Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine single foetal lambs with catheters chronically implanted in utero on day 122 of gestation into the left carotid artery, the right external jugular vein and the bladder were used. In these foetuses, between days 130 and 142 of gestation, urine flow rate was 0.48 +/- 0.09 ml X min-1. In the same time, an intravenous infusion of bovine parathyroid hormone (150 U per foetus in 30 min) induced hypercalcaemia and hypophosphataemia, associated with an increase in urinary flow rate and urinary phosphate concentration. Although urinary calcium concentration was unchanged, the urinary excretion of both calcium and phosphate increased. An intravenous infusion of salmon calcitonin (200 MRC mU per foetus in 30 min) induced hypocalcaemia and hypophosphataemia, associated with an increased urinary phosphate concentration. Urinary flow rate and urinary calcium concentration were not modified by the calcitonin which increased only urinary excretion of phosphate. Thus the high plasma phosphate levels measured in lambs during the perinatal period do not seem to be related to a previous unresponsiveness (just before birth) to the hormones regulating phosphate urinary excretion.
 ...
PMID:The influence of parathyroid hormone and calcitonin on urinary excretion of calcium, magnesium and inorganic phosphorus in chronically catheterized foetal lambs in utero. 718 65

In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to chemotherapy. Treatment with clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P=0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P=0.04). Fewer patients receiving clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P=0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P=0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant clodronate, both at plateau and at disease relapse. The frequencies of back pain and poor performance status were significantly lower at 24 months in clodronate than in placebo-treated patients (10.9% v 19.9%, P=0.05, and 18.3% v 30.5% P=0.03 respectively.) There was no statistically significant difference in survival between the clodronate and placebo treated patients. The study indicates that long-term oral clodronate slows the progression of skeletal disease in multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.
 ...
PMID:A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults. 948 19

The economic impact of using prophylactic clodronate as an adjunct to chemotherapy in the management of multiple myeloma for the first 4 years following diagnosis was established from the perspective of the National Health Service (NHS). A state-transition model of the course of multiple myeloma was constructed using the MRC VI myelomatosis trial results and information on patient management obtained retrospectively from clinical trialists. Data were collected on resource use and corresponding costs for standard management and managing severe hypercalcaemia, vertebral and non-vertebral fractures. Managing patients with prophylactic clodronate cost the NHS a mean 22 934 pound silver per patient; comprising 16 697 pounds silver for standard management, 4862 pound silver for clodronate therapy and 1376 pound silver for adverse events. Managing patients without prophylactic clodronate cost a mean 19 557 pound silver (16 697 pound silver and 2860 pound silver for standard management and adverse events respectively). Therefore prophylactic clodronate therapy increased the cost by 3377 pound silver, or 17% per patient. Hospitalization accounted for 32% of the total cost, whereas chemotherapy accounted for 5%. The results were robust to sensitivity analyses (range 2605 pound silver-4150 pound silver). Further studies are required to assess the impact of prophylactic clodronate on quality of life to enable the clinical benefits and additional cost of this treatment to be compared with other healthcare interventions.
 ...
PMID:Economic impact of using clodronate in the management of patients with multiple myeloma. 1005 Jul 20

Survival for myeloma has improved from a median of 7 months in the 1950s to about 30 months today. Progress in chemotherapy has contributed a great deal to this improvement, although it may also, in part, reflect the improved treatment of infections, renal failure and hypercalcaemia as well as earlier diagnosis. For over 30 years, the gold standard of treatment has been oral melphalan and prednisolone, producing a clinical response in approximately 60% of patients and a median survival of around 36 months. Relapse is unfortunately inevitable in all but a handful and, for the majority, treatment can only hope to produce significant periods of remission with minimal treatment-related morbidity and mortality. Recently, improved results have been seen with the introduction of aggressive chemotherapy and bone-marrow transplantation. Marrow ablative therapies produce remissions in virtually all patients, with complete remissions in approximately 1/3. The best response is seen in those with a lower tumour burden, which will reduce the development of secondary resistance. Current treatment is moving towards an approach using sequential therapy. This involves induction chemotherapy with VAD or a similar regimen such as VAMP (vincristine, adriamycin and methylprednisolone), proceeding to high-dose therapy, often with some form of stem-cell rescue. This ensures minimal tumour burden prior to high-dose treatment as well as reducing graft infiltration, improving general performance status and allowing recovery of renal function. Relapse remains a problem, although the use of IFN may reduce this by prolonging the plateau phase. High-dose therapy should be given early, before prolonged use of alkylating agents induces stem-cell dysplasia, before significant complications arise from the myeloma, and before drug resistance is significant. Unfortunately, these treatments come at a price, in terms of increased treatment-related toxicity. There also remains uncertainty as to the extra benefits of high-dose treatment with marrow rescue over high-dose chemotherapy alone. We await the current MRC trial with interest. For a very few, there is the tantalising possibility of cure with allografting. For those in complete remission after first-line induction therapy, allogeneic bone-marrow transplantation offers the best hope of survival, but comes at a greatly increased risk of toxicity, and it is uncertain if it is superior to autografting for the majority of patients. It may soon be possible to identify those poor prognosis patients in whom an allogeneic transplant should be offered at an early stage. Candidate biochemical markers include serum beta 2 microglobulin, neopterin, IL-6, plasma cell labelling index, CRP or LDH and prognostic clinical features include IgD myeloma or stage III disease at presentation. Many patients will have primary refractory of relapsing disease in whom survival is short despite all current therapeutic modalities. They should therefore be considered for trials of newer agents, drug combinations and therapeutic interventions such as cytokine manipulation or gene therapy. The lack of effective, curative treatment options for patients with myeloma places great importance on effective palliation. While improving survival duration remains elusive in this condition, all possible efforts must be made to ensure quality of life is maximized.
 ...
PMID:Treatment of myeloma. 1020 67


<< Previous 1 2