Gene/Protein Disease Symptom Drug Enzyme Compound
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The findings of 152 patients with proven primary hyperparathyroidism are reportedmthe purpose of the analysis was to find difference between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups, Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in an atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck; The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The sucess of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There ist still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are reposible for the different action on bone and kidney is discussed; In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting, abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in over 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcenia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary.
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PMID:[Primary hyperparthyroidism. Analysis of 152 patients with special reference to acute life threatening complications (acute hyperparathyroidism)]. 20 39

Tthe findings of 150 patients with proven primary hyperparathyroidism are reported. The purpose of the analysis was to find differences between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups. Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck. The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The success of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There is still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are responsible for the different action on bone and kidney is discussed. In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in ov er 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcemia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary.
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PMID:[Primary hyperparathyroidism. An analysis of 152 patients with special references to acute life threatening complications (acute hyperparathyroidism)]. 79 28

Thirty-eight patients with advanced breast cancer were treated with oral 4-demethoxydaunorubicin in a continuous weekly schedule at a dose of 15 mg/m2/week. Subjective toxicity consisted of mild nausea (grade 1) in 52% with more severe GI side effects (grade 2) in 15%. Three patients developed grade 1 alopecia and there were no episodes of cardiac failure. Significant neutropenia (grade 2/3) only occurred in patients with marrow involvement or widespread bone disease. There was one CR and 5 PRs, an overall response rate of 15.7% (95% confidence limits 6-31%). In addition 6 patients had disease stabilization for at least 6 months. Fourteen patients progressing on 4-demethoxydaunorubicin have received adriamycin 60 mg/m2 21 days. There have been 5 PRs in this group indicating possible non-cross-resistance between these two agents.
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PMID:A phase II study of oral weekly 4-demethoxydaunorubicin in advanced breast cancer. 347 4

Bisphosphonates are analogues of inorganic pyrophosphate, a naturally occurring chemical in bone. In vitro and animal experiments demonstrated that these agents were effective inhibitors of bone resorption. Subsequently they were applied to a variety of clinical problems in which increased bone resorption was an underlying feature of the pathology. In 1971 etidronate became the first bisphosphonate shown to inhibit bone resorption in humans when it was given to patients with Paget's disease. Subsequently this agent was also found to be useful in treating the hypercalcemia of malignancy. At the present time cyclic etidronate therapy is also used for the prevention of bone loss in patients with osteoporosis and for the prevention of heterotopic ossification in spinal cord-injured patients and in patients after hip replacement. Newer bisphosphonates are generally more potent than etidronate and do not produce a severe mineralization defect as do higher doses of etidronate. Pamidronate and clodronate are highly effective in the management of Paget's disease, hypercalcemia due to malignancy and immobilization, metastatic bone disease, and hematologic malignancies affecting bone. They are also promising agents for the prevention of osteoporosis. Alendronate, risedronate, and CGP 42446 are highly potent bisphosphonates that look very promising for the treatment of all disorders of bone resorption. It is fortunate that adverse reactions are not a prominent feature of bisphosphonate use. The main side effects are nausea and abdominal discomfort, mainly with oral use, a transient increase in bone pain in patients with Paget's disease, and an acute-phase reaction (fever, myalgia, mild leukopenia) in patients receiving aminobisphosphonates. The evolution of bisphosphonate therapy should be considered one of the major therapeutic events of the past 25 years. Future research should define the optimum use of these agents.
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PMID:Bisphosphonates in the treatment of disorders of mineral metabolism. 767 Oct 99

The management of the patient with inflammatory bowel disease (IBD) is challenging for both the physician and the patient. IBD imposes both a physical and emotional burden on patients' lives. Palliative care is important for IBD patients because it focuses on improving quality of life. While palliative care does not change the natural history of the disease, it provides relief from pain and other distressing symptoms. This article focuses on various aspects of care for IBD patients including pain control, management of oral and skin ulcerations, stomal problems in IBD patients, control of nausea and vomiting, management of chronic diarrhea and pruritus ani, evaluation of anemia, treatment of steroid-related bone disease, and treatment of psychological problems associated with IBD. Each of these areas is reviewed using an evidence-based approach. Evidence in category A refers to evidence from clinical trials that are randomized and well controlled. Category B Evidence refers to evidence from cohort or case-controlled studies. Category C is evidence from case reports or flawed clinical trials. Evidence from category D is limited to the clinical experience of the authors. Evidence labelled as category E refers to situations where there is insufficient evidence available to form an opinion. Algorithms for management of pain and nausea in IBD patients are presented.
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PMID:Palliative care in inflammatory bowel disease: an evidence-based approach. 1096 95

Between December, 1996 and July, 1997, 14 patients of advanced tuberculosis with a mean history of prior treatment of 27.4 months were put on oral Sparfloxacin 200 mg daily. One case each had lumbar spine and pelvic bone disease with abscesses, one had subcostal abscess and another had subpulmonic effusion. The remaining 10 cases had moderate clinical illness with tuberculosis (meningitis (1), massive pneumonia (1)). There was an early dramatic response to the new regime, (Sparfloxacin given along with PAS, isoniazide (2), PH with R or Doxy (2), SHRZ (4), RH (1), RHZ (2), SHRE (1), and RH + Cy Eth (1)). The only side-effect complaint was nausea. The response was good (clinical 3+ or more: 11; Radiographic > 50%: 11; smear conversion: 12) in 12 cases; one case with tuberculous meningitis died seven weeks after a temporary improvement.
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PMID:Early experience with sparfloxacin in tuberculosis. 1122 60

The skeletal complications of metastatic bone disease secondary to advanced prostate cancer result in significant morbidity. In particular, pathologic fractures often require clinical intervention and are independent predictors of mortality in men with advanced prostate cancer. Before the introduction of zoledronic acid, bisphosphonates had been shown to provide pain palliation in patients with prostate cancer and bone metastases but were not efficacious in preventing skeletal complications. Zoledronic acid is the first bisphosphonate to show efficacy in reducing skeletal complications associated with the predominantly osteoblastic bone lesions characteristic of prostate cancer. In a large phase III randomized trial, zoledronic acid 4 mg every 3 weeks for 15 months significantly reduced the percentage of men who experienced a skeletal complication and reduced the incidence of pathologic fractures. Additionally, zoledronic acid 4 mg significantly decreased the annual incidence of skeletal complications, including fractures, and provided better control of bone pain compared with placebo. Adverse events with zoledronic acid were primarily limited to the flu-like, acute-phase symptoms previously reported with intravenous bisphosphonates, namely fever, myalgia, nausea, and anemia. These adverse events were mild to moderate and easily managed with supportive care. Zoledronic acid is the first and only bisphosphonate shown to reduce skeletal morbidity, including fractures, in patients with advanced prostate cancer and bone metastases.
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PMID:Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone. 1504 89

(1) Patients who require dialysis for chronic renal failure develop phosphocalcium metabolic disorders that often lead to secondary hyperparathyroidism. Standard treatment consists of a phosphate chelator and vitamin D, along with the use of an appropriate calcium concentration in the dialysis bath, but is difficult to manage. (2) Parathyroid cancer is a rare malignancy frequently associated with hypercalcaemia. (3) Cinacalcet is a calcimimetic agent that reduces the parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. The optimal dose seems to range from 30 to 180 mg/day and varies widely from one patient to another. (4) 3 double-blind placebo-controlled trials, lasting for a maximum of one year and involving a total of 1136 dialysis patients with chronic renal failure, showed no improvement in quality of life with cinacalcet. The target parathormone level was reached by 40% of patients on cinacalcet versus 5% of patients on placebo, while the effects of cinacalcet on calcium levels (-7%) and phosphate levels (-8%) were modest. No impact on bone complications is mentioned in available reports. (5) The assessment of treatment of parathyroid cancer is limited to one ongoing non comparative trial involving 21 patients. (6) During clinical trials, 11% of dialysis patients had low parathormone levels, creating a risk of adynamic bone disease and fractures, but available data are sparse. (7) Two-thirds of patients receiving cinacalcet have episodes of hypocalcaemia, which may in part account for reports of seizures (1.4% of patients), nausea (31%) and vomiting (27%). Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction. Cinacalcet is a powerful CYP 2D6 inhibitor and is also metabolised by isoenzymes CYP 3A4 and CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of phosphate chelator and vitamin D therapy (especially as an alternative to surgery) or in parathyroid cancer.
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PMID:Cinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data? 1676 95

Bone disease is an important feature of multiple myeloma, and hypercalcaemia is a frequent complication of this disease. We examined the association between serum calcium and quality of life (QOL) scores of 686 multiple myeloma patients at the time of diagnosis. Data from two Nordic studies using the EORTC QLQ-C30 questionnaire were analysed by means of linear regression analysis and a curve fitting program. Serum calcium was independently related to appetite loss, nausea/vomiting and physical functioning (P < 0.001) and to cognitive functioning (P = 0.001), i.e. scores reflecting symptoms that are well known in non-malignant hypercalcaemia. In addition, we found a highly significant independent relationship between serum calcium and the scores for fatigue and pain (P < 0.001). Serum calcium appeared to be as strong a predictor for fatigue as the concentration of haemoglobin. A cubic model (y = a + bx3) fitted the data slightly better than the simple linear model (y = a + bx) and suggested worsening QOL scores at levels of serum calcium above 2.5-3.0 mmol/L. Hypercalcaemia in patients with multiple myeloma seems to be associated with the same symptoms as in non-malignant hypercalcaemia. In addition, an increased level of serum calcium may aggravate the pain and fatigue caused by the skeletal disease itself.
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PMID:Serum calcium is an independent predictor of quality of life in multiple myeloma. 1703 19

Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (> 15 micromol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation.
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PMID:Fluoride-related bone disease associated with habitual tea consumption. 1755 Jul 52


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