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Biomedical subjects

R Hammer

Publications and source records attributed to R Hammer.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacodynamic profile of the M1 agonist talsaclidine in animals and man.

In functional pharmacological assays, talsaclidine has been described as a functionally preferential M1 agonist with full intrinsic activity, and less pronounced effects at M2- and M3 receptors. In accordance with this, cholinomimetic central activation measured in rabbits by EEG recordings occurred at a 10 fold lower dose than that inducing predominantly M3-mediated side effects. This pharmacological profile is also reflected in the clinical situation: Both in healthy volunteers and in Alzheimer patients--unlike after unspecific receptor stimulation through cholinesterase inhibitors--the mainly M3-mediated gastrointestinal effects (like nausea and vomiting) were not dose-limiting. Rather, sweating and hypersalivation, mediated through muscarinic receptors, occurred dose-dependently and were finally dose-limiting. In contrast to talsaclidine, sabcomeline had a less pronounced functional M1 selectivity in pharmacological assays. This was also shown in anaesthetized guinea pigs where sabcomeline alone induced bronchoconstriction, and in the rabbit EEG where central activation and cholinergic side effects occurred in the same dose range. Neither drug, however, showed convincing improvement of cognitive functions in patients with mild-to-moderate Alzheimer's disease. This asks for a reassessment of the muscarinic hypothesis for the treatment of this disease.

Adrenergic beta-Antagonists↗
PubMed2001

RAB-plate versus sliding hip screw for unstable trochanteric hip fractures: stability of the fixation and modes of failure--radiographic analysis of 218 fractures.

BACKGROUND: The sliding hip screw has gained considerable acceptance in the treatment of unstable trochanteric fractures. However, the new type of 120 degrees fixed angle blade-plate with a buttress rod (RAB-plate) showed encouraging clinical results. The purpose of this study was to assess stability of fixation and analyze modes of failure in unstable trochanteric hip fractures treated with these devices. METHODS: A retrospective radiographic review of 218 unstable fractures was performed. Linear and angular displacements of the major fragments and implant migration into the femoral head during healing were assessed. Additionally, adequacy of the reduction and the location of the implant within the femoral head as predictors of fixation failure were evaluated. RESULTS: The postreduction neck-shaft angle was maintained in the majority of the fractures in both groups. However, there was a significantly higher incidence of varus angulation by 10 degrees or more by the completion of healing among fractures treated with the sliding hip screw (p = 0.04). There was no statistically significant difference in vertical migration of the device into the femoral head between the implants used (p = 0.3). There was a significant relationship between failure of the fixation and varus reduction (p = 0.04) as well as screw/neck angle deviation more than 20 degrees in the lateral projection (p = 0.005) or if the implant was in a superior or posterior position (p = 0.02). CONCLUSION: The RAB-plate provided a more stable fixation, especially with regard to maintained postoperative alignment. However, positive predictors for fixation failure were identical for both devices. Here, the screw/neck angle deviation has had the strongest significance for prediction of fixation failure.

Aged↗
PubMed2000

[Results of different incisions in treatment of carpal tunnel syndrome].

Various surgical techniques are used to treat the carpal tunnel syndrome. Besides the endoscopic technique, the "open-standard-technique" and the "Millesi technique" are very common. The success and the complication rate of all these techniques are discussed controversially. However, the aim of the current prospective study was to investigate the various open techniques to find the most successful method with the least complications. Therefore, 64 patients (20 male, 44 female) were examined after surgery. 23 patients were operated with an "Open-Standard-Technique" (OST) including long incision, 22 patients were treated according to the "Millesi-Technique", and 19 patients with the "Short-Incision-Technique" (SIT). All patients were evaluated using a prospectively designed examination check-list. Comparing these various techniques, the OST and the SIT yielded the best results with regard to complications, the SIT seems to be the most successful technique.

Adult↗
PubMed2000

Caring in forensic nursing. Expanding the holistic model.

Nurses have practiced forensic nursing for many years without formal recognition of the domain as a discipline for specialized study. Forensic nursing expands the traditional concept of holism to include the medical-legal aspects of potential or actual client problems. The American Nurses Association (ANA) and the International Association of Forensic Nurses (IAFN) recently have designated forensic nursing as a unique specialty. Recognition of forensic nursing as a specialty area of practice within nursing mandates that the specialty define and explicate its major conceptual base. A concept germane to the practice of forensic nursing is that of caring. Caring as a central concept to the role of this specialty is discussed, and the implications for its inclusion in a curriculum preparing forensic nurses are explored.

Crime Victims↗
PubMed1999

Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease.

Inhaled antimuscarinics, often called anticholinergics in clinical medicine, are established as first line bronchodilators in COPD. Tiotropium has been developed as a new generation antimuscarinic following ipratropium. Tiotropium is a specific, highly potent antimuscarinic, demonstrating very slow dissociation from muscarinic receptors. Dissociation from M2-receptors is faster than from M3 or M1, which in functional in vitro studies, appeared as kinetic receptor subtype selectivity of M3 and M1 over M2. The high potency and slow receptor dissociation found its clinical correlate in significant and long lasting bronchodilatation and bronchoprotection in patients with COPD and asthma. In asthma, protection against methacholine challenge exceeded the study period of 48 hours. In COPD, bronchodilatation of about 80% of the plateau was demonstrated after the first dose. Following chronic once daily inhalation for 28 days, the improvement in pulmonary function was sustained and there was a further increase in peak effects, but more importantly a rising baseline, achieving steady state within 2 weeks. Tiotropium achieves very stable long lasting effects with comparatively low variation of bronchodilatation between peak and trough (the level before the next administration). Stable 24 hour effectiveness profiles the compound as the first once daily bronchodilator. Clinical correlates of kinetic receptor subtype selective blockade remain to be shown. Plasma levels of tiotropium at trough are in the low pg/ml range and are unlikely to explain the sustained effectiveness in the airways. Slow dissociation from muscarinic receptors is likely to be responsible for the long duration of action.

Animals↗
PubMed1999

Use of delayed pushing with epidural anesthesia: findings from a randomized, controlled trial.

OBJECTIVE: To compare outcomes between women receiving epidural anesthesia assigned to a group following either a 1-hour "delayed" pushing protocol or directed to initiate pushing at full cervical dilation. STUDY DESIGN: Using a randomized, controlled design, multivariate analyses were used to evaluate second stage labor duration and Apgar scores. An estimated odds ratio equation evaluated fetal descent progress. RESULTS: A 13.68-minute difference occurred in second stage labor length (p = 0.225). No differences were found in Apgar scores (p > 0.09). An estimated odds ratio, that progress in terms of one fetal station unit would occur for control group subjects as compared with subjects with similar progress in the experimental group, was 1.51 (95% confidence interval: 1.16, 1.95). CONCLUSION: Second stage labor was not significantly lengthened, and a similar rate of fetal descent occurred in the absence of directed pushing. Findings support further research on the potential advantages of minimizing the duration of pushing in labor.

Anesthesia, Epidural↗
PubMed1999

Transgenic mice expressing a human apolipoprotein[a] allele.

The most important determinant of plasma levels of Lp[a] are sequence differences at the highly polymorphic apolipoprotein[a] (apo[a]) locus. To define the sequences that mediate the regulation of apo[a] expression, we cloned a 370 kb DNA fragment that included a 130 kb apo[a] gene, and 40 kb 5'- and 200 kb 3'-flanking region from an individual with high plasma levels of Lp[a] using a YAC vector. This genomic clone was used to generate transgenic mice. In the YAC-apo[a] transgenic mouse, apo[a] was only expressed in the liver, as it is in humans. The mean serum level of apo[a] in 4-week-old YAC-apo[a] transgenic mice was 20 mg/dl. In the female mice the levels of apo[a] varied over a 1.5-fold range during the 4-day estrus cycle and the levels correlated directly with serum progesterone levels. The serum levels of apo[a] decreased to almost undetectable level in male mice after puberty and this decrease was reversed by castration. Ingestion of a high-fat diet resulted in a approximately 100-fold fall in hepatic apo[a] mRNA levels and >60-fold decrease in serum apo[a] levels. To delimit the control elements that mediate tissue-specific and sex hormone-responsive apo[a] transcription, we derived a reporter YAC in which 40 kb of 5' flanking sequences from the cloned apo[a] allele were linked to a luciferase reporter gene. Analysis of four independent transgenic lines revealed no hepatic luciferase expression, suggesting that important cis -acting elements located outside the apo[a] 5'-flanking region are necessary for in vivo expression of apo[a].

Alleles↗
PubMed1998

Attempted unreamed nailing in tibial fractures: a prospective consecutive series of 55 patients.

We evaluated the possibility of unreamed insertion of an intramedullary nail (IMN) in a consecutive series of 55 tibial shaft fractures in 55 patients (30 men). 43 fractures were closed and 12 fractures were open. All surgeons involved were instructed to try unreamed insertion primarily. Selection of nail diameter was based on measurements of the narrowest part of the medullary canal on preoperative AP- and lateral radiographs, with a millimeter-ruler. Of the 25 cases where a 9 mm nail was chosen, 10 were impossible to insert without reaming. An 8 mm nail was selected in the remaining 30 cases, and here 10 required reaming. Mean time-to-union was 4.2 months. Delayed union was noted in 9 patients of whom 6 had been stabilized with an unreamed nail. The concept of unreamed insertion must be questioned since this could be done in only 35 patients and, in addition, we were not able to demonstrate any significant differences in time-to-union in fractures stabilized with an unreamed or a reamed nail. Implant failures were seen in 5 patients, all stabilized with an 8 mm nail. Failure of interlocking screws did not affect the final outcome. However, a possible combination of screw breakage and healing disturbances may lead to the need for more complex surgical procedures. Due to these reasons and the fact that the 8 mm nail could not be inserted unreamed in 10 of 30 patients, we stopped using the 8 mm nail.

Adolescent↗
PubMed1998

RAB-plate vs Richards CHS plate for unstable trochanteric hip fractures. A randomized study of 233 patients with 1-year follow-up.

We prospectively randomized 233 patients with unstable trochanteric hip fractures for treatment with a 120 degrees fixed angle blade-plate having a buttress rod (group A, n 111) or a 135 degrees compression hip screw (group B, n 122). The minimum follow-up time was 1 year. The ratio of technical failure was 9% in group A and 19% in group B (p = 0.06). 79 (87%) fractures in group A and 65 (68%) fractures in group B healed without any complication (p = 0.003). Malunion occurred in 2 cases in group A and in 15 cases in group B (p = 0.002).

Aged↗
PubMed1997

Compensation of muscarinic bronchial effects of talsaclidine by concomitant sympathetic activation in guinea pigs.

The aim of the present investigation was to determine the reasons why the muscarinic receptor agonist talsaclidine (WAL 2014 FU, 1-azabicyclo[2.2.2] octane,3-(2-propynyloxy)-, (R)-,(E)-2-butenedioate) is devoid of bronchospastic effects in anaesthetized guinea pigs but causes contracture in isolated tracheal muscle from this species. Effects on airway resistance were assessed with a modified Konzett-Rossler method in guinea pigs anaesthetized with urethane. Intravenous injection of 1-64 mg/kg talsaclidine did not cause substantial bronchospasm in control animals. After blockade of beta-adrenoceptors, the muscarinic receptor agonist induced dose-dependent bronchospasm which could be blocked by atropine. In despinalized animals and in animals with spinal transection, talsaclidine was bronchospastic but ED50 values were higher and maximal effects were smaller than in intact animals after beta-adrenoceptor blockade. In adrenalectomized guinea pigs, talsaclidine was nearly as bronchospastic as after blockade of beta-adrenoceptors. In contrast, the muscarinic ganglion stimulant McN-A-343, 4-(m-chlorophenylcarbamoyloxy)-2-butyn-trimethyl-ammonium chloride, (2-32 mg/kg i.v.), which has a muscarinic receptor profile similar to that of talsaclidine, i.e., full muscarinic agonism and highest affinity at muscarinic M1 receptors, partial agonism at muscarinic M3 receptors, but in contrast to talsaclidine does not penetrate the blood-brain barrier, caused dose-dependent bronchospasm in control animals. These results indicate that talsaclidine has bronchospastic potential which, however, does not become evident in vivo because of functional antagonism via beta-adrenoceptors resulting from concomitant activation of the sympathetic nervous system in general and the adrenals in particular. It can be concluded that the unique profile of action of talsaclidine is due to partial agonism at bronchial muscarinic M3 receptors, a prerequisite for susceptibility to functional antagonism, and to its ability to penetrate the blood-brain barrier readily and to induce sympathetic activation as a result of full agonism at peripheral ganglionic and adrenal as well as central muscarinic M1 receptors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1997

Mammalian glial cells in culture synthesize acetylcholine.

In the present study we demonstrate that acetylcholine is synthesized by cultured mammalian glial cells identified by cell-type specific markers. Primary cultures of rat brain astrocytes or microglia contained 2.0 and 1.6 pmol acetylcholine/10(6) cells on average respectively. Astrocyte cultures established from neonatal mouse brain contained even more acetylcholine (about 80 pmol acetylcholine/10(6) cells). Primary cultures of rat brain astrocytes showed choline acetyltransferase (ChAT) enzyme activity of 3 nmol/mg protein/h; ChAT activity was blocked by 10 microM bromoacetylcholine. In conclusion, these data demonstrate the synthesis of the "neurotransmitter" acetylcholine in cultured glial cells, a finding which opens a new view upon the role of acetylcholine in mammalian brain.

Acetylcholine↗
PubMed1997

In vivo consequences of M1-receptor activation by talsaclidine.

The aim of this investigation in anaesthetized dogs was to provide direct evidence for an activation of the sympathetic nervous system by the muscarinic agonist talsaclidine (WAL 2014 FU). Intravenous infusion at a rate of 1 mg/kg/min increased plasma catecholamines and in particular epinephrine, thus indicating a predominant stimulation of the adrenals. Sympathetic activation was also indicated by increases in renal vascular resistance, an effect which was sensitive to alpha-adrenolysis. It is concluded that the sympathetic activation by talsaclidine is due to full agonism at the M1-receptor and the ability to cross the blood-brain barrier. As talsaclidine is less potent and only a partial agonist at M2- and M3-receptors many peripheral actions mediated by these receptor subtypes are functionally antagonized by the concomitant sympathetic activation.

Animals↗
PubMed1997

Muscarinic contraction in isolated guinea-pig trachea and antagonism by noradrenaline.

In contrast to other muscarinic agonists, WAL 2014 FU does not induce bronchospasm in laboratory animals. The present investigation was intended to test the hypothesis that this is due to a particular susceptibility of the drug's effect to antagonism by catecholamines, as a result of partial M3-agonism. The tonic activity of the muscarinic agonists, aceclidine, arecoline, carbachol, McN-A-343, RS 86, thiopilocarpine and WAL 2014 FU, was tested in groups of isolated tracheal muscle of the guinea-pig. Susceptibility to functional antagonism by beta-adrenoceptor stimulation was measured by the displacement of the concentration-force curves by 3 microM noradrenaline. Evaluation of the concentration-force relationship revealed differences in potency and intrinsic activity (carbachol-100%) ranging from 114% for arecoline to 36% for thiopilocarpine (WAL 2014 FU-63%). The catecholamine increased the concentration of agonist which induced 5% of the maximum effect achievable (EC05) values fivefold (carbachol) to more than 4,680 fold (thiopilocarpine) (WAL 2014 FU: 2,860 fold). Regression analysis between the intrinsic activity of the seven compounds and the antagonistic effect of noradrenaline revealed a significant correlation (Spearman correlation coefficient (r[s])=-0.79; p=0.036). Inhibition of the effects of endogenous catecholamines by beta-adrenolysis with 50 microM toliprolol increased the maximal contraction induced by 1 mM WAL 2014 FU, but did not affect maximal contraction induced by 30 microM arecoline. Pretreatment with 0.3-1.0 mM dibutyrylcyclic adenosine monophosphate (DBcAMP) shifted the concentration-response curves of arecoline, WAL 2014 FU and thiopilocarpine in a similar manner to noradrenaline. The results exclude an important contribution of adenylate cyclase-coupled M2-receptors to the susceptibility of tracheal contraction by muscarinic agonists to functional antagonism by noradrenaline, but emphasize the importance of intrinsic activity at the M3-receptors. The pronounced susceptibility of WAL 2014 FU-induced contraction to functional antagonism by beta-adrenoceptor activation provides an explanation for the failure of the drug to induce bronchospasm in vivo.

Animals↗
PubMed1997

Spontaneous subcapital femoral neck fracture after healed trochanteric fracture.

Two hundred thirty-three patients with an unstable trochanteric hip fracture were randomized prospectively for stabilization with a fixed angle blade plate or a compression hip screw. Twenty patients had the implant removed after the fracture was healed (average, 20.5 months; range, 12-42 months). In seven of these 20 patients, a spontaneous fracture of the femoral neck occurred at an average of 19 days after implant removal. Four of the seven patients had been treated with the fixed angle blade plate and three with the sliding screw plate. The histologic examination of three specimens was inconclusive. The authors have not observed subcapital fracture among patients whose implants were not removed. The mechanism behind this complication is unknown.

Aged↗
PubMed1995

[Evaluation of sexual abuse in an infant with condyloma acuminatum].

Condyloma acuminatum is a skin infection affecting the anogenital area caused by the human papilloma virus and is usually sexually transmitted in adults. The disease in children is rare and the mode of transmission is controversial. Because of the possibility that children with condyloma acuminatum have been sexually abused, a thorough medical and social evaluation is essential. However, the physician should bear in mind the possibility of nonsexual transmission. Effective management of condyloma acuminatum in prepubertal children involves a multidisciplinary approach and cooperation. We present an 11-month-old girl with genital lesions of condyloma acuminatum. Similar lesions were found in her father's penile area. These findings suggested the possibility of sexual abuse as the cause of the infection. However, detailed, meticulous investigation of the case did not support this suspicion. Our final impression was that transmission was probably nonsexual, as there was no evidence for sexual abuse.

Adult↗
PubMed1994

Arteriovenous malformation of the uterus associated with a missed abortion.

Arteriovenous malformation of the uterus is a rare uterine abnormality. This entity is generally associated with the presence of molar disease, choriocarcinoma and uterine surgery, but may be congenitally acquired. The presence of an arteriovenous malformation generally leads to unexplained profuse uterine bleeding. The diagnosis of this entity has traditionally been made by arteriography, and the treatment is usually hysterectomy. We present a patient with an arteriovenous malformation of the uterus whose prior delivery was by Cesarean section. The patient experienced episodes of heavy vaginal bleeding in the first month following the procedure of suction curettage for a first-trimester pregnancy loss. Chorionic villus sampling performed prior to the procedure showed a chromosomally normal fetus. The diagnosis of an arteriovenous malformation was made by color Doppler velocimetry and confirmed with arteriography. The patient desired to maintain her fertility. Interventional radiological techniques were successfully utilized to obliterate the arteriovenous malformation with the use of polyvinyl alcohol particles (250 micro m) and gelfoam. Discussion includes the presenting signs and symptoms along with the method of both diagnosis and conservative management.

Journal Article↗
PubMed1994

Validation of the Multi-Attitude Suicide Tendency scale in adolescent samples.

The present study extended research on the factor structure and psychometric properties of the Multi-Attitude Suicide Tendency scale (MAST). A mixed sample of 215 adolescents, aged 15 to 18 years, participated in the study. Exploratory principal-components analysis of the 30 MAST items provided support for the four-factor structure of the scale: attraction toward and repulsion by life and death. The MAST subscales showed satisfactory levels of internal consistency. Specific and subset of the MAST subscales were identified for differentiating among adolescents who differed in degrees of psychopathology and suicidal behavior. Correlational and regression analyses examined the relations among the MAST subscales and self-report measures of suicidal behavior, social desirability, and general psychopathology. Limitations and suggestions for future research are discussed.

Adolescent↗