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Mechanical Affective Touch Therapy (MATT) is a safe, novel form of noninvasive peripheral nerve stimulation. Although mechanical stimulation activates nerves, we know little about its impact on psychiatric symptoms and their underlying cortical mechanisms. We examined the effects of open-label MATT on resting state functional connectivity (RSFC) and its relationship with anxiety and affective symptomatology (clinical results in separate report).A total of 22 adults with an Axis I anxiety disorder were recruited from the community. After two initial sessions assisted by research staff, participants self-administered 20-minute sessions of MATT at home at least twice daily for four weeks. Self-report measures of mood and anxiety severity were collected at baseline, two weeks, and four weeks. Resting state functional magnetic resonance imaging was collected before the initial MATT session (n = 20), immediately after the first session (n = 18), and following four weeks of MATT (n = 14). Seed-based whole-brain functional connectivity analyses identified brain connectivity patterns correlated with responsiveness to MATT. Seeds were based on Neurosynth meta-analytic maps for "anxiety" and "pain" given MATT's hypothesized role in anxiety symptom amelioration and potential mechanism of action through C-tactile afferents, which play an important role in detecting pain and its affective components. Connectivity results were corrected for multiple comparisons (voxel p 0.005, cluster p-FDR 0.05).Baseline RSFC is predictive of symptom improvement with chronic MATT. Acute increases in insula connectivity were observed between mid-cingulate cortex and postcentral motor regions following the first MATT session. Chronic MATT was associated with increased connectivity between pain and anxiety regions of interest (ROIs) and posterior default mode network (DMN) regions involved in memory and self-reflection; the connectivity changes correlated with decreases in stress and depression symptoms.MATT is associated with alterations in RSFC in the DMN of anxiety disorder patients both acutely and after long-term administration, and baseline RSFC is predictive of post-treatment symptom improvement.

Increased plasma concentrations of apolipoprotein A-IV (apoA-IV) in chronic renal disease suggest a metabolic role of the kidney for this antiatherogenic protein. Therefore, we investigated patients with various forms of proteinuria and found increased serum concentrations of apoA-IV in 124 nephrotic patients compared with 274 controls (mean 21.9 +/- 9.6 vs. 14.4 +/- 4.0 mg/dl; P0.001). Decreasing creatinine clearance showed a strong association with increasing apoA-IV levels. However, serum albumin levels significantly modulated apoA-IV levels in patients with low creatinine clearance, resulting in lower levels of apoA-IV in patients with low compared with high albumin levels (21.4 +/- 8.6 vs. 29.2 +/- 8.4 mg/dl; P = 0.0007). Furthermore, we investigated urinary apoA-IV levels in an additional 66 patients with a wide variety of proteinuria and 30 controls. Especially patients with a tubular type of proteinuria had significantly higher amounts of apoA-IV in urine than those with a pure glomerular type of proteinuria and controls (median 45, 14, and 0.6 ng/mg creatinine, respectively). We confirmed these results in affected members of a family with Dent's disease, who are characterized by an inherited protein reabsorption defect of the proximal tubular system. In summary, our data demonstrate that the increase of apoA-IV caused by renal impairment is significantly modulated by low levels of serum albumin as a measure for the severity of the nephrotic syndrome. From this investigation of apoA-IV in urine as well as earlier immunohistochemical studies, we conclude that apoA-IV is filtered through the normal glomerulus and is subsequently reabsorbed mainly by proximal tubular cells.

Lipoprotein(a)- and low-density lipoprotein–derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy?BackgroundPatients with nephrotic syndrome have the highest lipoprotein(a) [Lp(a)] concentrations known. Lp(a) is an low-density lipoprotein (LDL)-like particle consisting of 45% cholesterol. The usual methods to determine LDL cholesterol do not distinguish between cholesterol derived from LDL and Lp(a) and are thus the net result of cholesterol levels from both lipoproteins. High Lp(a) concentrations therefore significantly contribute to the measured or calculated LDL cholesterol levels. Since statins have no influence on Lp(a) levels, it can be expected that the LDL cholesterol-lowering effect of statins may be diminished in patients who have a pronounced elevation of Lp(a) levels accompanied by only moderate elevations of LDL cholesterol.MethodsWe investigated 207 patients with nondiabetic nephrotic syndrome in whom Lp(a) concentrations were strikingly elevated when compared to 274 controls (60.4 ± 85.4 mg/dL vs. 20.0 ± 32.8 mg/dL, P < 0.0001).ResultsAccording to National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Managing Dyslipidemias, almost 95% of these patients are candidates for a therapeutic intervention to lower LDL cholesterol. LDL cholesterol levels corrected for Lp(a)-derived cholesterol, however, were 27 mg/dL lower than uncorrected concentrations (compared to only 9 mg/dL in controls). If Lp(a)-corrected levels instead of total LDL cholesterol levels were used, 25.7% of patients with low-molecular-weight (LMW) apolipoprotein(a) [apo(a)] isoforms were classified no longer to be in need of LDL cholesterol-lowering therapeutic intervention compared to only 2.3% of patients with high-molecular-weight (HMW) apo(a) phenotypes (P < 0.00001). This (“pseudo”) pharmacogenetic effect results in incorrect determination of LDL cholesterol.ConclusionOur observation has an impact on the indication for, and assessment of efficacy of intervention. This potential artifact should be investigated in ongoing large trials in renal patients as well as in nonrenal African American subjects who have on average markedly higher Lp(a) levels. In nonrenal Caucasian subjects with much lower Lp(a) concentrations, this issue will be less relevant.

STUDY OBJECTIVES: To evaluate an association between catechol-O-methyltransferase (COMT) genotype and subjective daytime sleepiness in patients with Parkinson disease. DESIGN: Structured questionnaire study. SETTING: Tertiary Parkinson disease care center and sleep outpatients' department at the university hospital neurology department. PARTICIPANTS: All nondemented patients with idiopathic Parkinson disease who had been part of a previous study of D4-receptor polymorphisms in 1997 were eligible to participate. From the original sample of 113 patients, 46 participated in the study, 22 met exclusion criteria, and 43 were not available. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: In this study, 46 patients were included (27 men, 19 women; 68.4 +/- 9.9 years of age; symptomatic disease duration, 12.2 +/- 5.2 years; Hoehn and Yahr stage in "on" of 2.6 +/- 0.8). Out of the 46 patients, 13 had LL genotype, 22 LH, and 11 HH. The Epworth Sleepiness Scale scores were 9.5 +/- 4.8 in LL, 8.5 +/- 4.7 in LH, and 6.8 +/- 3.1 in HH (mean +/- SD) (NS). LL and LH were grouped together. The Epworth Sleepiness Scale score was 11 or more in 40% of the LL+LH group, compared to 9.1% of the HH group (P = .039). The levodopa or dopamine-agonist doses and types did not differ between the LL+LH group versus the HH group. CONCLUSIONS: These preliminary data suggest an association of the Lallele and daytime sleepiness in patients with Parkinson disease.

Objective: The neurophysiological assessment of intramedullary spinal cord lesions has been unsatisfactory. Previous studies in patients with syringomyelia suggest that testing of cutaneous silent periods (CSPs) may be useful to assess centromedullary lesions. Methods: The authors studied nine patients with intramedullary spinal cord lesions of different etiologies. Eight patients with cervical lesions presented with hypalgesia, hypothermesthesia, or pain in at least one upper extremity; five of them had also upper limb weakness or sensory impairment. One patient with a thoracic lesion had normal upper limb function. The authors recorded CSPs in abductor pollicis brevis muscle following digit II and digit V stimulation. Somatosensory evoked potentials (SEPs) were obtained following median and tibial nerve stimulation. Motor evoked potentials (MEPs) were obtained in biceps brachii, abductor digiti minimi and tibialis anterior muscles following transcranial magnetic or electrical stimulation. Results: CSP abnormalities were found in all patients with cervical lesions, but not in the patient with a thoracic lesion. Cortical median nerve SEPs had normal latencies in all patients, while tibial nerve SEPs, upper limb MEPs, and lower limb MEPs were delayed in five patients each. In one patient, abnormal CSP were the only neurophysiological finding. CSP abnormalities were associated with hypalgesia and hypothermesthesia in 95% of the studies. Conclusion: Upper extremity CSP testing is a sensitive neurophysiological technique for the assessment of cervical intramedullary lesions. In particular, abnormal CSPs are highly associated with spinothalamic dysfunction.

Patients with idiopathic Parkinson's disease (IPD) are described as having markedly decreased novelty seeking characteristics. Since recent publications suggest an association between the dopamine D4 receptor polymorphism and novelty seeking, we investigated this polymorphism in a group of 122 patients with IPD and 127 healthy control subjects. We found similar allele and genotype frequencies in both groups and no association with the age of onset of symptoms. Therefore, the dopamine D4 receptor polymorphism does not confer genetic susceptibility to IPD and cannot explain the decreased novelty seeking in IPD patients.

Traditional, complementary, and alternative medicine constitutes a major source of health care in developing countries and is also widely utilized, typically by around 50% of the population, in industrialized countries. This extensive use raises important public health questions relating to benefits and detriments, from medical, financial, and social perspectives. Investment in research is increasing, and some evidence-based clinical guidance is now available. National policies and legislation are being developed in many countries and often include partnerships between biomedical and traditional health practitioners. Social, cultural, economic, and health services dimensions for evaluation of priorities for public health actions are discussed.

In the KORA surveys, numerous candidate genes in the context of type 2 diabetes, myocardial infarction, atherosclerosis or obesity are under investigation. Current focus is on genotyping single nucleotide polymorphism (SNPs). Haplotypes are also of increasing interest: haplotypes are combinations of alleles within a certain section of one chromosome. Analysing haplotypes in genetic association studies is often more efficient than studying the SNPs separately. A statistical problem in this context is the reconstruction of the phase: genotyping the SNPs determines the alleles of an individual at one particular locus of the DNA, but does not reveal which allele is located on which one of the two chromosomes. This information is required when talking about haplotypes. There are statistical approaches to identify the most likely two haplotypes of an individual given the genotypes. However, a certain error in prognosis is unavoidable. There are also errors in the genotypes. These errors are assumed to be small for one SNP but can accumulate over the SNPs involved in one haplotype and thus can induce further uncertainty in the haplotype. It is therefore the aim of our project to quantify the uncertainties in the haplotypes particularly for genes investigated in the KORA surveys. We conduct computer simulations based on the haplotypes and their frequencies observed in the KORA individuals and compare the results with simulations based on mathematical modelling of the evolutionary process ("coalescent models"). The uncertainties in the haplotypes have an impact on the search for association between genes and disease: an association may not be detected as the haplotype uncertainty obscures the haplotype frequency differences between cases and controls. It is a further aim of our project to elucidate the extent of this problem and to develop strategies for reducing it.

The apolipoprotein(a) size polymorphism is associated with nephrotic syndrome.MethodsThe atherogenic serum lipoprotein(a) [Lp(a)] is significantly elevated in patients with nephrotic syndrome. The underlying mechanism for this elevation is poorly understood.MethodsWe investigated in 207 patients with nondiabetic nephrotic syndrome and 274 controls whether the apolipoprotein(a) [apo(a)] kringle-IV repeat polymorphism explains the elevated Lp(a) levels in these patients.ResultsPatients showed a tremendous elevation of Lp(a) concentrations when compared to controls (mean 60.4 vs. 20.0mg/dL and median 29.8 vs. 6.4mg/dL, P < 0.0001). Primary and secondary causes contributed to this elevation. The primary causes became apparent by a markedly elevated number of low-molecular-weight apo(a) phenotypes which are usually associated with high Lp(a) levels. This frequency was 35.7% in patients compared to only 24.8% in controls (P = 0.009). In addition, secondary causes by the pathogenetic mechanisms of the nephrotic syndrome itself resulted in a different increase of Lp(a) in the various apo(a) isoform groups. Based on the measured Lp(a) concentrations in each subject, we calculated separately the Lp(a) concentrations arising from the two expressed isoforms by estimating the relative proportion of the two serum isoforms in the sodium dodecyl sulfate (SDS) agarose gel electrophoresis. Low-molecular-weight isoforms were associated with 40% to 75% elevated Lp(a) concentrations when compared to matched isoforms from controls. High-molecular-weight apo(a) isoforms showed 100% to 500% elevated Lp(a) levels compared to matched isoforms from controls. The severity of the nephrotic syndrome as well as the degree of renal impairment did not influence the Lp(a) concentrations.ConclusionThe tremendously increased Lp(a) levels in nephrotic syndrome ar caused by primary genetic as well as disease-related mechanisms.

Lipoprotein(a) is a highly atherogenic particle. The plasma concentrations of this lipoprotein are strongly related to a genetically determined size polymorphism of apolipoprotein(a). This article reviews some pathogenetic characteristics of the apolipoprotein(a) polymorphism besides its known effect on the lipoprotein(a) plasma concentrations. Those are the relation of the apolipoprotein(a) phenotype with atherogenesis, the apolipoprotein(a) phenotype-specific elevation of lipoprotein(a) in hemodialysis patients and the advantages of this polymorphism for the atherosclerosis risk evaluation in high-risk patients. It furthermore discusses the observed association between the low molecular weight apolipoprotein(a) phenotype and Type I diabetes mellitus.

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.

Background: Activation of distinct muscle groups organized in a stereotyped manner (“muscle synergies”) is thought to underlie the production of movement by the vertebrate spinal cord. This results in movement with minimum effort and maximum efficiency. The question of how the vertebrate nervous system inhibits ongoing muscle activity is central to the study of the neural control of movement. Objective: To investigate the strategy used by the human spinal cord to rapidly inhibit muscle activation in the upper limb. Methods: The authors performed a series of experiments in 10 healthy subjects to assess the effect of nociceptive cutaneous stimulation on voluntarily contracting upper limb muscles. They recorded the electromyogram (EMG) with surface electrodes placed over various upper limb muscles. Results: The authors found evidence of a simple inhibitory strategy that 1) was dependent on the intensity of the stimulus, 2) was maximally evoked when stimulation was applied to the fingertips, 3) preceded the earliest onset of voluntary muscle relaxation, and 4) produced inhibition of EMG activity in specific upper limb muscle groups. Nociceptive fingertip stimulation preferentially inhibited contraction of synergistic muscles involved in reaching and grasping (intrinsic hand muscles, forearm flexors, triceps) while having little effect on biceps or deltoid. Conclusions: Neural circuitry within the human spinal cord is organized to inhibit movement by rapidly deactivating muscles that constitute distinct muscle synergies. This strategy of selective and concurrent deactivation of the same basic elements that produce synergistic movement greatly simplifies motor control.

Recent evidence suggests that at least one cancer patient in three uses some form of complementary and alternative medicine (CAM). We conducted a review of the published research on the efficacy of these treatments for breast cancer, which resulted in some observations about the current state of research and guidelines for future research. Although many of the papers reported encouraging results, the preponderance of phase I and II trials and other limitations precluded definitive conclusions about the efficacy of the treatments reported in these studies. A growing institutional base in this country has begun to facilitate improved research on CAM for cancer, yet many gaps remain. For example, there are no published reports of clinical trials or observational studies with survival endpoints for treatment agents used by many cancer patients. Clinical trials of a few CAM treatments are now in progress, but the results will not be available for several years. More complex and customized treatments may require innovative study designs and practitioner-investigator collaborations. Given the mounting evidence that CAM treatments are biologically active as well as widely used, CAM research may affect cancer outcomes.

To explore the use of complementary and alternative medicine (CAM) among African-American and Hispanic women residing in New York City, including use of specific treatments and practitioners, perceived effectiveness of CAM, and culturally specific words or expressions for CAM.Focus groups were conducted with two groups of African-American and two groups of Hispanic women (age 18-40 and 41-80) as preparation for the development of a quantitative instrument to assess the prevalence and determinants of CAM use among women of various ethnic backgrounds. Participants were recruited using a standard random digit dial procedure.The most commonly used CAM remedies were teas and herbs, vitamins and nutritional supplements, prayer and spiritual healing, meditation and relaxation techniques. Practitioners most frequently seen were chiropractors, herbalists, and acupuncturists. Use of alternative remedies and practitioners, particularly the latter, was most common among older women in both groups. Younger Hispanic women reported the most skepticism toward CAM, especially when it was used by relatives as a substitute for conventional medical care. Overall, these African-American and Hispanic women used CAM for a wide range of health conditions and for prevention. Few racial and ethnic differences emerged in patterns of CAM use for either self-care or treatment by practitioners, but there was a distinct age variation, especially in attitudes toward CAM.

Women in the United States are increasingly turning to botanical medicines to treat conditions throughout their life cycles. Many herbs traditionally used for women's health conditions have been found to contain phytoestrogens. Phytoestrogens and their metabolites can bind estrogen receptors and can have both estrogenic and anti-estrogenic effects. Many women are attracted to the idea of using phytomedicine as an alternative to hormone replacement therapy. It is unclear, however, whether these herbs are safe for women at risk for breast cancer or its recurrence. This paper considers the estrogenicity of herbs such as black cohosh (Cimicifuga racemosa) and the implications for women's health.

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).

Lipoprotein(a) (Lp(a)) is a complex in human plasma assembled from low-density lipoprotein (LDL) and apolipoprotein(a) (apo(a)). High plasma concentrations of Lp(a) are a risk factor for coronary heart disease (CHD) in particular in patients with concomitant elevation of LDL. We have analysed for elevated Lp(a) levels in patients with familial hypercholesterolaemia (FH), a condition caused by mutations in the LDL receptor (LDLR) gene and characterised by high LDL, xanthomatosis and premature CHD. To avoid possible confusion by the apo(a) gene which is the major quantitative trait locus controlling Lp(a) in the population at large, we used a sib pair approach based on genotype information for both the LDLR and the apo(a) gene. We analysed 367 family members of 30 South African and 30 French Canadian index patients with FH for LDLR mutations and for apo(a) genotype. Three lines of evidence showed a significant effect of FH on Lp(a) levels: (1) Lp(a) values were significantly higher in FH individuals compared to non-FH relatives (p0.001), although the distribution of apo(a) alleles was not different in the two groups; (2) comparison of Lp(a) concentrations in 28 sib pairs, identical by descent (i.b.d.) at the apo(a) locus but non-identical for LDLR status, extracted from this large sample demonstrated significantly elevated Lp(a) concentrations in sibs with FH (p0.001); (3) single i.b.d. apo(a) alleles were associated with significantly higher Lp(a) concentrations (p0.0001) in FH than non-FH family members. Variability in associated Lp(a) levels also depended on FH status and was highest when i.b.d. alleles were present in FH subjects and lowest when present in non-FH individuals. The study demonstrates that sib pair analysis makes it possible to detect the effect of a minor gene in the presence of the effect of a major gene. Given the interactive effect of elevated LDL and high Lp(a) on CHD risk our data suggest that elevated Lp(a) may add to the CHD risk in FH subjects.

Lipoprotein(a) [Lp(a)] and its characteristic glycoprotein apolipoprotein(a) [apo(a)] are risk factors for atherosclerosis in the general population. Patients with renal disease show an elevation of Lp(a). Recent studies have described an arteriovenous difference of Lp(a) in the renovascular bed as well as the plasma-derived fragmented LDL-unbound apo(a) in urine, suggesting that the kidney is involved in the metabolism of Lp(a). We therefore investigated whether patients with chronic renal failure have higher levels of LDL-unbound apo(a) and whether this could account for the increased Lp(a) concentrations in these patients. In addition, we studied the possible generation of apo(a) fragments in vitro by mimicking uremic plasma conditions and by investigating the assembly of Lp(a) in cell culture experiments. Patients treated by hemodialysis (N = 185) and by continuous ambulatory peritoneal dialysis (CAPD; N = 20) had markedly elevated absolute (1.22 +/- 1.55 mg/dl and 2.14 +/- 2.86 mg/dl) as well as relative (7.5% and 7.3%) amounts of LDL-unbound apo(a) in comparison to controls (0.46 +/- 0.48 mg/dl or 4.5%). Following renal transplantation the absolute amount decreased significantly. Lp(a) plasma concentration was the most important determining variable for the absolute amount of LDL-unbound apo(a) and showed a positive correlation in both hemodialysis patients (r = 0.85) and controls (r = 0.92). In vitro experiments demonstrated that "uremization" of plasma samples did not generate a higher amount of LDL-unbound apo(a). Although LDL of renal patients has different chemical and structural properties as compared to control LDL, the extracellular assembly of Lp(a) did not differ between patients and controls. Therefore, the higher amounts of LDL-unbound apo(a) found in renal disease are not caused by an impaired assembly of Lp(a), but rather indicate a catabolic role of the kidney for LDL-unbound apo(a) as was already shown for Lp(a). Despite a small contribution, these elevated levels cannot explain the higher Lp(a) values found in patients with end-stage renal disease.

We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.

A soluble form of intercellular adhesion molecule-1 (sICAM-1) has been described in serum and other body fluids. In order to determine whether sICAM-1 in serum and urine is a useful marker of inflammatory activity in kidney diseases we measured sICAM-1 in serum and urine of fifty patients who underwent renal biopsy, and of twenty healthy individuals. Expression of ICAM-1 on proximal tubular epithelial cells was investigated by immunohistochemistry. Soluble ICAM-1 in serum did not differ between patients and controls (354 +/- 129 ng/ml vs. 305 +/- 52 ng/ml). By multiple regression analysis sICAM-1 correlated with tubular expression of ICAM-1 (p0.01), but not with serum creatinine, infiltrating leukocytes, urinary ICAM-1 or proteinuria. In healthy controls mean urinary ICAM-1/cr was 2.5 +/- 3.0 ng/mg creatinine and differed significantly from that of patients (14.5 +/- 14.9 ng/mg) (p0.005). Patients with minimal-change disease had the highest uICAM-1 levels. The ratio of urinary ICAM-1 and proteinuria was remarkably constant in all patients with 6.0 +/- 0.9 ng/mg. By multiple regression analysis uICAM-1/cr correlated with proteinuria/cr (p0.001) and sICAM-1 (p0.005). These data show that sICAM-1 does to some degree reflect ICAM-1 expression in the kidney, whereas uICAM-1 is derived from glomerular filtration and closely parallels proteinuria. Both sICAM-1 and uICAM-1 are not useful to estimate ICAM-1 expression and inflammatory activity in the kidney.

Lipoprotein disorders are considered an important cause for the high cardiovascular morbidity and mortality in patients with end-stage renal disease and following renal transplantation. This article reviews the disease-associated changes of lipids and lipoproteins in these patients and, where known, the underlying causes and mechanisms. Further, we discuss the perturbed lipoprotein system in relation to the cardiovascular risk of patients on renal replacement therapy. Patients treated by hemodialysis are often hypertriglyceridemic with increased very low density lipoprotein (VLDL) levels and a type IV Frederickson pattern of hyperlipidemia. Total and LDL cholesterol concentrations are usually normal or subnormal. Treatment of end-stage renal disease by peritoneal dialysis results in increased total, VLDL and LDL cholesterol concentrations. Both treatment modalities are accompanied by a decrease of high density lipoprotein (HDL) cholesterol and apolipoprotein AI, whereas lipoprotein(a) [Lp(a)] concentrations are significantly elevated in both groups. Following renal transplantation a high incidence of hypercholesterolemia and hypertrigylceridemia is observed, which is attributed, at least in part, to the immunosuppressive therapy. Most patients normalize HDL cholesterol values and Lp(a) decreases to pre-disease plasma concentrations. Several studies have described elevated levels of cholesterol, triglycerides and Lp(a) in patients with cardiovascular complications during different phases of renal replacement therapy, which indicates a predictive (causative) role of these parameters for atherosclerotic diseases.

Recent studies have indicated a beneficial effect of one particular low molecular weight heparin preparation (Fragmin) on lipid metabolism in patients on chronic hemodialysis as compared to unfractionated heparin. We conducted a prospective crossover study with paired comparison of two different anticoagulant agents to examine the effects of a recently released new low molecular weight heparin (Sandoparin) on lipid and lipoprotein parameters in 24 patients starting hemodialysis. During the first six months of observation patients received Sandoparin. Then patients were switched to unfractionated heparin and observed for further six months. After switching from Sandoparin to unfractionated heparin we observed significant decreases in total cholesterol (from 168.6 +/- 42.2 to 154.4 +/- 41.9 mg/dl, p0.02), LDL cholesterol (from 106.4 +/- 35.2 to 89.9 +/- 32.3 mg/dl, p0.005), triglycerides (from 148.7 +/- 85.0 to 121.4 +/- 88.8 mg/dl, p0.05) and apolipoprotein B (from 100.0 +/- 35.3 to 89.9 +/- 30.4 mg/dl, p0.05) and a significant increase in HDL cholesterol (from 32.8 +/- 12.5 to 37.7 +/- 17.5 mg/dl, p0.02). This is in contrast to earlier results and can possibly be explained by a higher percentage of fractions with high M(r) in the investigated Sandoparin, which results in a more pronounced depletion of lipoprotein lipase. Together with the enhanced hepatic clearance of lipoprotein lipase induced by low molecular weight heparins, this may decrease lipoprotein lipase activity with a subsequent increase in plasma triglycerides, total and LDL cholesterol. We conclude from our data that a general recommendation for clinical use of low molecular weight heparin in hemodialysis patients cannot be given.

Summary The activity of jaw elevator muscles (masseter and anterior temporal muscle) was studied by surface electromyography in 17 patients wearing complete dentures with anterior-canine guidance. Baseline electromyography was recorded with the dentures and compared to recordings obtained with two different splints adapted to the upper denture, one providing anterior guidance leading to immediate disclusion of the posterior teeth during any jaw movement, the other providing posterior guidance buccally on the working side and lingually on the non-working side (bilaterally balanced occlusion). Recordings were obtained during a sequence of different jaw movements: postural position, maximal tooth contact in intercuspal position, protrusive movement of the mandible (under tooth contact) and during lateral excursions, also carried out under tooth contact. Muscle activity was not significantly different as recorded with dentures only versus with the splints providing anterior guidance. However, a significant increase in activity was observed with bilaterally balanced occlusion. The results of this study in edentulous people are similar to those found in patients with natural teeth.