray absorptiometry (DEXA). Bone mineral density (BMD) measurements with DEXA are currently used for the diagnosis of osteoporosis according to the WHO criteria. There is no consensus regarding the diagnosis of osteoporosis with QUS measurements of the calcaneus. In prospective studies in women of 65 years and older it has been shown that fracture risk assessment with QUS measurements is feasible. The value of QUS measurements for the follow-up of patients with skeletal disorders is not yet known. At present there are important differences between ultrasound devices and there is no standardisation. The development of quality standards for and cross-calibrations of QUS scanners is necessary, so that results from different devices can be compared. Although QUS of the calcaneus is a promising method for the prediction of osteoporotic fractures, its routine use in clinical practice cannot yet be recommended.

Absorptiometry, Photon↗
PubMed2001

Comparison of quantitative ultrasound parameters with dual energy X-ray absorptiometry in pre- and postmenopausal women.

BACKGROUND: Quantitative ultrasound (QUS) has been claimed as an alternative technique for risk assessment of hip fractures associated with osteoporosis. However, reports concerning modest correlations between QUS parameters and dual energy X-ray absorptiometry (DXA) in women raise questions about the reliability of QUS technology to predict bone mineral density (BMD). Partially, the lack of stronger correlations may be due to heterogeneity in bone architecture deterioration which may be more pronounced in older than in younger women. Therefore, it was thought important to study QUS/DXA interrelationships in subgroups of pre- and postmenopausal women. METHODS: We studied 217 pre- and postmenopausal women between the ages of 25 and 75 years, who were referred for a BMD measurement because of osteoporosis in at least one family member either in the first or in the second degree. All women had a calcaneal QUS and a DXA measurement at the lumbar spine, total hip and femoral neck. RESULTS: The linear regression coefficients between the QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) and DXA at the various sites in the group as a whole were 0.53 to 0.54 (P<0.0001). Significantly lower regression coefficients between BUA and DXA at the total hip and the femoral neck were found in premenopausal women (r=0.31 and 0.38, P<0.0001) compared to postmenopausal women (r=0.56 and 0.53, P<0.0001). For SOS there was no significant difference between the regression coefficients in the pre- and postmenopausal group. The overall prevalence of osteoporosis as assessed by DXA in the total group was 25% (6% in the pre- and 36% in the postmenopausal group). BUA failed to detect osteoporosis in all five premenopausal women but also in 20 out of 50 postmenopausal women with osteoporosis according to DXA measurements. SOS measurements were even worse in this respect. CONCLUSIONS: Linear regression coefficients between calcaneal QUS parameters and DXA are only modest considering a group of 25--75-year-old Dutch women. In the subgroup of premenopausal women correlations between BUA and BMD at the hip and femoral neck are worse compared to those in postmenopausal women. The predictive value of QUS parameters for BMD is limited, therefore it is not appropriate to use QUS as a surrogate for DXA.

Absorptiometry, Photon↗
PubMed2000

Treatment of hot flushes with mirtazapine: four case reports.

OBJECTIVE: To evaluate the effect of mirtazapine on the severity of hot flushes and bouts of perspiration in women. METHOD: In two women with depression a reduction in hot flushes was noticed by serendipity during treatment with mirtazapine 15-30 mg/daily. On the basis of this observation clinical studies were extended with two non-depressed and non-anxious women with hot flushes. Both subjects were prescribed mirtazapine daily. RESULTS: Four cases are described as case reports. All subjects reported a practically complete disappearance of hot flushes and associated perspiration, within the first week of treatment. CONCLUSION: Mirtazapine appears to have a substantial ameliorating effect on hot flushes and perspiration bouts. It is postulated that the 5-HT(2A) blocking properties of mirtazapine is accounted in the symptomatic relief of hot flushes. In addition it is hypothesized that the serotonergic system is crucially involved in the pathogenesis of hot flushes and perspiration bouts. Further evaluation in double-blind placebo-controlled studies is encouraged.

Adult↗
PubMed2000

[Man with cherubism].

Cherubism was diagnosed in a male when he was 6 years old. Cherubism is a benign, bilateral, painless lesion. It is commonly located in the mandible but in a minority of patients also in the maxilla. Cherubism is a familial condition with an autosomal dominant pattern of inheritance. At least one member of the family of the patient described had cherubism. The disease becomes manifest during early childhood and progresses until puberty when it spontaneously regresses. In the majority of patients no treatment is required. However, in the patient presented surgical procedures and odontological corrections were necessary. Due to a flare-up of the disease at the age of 22 years, the patient was treated with calcitonin for 1 year followed by bisphosphonates. During these treatments the disease symptoms diminished.

Adult↗
PubMed2000

Clinical and pharmacological aspects of accidental triamcinolone acetonide overdosage: a case study.

Local administration of corticosteroids for rheumatic diseases have had a long history of effective and well-tolerated use. We report here the pharmacodynamics and pharmacokinetics of an accidental triamcinolone acetonide (TCA) overdose. The presented patient was treated with 200 mg TCA and developed Cushing's syndrome 6 weeks later (cortisol and ACTH concentrations were below limits of detection, TCA concentrations were > 3 micrograms/l). Because of her severe symptoms, mifepristone was administered for a period of 19 days. Cortisol concentrations became detectable 2 days after initiation of mifepristone treatment and persisted, being detectable for a period of at least a week after cessation of the drug. Twenty days after cessation, cortisol concentrations were undetectable again. Cushing's syndrome persisted more than 6 months while TCA concentrations remained detectable for at least 80 days. Based on plasma TCA concentrations in our patient, we calculated a terminal half-life of TCA of 33 days as opposed to 5 days observed after intra-articular administration of a therapeutic dose of 40 mg TCA. We conclude that after an accidental overdose in this patient, body TCA disappearance was strongly prolonged due to a very slow (absorption) half-life of the drug in comparison to a therapeutic dose. This finding is explained by a 'flap-flop phenomenon' where drug absorption is the rate-limiting step of overall drug disposition. Caution is, therefore, needed to prevent undesired accumulation of TCA that may lead to protracted Cushing's syndrome.

Anti-Inflammatory Agents↗
PubMed1995

Interleukin-6 and the acute phase response during treatment of patients with Paget's disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate.

Bisphosphonates suppress bone resorption and are used in the management of bone diseases with increasing frequency. In some patients treated for the first time with potent nitrogen-containing bisphosphonates, there is a transient febrile reaction and transient hematological changes suggestive of an acute phase response. Because IL-6 is considered to be an important mediator of the acute phase response, we examined the changes in circulating IL-6 bioactivity in 38 patients with Paget's disease treated with the nitrogen-containing bisphosphonate (3-dimethyl-amino-1-hydroxypropylidene)-1,1-bisphosphonate (dimethyl-APD). 16 patients who had never received such bisphosphonate were treated with oral dimethyl-APD (100-400 mg/day) and 22 (9 for the first time) with intravenous dimethyl-APD 4 mg/day. Treatment was given for 10 days. Eleven of 38 patients, all first treatments, showed an increase in body temperature of more than 0.5 degrees C exceeding 37 degrees C associated with a significant decrease in lymphocyte count and an increase in serum CRP values. These changes were transient and did not occur in the patients with no febrile response. In patients with a febrile reaction circulating IL-6 bioactivity increased significantly and this increase generally preceeded the rise in temperature. Moreover, patients with an acute phase response had significantly higher peak IL-6 values than those without (128 +/- 30 vs. 31 +/- 4 U/ml, p < 0.001). The peaks in plasma IL-6 were further correlated with the peaks in temperature and in serum CRP values (r = 0.49, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗
PubMed1995

Parathyroid hormone related protein and interleukin-6 mRNA expression in larynx and renal cell carcinomas from normocalcaemic and hypercalcaemic patients.

AIMS: To determine the expression of parathyroid hormone related protein (PTHrP) and interleukin-6 (IL-6) mRNAs and their possible relation in malignant tumours, derived from patients with and without hypercalcaemia, commonly associated with humoral hypercalcaemia of malignancy. METHODS: PTHrP and IL-6 mRNA expression was studied by northern blot analysis in tumour specimens from 13 consecutive patients. Six patients (two with hypercalcaemia) had squamous cell carcinomas of the larynx and seven (one with hypercalcaemia) had renal cell carcinomas. RESULTS: There was no relation between the histological features of the tumours and the expression of either PTHrP or IL-6 mRNAs. PTHrP mRNA was detected in all squamous cell carcinomas, expression being highest in the two patients with hypercalcaemia. In the renal cell carcinomas PTHrP mRNA was expressed only in the patient with hypercalcaemia. IL-6 mRNA was detected in nearly all tumours studied but there was no apparent relation between its expression and that of PTHrP mRNA or serum calcium concentrations. CONCLUSIONS: PTHrP mRNA expression is increased in patients with hypercalcaemia but is not related to IL-6 mRNA expression. The results suggest a quantitative relation between PTHrP gene expression and hypercalcaemia, and imply that different mechanisms account for this expression in squamous and renal cell carcinomas.

Adult↗
PubMed1995

Recovery of serum calcium concentrations following acute hypocalcemia in patients with osteoporosis on long-term oral therapy with the bisphosphonate pamidronate.

Bisphosphonates, synthetic compounds that are taken up preferentially by the skeleton and that suppress bone resorption, are currently used in the management of patients with osteoporosis. Long-term uninterrupted administration of low oral doses is the preferred mode of treatment in current clinical trials with newer bisphosphonates. These compounds have, however, a long residence time in the skeleton, and there is no information about their long-term effects on blood calcium homeostasis. We examined the effect of long-term therapy with oral bisphosphonate on blood calcium homeostasis following an acute hypocalcemic stimulus. Twenty patients with vertebral osteoporosis (10 untreated controls and 10 treated with oral pamidronate, 150 mg/day for at least 5 yr) were given intravenous infusions of sodium EDTA, and the concentrations of calcium and PTH in blood were followed for 24 h. Serum calcium concentrations decreased similarly in both groups (maximum decrease 0.21 mmol/L and 0.22 mmol/L, respectively). The recovery of serum calcium concentrations was identical in both groups, and all patients had normal concentrations at 24 h. Plasma PTH increased to a peak of 17.3 +/- 2.5 pmol/L in the control group and to 17.0 +/- 3.1 pmol/L in the pamidronate-treated patients. During the whole study period, there was no difference in either the peak PTH response or in the recovery of plasma PTH values between the two groups. However, when only PTH responses between 60 min and 24 h were examined, there were differences between the two groups. Plasma PTH values, although strictly within the normal range, were significantly higher in the pamidronate-treated patients (P = 0.001). There were no differences in the calcemic responses during this period. Further, there were no detectable changes in immunoreactive PTH-related protein in either group after the EDTA infusions. In conclusion, our study showed that longterm therapy with oral pamidronate does not affect the calcemic response to an acute hypocalcemic stimulus in patients with osteoporosis.

Acute Disease↗
PubMed1994

Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia. DESIGN: Prospective, cross-sectional, single-centre study of patients with documented solid malignancies, hypercalcaemia and suppressed plasma PTH concentrations. PATIENTS AND METHODS: Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N-cAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid malignancies and hypercalcaemia and bone scans were performed. RESULTS: In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25-(OH)2D concentrations were not appropriately suppressed (> 92 pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1.6 pmol/l) had lower serum 1,25-(OH)2D concentrations than those with elevated levels (> 1.6 pmol/l) (47 +/- 6 vs 70 +/- 7 pmol/l, respectively; P < 0.04). Serum 1,25-(OH)2D concentrations were higher in patients with negative bone scans than in those with metastatic bone disease (80 +/- 9 vs 50 +/- 5 pmol/l; P < 0.01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25-(OH)2D (r = 0.51; P < 0.03) whereas there was no such correlation in those with a positive scan. CONCLUSION: Contrary to current belief, serum 1,25-(OH)2D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further insights into the pathophysiology of malignancy-associated hypercalcaemia and may help in the clinical management of these patients.

Aged↗
PubMed1993

Improved treatment of Paget's disease with dimethylaminohydroxypropylidene bisphosphonate.

A group of 89 patients with Paget's disease of bone were treated with different intravenous or oral doses of the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate (dimethyl-APD). Biochemical remission was obtained in 82% of treatments, and in the rest a clear response was found. Oral dimethyl-APD was well tolerated, and a dose of 200 mg/day for 10 days was sufficient to induce remission in the majority of patients. The remission probability was 3 months for 50% of patients, and the recurrence-free period was 27 months. The remission probability as well as the recurrence-free period did not differ among oral and intravenous treatments or among patients who had never been treated with nitrogen-containing bisphosphonates and those who had received pamidronate in the past and were treated for a recurrence of the disease. Dimethyl-APD is a very effective bisphosphonate devoid of side effects, which given for a short period can induce long-lasting remissions in patients with Paget's disease of bone.

Administration, Oral↗