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.     

Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures.

To evaluate changes in matrix molecules of the joint capsule, the right knees of 24 skeletally mature female NZW rabbits were immobilized while the contralateral limb served as an unoperated control. The immobilization was discontinued at 8 weeks and the rabbits were divided among four groups (n = 6) based on the number of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six knees) that did not have operations provided normal control joint capsules. The mRNA levels for collagen types I, II, and III, and MMP-1 and -13 were significantly increased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. In contrast, the mRNA levels for TIMP-1, -2, and -3 were decreased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. The mRNA levels for lumican and decorin were increased in the joint capsules of the contracture knees in all groups when compared to normal capsules. Many of the changes observed in this animal model are similar to those observed in human joint capsules from posttraumatic elbow contractures, supporting the value of this rabbit model.     

Reactivity of hydroxybenzoic acids in the hydrogen-isotope exchange reaction.

The hydrogen-isotope exchange reaction (T-for-H exchange reaction) between tritiated water vapor (HTO vapor) and 3-hydroxy-4-methoxybenzoic acid (and it's analog; 4-hydroxy-3-methoxybenzoic acid) were observed at 50 and 70 degrees C in a gas-solid system to reveal the reactivity of a functional group in an aromatic compound having two substituents in the aromatic ring. Further, it was shown that (a) the reactivity of the compounds used in this work follows the Hammett's rule, and (b) the reactivity of trisubstituted aromatic compound could be analyzed by applying the additive property of the Hammett's rule even if the compound contains a substituent at the ortho-position.     

医源性子宫内膜异位症的治疗进展

医源性子宫内膜异位症是指由于医学检查或治疗的影响而使子宫内膜异位种植，存活或已有的内膜异位灶进一步发展，近年发病率逐渐上升，原因主要与各种妇产科操作的增多有关，现就医源性子宫内膜异位症的治疗进展作一综述。     

体外培养的小鼠骨髓基质细胞对血细胞集落形成的支持

为探讨骨髓基质细胞在液体条件下支持造血的能力,对小鼠骨髓有核细胞体外培养,在液体培养基中形成基质细胞贴壁层,更换培养液,再种植骨髓有核细胞。结果在贴壁的基质细胞上形成了细胞集落。按细胞形态特征分为两类:一类为基质细胞集落,仅为偶见。另一类为造血细胞集落,数量较多,并且集落通过一定的结构与贴壁的基质细胞连接。结果提示,造血细胞集落的形成,需要有与骨髓基质细胞接触的微环境,并可对基质细胞的生长发育有一定的反作用。本文提出了造血细胞集落的液体培养法。     

围产儿与儿童胸腺的病理改变

The most outstanding pathological changes of perinatal babies and children, based on the review of the autopsy files in the 1st Affiliated Hospital of West China University of Medical Sciences, are lymphocytic depletion, and reticuloepithelial cell swelling and/or fusiform malformation in the cortex, while in the medulla apoptosis is more prominent. We suppose that these alterations are due to immaturity of cortical thymocytes, and in the diseased condition, they are easily affected by extraordinary factors, especially the influence of corticosterone inducing acute severe necrosis, so the number of lymphocytes are obviously diminished. But, in the medulla, as intact mature lymphocytes exist, physiological phenomenon such as apoptosis is rather prominent in it. While in the medulla, Hassall's corpuscles have various characteristic changes, such as cornification, calcification, fusion, cystic change and disintegration. Besides, we observed a new alteration in the thymus defined as vacuolization. All the above pathological changes reached the peak in the 28- day group; there after, they might become either worse or better according to the condition of the disease and growth of the body. However, these are still problems to be further studied separately.     

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.