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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 55 records · Page 3Linked to original sources

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study.

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

Aged↗

Intensification of the transition between inpatient neurological rehabilitation and home care of stroke patients. Controlled clinical trial with follow-up assessment six months after discharge.

OBJECTIVE: An intensified transition concept between neurological inpatient rehabilitation and home care was investigated for effects on the functional status of stroke patients and the physical and emotional health of their carers. DESIGN: Controlled clinical trial allocating patients to intervention group (intensified transition on ward II) or control group (standard transition on ward I); patients were allocated to whichever ward had a vacancy. Follow-up assessment was carried out six months after discharge. SUBJECTS: Seventy-one patients and their family carers were included, of which nine cases dropped out. Therefore 62 stroke patients with persisting disability and their family carers were available for assessment at follow-up--33 patients in the intervention group, 29 patients in the control group. INTERVENTION: The intensified transition concept consisted of therapeutic weekend care, bedside teaching and structured information for relatives during the second phase of the rehabilitation. MAIN MEASURES: Patients were assessed with the Barthel Index, Functional Independence Measure, Ashworth Spastic Scale, Frenchay Arm Test, and Timed Up and Go Test. The carers completed SF-36, and were assessed using the Giessen Symptom List, Depression Scale and Burden Scale for Family Caregivers. RESULTS: The intensified transition did not lead to significant change in the functional status of the patients or in the physical and emotional health of the family carers. Within the first four weeks after discharge, the patients in the intervention group had fewer new illnesses. In the observation period the use of outpatient care services was more frequent in the intervention group than in the control group. CONCLUSION: Even though there are few differences of moderate intensity between the two groups the intensified transition programme does not affect either the functional status of the stroke patients or the health of the carers.

Aged↗

GEMSS: grid-infrastructure for medical service provision.

OBJECTIVES: The European GEMSS Project is concerned with the creation of medical Grid service prototypes and their evaluation in a secure service-oriented infrastructure for distributed on demand/supercomputing. Key aspects of the GEMSS Grid middleware include negotiable QoS support for time-critical service provision, flexible support for business models, and security at all levels in order to ensure privacy of patient data as well as compliance to EU law. METHODS: The GEMSS Grid infrastructure is based on a service-oriented architecture and is being built on top of existing standard Grid and Web technologies. The GEMSS infrastructure offers a generic Grid service provision framework that hides the complexity of transforming existing applications into Grid services. For the development of client-side applications or portals, a pluggable component framework has been developed, providing developers with full control over business processes, service discovery, QoS negotiation, and workflow, while keeping their underlying implementation hidden from view. RESULTS: A first version of the GEMSS Grid infrastructure is operational and has been used for the set-up of a Grid test-bed deploying six medical Grid service prototypes including maxillo-facial surgery simulation, neuro-surgery support, radio-surgery planning, inhaled drug-delivery simulation, cardiovascular simulation and advanced image reconstruction. CONCLUSIONS: The GEMSS Grid infrastructure is based on standard Web Services technology with an anticipated future transition path towards the OGSA standard proposed by the Global Grid Forum. GEMSS demonstrates that the Grid can be used to provide medical practitioners and researchers with access to advanced simulation and image processing services for improved preoperative planning and near real-time surgical support.

Access to Information↗

Anatomical repair of lateral ligaments in patients with chronic ankle instability.

In a prospective study, 19 patients with chronic ankle instability underwent clinical and radiographic reexaminations 36 months after anatomical reconstruction. In addition, dynamic pedography was conducted and peroneal reaction time measured on a tilting platform for an evaluation of functional aspects. Prior to this examination, 32 patients had been asked to fill in a questionnaire and make a detailed subjective evaluation of current discomfort, stability, flexibility and sporting abilities. Eighty-eight percent of the patients reported satisfactory results; only 3% complained of persistent instability. In 71% the ability to take part in sports had improved after surgery, and 85% of the patients reported unrestricted walking abilities. Supination ability was impaired in 5% of the patients at the follow-up. The radiographic examination showed restored ankle stability with a significant reduction of talar tilt and talar translation; a postoperative increase in signs and symptoms of arthrosis was not observed. Dynamic pedography showed a large degree of symmetry of plantar pressure distribution after surgery. There were no significant differences in peroneal reaction time in the repaired and intact ankles. The results of the study show that it is possible to restore ankle stability with anatomical reconstruction without impairing the range of movement in the ankle joint complex. Progressive osteoarthrosis can be prevented.

Ankle Joint↗

White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease.

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Arterioles↗

CYP3A4, CYP2C9 and CYP2B6 expression and ifosfamide turnover in breast cancer tissue microsomes.

Ifosfamide is a prodrug that requires bioactivation by cytochrome P450 for antitumour activity. Up to now, little is known, to what extent in addition to the liver the ifosfamide metabolism may occur intratumorally. For this purpose, we investigated the expression of CYP3A4, CYP2C9 and CYP2B6 in breast cancer tissue using Western Blotting. Ifosfamide turnover was determined by detection of metabolites of the ifosfamide 4-hydroxylation and N-dechloroethylation in tumour microsomal incubations using HPLC/UV and LC/MS. The results demonstrate that all mammary tumours (n=11) reveal CYP3A4 expression; contents varied from 0.5 to 63 pmol mg(protein)(-1). CYP2C9 (n=9) was present in all tested breast tumour samples, too, while CYP2B6 (n=10) protein could not be detected. All measured breast cancer microsomes (n=4) showed an ifosfamide N-dechloroethylation capacity in the range from 0.04 to 0.21 pmol min(-1) mg(protein)(-1), while metabolites of the 4-hydroxylation could not be determined. In conclusion, the detected presence of CYP3A4 and CYP2C9 in breast tumours offers the possibility of intratumoral turnover of ifosfamide. For the first time in the literature, we could demonstrate a turnover of ifosfamide by microsomal preparations from human breast cancer tissue. A calculated modulation of intratumoral ifosfamide turnover could considerably influence its therapeutic efficiency.

Aged↗

[Treatment of trans-symphyseal instability with an internal fixator. Outcome of a surgical technique on the basis of a case report].

Treatment of traumatic trans-symphyseal instability by internal plate fixation is the most common procedure. Besides the trauma-induced muscle damage, the implantation induces additional damage at the symphyseal origin of the m. rectus abdominis. The aim of this clinical case study was to examine whether it is possible to reduce the iatrogenic soft tissue damage while correcting trans-symphyseal instability using an internal fixator. After a transverse skin incision, two pedicle screws were drilled into the corpus ossis pubis next to the symphysis. Afterwards the crossbar was implanted and fixed. Generally, implantation of two self-trapping pedicle screws using a skin incision with a length of 6 cm is possible. Additional detachment of the m. rectus abdominis is not necessary. As a result of the mobility of the skin and subcutaneous tissue, the implantation of the crossbar beneath the m. rectus abdominis is possible. Stabilization of traumatic trans-symphyseal instability by internal fixation is a safe and easy method. Additional soft tissue damage can be prevented, but to achieve multidirectional stability some small modifications of the implant are necessary.

Bone Plates↗

Gene expression profiles of three different models of reconstructed human epidermis and classical cultures of keratinocytes using cDNA arrays.

The gene expression profiles of three different models of reconstructed human epidermis were analyzed in a comparative study using cDNA array technology. The study also included normal human subconfluent keratinocytes cultured on plastic. Arrays were custom-made and comprised 504 known genes related to cutaneous biology. The gene expression profiles of the three reconstructed epidermis models shared 86% similarity; only 22 of the 504 examined genes showed a different expression level. A comparison of the 3D models with keratinocyte cultures on plastic dishes revealed a set of six genes with a considerably higher expression in the 3D models. These genes were keratin 1, corneodesmosin, filaggrin, loricrin, calmodulin-like skin protein and caspase 14, all related to keratinocyte terminal differentiation. The reported data may contribute to a better understanding and characterization of reconstructed epidermal models and may also serve as established references for investigations related to epidermal differentiation and proliferation.

Adult↗

CYP2C and IL-6 expression in breast cancer.

Besides hepatic P450 (cytochrome P450) metabolism, there is increasing interest in the possibility of intratumoral activation of oxazaphosphorines by P450. Therefore, we investigated the expression of P450 (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) by RT (reverse transcriptase)-polymerase chain reaction (PCR) and of CYP2C9 by Western blotting in 10 different breast tumor samples. Since P450 may be down regulated by interleukin (IL) IL-6, the receptor (R) for IL-6 was analyzed by RT-PCR and IL-6 in supernatants was calculated from ELISA data. None of the breast tumors was positive for CYP2C18 and CYP2C19 mRNA, whereas CYP2C8 and CYP2C9 were detected in all 10 breast tumors. Correspondingly, all breast tumors tested (9 of 10) revealed low, but nevertheless positive, staining of the CYP2C9 protein. All 10 samples were positive for the IL-6 receptor mRNA. ELISA measurement of IL-6 cytokine in supernatants revealed that all measured samples (8 of 10) were producing IL-6, the amounts ranging from 0.004 to 3.1 ng/g(tumor tissue). In summary, we have demonstrated that tumors of the breast express two out of four members of the CYP2C family, indicating that activation of such prodrugs as oxazaphosphorines may take place intratumorally. The presence of the IL-6 receptor and of IL-6 cytokine, which is produced in an autocrine manner, opens up the possibility that the well-known down regulating effect of IL-6 also takes place in breast tumors and might explain the weak or even absent expression of different CYP2C members.

Adult↗

Pharmaceuticals in the river Elbe and its tributaries.

Medicinal drugs were found to be ubiquitous in the river Elbe, its tributary the river Saale and in other tributaries at their points of entry into the Elbe. The distribution of concentration peaks along the investigated river stretches provides an indication that they are mainly due to the emission of treated waste water from municipal sewage treatment works. This leads to the conclusion that medicinal substances can be regarded as faecal indicators for water pollution caused by human activity. The main substances found in the Elbe in 1998 were diclofenac, ibuprofen and carbamazepine as well as various antibiotics and lipid regulators in the concentration range of <20-140 ng/l. The more thorough investigations carried out in 1999 and 2000 show that in addition to the drugs (phenazone, isopropyl-phenazone and paracetamol) metabolite concentrations contributed significantly to the total concentration of pharmaceuticals in the Elbe. The metamizole metabolites N-acetyl-4-aminoantipyrine (AAA) and N-formyl-4-aminoantipyrine (FAA) were found in concentrations from <20 to 939 ng/l. A multivariate statistical analysis revealed a high correlation in respect of the distribution of persistent substances. The metoprolol distribution throughout the Saale demonstrated that the tributaries cause either an increase (Weisse Elster, Unstrut, Ilm) or a reduction (Wipper, Bode) in the concentration, depending on the respective load of waste water. Wide scale sampling in Saxony during 2002 showed the ubiquitous occurrence of carbamazepine in surface waters. The ecotoxicological effects of this contamination cannot be assessed at present. This is due to the fact that no legal framework in respect of these medicinal drugs for human consumption has been established and therefore little research and no risk assessment has been carried out. Therefore it is urgently necessary to include at least the quantitatively most significant substances in the new assessment concept of the EC White Paper.

Cluster Analysis↗

[Vergence dynamics and variability of fixation disparity in school children with reading-spelling disorders].

BACKGROUND: New computer-controlled psychophysical procedures allow one to measure some temporal aspects of binocular coordination. The present study investigates whether these procedures can be operated by children and whether the tests are useful to detect previously reported impairments in dynamics and stability of vergence in children with disability in reading and writing. METHODS: To assess the variability in vergence accuracy (fixation disparity), a stationary fusion stimulus appeared on a computer monitor superimposed by short-term presentations of two dichoptic vertical nonius lines with varying horizontal offset. From the variability of the responses, a measure of vergence variability was deduced. Vergence velocity was estimated with nonius lines that appeared at a fixed delay of 400 ms after a sudden change in disparity of 30 minutes of arc. The full sample comprised 66 children, aged 7-16 years. 16 of these were not able to localize the nonius lines accurately in a control condition; therefore, these children were excluded from the following analysis. RESULTS: In the remaining 50 children, a group of 30 pupils with different aspects of disability in reading and writing had a nearly significant worse vergence performance both with respect to convergence velocity and to variability of fixation disparity (as compared to a control group of n = 20). These two findings corresponded to each other since convergence velocity and variability of fixation disparity were correlated. CONCLUSIONS: The results confirm previous reports and suggest further research on temporal aspects of vergence with respect to dyslexia. The computer-controlled test procedures are applicable in children of about 10 years or older.

Adolescent↗

Mitochondrial function in turkey skeletal muscle--impact on meat quality.

1. M. iliotibialis (MIT) and M. pectoralis (MP) of the BUT Big 6 and Kelly BBB turkey were characterised with respect to physical properties, mitochondrial function, metabolic state, morphology and meat quality. 2. Mitochondrial enzyme activity and respiration rates in MP declined with increasing age while glycolytic enzyme activity remained nearly constant. 3. There were no major differences between BUT Big 6 and Kelly BBB with respect to histological, histochemical or biochemical variables. In spite of the greater adult weight of BUT Big 6, body proportion was equal in both strains. 4. In agreement with the histochemical findings MIT showed higher oxidative capacities, while glycolytic enzyme activity was higher in MP. 5. Pyruvate was the best substrate for oxidative phosphorylation in MIT, but not in MP. Pyruvate dehydrogenase (PDH) activity was up to 15 times less in MP and blood lactate was correlated with intramuscular pH. 6. Turkey breast muscle was restricted in its ability to oxidise pyruvate, especially in those animals that tended to develop intramuscular acidosis post mortem. 7. It is concluded that the in vivo metabolic environment results in acidosis and impaired meat quality, at least in turkey M. pectoralis.

Acidosis↗

Performance of electronic portal imaging devices (EPIDs) used in radiotherapy: image quality and dose measurements.

The aim of our study was to compare the image and dosimetric quality of two different imaging systems. The first one is a fluoroscopic electronic portal imaging device (first generation), while the second is based on an amorphous silicon flat-panel array (second generation). The parameters describing image quality include spatial resolution [modulation transfer function (MTF)], noise [noise power spectrum (NPS)], and signal-to-noise transfer [detective quantum efficiency (DQE)]. The dosimetric measurements were compared with ionization chamber as well as with film measurements. The response of the flat-panel imager and the fluoroscopic-optical device was determined performing a two-step Monte Carlo simulation. All measurements were performed in a 6 MV linear accelerator photon beam. The resolution (MTF) of the fluoroscopic device (f 1/2 = 0.3 mm(-1)) is larger than of the amorphous silicon based system (f 1/2 = 0.21 mm(-1)), which is due to the missing backscattered photons and the smaller pixel size. The noise measurements (NPS) show the correlation of neighboring pixels of the amorphous silicon electronic portal imaging device, whereas the NPS of the fluoroscopic system is frequency independent. At zero spatial frequency the DQE of the flat-panel imager has a value of 0.008 (0.8%). Due to the minor frequency dependency this device may be almost x-ray quantum limited. Monte Carlo simulations verified these characteristics. For the fluoroscopic imaging system the DQE at low frequencies is about 0.0008 (0.08%) and degrades with higher frequencies. Dose measurements with the flat-panel imager revealed that images can only be directly converted to portal dose images, if scatter can be neglected. Thus objects distant to the detector (e.g., inhomogeneous dose distribution generated by a modificator) can be verified dosimetrically, while objects close to a detector (e.g., a patient) cannot be verified directly and must be scatter corrected prior to verification. This is justified by the response of the flat-panel imaging device revealing a strong dependency at low energies.

Equipment Failure Analysis↗

Reconstruction of the lateral ligaments: do the anatomical procedures restore physiologic ankle kinematics?

BACKGROUND: If conservative therapy fails, the standard treatment for chronic ankle instability is surgical reconstruction of the lateral ligaments. For the last seventy years, the tenodesis principles have been used for reconstruction. Recently however, surgical reconstructions--respecting the intact joint anatomy--have been developed, thus called "anatomical reconstruction principles". METHODS: This study focused on the investigation of the range of motion of the ankle and the subtalar joint following anatomical reconstruction surgery. Three different types of anatomical reconstruction procedures were compared: Direct ligament repair, tendon graft and carbon-fiber implant. RESULTS: All procedures restored the original range of motion of the subtalar joint, except for the plantarflexed/dorsiflexed positions. As for the talocrural joint, the tendon graft and the carbon fiber implant left a small laxity for movements of inversion/eversion and internal/external rotation. The direct repair procedure achieved a more accurate result and restored the physiologic kinematics almost completely. During each procedure the insertion points and the direction of the original ligaments were maintained. However, the different results for the procedure of direct ligament repair compared to the other two anatomical reconstruction procedures showed that this condition alone is not sufficient to perfectly restore the kinematics of the talocrural and subtalar joints. It is important to note that none of the procedures caused a restriction of the range of motion. CONCLUSIONS: The maintenance of the range of hindfoot motion decreases the risk of osteoarthritis as well as chronic pain or problems for the patient to walk on uneven surface. Therefore, we believe that standard therapy for chronic instability of the ankle should include direct surgical reconstruction of the ligaments. If this direct procedure cannot be performed because of poor quality of the ligaments an alternative anatomical reconstruction procedure should be considered.

Aged↗

Alveolar antioxidant status in patients with acute respiratory distress syndrome.

In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20). Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas-liquid chromatography), and F2-isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF. GSSG (ARDS: 0.13+/-0.02 microM; control: 0.03+/-0.01 microM; mean+/-sem) and F2-isoprostanes (ARDS: 78+/-10 pM; control: 26+/-5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77+/-15 nM; control: 26+/-3 nM) and uric acid (ARDS: 11.8+/-2.2 microM; control: 0.7+/-0.0 microM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of approximately 3 in patients, but plasmalogens showed a significant decrease. In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding.

Adult↗

Active "itch fibers" in chronic pruritus.

An itch-specific neuronal pathway was recently discovered in healthy humans and animals. Here the authors report that activity in this specific pathway coincides with itch under pathophysiologic conditions in a patient with chronic pruritus. Microneurographic recordings from the symptomatic area revealed spontaneous activity in six single C-fiber afferents that had the characteristic features of "itch fibers." Itch may be caused by activity in a specific subpopulation of C-fiber afferents.

Chronic Disease↗

Action potential conduction in the terminal arborisation of nociceptive C-fibre afferents.

Recordings of single human peroneal C-fibres and rat saphenous C-fibres confirm two different patterns of conduction at branching points. In general, an action potential (AP) arising from one terminal branch may be propagated not only centrally, but also antidromically into the other branches of the terminal arborisation. If a stimulus activates several converging branches of one unit, at each branching point only the AP arriving first from the simultaneously activated daughter branches will be propagated centrally, resetting the slower branches. However, occasionally a single electrical stimulus may evoke a double response in the parent axon. In this case, these two responses apparently originate from different terminal branches and require unidirectional conduction block to prevent the faster AP from invading and resetting the slower-conducting terminal. This conclusion is supported by the notion that when such a double response occurs, both responses immediately show additional activity-dependent slowing of the conduction velocity due to frequency increase in the parent axon (two spikes per stimulus, one from each of the two excited branches). A comparable discharge pattern in the stem axon can be induced by repetitive paired stimulation of one terminal branch. Then the slowing is induced by the doubled frequency along the whole nerve fibre including the terminal branch. Since in this case not only the stem axon, but also the terminal branches carry two spikes per pulse, activity-dependent slowing is predictably more pronounced. Unidirectional block thus provides insight into the differential amount of activity-dependent slowing (and hence postexcitatory hyperpolarisation) in the stem axon and terminal branches of cutaneous C-fibres. This comparison reveals that more than two-thirds of the slowing can be attributed to the terminal branches, since it is two- to fourfold that observed during double stimulation as compared with the unidirectional block condition. This indicates that the terminal branches are equipped with membrane proteins that are different from those of the parent axon.

Action Potentials↗

Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens.

Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E(2) (PGE(2)) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi(His-)), and 24 mechanoinsensitive, histamine-positive (CMi(His+)) units were compared. CMi(His+) units were most responsive to histamine and to PGE(2) and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi(His-) units showed significantly weaker responses to histamine, PGE(2), and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi(His+) units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi(His+) units but decreases with activation of CMH and CMi(His-) units.

Acetylcholine↗