Piperacillin-tazobactam-induced hypokalemia and metabolic alkalosis

Piperacillin/tazobactam is a commonly prescribed antibiotic and is generally considered safe. We report a case of a 2-year-old girl who developed hypokalemic metabolic alkalosis and bradycardia after receiving intravenous piperacillin-tazobactam for bronchopneumonia. Upon withdrawal of the drug, serum potassium normalized in 2 days. Hypokalemia is a serious adverse effect of piperacillin-tazobactam and should be suspected while treating patients with this drug. Early recognition and prompt withdrawal of the drug will result in lesser morbidity.     

Acute fluoride toxicity: influence of metabolic alkalosis.

Acute fluoride toxicity was induced in anesthetized rats by the continuous iv infusion of fluoride at 1.40 μmol/min. This infusion continued until the death of the animals. Early signs of toxicity, which developed in all animals during the first hour of fluoride infusion, included diuresis, falling urinary osmolality, and glomerular filtration rate at plasma fluoride concentrations of 0.4 to 0.5 mm. The animals were then assigned to three groups. Groups 1, 2, and 3 received intravenous infusions of isotonic saline (control), isotonic sodium bicarbonate, and isotonic sodium bicarbonate plus acetazolamide, respectively. Compared to group 1, groups 2 and 3 survived the high fluoride infusion longer (5.93 vs 7.61 and 10.27 hr, respectively) and tolerated more fluoride (47.8 vs 61.9 and 80.7 mg/kg, respectively). At any given time (dose) after starting the high fluoride infusion, plasma fluoride concentrations were lower and mean arterial blood pressures, glomerular filtration rates, fluoride renal excretions, clearances and fractional clearances, and blood and urine pH values were higher in animals from groups 2 and 3 compared to group 1. Further, group 3 was more resistant to fluoride toxicity than group 2. Terminal tissue-to-plasma fluoride concentrations for heart were lowest in groups 2 and 3 while there were no differences among the groups for brain. It is concluded that metabolic alkalosis can favorably influence the course of a developing episode of acute fluoride toxicity and that this maneuver should be an important addition to the currently accepted therapeutic regimen.     

盐酸精氨酸治疗脑外伤严重代谢性碱中毒30例分析

目的分析盐酸精氨酸持续微量泵输入治疗脑外伤患者严重代谢性碱中毒的量效关系及对近期患者预后的影响。方法选择成年严重颅脑外伤合并严重碱中毒患者30例,持续微量泵输注盐酸精氨酸0.55 g/（h.kg）,通过血气分析观察治疗前后碱剩余（BE）变化情况,计算精氨酸治疗碱中毒的量效关系。结果盐酸精氨酸治疗严重代谢性碱中毒后,BE下降（11.94±3.45,8.74±3.67,P〈0.001）,pH（7.47±0.06,7.45±0.05,P〈0.05）,PaCO2也同时有下降（49.73±10.48,46.53±9.26,P〈0.05）,Na^＋、Cl^-和K^＋变化不明显;BE下降梯度为△3.19±2.24。结论盐酸精氨酸持续微量泵输入可以有效纠正脑外伤患者严重碱中毒。     

Hypokalemic, metabolic alkalosis induced by high-dose ampicillin sodium.

A case of hypokalemic metabolic alkalosis precipitated by high-dose intravenous ampicillin sodium is discussed. Cases of hypokalemic metabolic alkalosis attributable to ampicillin sodium have not been reported previously. There have been reports of this phenomenon associated with high doses of penicillin sodium and carbenicillin disodium. The possible mechanism of antibiotic-induced hypokalemic metabolic alkalosis is discussed. It is suggested that most cases of antibiotic-induced hypokalemia respond to oral or intravenous potassium chloride.     

Effects of respiratory and metabolic alkalosis and acidosis on pipecuronium neuromuscular block

Acute respiratory and metabolic acidosis as well as metabolic alkalosis increased (by 11, 11, 21%) whereas respiratory alkalosis antagonized (by 10%) the partial steady state block produced by pipecuronium infusion on the anterior tibialis muscle of the cat. The duration of neuromuscular block following six successive doses of pipecuronium was prolonged 1.4-fold during long-lasting metabolic alkalosis while this parameter was shortened to half of that in control cats during acidosis. Pipecuronium block could be fully antagonized by neostigmine.     

Prevention of metabolic alkalosis induced by gastric fluid loss using H2 receptor antagonist

Gastric fluid loss is a common cause of metabolic alkalosis. We studied various acid-base parameters in 20 patients undergoing continuous nasogastric (NG) suctioning for periods ranging from 3 to 17 days. Ten patients received cimetidine 300 mg intravenously every 6 hr (cimetidine-treated group). The remaining 10 patients received an antacid compound through the NG tube (control group). The rise in plasma bicarbonate concentration was significantly greater in the control group as compared to the cimetidine-treated group. As expected, gastric acid output was considerably lower in the cimetidine-treated group than in the control group. We conclude that cimetidine administration may be used in preventing metabolic alkalosis associated with gastric fluid loss by inhibiting gastric secretion of HCl.     

Treating the metabolic syndrome: acetyl-CoA carboxylase inhibition

Metabolic syndrome is defined as a clustering of cardiovascular risk factors (abdominal obesity, hyperinsulinaemia, atherogenic dislipidaemia, hypertension, hypercoagulability) that together increase the risk of developing coronary heart disease and Type-2 diabetes. Inhibition of acetyl-CoA carboxylase (ACC), with its resultant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favourably affect, in a concerted manner, a multitude of cardiovascular risk factors associated with metabolic syndrome. Studies in ACC2 knockout mice and in experimental animals treated with isozyme-nonselective ACC inhibitors have demonstrated the potential for treating metabolic syndrome through this modality. A variety of structurally diverse, mechanistically distinct classes of ACC inhibitors have been disclosed in the scientific and patent literature. Isozyme-nonselective ACC inhibitors may provide the optimal therapeutic potential for beneficially affecting metabolic syndrome. However, demonstration of the full potential of isozyme-selective inhibitors, once identified, should reveal advantages and liabilities associated with single isozyme inhibition. Whereas demonstrating clinical efficacy of an ACC inhibitor should be straightforward, the heterogeneity of the patient population and absence of established guidelines regarding approval end points for agents simultaneously affecting multiple aspects of metabolic syndrome will pose developmental challenges for initial market entries.     

Reversal of hypercapnia induces endothelin-dependent constriction of basilar artery in rabbits with acute metabolic alkalosis

We recently concluded that constriction of basilar artery due to respiration-induced hypocapnia in rabbits with acute metabolic alkalosis and accompanying compensatory hypercapnia was independent of NO and K(ATP) channels. Based on reports that endothelin-1-mediated hypocapnic constriction of the rabbit basilar artery in vitro, we further investigated whether the respiration-induced hypocapnic constriction was endothelin-1 mediated. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. The ET(A) plus ET(B) receptor antagonist, PD145065 (1 microM), and the selective ET(A) receptor antagonist, BQ610 (3 microM), completely relaxed the hypocapnic constriction, as determined in a cranial window. Unexpectedly, the ET(B) receptor antagonists, BQ788 and RES-701-1 (3 microM), relaxed the constriction by 72.1+/-2.8% (4) and 77.2+/-8.7% (5), respectively (means+/-S.E. (n)). To investigate whether the large magnitudes of relaxation to both ET(A) and ET(B) receptor antagonists were due to nonselectivity of the antagonists, the effects of the antagonists on the constriction to exogenous endothelin-1 were evaluated. BQ610, BQ788, and RES-701-1 relaxed the 3-5 nM endothelin-1 constriction by only 64.3+/-7.6% (4), 43.5+/-8.5% (5), and 26.7+/-4.8% (3) (means+/-S.E. (n)), respectively, consistent with the selective blocking action of these antagonists. To investigate whether the greater magnitude of BQ610, BQ788, and RES-701-1 relaxation of hypocapnic constricted versus exogenous endothelin-1-constricted vessels was due to differences between constriction elicited by endogenous versus exogenous endothelin-1, the effects of the endothelin receptor antagonists on constriction to isocapnic alkaline suffusate were evaluated. PD145065 (1 microM) and 0.1 mM phosphoramidon, an endothelin-converting enzyme inhibitor, inhibited the constriction to isocapnic alkaline suffusate by 83.8+/-7.8% (6) and 74.3+/-9.7% (8) (means+/-S.E. (n)), respectively, consistent with the endothelin-1 dependency of the constriction. BQ610, BQ788, and RES-701-1 relaxed the isocapnic alkaline suffusate constriction by 74.9+/-6.7% (5), 65.5+/-6.4% (5), and 78.0+/-6.5% (4) (means+/-S.E. (n)), respectively. Thus, the relaxation profile to the selective endothelin receptor antagonists in isocapnic alkaline constricted vessels more closely approximated the relaxation profile observed in hypocapnic constricted as compared to endothelin-1-constricted vessels. Hypocapnia did not alter the 5 nM endothelin-1 constriction. These results suggest that, under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent hypocapnic constriction is endothelin mediated. Both ET(A) and ET(B) receptor activation may mediate the hypocapnic constriction. The hypocapnic constriction is not due to enhanced endothelin-1 constriction and, thus, is due to the release of endothelin-1 and/or additional endothelins.     

Reversal of hypercapnia induces KATP channel and NO-independent constriction of basilar artery in rabbits with acute metabolic alkalosis

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid-base balance has not been investigated. As K(ATP) channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO(2) in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Lowering blood pCO(2) from initial baseline hypercapnic levels to near normocapnic and hypocapnic levels constricted basilar artery by 10.2+/-0.8% (4) and 16.2+/-0.6% (44), respectively (means+/-S.E., n), as determined in an in situ cranial window preparation. The constrictions were maintained for 4-5 h and return of pCO(2) to hypercapnic levels relaxed the constriction. Changing the suffusate pH to either the pH of the cerebral spinal fluid observed during initial baseline hypercapnia or following lowered pCO(2) did not alter the magnitude of constriction due to lowered pCO(2). Neither 0.3 mM N(G)-monomethyl-L-arginine monoacetate, an NO synthase inhibitor, nor 10 microM glibenclamide, a K(ATP) channel blocker, altered the magnitude of hypocapnic constriction. These results demonstrated that under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent pCO(2) reduction induces prolonged constriction of the basilar artery that is independent of (1) cerebral spinal fluid pH over a physiologic range, and (2) NO and K(ATP) channels.     

Improvement bioavailability of silymarin ameliorates severe dyslipidemia associated with metabolic syndrome

Abstract

1. To compare the effectiveness of different drug forms of silymarin: standardized extract of silymarin (SS), micronized silymarin (MS) and silymarin in the form of phytosome (PS) on dyslipidemia and liver fat accumulation in a model of metabolic syndrome, in non-obese hereditary hypertriglyceridemic rats. The second aim of this study was to slightly uncover the silymarin action on enzymes and proteins involved in cholesterol metabolism and excretion.

2. Silymarin administered to hereditary hypertriglyceridemic rats as dietary supplements (1%) for 4 weeks significantly lowered the plasma levels of triglycerides, total cholesterol and markedly increased HDL cholesterol level. Western blot analyses showed significant increase in the protein expression of CYP7A1 and CYP4A and increase in protein expression of selected ABC transporters. Silymarin in the form of phytosome and micronized silymarin were more effective forms of silymarin.

3. These findings suggest that silymarin may favorably affect the metabolism of cholesterol and triglycerides in rats with metabolic syndrome. Raising HDL levels suggests potentially important anti-atherogenic effect of silymarin. The changes in expression of cytochromes P450 and ABC transporters involved in cholesterol metabolism and excretion could be partially responsible for the hypolipidemic effect of silymarin.     

重症须用重典--关于抗击非典的几个法律问题

当“非典”成为一种重大的传染病向人们袭来的时候,各级政府和有关部门应依照《传染病防治法》、《传染病防治法实施办法》等有关规定,积极组织和调集力量进行抗击,采取一切必要的措施,控制“非典”的传播和在更大范围内流行。     

Treating substance abuse in the context of severe and persistent mental illness: clinicians' perspectives

Patients with comorbid substance use and major mental disorders are treated frequently in the mental health system. Treatment models relevant for this subset of patients have emerged in recent years, however, few have been validated empirically and so relatively few sites benefit from this treatment development activity. Important additional sources of information about good treatment practices are the clinicians who have adopted the treatment of patients with dual disorders as a specialty. We conducted four focus groups (N = 12) with clinicians who were nominated by their peers as experienced and/or expert in treating persons with comorbid substance use and psychiatric disorders. Discussions followed a four-part outline that included (a) general questions about training and experience with the population, (b) preferred treatment methods, (c) motivational issues, and (d) recommendations to the field. Participants were trained in a variety of mental health disciplines and pursued substance abuse treatment credentials or other educational experiences outside of their primary training programs. Their treatment approaches emphasized psychoeducation, a good therapeutic relationship, and the need to be flexible regarding methods and goals. Abstinence was the preferred goal among most clinicians; even so, they expressed a pragmatic flexibility and other views consistent with the principles of harm reduction. Clinicians tended to respond to patients' ambivalent motivational states by addressing the consequences of behaviors in a nonconfrontive style; they also made use of positive incentives and external support. A number of recommendations were made to improve treatment, including greater institutional and programmatic support for the unique needs of this population.     

羊膜移植联合角膜缘干细胞移植治疗重度眼烧伤

目的 评价适时进行羊膜移植或联合角膜缘干细胞移植治疗重度跟烧的疗效.方法 选择 2003年1月～2005年12月在我科住院的眼烧伤病人18例,22眼,其中酸碱烧伤12例,热烧伤6例.Ⅲ度烧伤12眼,Ⅳ度烧伤10眼.在Ⅳ度烧伤中.角膜缘缺血达四个象限者3眼,角膜缘缺血＜4个象限者7跟,结膜严重坏死累及巩膜者6眼.对于Ⅲ度眼烧伤者,仅行单纯羊膜移植治疗,对于Ⅳ度眼烧伤者,行羊膜移植联合自体或异体角膜缘干细胞移植治疗.对术后每1d、3d、1周、2周、1个月、3个月、6个月、12个月、18个月及24个月患者的视力、角膜溃疡及上皮愈合时间、角膜水肿及透明度、羊膜愈合或脱落情况、角膜新生血管、假性胬肉形成及睑球粘连等眼表情况,角膜缘干细胞的成活或排斥等进行裂隙灯显微镜检查.结果 4例失访.在随访到的14例17眼中,角膜上皮愈合时间为9～16(28.8±16d),所有患眼均有新生血管长人,假性胬肉形成者8眼,睑球粘连者5眼.视力大于0.3者2眼,0.1～0.3者3眼,0.02～0.1者6眼,0.02以下者6眼.角膜缘四个象限均缺血者.行羊膜移植联合角膜缘干细胞移植无效.结论 重度眼烧伤通过羊膜移植或联合角膜缘干细胞移植,可以有效缩短角膜上皮愈合时间,减少角膜新生血管、假性胬肉及睑球枯连的形成,并能不同程度的保存部分视力.     

Modification of transplacental distribution of salicylate in rats by acidosis and alkalosis.

1. The basis for the existence of a lower concentration of salicylate in the foetal than in the maternal blood was investigated in rats on day 20 of gestation. 2. Bolus injections of sodium salicylate were made into the mother and of [14C]-salicylic acid into its foetuses and serial maternal and foetal blood samples were collected. When derived on the basis of serum salicylic acid uncorrected for differences in ionization in the maternal and foetal blood, the placental clearance was 2.2 fold greater from the foetal to maternal side than that from the maternal to foetal side. 3. The greater foetal placental clearance relative to the maternal placental clearance was not due to any active placental transfer, since there was no evidence of saturation of this process and it was not affected by pretreatment with probenecid. Moreover, salicylic acid was not concentrated by placental slices in vitro and its placental uptake was not affected by dinitrophenol or by cooling. 4. Maternal blood pH was 0.19 units higher than the foetal blood pH. Administration of ammonium chloride or of sodium bicarbonate into the mother increased the foetal to maternal ratio of salicylic acid from 0.6 to approximately 1. 5. It is concluded that a foetal to maternal serum salicylate concentration-ratio of less than 1 simply reflects lower ionization in the foetus than in the mother, because foetal blood pH is lower than the maternal blood pH.