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Biomedical subjects

C Weiss

Publications and source records attributed to C Weiss.

At least 19 recordsLinked to original sources

Connections of the caudal anterior cingulate cortex in rabbit: neural circuitry participating in the acquisition of trace eyeblink conditioning.

The caudal anterior cingulate cortex (cAC) is an essential component of the circuitry involved in acquisition of forebrain-dependent trace eyeblink conditioning. Lesions of the cAC prevent trace eyeblink conditioning [Weible AP, McEchron MD, Disterhoft JF (2000) Cortical involvement in acquisition and extinction of trace eyeblink conditioning. Behav Neurosci 114(6):1058-1067]. The patterns of activation of cAC neurons recorded in vivo suggest an attentional role for this structure early in training [Weible AP, Weiss C, Disterhoft JF (2003) Activity profiles of single neurons in caudal anterior cingulate cortex during trace eyeblink conditioning in the rabbit. J Neurophysiol 90(2):599-612]. The goal of the present study was to identify connections of the portion of the rabbit cAC previously demonstrated to be involved in trace eyeblink conditioning, using the neuronal tract tracer wheat germ agglutinin conjugated to horseradish peroxidase, to better understand how the cAC contributes to the process of associative learning. Reciprocal connections with the claustrum provide a route for the transfer of sensory information between the cAC and neocortical and allocortical regions also involved in learning. Connections with components of the basal forebrain cholinergic system are described, with relevance to the proposed attentional role of the cAC. Reciprocal and unidirectional connections were in evidence in multiple thalamic regions, including the medial dorsal nucleus, which have been implicated in a variety of conditioning paradigms. Anterograde connections with the caudate and lateral pontine nuclei provide access to forebrain motor and brainstem sensory circuitry, respectively. The relevance of these connections to acquisition of the trace conditioned reflex is discussed.

Animals↗

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

Animals↗

Comparisons of dorsal and ventral hippocampus cornu ammonis region 1 pyramidal neuron activity during trace eye-blink conditioning in the rabbit.

Previous studies demonstrating a critical role of the hippocampus during trace eye-blink conditioning have focused primarily upon the dorsal portion of the structure. However, evidence suggests that a functional differentiation exists along the septotemporal axis of the hippocampus. In the present study, the activity of 2588 single cornu ammonis region 1 pyramidal neurons of the dorsal hippocampus and ventral hippocampus were recorded during trace and pseudo-eye-blink conditioning of the rabbit. Learning-related increases in dorsal hippocampus neuron firing rates were observed immediately prior to behavioral criterion, and increased over the course of training. Activation of dorsal hippocampus neurons during trace conditioning was also greater than that of ventral hippocampus neurons, including during the trace interval, in well-trained animals. An unexpected difference in the patterns of learning-related activity between hemispheres was also observed. Neurons of the dorsal hippocampus ipsilateral and contralateral to the trained eye, exhibiting significant increases in firing rate [rate increasing neurons], demonstrated the greatest magnitude of activation early and late in training, respectively. Rate increasing neurons of the dorsal hippocampus also exhibited a greater diversity of response profiles, with 69% of dorsal hippocampus rate increasing neurons exhibiting significant increases in firing rate during the conditioned stimulus and/or trace intervals, compared with only 8% of ventral hippocampus rate increasing neurons (the remainder of which were significantly responsive during only the unconditioned stimulus and/or post-unconditioned stimulus intervals). Only modest learning-related activation of ventral hippocampus neurons was observed, reflected as an increase in conditioning stimulus-elicited rate increasing neuron response magnitudes over the course of training. No differences in firing rate between dorsal hippocampus and ventral hippocampus neurons during a 1-day pre-training habituation session were observed. Thus, dorsal hippocampus activation is more robust, suggesting a more substantial role for these neurons in the processing of temporal information during trace eye-blink conditioning.

Action Potentials↗

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted.

Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactate-based matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

Adenocarcinoma↗

Efficacy of botulinum-A toxin bladder injections for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: an objective and subjective analysis.

AIMS: We studied the use of botulinum-a toxin (BTX-A) injections into the bladder as an alternative approach in patients with neurogenic detrusor overactivity due to multiple sclerosis (MS) with drug-refractory overactive bladder (OAB) symptoms. METHODS: Sixteen MS patients--11 women, 5 men; mean age 48.6 years--with refractory OAB symptoms were included in a one-center prospective study. For outcome analysis, we used a bladder diary, a complete urodynamic study, and validated questionnaires for subjective assessment. We injected 300 U of BTX-A (Botox) into the bladder and into the external sphincter muscle to reduce the probability of posttreatment urine retention. RESULTS: There was an increase in residual volume from 81.3 +/- 23.8 to 126.3 +/- 32.9 ml after 4 weeks. In one woman, transient self-catheterization was unavoidable. Four weeks and 3 and 6 months after BTX-A injection, the significant results were as follows: daytime frequency was reduced by 29%, 44%, and 30%, respectively. Nocturia diminished by 33%, 72%, and 40%. Use of pads was be reduced by 38% after 4 weeks and by 64% after 3 months. Urodynamically, reflex volume and maximal cystometric bladder capacity increased by 73%, 77%, and 58% (at 6 months, the increase was not significant) and by 36%, 27%, and 36% (not significant). Maximal detrusor pressure decreased by 35%, 22%, and 57%. Subjective outcome indicated significant improvement of symptoms at 4 weeks and 3 months, but not at 6 months. Patient satisfaction with the therapy was very high. CONCLUSIONS: BTX-A detrusor injections are very effective in the treatment of drug-resistant OAB symptoms in MS patients as reflected in urodynamic measurements and in patient satisfaction. Build up of residual urine remains a problem of which patients must be informed.

Adult↗

Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings.

BACKGROUND: The process of bone remodelling is disturbed in the development of osteoporosis. OBJECTIVE: To investigate if proteins in osteoporotic bone are modified by advanced glycation end products (AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings. METHODS: Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and N(epsilon)-carboxymethyllysine. RESULTS: Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs. CONCLUSIONS: It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling.

Adult↗

Persistence, recurrence, and progression rates of superficial bladder tumours after resection using the differentiated technique.

OBJECTIVE: To investigate whether the differentiated resection technique for excising superficial bladder cancer leads to higher recurrence and progression rates as compared with regular resection. SUBJECTS AND METHODS: We evaluated 163 patients, 66 undergoing a differentiated and 97 a regular resection. All patients underwent a routine second resection within 6-10 weeks. Recurrence and progression rates as well as tumour persistence on second resection were analyzed. RESULTS: Patients with differentiated resections of bladder tumours did not have higher tumour recurrence and progression rates. Also, these patients had a significantly higher percentage of tumour-free second resections (p = 0.03). CONCLUSION: The differentiated resection technique for excising superficial bladder cancer has no negative influence on recurrence and progression rates, but it leads to a reduced tumour persistence.

Aged↗

Depth of endoscopically placed sutures: an experimental study in a human cadaver model.

BACKGROUND: Endoscopic suturing devices offer interesting access for interventional procedures used on the gastrointestinal tract. For the time being, the main indication is endoluminal suturing at the gastroesophageal junction for the management of gastroesophageal reflux disease. There is some evidence that endoluminal endoscopic suturing offers an alternative to the closure of esophageal fistulas and to the fixation of feeding tubes and stents in the near future. A review of the literature found no anatomic data on wall layers stitched by sutures. The aim of this study was to determine the depth of sutures placed endoscopically in the esophagus of a human cadaver model. METHODS: Altogether, 62 sutures were placed in the esophagi of 10 cadavers (complete exenterative cadaver model) at three different suction levels (0.4, 0.6, and 0.8 bar) using the EndoCinch suturing machine. After preparation of the esophagus from its mediastinal bed, all sutures were fixed in formalin and stained with hematoxylin and eosin for histologic examination. RESULTS: No sutures were placed in the mucosa alone. As observed, 1.6% were placed in the submucosa, 4.8% in the circular muscularis propria, and 56.5% in the longitudinal muscularis propria, with 37% placed transmurally. At a suction level of 0.4 bar (0.6, 0.8 bar), 0% (0%, 1.6%) were placed in the submucosa, 3.2% (0%, 1.6%) in the circular muscularis propria, and 11% (25.8%, 12.9%) in the longitudinal muscularis propria, with 12.9% (6.5%, 17.7%) placed transmurally. CONCLUSIONS: This study reports, for the first time, a systematic examination of the depth of sutures placed endoscopically in the esophagus. Most of the sutures were found in the muscular wall of the esophagus at a suction level of 0.6 bar. Also, transmural placements were seen. Reduction of suction pressure may lead to a decrease in transmural sutures.

Aged↗

Intraabdominal adhesion formation of polypropylene mesh. Influence of coverage of omentum and polyglactin.

BACKGROUND: Adhesions after intraabdominal surgical procedures are related to high morbidity and mortality. Biomaterials, particularly those made of polypropylene, in the intraabdominal position have to be considered as pathophysiological cofactor in a multifactorial process of adhesion formation. To investigate the adhesive potential induced by the biomaterial, an animal model was performed. In addition, the influence of coverage by omentum or a polyglactin barrier was investigated. METHODS: In, 18 Chinchilla rabbits the biomaterial was placed laparoscopically using the intraperitoneal onlay mesh technique. Using this model, a polypropylene-polyglactin mesh compound (PPMC) was used with three different implantation techniques: group 1, PPMC implantation without coverage (PPMC): group 2, PPMC implantation with additional omentum coverage (PPMC-O): and group 3, PPMC implantation with coverage of an absorbable polyglactin mesh (PPMC-V). The degree of adhesion formation was measured 90 days after implantation by computer-assisted planimetry. Morphometric examination followed the explantation analyzing the amount of foreign body response. RESULTS: We found a significant reduction of adhesion formation for the PPMC and PPMC-O groups compared to the PPMC-V group, in which dense adhesions were found. Morphometric investigations of the perifilamental granulomas of the pure (PPMC) group revealed a typical foreign body reaction with a mild to moderate fibrosis around all mesh fibers. However, tissue specimens of the PPMC-O and PPMC-V groups indicated a similar inflammatory reaction but significantly increased connective tissue formation around the polymer fibers compared to the pure PPMC group. CONCLUSION: The intraabdominal placement of a pure PPMC shows a neoperitonealization and perifilamental collagenous ingrowth with almost no adhesions. Coverage with omentum (PPMC-O) or polyglactin mesh (PPMC-V) resulted in a significant increase in inflammation and perifilamentary connective tissue formation.

Animals↗

A new option for the management of urethral trauma: primary reconstruction of posterior urethral disruption with a buccal mucosa transplant.

Up to now, the management of traumatic posterior urethral disruption ranges from primary realignment to delayed urethroplasty. However, we reconstructed the membranous part of the urethra with an onlay graft of buccal mucosa after traumatic complete disruption as a first line therapy. After 7 months followup, the clinical outcome is very good. Because primary reconstruction of the urethra with a buccal mucosa graft after traumatic disruption has not yet been reported, the question arises whether this technique should be routinely included as an option for primary urethral reconstruction after trauma of the posterior urethra.

Humans↗

[Subjective patient satisfaction after injection of botulinum-a toxin in detrusor overactivity].

PURPOSE: The established treatment for overactive detrusor function consists of anticholinergic drugs. But this treatment can fail or produce intolerable side effects. We therefore investigated the effect of botulinum-A toxin in treating overactive detrusor function in patients with neurogenic and nonneurogenic bladder dysfunction. We were particularly interested in patient satisfaction with this therapy. MATERIAL AND METHODS: The subjects were 38 patients who had overactive detrusor function of different origins and in whom therapy with anticholinergic drugs had failed. To measure results, we used urodynamic studies and a questionnaire that consisted of 27 validated questions ("Urogenital Distress Inventory UDI-6", "Symptom Severity Index" and "Symptom Impact Index") as well as a satisfaction questionnaire. We injected 200 - 300 U of botulinum-A toxin (Botox) cystoscopically. RESULTS: At least 4 weeks after injection, 90 % of the patients reported clear improvement of their voiding situation and 93 % stated that they would undergo this procedure again. The frequency of micturition decreased by 29 % in average, and the increased postvoid residual volume was clinically irrelevant. Patients reported side effects or complications in 6.7 % of cases. The satisfaction scale (0 - 10) averaged 6.9. Urodynamically, reflex volume increased by 85 %, maximal bladder capacity increased by 47 %, and bladder pressure decreased by 33 %. CONCLUSIONS: Botulinum-A toxin injection into the overactive detrusor muscle seems to be very effective. The effect is not only reflected in urodynamic studies but also in the subjective patient satisfaction.

Adult↗

Partial percutaneous discectomy for treatment of thoracolumbar disc protrusion: retrospective study of 331 dogs.

OBJECTIVES: To determine retrospectively the prognosis and outcome for dogs diagnosed with thoracolumbar intervertebral disc disease treated with partial percutaneous discectomy (PPD). METHODS: Three hundred and thirty-one dogs presenting with symptoms of thoracolumbar intervertebral disc disease from 1998 to 2003 were treated with PPD. Diagnosis and location of intervertebral disc disease was confirmed by clinical examination, radiography, myelography and magnetic resonance imaging. PPD was performed via fluoroscopy-guided removal of a 5 mm bore cylinder out of the central intervertebral space. RESULTS: Clinical success after surgery was achieved in 159 (88.8 per cent) grade II to IV patients and 58 (38.2 per cent) grade V patients. The mean (sd) time from percutaneous discectomy to first improvement was 8.3 (13.2) days. CLINICAL SIGNIFICANCE: The PPD approach to the thoracolumbar spine involves minor trauma (yielding rapid recovery) and less pain, and produces results comparable with open fenestration. Consequently, this simple minimal invasive technique can be recommended as an alternative to the technique of fenestration and can be easily performed in addition to open surgical decompression techniques or prophylactically. However, it is not a replacement for surgical treatment in dogs with thoracolumbar disc disease that require removal of disc fragments causing spinal cord or nerve root compression.

Animals↗

Periodic field emission from an isolated nanoscale electron island.

We observe field emission from an isolated nanomachined gold island. The island is able to mechanically oscillate between two facing electrodes, which provide recharging and detection of the emission current. We are able to trace and reproduce the transition from current flow through a rectangular tunneling barrier to the regime of field emission. A theoretical model via a master equation reproduces the experimental data and shows deviation from the Fowler-Nordheim description due to the island's electric isolation.

Journal Article↗

Trace eyeblink conditioning is hippocampally dependent in mice.

The goal of this study was to determine whether trace eyeblink conditioning is a hippocampally dependent associative learning task in the mouse. First, we examined trace intervals of 0, 250, and 500 ms to determine a relatively long trace interval that would support eyeblink conditioning in young adult C57BL/6 mice. Mice rapidly acquired conditioned responses (CRs) with a 0-ms trace interval, acquired CRs with a 250-ms trace interval in approximately 2 days (2 sessions per day), and showed little acquisition with a 500-ms trace interval. Control mice were presented randomly unpaired stimuli and failed to show conditioning. We then determined the effect of lesioning dorsal hippocampal neurons on trace eyeblink conditioning. The hippocampus was injected bilaterally with vehicle (phosphate-buffered saline), 0.1% ibotenic acid, or 1% ibotenic acid. The vehicle group showed >60% CRs. The 0.1% group showed significantly fewer CRs (35-45%). The 1% group showed a level of CRs similar to that of the control mice. All the lesioned mice exhibited >60% CRs when subsequently trained with a 0-ms trace interval. A regression analysis indicated that the volume of area CA1 lesioned was more predictive of the behavioral impairment than the lesion volume of either CA3 or dentate gyrus, or even the total lesion volume. We conclude that dorsal hippocampal neurons play a critical role in eyeblink conditioning when a 250-ms trace interval is used with the C57BL/6 mouse, and that this paradigm will be useful for studying behavior and the in vivo and in vitro electrophysiology of hippocampal neurons in normal and transgenic or knockout mice.

Animals↗

Polypropylene in the intra-abdominal position: influence of pore size and surface area.

BACKGROUND: Polypropylene is a material widely used in surgery. Because of its association with formation of enterocutaneous fistulae and adhesions, direct contact between mesh and intestine is avoided. The following study was designed to investigate the adhesive potential of different polypropylene meshes when placed in direct contact with intestine. MATERIAL AND METHODS: In an established experimental model, a total of 45 chinchilla rabbits underwent laparoscopic placement of meshes with different pore size (Group I: monofilament PP 0.6 mm, Group II: monofilament PP 2.5 mm, Group III: multifilament PP 4.0 mm) with the Intra-Peritoneal-Onlay-Mesh Technique (IPOM). The degree of adhesion formation was measured after 7, 21, and 90 days, evaluated by an adhesion score, quantified by computer-assisted planimetry, followed by histological and morphometric investigation of the perifilamental granuloma formation. RESULTS: The heavyweight, small porous polypropylene meshes (PP 0.6) showed significantly stronger adhesion formation at all intervals of investigation compared with the lightweight meshes with a pore size >2.5 mm. Between the two different lightweight mesh variations, there was no significant difference. Granuloma formation was lowest in large-pore-size monofilament meshes (PP 2.5). CONCLUSION: The IPOM rabbit model is suitable for investigation of biomaterials in the intra-abdominal position. Our results show that the adhesive potential is significantly influenced by the pore size. However, the extent of the foreign-body reaction seems also to be influenced by the filament structure, respectively, the surface area, favoring monofilament material.

Abdominal Cavity↗

Chemokine inhibition--why, when, where, which and how?

Chemokines are small chemoattractant cytokines that control a wide variety of biological and pathological processes, ranging from immunosurveillance to inflammation, and from viral infection to cancer. Genetic and pharmacological studies have shown that chemokines are responsible for the excessive recruitment of leucocytes to inflammatory sites and damaged tissue. In the present paper, we discuss the rationale behind interfering with the chemokine system and introduce various points for therapeutic intervention using either protein-based or small-molecule inhibitors. Unlike other cytokines, chemokines signal via seven-transmembrane GPCRs (G-protein-coupled receptors), which are favoured targets by the pharmaceutical industry, and, as such, they are the first cytokines for which small-molecule-receptor antagonists have been developed. In addition to the high-affinity receptor interaction, chemokines have an in vivo requirement to bind to GAGs (glycosaminoglycans) in order to mediate directional cell migration. Prevention of the GAG interaction has been shown to be a viable therapeutic strategy. Targeting chemokine intracellular signalling pathways offers an alternative small-molecule approach. One of the key signalling targets downstream of a variety of chemokine receptors identified to date is PI3Kgamma (phosphoinositide 3-kinase gamma), a member of the class I PI3K family. Thus the chemokine system offers many potential entry points for innovative anti-inflammatory therapies for autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and allergic contact dermatitis.

Animals↗