Stability after medial collateral ligament release in total knee arthroplasty.

Six knees from cadavers were tested for change in stability after release of the medial collateral ligament with posterior cruciate-retaining and substituting total knee replacements. Load deformation curves of the joint were recorded in full extension and 30 degrees, 60 degrees, and 90 degrees flexion under a 10 N-m varus and valgus torque, 1.5 N-m internal and external rotational torque, and a 35 N anterior and posterior force to test stability in each knee. The intact specimen and posterior cruciate ligament-retaining total joint replacement were tested for baseline comparisons. The superficial medial collateral ligament was released, followed by release of the posterior cruciate ligament. The knee then was converted to a posterior-stabilized implant. After medial collateral ligament release, valgus laxity was statistically significantly greater at 30 degrees, 60 degrees, and 90 degrees flexion after posterior cruciate ligament sacrifice than it was when the posterior cruciate ligament was retained. The posterior-stabilizing post added little to varus and valgus stability. Small, but significant, differences were seen in internal and external rotation before and after posterior cruciate ligament sacrifice. The posterior-stabilized total knee arthroplasty was even more rotationally constrained in full extension than the knee with intact medial collateral ligament and posterior cruciate ligament.     

Sympathetic Neural Adaptation to Hypocaloric Diet With or Without Exercise Training in Obese Metabolic Syndrome Subjects

OBJECTIVE

Sympathetic nervous system (SNS) overactivity contributes to the pathogenesis and target organ complications of obesity. This study was conducted to examine the effects of lifestyle interventions (weight loss alone or together with exercise) on SNS function.

RESEARCH DESIGN AND METHODS

Untreated men and women (mean age 55 ± 1 year; BMI 32.3 ± 0.5 kg/m²) who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated to either dietary weight loss (WL, n = 20), dietary weight loss and moderate-intensity aerobic exercise (WL+EX, n = 20), or no treatment (control, n = 19). Whole-body norepinephrine kinetics, muscle sympathetic nerve activity by microneurography, baroreflex sensitivity, fitness (maximal oxygen consumption), metabolic, and anthropometric measurements were made at baseline and 12 weeks.

RESULTS

Body weight decreased by −7.1 ± 0.6 and −8.4 ± 1.0 kg in the WL and WL+EX groups, respectively (both P < 0.001). Fitness increased by 19 ± 4% (P < 0.001) in the WL+EX group only. Resting SNS activity decreased similarly in the WL and WL+EX groups: norepinephrine spillover by −96 ± 30 and −101 ± 34 ng/min (both P < 0.01) and muscle sympathetic nerve activity by −12 ± 6 and −19 ± 4 bursts/100 heart beats, respectively (both P < 0.01), but remained unchanged in control subjects. Blood pressure, baroreflex sensitivity, and metabolic parameters improved significantly and similarly in the two lifestyle intervention groups.

CONCLUSIONS

The addition of moderate-intensity aerobic exercise training to a weight loss program does not confer additional benefits on resting SNS activity. This suggests that weight loss is the prime mover in sympathetic neural adaptation to a hypocaloric diet.The metabolic syndrome (MetS) is an increasingly prevalent multidimensional risk factor for cardiovascular disease and type 2 diabetes (1). Its etiology is complex and incompletely understood, but thought to involve the interplay between metabolic susceptibility, lifestyle factors, and the acquisition of excess visceral adiposity (2). Scientific studies performed over the last 2 decades strongly support the relevance of the sympathetic nervous system (SNS) in both the pathogenesis and target organ complications of MetS obesity (3).Several indexes of SNS activity, such as urinary norepinephrine excretion, norepinephrine spillover from sympathetic nerves, and postganglionic muscle sympathetic nerve activity (MSNA) are increased in subjects with MetS, even in the absence of hypertension (4–7). Among the adiposity indexes, abdominal visceral fat is most strongly associated with elevated MSNA (8). Because of the bidirectional relationship between sympathetic activation and insulin resistance, much debate has focused on their chronology. Prospective studies with 10–20 years follow-up indicate that elevated plasma norepinephrine concentration (9) and sympathetic reactivity (10) precede and predict future rise in BMI and development of insulin resistance. Although seemingly counterintuitive, sympathetic activation may be causally linked to obesity via β-adrenoceptor desensitization (11) and insulin resistance (12,13). In established obesity, metabolic, cardiovascular (baroreflex impairment), and medical conditions (obstructive sleep apnea) contribute significantly to sympathetic neural drive and further aggravate insulin resistance, hence establishing a vicious cycle (3,7). Chronic sympathetic activation is associated with an increased prevalence of preclinical cardiovascular and renal changes that are recognized predictors of adverse clinical prognosis (3,14,15).Weight loss and exercise are recommended as first-line treatments for MetS. The Diabetes Prevention Program and the Oslo Diet and Exercise Study have shown the marked clinical benefits of intensive lifestyle intervention on the resolution of the MetS (16,17). Individually, both weight loss (5) and exercise training (18,19) cause sympathoinhibition and improvement in MetS components. We have previously reported that moderate weight loss (7% of body weight) by diet alone is accompanied by reductions in whole-body norepinephrine spillover and MSNA and improvement in spontaneous cardiac baroreflex function in middle-aged MetS subjects (5). Because exercise is often added to energy restriction in the treatment of obesity, it is pertinent to clarify its additive benefits. Augmented improvements in metabolic, anthropometric, and cardiovascular parameters have been observed after combined exercise training and dietary weight loss in some (17,20,21), but not other studies (22), and there are limited data regarding their combined effect on sympathetic activity (23). Exercise training may potentially augment weight loss induced sympathoinhibition by promoting a greater loss of fat relative to lean mass (20,21), by further improvement in insulin sensitivity (24) and reduction in plasma leptin concentration (21), and by potentiation of baroreceptor sensitivity (18).The present study was conducted to 1) test the hypothesis that weight loss by combined hypocaloric diet and aerobic exercise training would be associated with greater sympathoinhibition and improvement in MetS components than hypocaloric diet alone and 2) to examine the interrelationships between reduction in sympathetic tone and concurrent changes in anthropometric, metabolic (insulin sensitivity, plasma leptin concentration), and cardiovascular parameters. A moderate-intensity bicycle riding protocol was chosen as the exercise intervention, based on an earlier study that demonstrated attenuation in whole-body and renal norepinephrine spillover rates with this regimen in healthy men (19).     

Stimulation by ionophores of tyrosinase activity of mouse melanoma cells in culture

The hypothesis that the melanosome is an acidic vesicle in which the tyrosinase action is suppressed under the ordinary culture conditions was examined with a variety of ionophores added in cultures of mouse melanoma cell line B16-C2M. In the presence of monensin or nigericin, which exchange H+ for Na+ or K+, respectively, through bio-membrane, the tyrosinase activity of cells in culture was more than 10 times that in the control culture. This stimulation was observed without delay after addition of the chemicals and was not inhibited by cycloheximide. The enzyme activity of sonicated cell-free extracts, in which melanosomes were disrupted, was not stimulated by these ionophores. The tyrosinase activity was stimulated to a lesser extent by a proton ionophore, p-trifluoromethoxyphenylhydrazone (FCCP). The activity was also stimulated by kryptofix 221, valinomycin (Na+ and K+ carrier, respectively), and tetraethylammonium ions (permeant cations) but only in the presence of a limited concentration of FCCP. N-Ethylmaleimide and N, N'-dicyclohexylcarbodiimide, inhibitors of lysosomal proton pump, stimulated tyrosinase activity of cells in the presence of FCCP. These facts are consistent with the hypothesis described above.     

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.     

Drug survival rates in patients with psoriasis after treatment with biologics

Clinically, patients' adherence to biologic treatment is not only related to efficacy but also to adverse events, cost and other factors. To evaluate long‐term viability of biologic treatment, both the percentage of and reasons for discontinuation of treatment were investigated. In this study, patients treated with infliximab (n = 38), adalimumab (n = 59) and ustekinumab (n = 30) were included and observed for 12 months. Clinical efficacy was evaluated using a 75% reduction of Psoriasis Area and Severity Index score (PASI‐75), and patients who discontinued treatment were considered as not having achieved PASI‐75. In addition, drug survival rate (DSR) was investigated. In patients treated with infliximab, PASI‐75 was 68.4% and DSR was 73.3% by the end of treatment. In patients treated with adalimumab, PASI‐75 was 50.8% and DSR was 79.7%. In patients treated with ustekinumab, PASI‐75 was 63.3% and DSR was 96.7%. Several patients discontinued treatment because of insufficient efficacy due to secondary failure in infliximab or primary failure in adalimumab. To increase treatment efficacy, it will be necessary for these patients to use an additional concomitant treatment. Higher efficacy is expected with biologics than with conventional treatments; however, the actual clinical efficacy over a long period of time may be insufficient if they are used without any concomitant treatments.     

从母婴分离的念珠菌DNA分型研究

目的 探讨念珠菌在母婴间垂直传播的可能途径.方法 采用分子生物学方法,对11对分离于分娩前母亲阴道分泌物及其新生儿口腔并经常规形态学和生化学鉴定为同种念珠菌的母婴分离株,再次进行大亚基rDNA的D1/D2区域DNA序列鉴定.采用电泳核型和随机扩增DNA多态性进行分型研究,以确定是否为同一来源的菌株.结果 11对22株菌,其中8对母婴分离株的16株菌的DNA序列经DDBJ Gene Bank(登录号U45776)搜索与白念珠菌参考株Cal_Y12983具有100%的同源序列,被确认为白念珠菌;另2对的4株菌和1对的2株菌的DNA序列经DDBJ Gene Bank搜索与Cgra_Y65(U44808)和C.krusei Y-5396(U76347)具有100%的同源序列,分别被确认为光滑念珠菌和克柔念珠菌.电泳核型分析,每一对白念珠菌和克柔念珠菌的母婴分离株都具有完全相同的谱带.每一对光滑念珠菌的母婴分离株尽管产生1、2条不同谱带,但仍被认为是来源于同一个体,因为主要谱带是相同的.RAPD DNA带谱分析,对母婴分离株除1对2株菌的DNA谱带略有不同外,其余10对皆具有同样的DNA谱带.结论 1111株婴儿株与其母亲株分子生物学特征完全相同,可认为是经母亲产道垂直传播所致.     

Chemosensitivity tests in colorectal cancer patients

In order to assess the usefulness of chemosensitivity tests in the treatment of colorectal cancer, 71 tumor specimens were tested for chemosensitivity in the following assays: nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA). The agents examined were: mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-diamminedichloroplatinum (CDDP). The evaluability rates were 90.8, 93.9 and 92.3 per cent in NMIA, SRCA and ATPA, respectively, but only 42.9 per cent in HTCA. The tumor response rates were 50.8, 45.2, 16.7 and 33.3 per cent in NMIA, SRCA, HTCA and ATPA, respectively. Individual drug sensitivity rates differed among all 4 assays, ranging from 0 to 33.3 per cent. In the arbitrary judgment of the 4 assays, the most sensitive agent was CDDP, followed by CPM, ADM, 5-FU and MMC. In the prospective study, predictive accuracy rates of the clinical responses were 81.3, 66.7, 100, 100 and 76.5 per cent in NMIA, SRCA, HTCA, ATPA and the arbitrary judgment, respectively. A significant correlation between the survival time and the results of SRCA was detected retrospectively. These results suggested that colorectal cancer might not be completely resistant to anticancer agents, and that chemosensitivity tests might be useful in the individual therapy of colorectal cancer patients.     

A case of postpartum fever caused by Mycoplasma hominis infection

A 26-year-old housewife was admitted to our hospital with a history of high fever after previous cesarean delivery. She had premature rupture of the membrane on the 41st week of pregnancy and the amniotic fluid was found to be cloudy on the fourth day after rupture. Therefore, cesarean delivery was performed. On the first day of operation, her body temperature increased up to 38 degrees C in spite of the treatment with Latamoxef (LMOX), 3 g/day. A sample of intrauterine material yielded M. hominis in pure culture. After administration of Minocycline (MINO) with antimycoplasmal activity, the clinical symptoms improved by the 11th day of operation. Sera obtained after the infection showed antibodies to M. hominis in ELISA study. These results suggested that the cause of this postpartum fever was M. hominis infection.     

Increased dependence on slow filling for left ventricular diastolic filling in patients with coronary artery disease and a depressed systolic function--assessment with radionuclide ventriculography

Contributions of rapid filling, slow filling and atrial systole to the left ventricular (LV) filling volume were analyzed with the use of radionuclide ventriculography at rest, both globally and regionally, in 34 patients with isolated disease of the left anterior descending coronary artery. The patients included 17 with a normal ejection fraction (EF greater than or equal to 50%; group 1) and 17 with a depressed EF (less than 50%; group 2), and the data were compared with those obtained from 13 normal subjects. A computer program subdivided the LV image into 4 regions, and time-activity curves were constructed globally and regionally by reverse-gating from the R wave. In both groups the contribution of rapid filling to the LV filling volume was decreased significantly in the affected septal and apical regions, and in the global left ventricle compared with that in normal subjects. In group 1, the contribution of atrial systole showed an increase in these affected regions and in the global left ventricle. In contrast, in group 2, the atrial contribution was not increased globally or regionally as much as was expected. However, the contribution of slow filling was either increased significantly or tended to increase in the affected regions and in the global left ventricle. There were negative correlations between the contribution of rapid filling and that of slow filling in the global left ventricle (r = -0.73, p less than 0.001) and in each of the septal, apical and lateral regions (r greater than or equal to -0.60, p less than 0.001), which suggested that the contribution of slow filling as well as of atrial systole undergoes an increase as rapid filling is impaired. Thus, in patients with coronary artery disease, the left ventricle relies on slow filling as well as atrial systole to affect diastolic LV filling in the affected regions and in the global left ventricle in the presence of LV systolic dysfunction.     

An autopsy case of Ph1--positive acute lymphoblastic leukemia with disseminated infection of Fusarium solani

A 56-year-old woman with Ph1--Positive acute Lymphoblastic Leukemia was admitted to our hospital for induction chemotherapy in June 1999. The patient was presented with a central scotoma of left eye during treatment course and was given diagnosis of endophthalmitis. Thereafter she also developed skin induration and suffered from serious pneumonia. Amphotericin B administration was started because of high titer of beta-D-glucan, but soon discontinued due to its adverse effect. Blood cultures yielded colonies of fungus and it was identified Fusarium solani. Her general condition deteriorated with progression of pneumonia, and she died of respiratory insufficiency. Autopsy was performed, and its specimen revealed the disseminated infection of Fusarium solani (lung, eye, heart, kidney and skin). We should pay special attention to the fusariosis in Japan also.