Efficacy of oral administration of etidronate disodium in maintaining normal serum calcium levels in previously hypercalcemic cancer patients

As part of a multicenter trial of etidronate disodium for control of hypercalcemia in patients with malignancies, patients achieving normocalcemia within seven days after starting intravenous therapy with etidronate disodium plus saline were enrolled into a double-blind, placebo-controlled trial of oral etidronate disodium to maintain normocalcemia. By random assignment, patients received either oral etidronate disodium, 20 mg/kg/day, or placebo for up to three months. Efficacy was evaluated after 30 days of maintenance therapy: patients who were normocalcemic on day 30 were considered treatment successes. Of 81 patients who entered this phase of the study, 63 were evaluable for efficacy. Analysis of this group revealed that significantly (P less than 0.01) more patients in the etidronate disodium group (35%) than in the placebo group (6%) were normocalcemic at day 30. Life-table analysis of response indicated that patients treated with etidronate disodium maintained normocalcemia significantly (P less than 0.01) longer than did patients receiving placebo (median, 29 days versus 11 days). These results suggest that in patients whose calcium levels were normalized with IV etidronate disodium, oral etidronate disodium maintained normocalcemia significantly longer than no maintenance therapy in patients treated for hypercalcemia secondary to malignancy.     

Beneficial effect of etidronate therapy in immobilized hip fracture patients

OBJECTIVES: Hip fracture is among the most common causes of acute immobilization in elderly patients leading to increased bone resorption, and elderly patients with hip fracture are at high risk for a subsequent hip fracture. DESIGN: In this double-blind, randomized, prospective study, 80 female patients who were immobilized because of a hip fracture were divided into two groups. The etidronate group received oral administration of 200 mg/day etidronate for 2 wks starting 1 day after the surgery. Then, after a 9-wk intermission, etidronate administration was resumed for 2 wks. The placebo group received placebo in a similar manner. RESULTS: At baseline, both groups had high serum concentrations of ionized calcium, high urinary deoxypyridinoline (D-Pyr) concentrations, and decreased calcitriol concentrations, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of calcitriol. After treatment, serum calcitriol concentrations increased in the etidronate and placebo groups. The etidronate group had significant decreases in serum ionized calcium and urinary D-Pyr, and the placebo group had higher serum calcium and urinary D-Pyr concentrations. CONCLUSIONS: Etidronate therapy inhibits bone resorption and improves calcium balance, and such therapy may prevent bone loss and reduce the risk of subsequent hip fracture.     

Systematic review of bisphosphonates for hypercalcaemia of malignancy

BACKGROUND: Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (HCM) but there is no consensus regarding which drug or dose should be given. We designed a systematic review to investigate the efficacy of bisphosphonates in the treatment of HCM. METHODS: We identified randomized controlled trials (RCTs) by searching electronic databases, scanning of reference lists, and consultation with experts and pharmaceutical companies. Foreign papers were translated. Inclusion criteria were RCTs, confirmed malignant disease and measurement of serum calcium (ionized or corrected for albumin) postrehydration. The primary outcome was number of patients achieving normocalcaemia. Secondary outcomes were time to normocalcaemia, time to relapse and toxicity. RESULTS: Twenty-seven papers and two abstracts, using intravenous bisphosphonates, fulfilled the inclusion criteria. Data from 26 studies were used in analyses. Due to the heterogeneity of studies, meta-analysis could not be performed. Pamidronate was more effective than placebo, mithramycin, etidronate (7.5 mg/kg) and low-dose clodronate (600 mg), but equal to higher dose clodronate (1500 mg). Clodronate and etidronate were superior to placebo; incadronate was superior to elcatonin; gallium nitrate was superior to etidronate. No difference was seen between alendronate and clodronate. Three dose finding studies showed no difference between 30-90 mg of pamidronate, but one well designed study showed increasing efficacy with increasing dose. Studies using increasing doses of ibandronate (0.6-4 mg), alendronate (2.5-15 mg), and incadronate (2.5-10mg), showed a dose response. Duration of administration of pamidronate did not affect efficacy (six studies). CONCLUSION: Bisphosphonates normalize calcium in >70% patients with minimal side effects. Aminobisphosphonates are most effective at maintaining normocalcaemia and should be given in high dose irrespective of baseline serum calcium.     

大剂量呋塞米联合氨茶碱对老年危重症合并急性肾衰竭的影响

目的：探讨大剂量呋塞米联合氨茶碱微泵连续输注方法,对部分伴发急性肾功能衰竭的可暂缓连续性静脉静脉血液滤过（CVVH）老年危重病患者是否有效。方法选择符合急性肾衰竭的可暂缓CVVH老年危重患者58例,按照入住先后分为治疗组和对照组：治疗组予大剂量呋塞米针200～800 mg/d和氨茶碱0.25 g加入0.9％氯化钠注射液稀释成50 ml,对照组予呋塞米针200～800 mg/d 加入0.9％氯化钠注射液50 ml,均采用微泵静脉内注射,0～4 ml/h静脉维持。记录两组患者治疗前及治疗后第1天、第7天的24 h 尿量,治疗后第1天、第7天的24 h呋塞米用量,治疗前后血肌酐值,治疗后第7天心率及治疗过程中需要进行CVVH的患者比例和28 d 病死率。结果治疗组治疗后第1天和第7天的24 h 尿量明显高于对照组,差异均有统计学意义（t分别=-8.22、-3.30,P均＜0.05）,治疗组治疗过程中需要进行CVVH的患者比例明显低于对照组,差异有统计学意义（χ2=5.51,P＜0.05）。两组治疗后第1天和第7天的24 h呋塞米用量、治疗前及治疗后第7天血肌酐值、治疗后第7天的心率和28 d 病死率比较,差异均无统计学意义（t分别=-0.64、-1.42、0.71、2.79、-2.03,χ2=0.30, P均＞0.05）。结论大剂量呋塞米联合氨茶碱微泵连续输注,能明显增加伴发急性肾衰竭的老年危重病患者的尿量,减少CVVH治疗。     

Comparison of the renal and skeletal actions of calcitonin in the treatment of severe hypercalcaemia of malignancy

The hypocalcaemic response to salmon calcitonin was separated into its renal and skeletal components during the treatment of 21 patients with severe hypercalcaemia complicating malignant disease. Inhibition of renal tubular calcium reabsorption by calcitonin may induce a rapid fall in serum calcium. The magnitude of this response depends in part upon the correction of volume depletion which is a common feature of hypercalcaemia from any cause. The adequacy of rehydration can be assessed from the relationship between serum calcium and the calcium excretion rate expressed in mumol/l glomerular filtrate (CaE). Not all patients show a good renal response to calcitonin and this may reflect secretions by the primary tumour of substances which inhibit the renal tubular actions of calcitonin. The response to rehydration may identify such patients and this has obvious practical implications for the choice of treatment.     

Comparative study of incadronate and elcatonin in patients with malignancy-associated hypercalcaemia

The clinical usefulness of incadronate was compared with elcatonin in 26 patients with malignancy-associated hypercalcaemia. Data from 21 and 24 patients could be used to assess efficacy and safety, respectively. Eleven patients were given a single 10-mg intravenous infusion of incadronate and 10 received twice-daily intramuscular injections of 40 IU of elcatonin for 7 consecutive days. After treatment, corrected serum calcium levels decreased significantly in both groups. The anti-hypercalcaemic effect of elcatonin was characterized by its rapid onset, with serum calcium levels reduced 1 day after administration. In contrast, the anti-hypercalcaemic effect of incadronate was more sustained but only became apparent a few days after infusion. Evaluation of symptoms revealed significantly greater improvement rates in the incadronate group compared with the elcatonin group. Adverse drug reactions were observed in three patients in the incadronate group, i.e. mild and transient fever in two cases and exacerbation of disturbance of consciousness in one case. These findings suggest that incadronate produces more marked and sustained hypocalcaemic effects than elcatonin, and that co-administration of these two drugs may yield both rapid and sustained control of malignancy-associated hypercalcaemia.     

Clinical experience with aminohydroxypropylidene bisphosphonate (APD) in the management of cancer-associated hypercalcaemia

Fifty-five patients with symptoms caused by hypercalcaemia associated with cancer were treated with varying regimens of intravenously-administered aminohydroxypropylidene bisphosphonate after initial rehydration. Of 48 patients where adequate data were available, 32 (66 per cent) were rendered normocalcaemic and 16 (33 per cent) remained mildly hypercalcaemic. In these cases, failure to restore normocalcaemia was attributable to elevated renal tubular reabsorption of calcium in nine (18 per cent) and to inadequate suppression of bone resorption in seven (14 per cent). There was no significant difference in response and duration of effect (median 20 days) between single doses of 15, 25 and 45 mg, or when the 45 mg dose was administered over three, six or 24 h. These single dose regimens were similar in terms of effect on calcium levels and duration of action, to multiple daily doses of 15 mg for a mean of six days. While the effect of 5 mg dose was not significantly different from the higher doses, suppression of serum calcium levels was less marked and the effect on duration of action significantly shorter than with the 45 mg dose. In seven cases, treatment with a second course was less effective even with higher doses because suppression of bone resorption was poorer. These data indicate that there is little difference between the therapeutic effects of multiple 15 mg and single 15-45 mg intravenous infusions of aminohydroxypropylidene bisphosphonate in hypercalcaemia associated with cancer. A single intravenous infusion of a moderate dose (for example 15-30 mg) would be a convenient and effective way of treating most patients.     

托拉塞米对糖尿病肾病性水肿的疗效

目的观察托拉塞米及呋塞米对糖尿病肾病(diabetic nephropathy,DN)水肿的临床疗效。方法将60例DNⅣ期水肿患者随机分为呋塞米静脉注射组(对照组)、托拉塞米静脉注射组(托拉塞米A组)、托拉塞米持续泵入组(托拉塞米B组)。监测患者治疗前、治疗后第1天、第4天及第7天24小时尿量、血肌酐、血钾及血钠;治疗前及治疗后第7天脑钠肽(BNP)指标变化。结果治疗前,3组患者24小时尿量、血肌酐、血钾及血钠比较差异无统计学意义;治疗后,托拉塞米A组及B组24小时尿量均高于对照组,而托拉塞米B组较托拉塞米A组尿量增加(P0.01);3组患者血肌酐水平、血钾比较差异无统计学意义(P0.05);与治疗前比较,3组患者血钠均较前下降,但托拉塞米B组降钠作用强于其他两组;3组患者治疗后第7天BNP均明显下降(P0.01)。结论托拉塞米利尿作用强于呋塞米,托拉塞米采用持续静脉泵入具有更强的利尿作用。     

Comparison of the Renal and Skeletal Actions of Calcitonin in the Treatment of Severe Hypercalcaemia of Malignancy

The hypocalcaemic response to salmon calcitonin was separatedinto its renal and skeletal components during the treatmentof 21 patients with severe hypercalcaemia complicating malignantdisease. Inhibition of renal tubular calcium reabsorption bycalcitonin may induce a rapid fall in serum calcium. The magnitudeof this response depends in part upon the correction of volumedepletion which is a common feature of hypercalcaemia from anycause. The adequacy of re hydration can be assessed from therelationship between serum calcium and the calcium excre tionrate expressed in µmol/l glomerular filtrate (Ca_E). Notall patients show a good renal response to calcitonin and thismay reflect secretions by the primary tumour of substances whichinhibit the renal tubular actions of calcitonin. The responseto rehydration may identify such patients and this has obviouspractical implications for the choice of treatment.     

Concomitant treatment with urodilatin (ularitide) does not improve renal function in patients with acute renal failure after major abdominal surgery--a randomized controlled trial

Acute renal failure after major abdominal surgery is a severe complication in critically ill patients in intensive care units (ICU). The aim of the study was to investigate the effect of urodilatin on the peak value and course of serum creatinine in patients with acute renal insufficiency after major abdominal surgery and the necessity of apparatus-based renal replacement treatment. Furthermore, the incidence and nature of adverse events under urodilatin was documented. In a prospective randomized double-blind placebo-controlled study, 12 critically ill patients after major abdominal surgery with acute renal failure in an intensive care unit (ICU) received 20 ng/kg b.w./min urodilatin (ularitide, INN) or placebo in addition to the standard diuretic therapy or low-dose dopamine (2.5 micrograms/kg b.w./min) and furosemide (1000 mg/24 hr) for a minimum of 96 hours. All patients received mechanical ventilation. Both groups had similar serum creatinine values on the day before the onset of urodilatin/placebo infusion (2.80 +/- 0.24 mg/dl, 2.93 +/- 0.48 mg/dl). Peak serum creatinine was lower in the urodilatin group (4.65 +/- 0.57 mg/dl) compared to vehicle treatment (5.78 +/- 1.58 mg/dl), although the difference did not reach statistical significance (P = 0.148). The total number of hemodialyses due to oligo-/anuria and/or hyperkalemia was the same in both groups during the study. In 4 patients of the placebo group, diuresis was reduced to anuria, whereas only 1 of the patients treated with urodilatin became anuric. No hemodynamic side effects or adverse events due to urodilatin were observed. This clinical study under double blind conditions revealed that the addition of urodilatin to the standard diuretic therapy of low-dose dopamine and furosemide failed to improve renal function in patients with established acute renal failure and that urodilatin did not eliminate the need for apparatus-based renal replacement treatment.     

Carvedilol accelerate elevation of serum potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate or candesartan cilexetil

OBJECTIVE: To retrospectively investigate the effect of carvedilol and spironolactone plus furosemide, administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) to patients with chronic heart failure (CHF). METHODS: Patients with CHF, who visited Departments of Cardiovascular Internal Medicine at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine (Scr) and serum sodium were measured in every patient at the time of start of treatment and after 3 and 12 months of treatment. Data from patients in groups A (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I) and B (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + ARB) were compared. RESULTS: When 20 mg/day carvedilol plus 25 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril, group A) or 8 mg/day candesartan cilexetil (candesartan, group B) plus 40 mg/day furosemide were used concomitantly, the mean serum potassium increased significantly in both groups of patients. Seven of 59 (11.9%) patients had hyperkalemia (>5.5 mEq/L) during 12 months of treatment whereas 8.5% of patients (five of 59) had hypokalemia (< or =3.5 mEq/L). CONCLUSION: When carvedilol is used concomitantly with spironolactone, furosemide and enalapril or candesartan, it is necessary to monitor serum potassium concentration, even if spironolactone is administered at a low dose of 25 mg/day.     

Clinical Experience with Aminohydroxypropylidene Bisphosphonate (APD) in the Management of Cancer-associated Hypercalcaemia

Fifty-five patients with symptoms caused by hypercalcaemia associatedwith cancer were treated with varying regimens of intravenously–administeredaminohydroxypropylidene bisphosphonate after initial rehydration.Of 48 patients where adequate data were available, 32 (66 percent) were rendered normocalcaemic and 16 (33 per cent) remainedmildly hypercalcaemic. In these cases, failure to restore normocalcaemiawas attributable to elevated renal tubular reabsorption of calciumin nine (18 per cent) and to inadequate suppression of boneresorption in seven (14 per cent). There was no significant difference in response and durationof effect (median 20 days) between single doses of 15,25 and45 mg, or when the 45 mg dose was administered over three, sixor 24 h. These single dose regimens were similar in terms ofeffect on calcium levels and duration of action, to multipledaily doses of 15 mg for a mean of six days. While the effectof 5 mg dose was not significantly different from the higherdoses, suppression of serum calcium levels was less marked andthe effect on duration of action significantly shorter thanwith the 45 mg dose. In seven cases, treatment with a second course was less effectiveeven with higher doses because suppression of bone resorptionwas poorer. These data indicate that there is little difference betweenthe therapeutic effects of multiple 15 mg and single 15–45mg intravenous infusions of aminohydroxypropylidene bisphosphonatein hypercalcaemia associated with cancer. A single intravenousinfusion of a moderate dose (for example 15–30 mg) wouldbe a convenient and effective way of treating most patients.     

Single-dose treatment of cholera with furazolidone or tetracycline in a double-blind randomized trial.

To evaluate single doses of 400 mg of furazolidone and 1 g of tetracycline given orally to patients with diarrhea due to Vibrio cholerae, we studied 87 adults in a randomized, double-blind, placebo-controlled trial. All patients received intravenous fluids for rehydration and no other drugs. The total volumes of stool (mean +/- standard deviation) during a 6-day period after treatment were significantly smaller in the tetracycline group (10.5 +/- 8.6 liters) than in the furazolidone group (20.9 +/- 15.9 liters) and the placebo group (19.1 +/- 10.5 liters) (P less than 0.01). The duration of diarrhea and volumes of intravenous fluids were also significantly reduced in the tetracycline group (P less than 0.05). However, there were no differences between the furazolidone and the placebo groups with regard to stool volume, intravenous fluid, and duration of diarrhea. Within 48 h of treatment, tetracycline significantly reduced the number of patients with positive stool cultures for V. cholerae (37%) compared with furazolidone treatment (96%) and the placebo (97%) (P less than 0.001). Although the tetracycline group had a significantly higher incidence (61%) of bacteriologic relapse (negative stool cultures on days 2 and 3, followed by positive cultures afterward) compared with that in the furazolidone group (40%) and the placebo group (33%), this was not associated with clinical relapse. There were no differences between the furazolidone and placebo groups with regard to any of the bacteriologic responses examined. These data indicate that a single dose of 1 g of tetracycline is effective in the treatment of cholera, but it is asymptomatic bacteriologic relapse. A single dose of 400 mg of furazolidone is not therapeutically effective in cholera.     

Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies

BACKGROUND: In a pilot study, naratriptan was significantly more effective than placebo in preventing menstrually related migraine (MRM) when given as 1 mg twice daily for 5 days beginning 2 days before the predicted onset of MRM for up to 4 menstrual cycles. OBJECTIVE: To evaluate the efficacy and tolerability of naratriptan for short-term prevention of MRM in 2 large, identically designed, randomized, double-blind, placebo-controlled, parallel-group studies. METHODS: MRM was defined as any migraine beginning during the perimenstrual period (PMP). By definition, the PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being the first day of menstrual flow. Adult women were eligible if they reported a history of MRM, had regular menstrual cycles, and could predict within 2 days both the onset of menstrual flow and MRM. The studies comprised a baseline phase and a treatment phase. During the baseline phase, patients prophylactically treated their first PMP after the screening visit with single-blind placebo. Patients who documented an MRM while receiving placebo were eligible for the treatment phase. During the treatment phase, patients were randomized to receive either naratriptan 1 mg twice daily or placebo beginning 3 days before the predicted onset of MRM for a total of 6 days for 4 PMPs or 6 months, whichever occurred sooner. The primary efficacy endpoint was the mean percentage of treated PMPs without MRM per patient. Secondary efficacy endpoints included the percentage of patients who were free of MRM during all treated PMPs, the median number of days with MRM over 4 PMPs, and patient satisfaction. Safety and tolerability measures included adverse events, standard clinical laboratory tests, and vital signs. RESULTS: The intent-to-treat population was 287 in Study 1 (149 in the naratriptan group and 138 in the placebo group) and 346 in Study 2 (173 in each treatment group). Approximately 20% of randomized patients in each treatment group in Study 1 and 10% in each treatment group in Study 2 withdrew prematurely from the studies over the 4-month treatment period. The mean percentage of PMPs without MRM per patient was 38% and 34% among naratriptan-treated patients treating at least 1 PMP compared with 29% and 24% among placebo-treated patients in each respective study (P < .05 naratriptan vs placebo for both studies). Efficacy of naratriptan did not vary as a function of age, use of oral contraceptives, or use of migraine prophylaxis. More patients who had received naratriptan reported attacks posttreatment compared to patients who had received placebo. Among patients treating at least 1 PMP, the percentage of patients with no MRM in any treated PMP was significantly (P < .05) higher in the naratriptan group (11%; 19/173) than the placebo group (3%; 6 of 173) in Study 2. There were no differences in the percentages of patients with no MRM in any treated PMP in Study 1. The number of MRM days per patient across 4 PMPs was significantly lower in the naratriptan group than in the placebo group in both studies (median 5.0 days vs 6.5 days in Study 1 [P= .005] and 5.3 days vs 6.0 days in Study 2 [P= .018]). Significantly more patients receiving naratriptan were satisfied with the ability of naratriptan to control MRM either by preventing their occurrence or reducing their severity or duration compared with patients receiving placebo. No single drug-related adverse event was reported by more than 2% of patients in a treatment group in either study, and no serious drug-related adverse events were reported. CONCLUSIONS: Naratriptan 1 mg twice daily for 6 days per month is effective and well tolerated when used for short-term prevention of MRM. More patients receiving naratriptan than placebo were satisfied with treatment. The observed increase in posttreatment attacks needs further study.     

Efficacy,tolerability and development of resistance in HIV-positive patients treated with fluconazole for secondary prevention of oropharyngeal candidiasis: a randomized,double-blind,placebo-controlled trial

Over 37 months, we conducted a prospective double-blind, randomized study in a cohort of 138 HIV-infected patients to compare the effect of two different strategies on the prevention and treatment of oropharyngeal candidiasis relapses and on the development of clinical and microbiological resistance to fluconazole. Each episode was treated with a 7 day course of fluconazole 200 mg/day, followed by secondary prophylaxis with fluconazole 150 mg once weekly matched to placebo. The duration of the double-blind phase of the study, from the day of randomization to the first primary end-point, was 347 +/- 186 days for the fluconazole group and 196 +/- 128 days for the placebo group (P < 0.001). A total of 33 patients remained relapse-free during the course of the study. Clinical failure was observed in a total of five patients (four in the fluconazole group, one in the placebo group; P = 0.15). Microbiological resistance was recorded in 12 patients (eight in the fluconazole group, four in the placebo group; P = 0.20). There were no significant treatment group differences in microbiological resistance whether comparisons were made for all cases or for cases up to 1 month post-study. In the few patients who developed clinical and/or microbiological resistance, the cumulative dose of fluconazole before entry into the study was a mean value of 8.6 g (compared with 2.9 g in patients without clinical and/or microbiological resistance). In summary, patients treated with secondary prophylaxis suffered fewer relapses of oropharyngeal candidiasis. Development of resistant candidiasis (clinical and/or microbiological) was rarely seen in either group and its incidence was not significantly different.     

Should bisphosphonates be standard therapy for bone pain?

 We have been studying bisphosphonates since the early 1980s, initially investigating etidronate in the management of hypercalcaemia and, since the mid-1980s, clodronate in the management of hypercalcaemia, bone pain, and skeletal complications in patients with bone metastases. We have also recently reported that bone metastases can be prevented or delayed in patients without evidence of bone disease but with recurrent disease at other sites. Bisphosphonates are now the standard therapy for hypercalcaemia after rehydration. For patients with bone metastases and bone pain, a trial of clodronate 600–1500 mg i.v. in 500 ml normal saline over 3 h given every 1–2 weeks is worthwhile in association with other modalities such as radiotherapy and analgesic medications. Oral clodronate or intravenous pamidronate should be given as a preventive measure in patients with established bone metastases from breast cancer and myeloma. In patients with no evidence of bone metastases, it may be that bisphosphonates can delay the emergence of bone metastases; at present this remains under clinical investigation and our pioneer trials require confirmation. Clinical trials of bisphosphonates in the treatment of hypercalcaemia, bone pain, management of patients with bone metastases and management of patients with recurrent cancer but no evidence of bone metastases will be discussed.     

SERUM CALCIUM LEVELS IN VARIOUS LUNG DISEASES

Calcium levels were determined in sera of patients suffering from various lung diseases. Healthy volunteers served as controls. Significant differences were found between the serum calcium levels of patients with active lung tuberculosis and those of controls (P less than 0.01). After treatment, serum calcium levels decrease to normal values in these patients. It was also found that there were significant differences in serum calcium levels of patients with primary lung carcinoma (P less than 0.01) and of patients with metastatic lung carcinoma as compared to controls (P less than 0.01). On the other hand, normal serum calcium levels were found in patients with pulmonary diseases with or without an infection. In conclusion, it seems likely that a combination of mechanisms plays a role in the pathogenesis of hypercalcaemia in pulmonary tuberculosis and primary and metastatic lung carcinoma.     

糖尿病合并腰椎骨质疏松的治疗

目的：评价羟乙膦酸钠(邦特林)治疗糖尿病并骨质疏松症的有效性及安全性。方法：140例糖尿病并腰椎骨质疏松症患者随机分成治疗组及对照组各70例。治疗组服邦特林0．2／次,每天2次,二周后服磷酸氢钙0．6／次。每天3次。其中女性患者加服尼尔雌醇2mg,每15天一疗程,共一年;对照组不加用邦特林,其余治疗相同。结果：治疗组患者腰椎骨密度与对照组的比较有统计学差异。且治疗组椎体仅有1例新发压缩性骨折,而对照组新发3例。骨痛缓解率也明显高于对照组。未发现明显副反应。结论：口服邦特林加用磷酸氢钙、女性患者加服尼尔雌醇对糖尿病并骨质疏松疗效肯定,能明显缓解骨痛、减少患者骨折发生率,提高患者的生活质量。     

脓毒症患者血清甲状旁腺激素及钙水平与疾病严重程度及预后的关系

目的：研究甲状旁腺激素（PTH）及血清钙水平与ICU脓毒症患者疾病严重程度和预后的关系。方法：将ICU20例脓毒症患者分为生存组和死亡组进行回顾性研究。在SIRS发生48h内开始监测PTH及血钙水平。并在1周内每天检测两组PTH及血钙水平。病情严重程度用急性生理和慢性健康评分（APACHEⅡ）来评估。将两组PTH和血钙水平进行比较,并分析APACHEⅡ评分与PTH、血钙水平的相关性。结果：第1天PTH平均水平生存组患者66.7%高于正常,死亡组患者100%高于正常;血钙平均水平生存组患者77.8%低于正常,死亡组100%低于正常。死亡组PTH水平在第1～6天显著高于生存组（P〈0.05）,死亡组血钙水平在第1～5天显著低于生存组（P〈0.05）。并且APACHEⅡ评分与PTH水平（r=0.969,P〈0.05）呈正相关,与钙水平（r=-0.827,P〈0.05）呈负相关。结论：低钙血症及高PTH水平在脓毒症患者中很常见,且与疾病严重程度相关,并可能提示预后较差。     

Zoledronic acid: a new parenteral bisphosphonate

BACKGROUND: Inhibition of bone resorption using bisphosphonates is an important step in palliation of complications of advanced cancer, such as hypercalcemia and metastatic bone disease. OBJECTIVE: The goal of this article was to describe the pharmacologic properties of zoledronic acid (zoledronate) and discuss findings from preclinical and clinical studies of its use in skeletal disorders. METHODS: Relevant English-language literature was identified using the terms zoledronic acid, zoledronate, Zometa, and 118072-93-8 through searches of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1970-June 2003), and abstract proceedings from the American Society of Clinical Oncology (1997-2002). RESULTS: Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone resorption. It is indicated for the treatment of hypercalcemia of malignancy and for the treatment of patients with multiple myeloma or documented metastasis from solid tumors, in conjunction with standard antineoplastic therapy. The recommended dosage is 4 mg via IV over >or= 15 minutes every 3 or 4 weeks. Compared with pamidronate 90 mg, zoledronic acid 4 and 8 mg provided a higher complete response rate for hypercalcemia of malignancy by day 10 (88.4% and 86.7% vs 69.7%; P = 0.002 and P = 0.015) and longer duration of action (median time to relapse, 30 and 40 days vs 17 days; P = 0.001 and P = 0.007). In patients with breast cancer or multiple myeloma, zoledronic acid was as effective as pamidronate in delaying time to a first skeletal-related event (373 days vs 363 days). In patients with hormone-refractory prostate cancer and bone metastases, zoledronic acid 4 mg reduced the proportion of patients who experienced a skeletal-related event (33% vs 44% with placebo; P = 0.021) or a skeletal fracture (13% vs 22% with placebo; P = 0.015). In patients with bone metastases from solid tumors, zoledronic acid delayed the median time to a first skeletal-related event (230 days vs 163 days with placebo; P = 0.023). Common adverse events include fever, nausea, constipation, fatigue, and bone pain. CONCLUSION: Zoledronic acid is an effective and generally well-tolerated treatment for hypercalcemia of malignancy and skeletal complications of metastatic bone disease.