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Biomedical subjects

M Reif

Publications and source records attributed to M Reif.

17 recordsLinked to original sources

Size-dependent magnetism of deposited small iron clusters studied by x-ray magnetic circular dichroism.

The size-dependent magnetic properties of small iron clusters deposited on ultrathin nickel films have been studied with circularly polarized synchrotron radiation. With the use of sum rules, orbital and spin magnetic moments have been extracted from x-ray magnetic circular dichroism spectra. The ratio of orbital to spin magnetic moments varies considerably with cluster size, reflecting the dependence of magnetic properties on cluster size and geometry. These variations can be explained in terms of enhanced orbital moments in small clusters.

Journal Article↗

Safety, tolerability, and efficacy of orally administered cannabinoids in MS.

The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression.

Administration, Oral↗

Molecular physiology of urinary concentration defect in elderly population.

It is estimated that by the year 2050 one in five Americans will be 65 years or older. This mandates the growing need for clinical and basic research in the field of geriatric medicine to understand age-related maladies. The most prominent abnormality in renal function in the aging population is the inability to handle water, frequently resulting in hypo- or hyperosmolar states, and the associated electrolyte imbalances. During the past decade, thanks to the advent of powerful molecular techniques, rapid strides have been made in the approaches employed to understand and dissect the physiology of renal function in general and the urinary concentration mechanism in particular. Using an integrated approach of clinical observations, experimental model systems, molecular analysis, and functional genomics, a more comprehensive picture of the interplay of physiological systems in the genesis of urinary concentration defect in the elderly is beginning to emerge. Much remains to be deciphered regarding the complex interactions between the role of environment, genetics, diet, pharmacological agents and the general effects of aging on kidney function. The emerging importance of socio-economic and quality of life issues surrounding geriatric medicine encourage public and private support and funding for research in the area of age-related diseases, especially as they are related to the kidney.

Aged↗

[Results of a standardized survey on the medical use of cannabis products in the German-speaking area].

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications.

Adolescent↗

Tolerability of an extract of European mistletoe among immunocompromised and healthy individuals.

CONTEXT: European mistletoe (Viscum album L) has been used parenterally for more than 80 years as an anticancer medication with significant immunomodulating action. Since 1984, clinical experience with a Viscum album extract (Viscum album Quercus Frischsaft [Qu FrF]) among HIV-positive patients has suggested that it inhibits HIV disease progression. OBJECTIVE: To determine the toxicity profile and biochemical effects of a Viscum album extract. DESIGN: A dose-escalating phase I/II study. PATIENTS: 32 HIV-positive and 9 healthy participants. INTERVENTION: Standardized for its lectin and viscotoxin content, the extract was administered subcutaneously twice weekly in gradually increasing doses for 2 to 17 weeks per dose increase. Doses of 0.01 mg to 10.0 mg were administered. MAIN OUTCOME MEASURES: Adverse events, hematology, and biochemistry. RESULTS: No severe side effects were found. During gradual dose escalation, more adverse events occurred at the lower dose range. The hazard rate of systemic adverse events was highest among HIV-positive patients. Drug-related adverse events were flu-like symptoms and transient exacerbations of gingivitis, fever, and eosinophilia. An increase of serum urea nitrogen and serum creatinine levels occurred, as did a slight decrease in total protein caused by a minor fall in albumin concentrations. Dose dependence was apparent for inflammation and fever, which may or may not have been side effects of the preparation. CONCLUSIONS: Viscum album Qu FrF can be administered safely to HIV-positive patients. It induces immunomodulation in HIV-positive and healthy individuals and may inhibit the progression of HIV disease.

Adolescent↗

Effects of candesartan cilexetil in patients with systemic hypertension. Candesartan Cilexetil Study Investigators.

The objectives of this double-blind, multicenter, randomized, parallel-arm, placebo-controlled study were to evaluate the dose-related efficacy, tolerability, and safety of candesartan cilexetil, a potent, AT1 selective, long-acting angiotensin II receptor blocker, in 365 adult patients with systemic hypertension and mean sitting diastolic blood pressure (BP) of 95 to 114 mm Hg. Patients received either placebo or candesartan cilexetil 2, 4, 8, 16, or 32 mg once daily for 8 weeks. All doses of candesartan cilexetil reduced trough (24 hours after treatment) sitting diastolic and systolic BP significantly compared with placebo (p < 0.005). A significant (p < or = 0.0001) dose response was evident, with greater decreases in BP at higher doses. Mean changes in BP were -10.7/-7.8 mm Hg and -12.6/-10.2 mm Hg in the 16- and 32-mg groups, respectively, versus -0.3/-2.6 mm Hg in the placebo group. The 16- and 32-mg doses were consistently significantly superior to placebo in antihypertensive effect with regard to all BP measurements, including peak (6 hours after treatment), trough, sitting, and standing measurements of diastolic and systolic BP. Responder rates (trough sitting diastolic BP < 90 or > or = 10 mm Hg BP decrease) were 54% and 64% for the 16- and 32-mg groups, respectively. Tolerability and safety profiles were similar to placebo at all doses. In conclusion, candesartan cilexetil administered once daily effectively reduces BP in a dose-related manner while maintaining safety and tolerability; doses of 16 and 32 mg are most effective for treatment of hypertension.

Adult↗

Genetic markers at the leptin (OB) locus are not significantly linked to hypertension in African Americans.

Increased body mass index (BMI) has been correlated with increased blood pressure in human populations. To examine the role of the leptin gene (OB) in essential hypertension in African Americans, we performed affected sib pair analysis on a set of 103 hypertensive African American sibships using four highly polymorphic markers at the human leptin locus. No evidence of linkage was detected between these markers and the phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI > or = 85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found significant linkage for the marker D7S504 (P=0.029) but not for the other markers. Significance strengthened in the overweight subset of sibships for this marker (P=0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and the leptin locus did not demonstrate a statistically significant relationship. Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. These results suggest that the OB gene is not a major contributor to the phenotype of essential hypertension in African Americans, although a minor contribution to the phenotype of extreme obesity in this group cannot be ruled out.

Adipose Tissue↗

Loss of protein kinase C inhibition in the beta-T594M variant of the amiloride-sensitive Na+ channel.

We previously reported the presence of a novel variant (beta-T594M) of the amiloride-sensitive Na+ channel (ASSC) in which the threonine residue at position 594 in the beta-subunit has been replaced by a methionine residue. Electrophysiological studies of the ASSC on Epstein-Barr virus (EBV)-transformed lymphocytes carrying this variant showed that the 8-(4-chlorophenylthio) adenosine 3':5'-cyclic monophosphate (8cpt-cAMP)-induced responses were enhanced when compared to wild-type EBV-transformed lymphocytes. Furthermore, in wild-type EBV-transformed cells, the 8cpt-cAMP-induced response was totally blocked by the phorbol ester, phorbol 12-myristate 13-acetate (PMA). This inhibitory effect of PMA was blocked by a protein kinase C inhibitor, chelerythrine. We now have identified individuals who are homozygous for this variant, and showed that PMA had no effect on the 8cpt-cAMP-induced responses in the EBV-transformed lymphocytes from such individuals. Cells heterozygous for this variant showed mixed responses to PMA, with the majority of cells partially inhibited by PMA. Our results demonstrate that an alteration in a single amino acid residue in the beta-subunit of the ASSC can lead to a total loss of inhibition to PMA, and establish the beta-subunit as having an important role in conferring a regulatory effect on the ASSC of lymphocytes.

Amiloride↗

Nocturnal blood pressure in treated hypertensive African Americans Compared to treated hypertensive European Americans.

Previous studies have shown that African Americans (blacks) tend to have higher nocturnal blood pressure than European Americans (whites). The study presented here was undertaken to determine whether treatment of hypertension influences nocturnal blood pressure differently in blacks than in whites. To answer this question, this study measured nocturnal blood pressure by ambulatory blood pressure monitoring (ABPM) in treated hypertensive blacks and whites whose daytime blood pressures were comparable. Inclusion criteria for this study were: diagnosis of essential hypertension, absence of renal failure, and documentation of antihypertensive therapy, diabetic status, proteinuria status, and body weight. All of the black patients in our programs who underwent ABPM and met the above criteria were included in this study. White patients were included on the basis of having the same inclusion criteria as blacks and showing, by ABPM, daytime mean arterial pressure (MAP) in the same range as that of the blacks selected for this study. The results of nocturnal blood pressure were unknown to the investigators when the patients were selected for this study. In the blacks (N = 62) and whites (N = 72) selected for study, the mean daytime (0600 to 2200 h) MAP was 107 +/- 1 SE mm Hg for both the black and white cohorts. To assess nocturnal blood pressure, the period from 0100 to 0500 h was chosen because it likely encompassed an interval of sleep, which is associated with the nadir of nocturnal blood pressure. This interval was termed 0100 to 0500 h, "middle night." Mean middle night MAP was 97 +/- 12 mm Hg in blacks versus 90 +/- 14 mm Hg in whites (P < 0.006, unpaired t test). The greater middle night MAP in blacks compared with whites was a result of the higher diastolic pressure in blacks (80 +/- 11 mm Hg) versus whites (75 +/- 11 mm Hg) (P = 0.003). Mean middle night systolic blood pressure was numerically higher in blacks than whites (131 +/- 18 mm Hg versus 128 +/- 17 mm Hg), but this difference did not achieve statistical significance. The higher middle night blood pressure in blacks versus whites could not be explained by differences between the groups in daytime MAP, age, gender, body weight, serum creatinine level, proteinuria, diabetic status, or greater use of short-acting antihypertensive agents in blacks versus whites. It was concluded that when treated hypertensive blacks and whites are matched for the same daytime blood pressure, blacks tend to have significantly higher nocturnal blood pressure than whites. The magnitude of this difference suggests that it could contribute importantly to the greater target-organ damage that is seen in hypertensive blacks compared with hypertensive whites.

Antihypertensive Agents↗

A novel variant of the beta-subunit of the amiloride-sensitive sodium channel in African Americans.

The amiloride-sensitive sodium channel is responsible for the rate-limiting step of sodium reabsorption in the distal renal tubule, and thus may play a key role in the maintenance of sodium balance and blood pressure. In this study, a genetic variant that results in a change of threonine to methionine at amino acid 594 (T594 M) in the carboxy-terminus of the beta-subunit of the amiloride-sensitive sodium channel has been identified. This variant was present in 6.1% of African-American subjects (N = 231) but was not seen in Caucasians (N = 192). Whole cell voltage clamp of B-lymphocytes from individuals with the T594 M variant showed similar basal membrane slope conductance, compared with the wild-type but increased response to cAMP analog.

Aldosterone↗

Growth of cultured human cerebral meningiomas is inhibited by dopaminergic agents. Presence of high affinity dopamine-D1 receptors.

We have found that microM concentrations of the dopamine agonist bromocriptine significantly decrease the proliferation rate of human meningioma cells in culture (25-56% inhibition). This effect was also seen with direct application of dopamine, as well as the dopamine-D1 agonist (+)-SKF-38393 (both applied in microM concentrations) to meningioma cell cultures. Receptor studies with the dopamine-D1 ligand (125I)SCH-23982 (dopamine-D1 antagonist) indicated that dopamine-D1 binding sites were present in the membranes of meningioma tissue. The mean dissociation constant (Kd) was 325 ( +/- 74.5 SEM) pM and the receptor density (Bmax) was 25.4 ( +/- 1.5 SEM) fmol/mg pellet protein in 5 human meningiomas. The pharmacological specificity was proven by (+)-SKF-38393, ( +/-SKF-83566 or (+)-butaclamol and their inactive isomers (-)-SKF-38393 and (-)-butaclamol in a 1000 fold excess. These results provide evidence that human meningiomas possess high affinity dopamine-D1 receptors and that dopamine agonists have an antiproliferative effect on these tumors in culture. We conclude that the proliferation of cerebral meningiomas may be under dopaminergic control and that dopamine agonists may have a role in the medical treatment of patients with meningiomas.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Psychological issues in genetic counselling.

In the case of prenatal diagnosis and its possible consequences, there is discussion on the limits of freedom of decision. Nevertheless, there is considerable agreement that the individual family should be helped to make its own decisions and to live with these decisions. To attain these goals psychological issues are necessarily of importance. This paper presents concepts on these psychological issues and how they have to be taken into account in counselling. The character of mutuality in providing information is emphasized as well as cognitive and affective processes determining the understanding and outcome of genetic counselling. The role of prior knowledge, expectations, experience, and meaning attached to the disease and its consequences are discussed. Tasks for the counselling staff ranging from preparation for genetic counselling to follow-ups, counselling skills, and methods facilitating the counselling process are specified.

Affect↗

Haemodynamic response to slow plasma volume expansion in uncomplicated myocardial infarction.

Left ventricular performance in 16 patients with uncomplicated acute myocardial infarction (AMI) has been estimated, by measuring the haemodynamic response to a moderate increase in left ventricular filling pressure (LVFP), obtained by an espansion in blood volume with a slow infusion of 250 ml of plasma. In 9 cases the infusion was repeated. This represents a total of 25 tests. In 17 tests (group A) cardiac index (CI) and left ventricular stroke work index (LVSWI) did not increase significantly and sometimes decreased. In 8 tests (group B) The same plasma volume expansion (PVE) induced a moderate but significant increase in CI(p less than 0.001) and LVSWI (p less than 0.001). A higher incidence of inferior wall infarction was present in group B. Control CI and LVFP did not differ between the two groups and there was no correlation between the initial LVFP and the type of response to PVE. For the same volume load, the increase in pulmonary capillary wedge pressure (CWP) showed large individual variations (+1 to +8 mm Hg). As a general rule when CI improved, the increment in CWP was minimal (+1 mm Hg). It is concluded that there is no unique optimal LVFP and that PVE must be carefully monitored, in all cases.

Adult↗

Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study.

An 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study was conducted to evaluate the antihypertensive efficacy of candesartan vs. losartan in 654 hypertensive patients with a diastolic blood pressure between 95 and 114 mm Hg from 72 sites throughout the U.S. Eligible patients were randomized to candesartan cilexetil 16 mg once daily, or losartan 50 mg once daily. Two weeks following randomization, patients doubled the respective doses of their angiotensin receptor blockers for an additional 6 weeks. At week 8, candesartan cilexetil lowered trough systolic/diastolic blood pressure by a significantly greater amount than did losartan (13.3/10.9 mm Hg with candesartan cilexetil vs. 9.8/8.7 mm Hg with losartan; p less than 0.001). At the same period, candesartan cilexetil also lowered peak blood pressure by a significantly greater amount than did losartan (15.2 to 11.6 mm Hg with candesartan cilexetil vs. 12.6 to 10.1 mm Hg with losartan; p less than 0.05). There were statistically significantly (p less than 0.05) higher proportions of responders and controlled patients in the candesartan cilexetil group (62.4% and 56.0%, respectively) than in the losartan group (54.0% and 46.9%, respectively). Both treatment regimens were well tolerated; 1.8% in the candesartan cilexetil group and 1.6% in the losartan group withdrew because of adverse events. In conclusion, this forced-titration study confirms that candesartan cilexetil is more effective than losartan in lowering blood pressure when both are administered once daily at maximum doses. Both drugs were well tolerated. (c)2001 by Le Jacq.

Adult↗

DNA-grading of malignant lymphomas. II. Correlation with clinical parameters.

The clinical significance of the DNA-malignancy grade (DNA-MG) was tested in 90 malignant lymphoma patients. Feulgen stained imprint smears from freshly cut lymph-nodes were investigated. DNA measurements were performed using various cytophotometers. The scalar DNA-MG, ranging from 0.1 to 3.0, was calculated from the variance of the tumor cells around the 2c peak. Except for the CLL, all entities of the Kiel classification for non-Hodgkin's malignant lymphomas showed considerable variation of the DNA-MGs. The DNA-MG, the age of the patients and the response to treatment were seen to have a significant influence on the survival time of non-Hodgkin's lymphoma patients. In high grade lymphoma patients of the Kiel classification, the DNA-MG was found to provide additional prognostic information. The DNA-MG was strongly correlated with the ESR, low albumin concentration, low lymphocyte counts in peripheral blood, clinical and pathological staging, and the response to treatment.

Adolescent↗