The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

Risk factors of acute pancreatitis]

A total of 689 operative cases of acute necrotic pancreatitis (ANP) were collected from 42 hospitals all over the country by the ANP Cooperative Study Group in the years of 1987 to 1989. General data, laboratory findings, pathology of the pancreas and the type of surgical treatment were analysed according to the outcome of the patient. The results showed that 37% of the cases were related to cholelithiasis, the highest incidence was in age above 60, and female patients were predominant and with higher mortality. Laboratory findings at admission, WBC greater than 20,000/mm3, Hb greater than 15 g%, blood sugar greater than 200 mg%, serum bilirubin greater than 5 mg%, BUN greater than 20 mg%, and serum calcium less than 7 mg% were related to the markedly elevated mortality rate. Operative findings noted in patients with bloody or cloudy peritoneal fluid, necrotic changes up to 75% of the pancreas, more than 2 areas of extrapancreatic involvements and resection of a large portion of the pancreas was found to be necessary were all related to a higher mortality. And emergency operations performed within 24 hours after the onset of the disease was also related with a highest mortality rate.     

移植肾破裂的处理

目的　提高移植肾破裂的防治水平。方法　 6例移植肾破裂 ,手术前 2例 ,手术后 4例。 2例术前供肾破裂 ,采用切开移植肾破裂处包膜 +裂口内明胶海绵填塞 +肠线修补 +肠线编织肾袋收缩保护移植肾。 1例术后移植肾破裂早期 ,出血少 ,针对顽固性高血压采用“硝普钠”降压 ,配合常规抗排斥药物。 3例术后移植肾破裂出血量估计超过 10 0 0ml者 ,采用手术延长移植肾破裂处包膜 +裂口内明胶海绵填塞 +肠线修补 +肠线编织肾袋收缩保护移植肾。结果　 ( 1)手术前 2例手术后 4例 ,采用切开或者延长移植肾破裂处包膜 +裂口内明胶海绵填塞 +肠线修补 +肠线编织肾袋收缩保护移植肾并配合“硝普钠”降压的方法处理 ,均未再破裂出血 ,移植肾功能恢复良好。 ( 2 ) 1例术后移植肾破裂早期的患者 ,针对顽固性高血压采用“硝普钠”降压 ,配合常规抗排斥药物 ,非手术治疗成功。结论　 ( 1)采用手术切开或延长移植肾破裂处包膜 +裂口内明胶海绵填塞 +肠线修补 +肠线编织肾袋收缩保护移植肾可以有效治疗移植肾破裂。 ( 2 )移植肾破裂出血少的情况下 ,可以在密切观察下非手术治疗     

前列腺癌去雄激素治疗不良反应的预防和处理

目的观察去雄激素治疗前列腺癌的不良反应,并探讨其预防和治疗。方法回顾性分析1998年7月-2006年1月112例去雄激素治疗晚期前列腺癌的临床资料。结果112例患者中,97例完成了不良反应的调查。随访3-36月,去雄激素治疗后潮热、性功能障碍、病理性骨折发生率分别为46％、75％、4％;患者潮热、精神疲乏、四肢乏力、纳差症状明显加重(P<0．05);性功能明显减退(P<0．05)。12例潮热症状严重者使用抗抑郁药博乐欣(25mg,tid)1-2周症状减轻。7例有骨转移性疼痛或严重骨质疏松患者,应用唑来膦酸4mg静脉滴注,每45d一次,骨痛症状缓解。结论去雄激素对前列腺癌患者生活质量有一定影响。博乐欣可减轻患者潮热症状,唑来膦酸可预防和治疗去雄激素相关的骨质疏松并发症。     

Innervation of the trapezius muscle: is cervical contribution important to its function?

OBJECTIVE: To study the effect of the cervical plexus and the accessory nerve to the function of the trapezius muscle. STUDY DESIGN AND SETTING: Eighteen adult male Sprague-Dawley rats were randomly divided into three groups. The neurotomies were performed in the left sides and the right sides served as within-subject controls. In group A, the accessory nerve was transected. The C2-5 were transected in group B, and both of the accessory nerve and C2-5 were cut in group C. The electrophysiologic, myophysiologic, and histologic changes of the muscles were measured. RESULTS: There were significant differences (P < 0.05) between the three groups in the recovery rates of the transverse area of the muscles. The CMAP recorded from the experimental sides in group B were similar to the control sides. The values of the maximum tension of the tetanus contraction between the two sides showed no differences either (P > 0.05). CONCLUSION: The accessory nerve supplies the most important motor input to the trapezius. Motor innervations of the cervical plexus are not very significant.     

Loss of cables, a novel gene on chromosome 18q, in ovarian cancer.

Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11. Cables appears to be primarily involved in cell cycle regulation and cell proliferation. Overexpression of Cables in Hela and other cell lines inhibits cell proliferation and tumor formation. We hypothesize that loss of Cables expression is associated with ovarian cancer. To test our hypothesis, we examined Cables expression in the four most common subtypes of ovarian carcinomas: serous, endometrioid, mucinous, and clear cell. In addition, mucinous and serous borderline tumors were also included. Loss of Cables expression was observed at high frequency in ovarian serous (11 of 14 cases, 79%) and endometrioid (5 of 10 cases, 50%) carcinomas. In contrast, strong Cables staining was detected in all clear cell carcinomas (10 cases) and mucinous tumors (5 carcinomas and 5 borderline tumors). The majority of serous borderline tumors (11 of 14 cases, 79%) showed positive Cables staining, with the rest showing focal loss of Cables expression. Furthermore, RT-PCR revealed the lack of Cables mRNA in a human ovarian cancer xenograft. No correlation was noted between loss of Cables and histologic grade, tumor stage, and survival. In conclusion, our results indicate that loss of Cables is common in ovarian serous and endometrioid carcinomas and imply that Cables may be involved in the pathogenesis of these two types of ovarian carcinomas.     

Managing the premenstrual syndrome

The definition, classification, proposed etiologies, diagnosis, and treatment of the premenstrual syndrome (PMS) are discussed, and guidelines for the clinical management of PMS are presented. PMS encompasses a cluster of physical and psychosocial symptoms that recur during each menstrual cycle. Proposed etiologies for the syndrome include a hormonal imbalance between estrogen and progesterone, pyridoxine hydrochloride deficiency, hypoglycemia, excess prostaglandin production, and increased aldosterone concentrations in the luteal phase of the menstrual cycle. Diagnosis of PMS is usually based on a patient's history of recurrent symptoms accompanied by a seven-day, symptom-free period in the first half of the menstrual cycle. Management of PMS is complicated by the difficulty in diagnosing the syndrome and its unclear etiology. If possible, conservative nonpharmacologic treatment should be tried initially; suggested measures include modifications in diet, exercise, substance use, stress factors, rest patterns, and social support. Pharmacologic treatment should be considered when conservative therapies are ineffective or when PMS symptoms are more severe. Although most therapies are empirical, treatment with progesterone, pyridoxine, bromocriptine, or diuretics might prove beneficial. Once the decision is made to initiate drug therapy, the treatment regimen should be individualized and based on the patient's PMS symptom complex. The clinical management of PMS is complicated by the lack of well-designed clinical investigations of proposed treatments. Future research should be directed toward evaluating the efficacy of proposed therapeutic regimens.     

Modulation of high-dose methotrexate toxicity by a non-toxic level of 5-fluorouracil

High-dose methotrexate (MTX) toxicity is reduced by a non-toxic dose of 5-fluorouracil (FU) when these agents are used in combination. Changes in the hematopoietic system (platelets, erythrocytes, leukocytes, hemoglobin, and hematocrit), ileal tissue, body weight, and mean survival were used as parameters to assess toxicity. For all parameters studied, there were no significant differences between the scheduling of MTX (245 mg/kg) after a priming dose of FU (25 mg/kg), simultaneous MTX and FU, FU alone, and control. However, sequential treatment with MTX followed by FU, and MTX alone resulted in: a marked decrease in the hematopoietic parameters; significant morphological changes in ileal tissue; a reduction of body weight; and increased mortality of animals. Hence, this study suggests that FU, a cytotoxic agent, may protect against MTX toxicity and improve its therapeutic index when FU administration precedes MTX or when these agents are given simultaneously.