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Biomedical subjects

M Rath

Publications and source records attributed to M Rath.

At least 19 recordsLinked to original sources

Atypical facial pain--application of the IHS criteria in a clinical sample.

Atypical facial pain is a residual category for otherwise unclassifiable pain syndromes in the facial region. In 35 patients (31F, 4M) with a mean age of 53.2 +/- 14.9 years and a chronic facial pain syndrome we tested the new diagnostic criteria of the International Headache Society (IHS). There was a marked female preponderance, vague description of symptoms and a long history of incorrect diagnoses. A high number of invasive procedures (3.5 +/- 3.0 (1-13)) were performed in this group. In agreement with the IHS criteria, an operation or injury to the face was a suspected cause in 43%. In contrast to the IHS criteria, our patient sample had dysaesthesiae (63%), bilateral occurrence (37%), remission periods (57%), pain attacks (23%) and superficial as well as deep pain. The IHS classification is insufficient to separate atypical facial pain from other primary headache and facial pain syndromes. We suggest a modified version of the IHS criteria for atypical facial pain.

Adult

[Atypical facial pain--quality of IHS (International Headache Society) criteria and psychometric data].

Atypical facial pain is generally an unclearly defined pain syndrome. We tested in 35 patients (31 women, 4 men) with a mean age of 53.2 +/- 14.9 years and a chronic facial pain syndrome the quality of the new diagnostic criteria of the International Headache Society (IHS), at the same time using the SCL-90-R (Self-Report Symptom Inventory), to identify any associated psychopathology. In accordance with the literature there is a marked female preponderance, an altogether vague description of symptoms and a long history of incorrect diagnoses. Of note is the high number of invasive procedures (3.5 +/- 3.0). In agreement with the IHS commentary, an operation or injury to the face was a suspected cause in 43%. In contrast to the IHS criteria, we found in our patient sample dysaesthesia (63%), bilateral occurrence (37%), remission periods (57%), pain attacks (23%) and presence of superficial as well as deep pain. Depression is by no means the only psychopathological abnormality in atypical facial pain; a broad spectrum of complaints is seen. The IHS classification appears insufficient to separate atypical facial pain from other primary headache and facial pain syndromes. We therefore suggest a modified version of the IHS criteria for atypical facial pain.

Adult

Cerebrovascular risk factors in migraine with prolonged aura and without aura.

The role of cerebrovascular risk factors such as mitral valve prolapse, platelet aggregation, platelet activation and cardiac arrythmias in migraine was investigated in a total of 44 migraineurs (32 migraineurs without aura and 12 with prolonged aura) and 32 controls. Comparing the total of migraineurs and the two subgroups with controls, mitral valve prolapse, a raised thromboxane B2 level, at least one platelet aggregation dysfunction or an abnormality in 24-h ECG was statistically seen no more often than in the control group. Neither did combinations of the variables occur more frequently. Altogether, this study showed no increased coincidence of migraine with prolonged aura and migraine without aura with the above parameters. The absence of cardiac and haematological abnormalities in migraine with prolonged aura focuses attention on the control of the cortical microcirculation.

Adolescent

MMPI personality profiles in patients with primary headache syndromes.

The role of psychological factors in the course of primary headache syndromes is still controversial. Using the Minnesota Multiphasic Personality Inventory (MMPI) we investigated the personality profiles of 434 headache patients (160 migraineurs, 95 with tension type headache, 30 with cluster headache and 149 with combination headache) in accordance with the IHS criteria. In the first three MMPI scales (hypochondria, depression, hysteria) there was a slight increase in T mean values to over 60, but still in the range of two standard deviations of the normal population. There were no statistically significant differences between the four headache groups and between patients with and without analgesic abuse. It was impossible to distinguish headache groups on the basis of their personality profiles by means of reclassification with discriminant analysis. In a cluster analysis, patients with cluster headache showed the highest number (20%) of abnormalities, but also the highest percentage (13%) of completely normal results. Our findings--a cross section analysis of personality profiles--contradict many other MMPI-based studies.

Adolescent

Effect of bovine somatotropin on production and reproduction in prepubertal Friesian heifers.

This experiment was conducted to evaluate the effect of bST on average daily gain, onset of puberty, first lactation milk yield, and reproductive efficiency in Friesian heifers. Heifers (n = 16 per treatment) were allocated to either: 1) control (1.5 ml of vehicle) or 2) bST (15 mg of bST in 1.5 ml of vehicle) using a randomized complete block design. Subcutaneous injections of bST were administered once daily from 7 mo of age for 120 d or until heifers reached puberty. Heifers were weighed every 2 wk, and blood samples were collected twice weekly after heifers reached 200 kg. Progesterone concentrations were used to determine onset of puberty. Heifers were bred between 16 and 18 mo of age and, following parturition, milk yield and composition were recorded twice weekly and once every 2 wk, respectively. Heifers assigned to bST treatment had an average daily gain (kg) of .8 compared with .7 in control heifers. Number of days from birth to onset of puberty for bST-treated heifers was 401 compared with 381 for control heifers. Treatment with bST had no effect on milk yield, milk composition, or reproductive efficiency during the first lactation. These data demonstrate that daily administration of bST to Friesian heifers from 7 to 11 mo of age does not affect average daily gain, onset of puberty, reproductive efficiency, or first lactation milk yield of heifers.

Animals

Antiatherosclerotic effect of probucol in WHHL rabbits: are there plasma parameters to evaluate this effect?

Probucol has been used as a lipid-lowering agent for over 10 years. Lately it has been found that its antiatherogenic action is due mainly to its antioxidative capacity, in addition to its known lipid-lowering effect. To study the antioxidative capability of probucol and its influence on plaque development we used the animal model of the LDL-receptor-defective Watanabe heritable hyperlipidemic (WHHL) rabbit. In this study we measured all lipid values before and after probucol feeding and compared them with corresponding values in untreated controls. Probucol levels were determined, as were the physiological antioxidants alpha and gamma tocopherol (vitamin E). Thiobarbituric reactive substances were measured in plasma as a parameter for lipid peroxidation. In addition to the biochemical measurements the plaque area was analyzed macroscopically and microscopically to check the antiatherosclerotic effect and correlate it with the biochemical parameters. In four experiments we showed that probucol treatment in WHHL rabbits decreases the progression of atherosclerotic plaques by way of a combined lipid-lowering and antioxidative effect.

Animals

Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries.

Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n = 74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.

Adolescent

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

The concept that lipoprotein(a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wound healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms of atherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.

Animals

Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig.

Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis.

Animals

Lipoprotein(a) in the arterial wall.

We compared CHD patients with healthy blood donors to confirm the role of Lp(a) as an independent risk factor. More important, we performed biochemical and immunohistochemical studies to evaluate the potential mechanism by which Lp(a) causes CHD. We measured the Lp(a) concentration in comparison with other lipoprotein parameters in fresh human arterial wall biopsies and, in autopsy tissue, we localized apo (a) and apo B, as well as fibrin, with immunohistochemical methods in different vessel areas. Density gradient ultracentrifugation was used to analyse lipoprotein fractions isolated from human arterial wall. Lp(a) accumulates in the intima, preferentially in plaque areas, dependent on the serum Lp(a) level. Most of the Lp(a) can be located extracellularly, but apo(a) can also be detected in foam cells. A strong co-localization has been observed for apo(a) and apo B; only a few areas containing only apo B were detected. Moreover, a striking co-localization for apo(a) and fibrin was found. The possibilities for the pathways by which Lp(a) enters the arterial wall and accumulates extracellularly are discussed on the basis of the present data and recent data published by other groups.

Aorta

The effect of D- versus L-propranolol in the treatment of hyperthyroidism.

The purpose of this study is to determine whether there is a difference in treatment of hyperthyroidism using either the D- or L-isomer of propranolol. Two groups of 20 patients with overt hyperthyroidism received either 120 mg L- or D-propranolol each for a period of 5 days. In the D-propranolol administered group there was a significant decrease in TT3 and fT3 plasma levels and in the ratio of TT3 to TT4; however, a significant increase occurred in rT3 values up to day 5. On the other hand, L-propranolol treatment resulted in a less pronounced decrease in TT4 and TT3 values, while all other thyroid hormone levels remained unchanged as, above all, did the T3/T4 ratio. The well known effect of D,L-propranolol upon peripheral conversion of T4 to T3 is thus not due to the beta-blocking action of L-propranolol but is mainly conditioned by the D-isomer which has no beta-blocking action itself.

Adult

Enantioselective drug monitoring of (R)- and (S)- propranolol in human plasma via derivatization with optically active (R,R)-O,O-diacetyl tartaric acid anhydride.

A sensitive high-performance liquid chromatographic method was developed for the stereoselective assay of (R)- and (S)-propranolol in human plasma. The method involves diethyl ether extraction of the drugs and a racemic internal standard, N-tert.-butylpropranolol, followed by derivatization of the compounds with the chiral reagent (R,R)-O,O-diacetyl tartaric acid anhydride. The resulting diastereomeric derivatives were separated isocratically on a reversed-phase column. Quantitation was achieved by the peak-height ratio method with reference to the internal standard. The assay was accurate and reproducible in the concentration range 1-100 ng of (R)- and (S)-propranolol per ml plasma, using fluorescence detection at lambda ex 290 nm and lambda em 335 nm. The applicability of this method was demonstrated for the determination of concentration-time profiles of propranolol enantiomers in the course of comparative pharmacokinetic studies.

Administration, Oral

Pharmacokinetic data of propranolol enantiomers in a comparative human study with (S)- and (R,S)-propranolol.

The pharmacokinetics of (S)-propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)-propranolol. The results of this study indicate that the bioavailability of (S)-propranolol, as expressed by the mean area under the concentration-time curve (AUC) and maximum serum concentration, is lower after 40 mg of the optically pure drug than after the racemic drug.

Adult

Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man.

In a randomized, double-blind, placebo-controlled, cross-over study 24 healthy volunteers were examined before and 2 h after oral administration of 80 mg (R,S)-, 40 mg (R)- and 40 mg (S)-propranolol.HCl; 8 of them received placebo in an additional run. During exercise on a bicycle ergometer and a rest period the rate pressure product was decreased by 80 mg (R,S)-propranolol.HCl (-32.8% p less than 0.0001) and 40 mg (S)-propranolol.HCl (-32.3%; p less than 0.0001), whereas 40 mg (R)-propranolol.HCl as well as placebo showed no effect. Corresponding binding inhibition experiments using (-)-(125I)iodocyanopindolol in a sarcolemma-enriched cardiac membrane preparation yielded a eudismic ratio of 179 for (S)- over (R)-propranolol. 2 h after oral application, stereospecific HPLC analysis revealed different individual concentrations in plasma of (R)- 22.3 +/- 21.7 ng/ml) and (S)-propranolol (30.4 +/- 26.9 ng/ml) when 80 mg of (R,S)-propranolol.HCl was administered. The plasma levels were similar when 40 mg of the pure enantiomer of (R)- (22.7 +/- 20.3 ng/ml) or (S)-propranolol.HCl (28.7 +/- 22.5 ng/ml) was applied. (R)- and (S)-propranolol are two substances with different pharmacodynamic and pharmacokinetic properties. As there are methods available to produce the optically pure enantiomers, they should be used rather than the racemic mixture.

Adult

Quantitative receptor autoradiography in the human brain. Methodical aspects.

Quantitative receptor autoradiography on sections of the human brain raises methodical problems of which some are relevant also for studies in animal tissue, but others are unique in studies of human brain tissue. Procedures for the following methodical aspects are discussed: image analysis for quantitation of the regional distribution of receptor densities, saturation analysis on autoradiographs, influence of age and post-mortem delay and quenching of beta-radiation in brain tissue. The solutions proposed to these problems make receptor autoradiography in the human brain to a reliable method for studies of chemical neuroanatomy.

Adult