Relationship of periodic leg movements and severity of restless legs syndrome: a study in unmedicated and medicated patients.

OBJECTIVE: To evaluate the relationship of the severity of restless legs syndrome (RLS) as assessed by a subjective, patient-rated scale (International RLS Study Group Rating Scale, IRLS), and of periodic leg movements in sleep (PLMS) as an objective parameter, in two different patient populations. METHODS: Data of 200 unmedicated patients with idiopathic RLS were evaluated. Group 1 (n=100) consisted of selected patients participating in the Pergolide European Australian RLS (PEARLS) study. Group 2 (n=100) represented an outpatient RLS population investigated in a Sleep Disorders Center. Additionally, Group 1 was also evaluated after a 6 week double-blind treatment period, where 47 patients received pergolide and 53 patients placebo. RESULTS: In unmedicated patients, IRLS scores correlated with the PLMS-arousal index (r=0.22, p=0.033) but not with the PLMS index in Group 1 while no correlation was found in Group 2. The change of the IRLS score under treatment in Group 1 correlated significantly both with the change of the PLMS index (r=0.42, p<0.001) and the change of the PLMS-arousal index (r=0.38, p<0.001). CONCLUSIONS: The IRLS adequately reflects treatment changes of PLMS indices. In unmedicated patients, the IRLS correlates with PLMS indices probably only in selected RLS populations with predefined PSG criteria and high PLM activity. SIGNIFICANCE: The IRLS is an appropriate subjective rating scale for measuring treatment effects in RLS.     

Isolated human hepatocytes in culture display markedly different gene expression patterns depending on attachment status

In vitro human hepatocyte cultures are a key tool in the investigation of xenobiotic toxicity and metabolism. In most in vitro hepatocyte studies, the cells are allowed to adhere to an extracellular matrix, such as collagen. Unfortunately, the ability of freshly isolated hepatocytes to adhere to collagen varies from donor to donor. We used microarray analysis to determine what gene expression differences exist between hepatocytes in suspension and hepatocytes attached to collagen. Results from different donors showed a considerable difference in gene expression patterns between the two hepatocyte populations. In addition, we also compared the gene expression profiles of hepatocytes in culture with liver tissue. The results showed that both hepatocytes in suspension and hepatocytes attached to collagen display significant gene expression differences compared with liver tissue. Finally, we show that both populations of hepatocytes are responsive to dexamethasone and regulate some of the same genes. Overall, our results suggest that either significant gene expression changes occur in isolated hepatocytes or that suspended and attached cells represent different populations of hepatocytes found in intact livers.     

Microalbuminuria and nerve conduction velocity in type-I diabetics during conventional therapy and during continuous I.V. insulin infusion

Summary The objective of this study was to follow the development of microalbuminuria and nerve conduction velocity under continuous i.v. insulin therapy over a limited period of 4 months. For this purpose, 8 labile type I diabetics were selected (age 33±8 years, duration of diabetes 16±9 years) and treated conventionally with two insulin injections daily over 4 months. Afterwards, the same patients were treated with continuous i.v. insulin infusion and finally again with two injections daily over 4 months each. This procedure allowed each diabetic to serve as his own control. HbA₁, microalbuminuria, nerve conduction velocity and relative refractory period of the ulnar nerve were checked at montly intervals. During the continuous i.v. infusion over 4 months, blood sugar values were significantly lower, glucosuria had disappeared almost completely and the glycosylated hemoglobin had fallen to near normal values. The mean rate of albumin excretion was 16±5 μg/min at rest and 76±26 μg/min during exercise (normal: 3.9±0.4 and 4.8±1.2 μg/min, respectively) and did not change significantly. Nerve conduction velocity in the ulnar nerve rose significantly under i.v. insulin therapy from 47.9±0.6 m/sec to 52±0.6 m/sec. Similarly, the relative refractory period of the same nerve fell significantly from 3.7±0.2 to 1.9±0.1 msec (i.e. to within normal range). It is concluded that functional disturbances of peripheral nerve can regress by improved blood sugar control with continuous i.v. insulin infusion over 4 months. On the other hand, incipient microangiopathy measured as microalbuminuria remains unchanged over the same period of time. If an improvement is at all possible, considerably longer periods of euglycemia are likely to be necessary. Supported by Grant No. 3.964-0.80 from the Swiss National Science Foundation.     

Trehalose dimycolate enhances resistance to infection in neutropenic animals.

Bacterial infections are lethal complications of neutropenia, and antibiotics alone are inadequate therapy for these infections. Irradiated mice become severely neutropenic and remain susceptible to infection for 2 to 3 weeks, depending on the dose and quality of radiation. Some bacterial cell wall derivatives stimulate nonspecific host defense mechanisms against a variety of microbes which might cause postirradiation infection. In this study we determined if the cell wall glycolipid trehalose dimycolate (TDM), derived from Mycobacterium phlei, or a synthetic preparation of TDM was able to (i) enhance survival in mice when given before or after lethal doses of 60Co radiation and (ii) increase nonspecific resistance to postirradiation infection. Treatment with TDM oil-in-water emulsions and with synthetic TDM significantly enhanced survival before and after lethal doses of 60Co irradiation. This result correlated with the ability of TDM to reduce the translocation of intestinal bacteria and to stimulate hematopoiesis. With respect to nonspecific resistance to infection, TDM injected 1 h after sublethal irradiation increased resistance to a lethal Klebsiella pneumoniae challenge (10 50% lethal doses of K. pneumoniae in 30 days [LD50/30]) 4 or 14 days later. Increasing the dose of K. pneumoniae to 5,000 LD50/30 on day 4 overwhelmed the ability of TDM-treated mice to overcome infection. However, TDM treatment 1 h postirradiation combined with ceftriaxone antibiotic therapy (days 5 through 14) enhanced survival, even when the higher dose of bacteria (5,000 LD50/30) was used. These results indicate that in irradiated mice, TDM can be used to enhance survival and, as a potent stimulant of nonspecific resistance to infection in neutropenic mice, can act synergistically with antibiotic therapy to reduce sepsis and mortality.     

Intra-observer and inter-observer agreement of the manual examination of the lumbar spine in chronic low-back pain

Examination is a cornerstone in the manual procedures leading to mobilisation/manipulation of the low back. The observer variation of the more specific segmental tests remains to be investigated. Two skilled specialists in manual medicine examined the segmental changes in the lumbar spine. The patients were unknown to the examiners and no information of the case history was given. All test results were recorded by an observer present in the room who ensured that no conversation was allowed during the examination. The primary outcome measures were the kappa values for each test. The matching was defined as acceptable (acc) within two neighbouring levels and perfect (per) on the same level. Intra-observer variation (tested in 33 patients and 10 subjects without low-back pain): The agreement between first and second segmental diagnosis examination was 70% (per) and 82% (per + acc). Kappa values were: segmental diagnosis 0.60 (per) and 0.70 (per + acc), multifidus test 0.51 (per) and 0.60 (per + acc), sideflexion 0.57 (per) and 0.69 (per + acc), and ventral flexion 0.31 (per) and 0.45 (per + acc). Inter-observer variation (tested in 60 patients): The agreement for segmental diagnosis between the examiner A and B was 42% (per) and 75% (per + acc). Kappa values were: segmental diagnosis 0.21 (per) and 0.57 (acc), multifidus test 0.12 (per) and 0.48 (acc), sideflexion 0.22 (per) and 0.45 (acc), and ventralflexion 0.22 (per) and 0.44 (acc). By manual tests, skilled examiners seem to be able to diagnose segmental dysfunctions in the low back. The clinical implication of these dysfunctions remains to be clarified.     

Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

In vivo gene transfer: focus on the kidney

Renal gene transfer techniques are being developed as a novelexperimental approach to understand the pathogenesis of renaldisease and to potentially develop new therapeutic tools. Wereview the currently available technology to introduce foreigngenetic material into renal tissue, i.e., retroviral, adenoviral,and liposomal transfer systems with their respective advantagesand caveats. Today, the transfer efficiency of these methodsappears to be sufficiently high to study the effects of transducedgenes on renal function and morphology in rat kidney. This willallow (i) the elucidation of the function of genes on the courseof renal disease in experimental animal models and (ii) themodulation of local expression of endogenous genes which presumptivelycontribute to renal pathology in these models. One strategyto accomplish this aim is the use of recombinant DNA technologyto design antisense DNA constructs or oligonucleotides, whichinterfere with the renal expression of target genes. We willalso discuss some of the shortcomings of the currently usedtechniques with respect to potential therapeutic use of genetransfer systems and gene modulation.     

Gallstone recurrence after direct contact dissolution with methyltert-butyl ether

To determine the rate and characteristics of gallstone recurrence after direct contact dissolution with methyltert-butyl ether, 60 consecutive patients were followed for up to 4.5 years (median 2.2 years) after complete disappearance of all stone residues and debris and cessation of adjuvant bile acid therapy. Initial gallstones had been multiple in all but four patients. Twenty-eight of the 60 patients developed recurrent gallstones. The cumulative risk of gallstone recurrence (actuarial analysis) was 23±6%, 34±7%, 55±8%, and 70±9% at one, two, three, and four years, respectively. The recurrent stones were usually multiple and small (6±4 mm). Gallstone recurrence was associated with recurrent biliary pain in two patients, one of whom developed acute cholecystitis. Recurrent stones were cleared completely by bile acid medication with or without shock-wave lithotripsy in 61±15% of patients at one year (actuarial analysis). In conclusion, gallstone recurrence after successful contact dissolution of multiple stones with methyltert-butyl ether has to be expected in a high percentage of patients. Most patients, however, remain free of biliary pain during long-term follow-up.     

Velocity profiles in the ascending aorta in pigs: Axial development and influence of changes in left ventricular contraction pattern

Summary Earlier studies using hot-film anemometry in pigs have revealed skewed tangentially rotating velocity profiles in the ascending aorta during systole. The reason for this phenomenon has been postulated to be caused by the left ventricular contraction pattern. Therefore, the aim of this study was to investigate the influence of the left ventricular contraction pattern on the velocity fields in the ascending aorta of pigs. We used a 10 MHz perivascular pulsed Doppler ultrasound system to measure point blood velocities at two axial locations over the entire cross sectional area in the ascending aorta of 90 kg pigs. The axial component of the velocity profiles was visualized dynamically by computerized 3-dimensional animation techniques. Changing left ventricular contraction patterns were accomplished by reversible occlusion of either the left anterior descending or right posterior descending coronary artery. The axial development of the systolic rotating and skewed velocity profiles in the ascending aorta was described. The appearance of the systolic velocity profiles were virtually unaffected by changes in left ventricular contraction pattern.This study was kindly supported by The Danish Heart Foundation, Civilingeniør Frode Nyegaard og Hustru's Fond and NOVO's Forskningsfond     

Vigilance--a state of order or a force that produces order?

The variety of meanings nowadays attached to the notion of "vigilance" essentially mask H. Head's original intentions when he introduced the term more than half a century ago. In an attempt to overcome the obviously existing disturbance in scientific communication, we contrast the new meanings, both with each other and with Head's original conception. We also discuss the importance of "vigilance" as a precursor of a current change of paradigms. We conclude that the original intention of "vigilance" is in line with recently elaborated proposals stressing the self-referential character of living systems. This revised notion of "vigilance" might serve as a conceptual base for empirical research taking self-reference into consideration, and hence for biological research in the true sense of the word.