Control of pacemaker rate by impedance-based respiratory minute ventilation

Several studies have shown that the capability for exercise can be increased in patients with pacemakers by means of adjusting the rate. Respiration is one of the parameters considered for rate control. The aim of our study was to determine how respiratory parameters such as ventilation, tidal volume, and respiratory rate are capable of controlling the pacemaker rate, especially when measured indirectly by means of impedance plethysmography. We examined four volunteers and eight patients with implanted cardiac pacemakers using bicycle ergometry at increasing work loads. We recorded heart rate, uptake of oxygen, and ventilation directly (by pneumotachygraphy) and indirectly (by chest wall impedance plethysmography). A good correlation of directly to indirectly measured ventilation (r = 0.8687) was found. Our study suggests that respiratory minute volume is more appropriate for rate control of physiologic pacemakers than tidal volume or respiratory rate alone. Measurement by means of impedance plethysmography is sufficiently precise to be used for this purpose. Further studies must be conducted as to the optimum realization within an implantable device.     

Mutagenicity and cytotoxicity of 2-chlorobenzylidene malonitrile (CS) and metabolites in V79 Chinese hamster cells

The genotoxicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated using the induction of gene mutations, micronuclei and DNA repair synthesis as biological endpoints. CS efficiently induced micronuclei and mutants resistant to 6-thioguanine in these cells, but it did not elicit DNA repair synthesis. Induction of micronuclei and mutants showed very similar courses of concentration dependence, suggesting that both events were caused by the same mechanism. The hydrolysis products of CS, o-chlorobenzaldehyde and malononitrile dit not induce micronuclei and were much less cytotoxic than CS. The observation of heritable genetic changes in cells exposed to CS in the absence of detectable DNA damage suggests that the genetic effects of CS are not caused by an interaction of the compound or its hydrolysis products with DNA. It appears more likely that the mutagenic activity is the consequence of effects of CS on the mitotic apparatus of the cells causing chromosomal aneuploidy.     

Source localization of interictal epileptiform discharges: comparison of three different techniques to improve signal to noise ratio.

OBJECTIVE: To investigate the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) using a new relative averaging (RELAVG) technique for noise reduction. METHODS: We analyzed 19 patterns of mesial temporal IED recorded simultaneously with scalp and foramen ovale (FO) electrodes in 15 consecutive patients who underwent presurgical assessment for intractable temporal lobe epilepsy. The scalp signals were time-locked to the peak activity in the FO electrode recordings and source modeling was performed using the RELAVG technique. Random noise of various amounts was then applied. The results were compared to intracranial data obtained from the FO electrode recordings and to LORETA source solutions obtained using two other approaches to improve signal to noise ratio (SNR): statistical non-parametric mapping (SNPM) and the commonly applied averaging (AVG) technique. RESULTS: The RELAVG technique allowed for reasonable mesial temporal localization in 52.6% (10/19) of IED patterns, compared with 73.7% (14/19) using SNPM. The AVG technique provided no strictly mesial temporal solutions. Nine of the IED patterns revealed relative current density quotient changes >10; all of these were accurately localized by RELAVG into mesial temporal structures. Increasing amounts of white and physiological noise had no influence on the accuracy of RELAVG and SNPM solutions, whereas AVG source reconstructions became progressively spurious. CONCLUSION: The RELAVG technique and SNPM, but not the commonly used AVG technique, allow for reasonable source localization of mesial temporal IED. SNPM is the most accurate but also the most time-consuming noise reduction technique. SIGNIFICANCE: The RELAVG LORETA technique might provide a simple and fast semi-quantitative alternative for localizing IED with low single to noise ratio.     

Effect of Pentoxifylline and Tocopherol on Radiation Proctitis/Enteritis

BACKGROUND AND PURPOSE: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. PATIENTS AND METHODS: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. RESULTS: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). CONCLUSION: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration.     

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [¹²³I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [¹²³I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology. Received 2 October and in revised form 29 December 1997     

HIV-associated Cutaneous Kaposi's Sarcoma—Palliative Local Treatment by Radiotherapy

The increasing number of HIV-infected patients makes palliative treatment of HIV-associated Kaposi's sarcoma more common. We retrospectively evaluated a reduced fractionated radiotherapy with 20 Gy in respect to response rates and acute side-effects. From January 1992 to January 1995, 52 patients with HIV-associated Kaposi's sarcoma were treated with 133 single portals. Six weeks after the end of radiotherapy 42 patients with 124 portals were evaluable with respect to response rates and side-effects. Of the treated portals 32% were judged as complete responses (CR), 55% as partial responses (PR) and 12% as no change (NC). Skin reactions RTOG, grade I were seen in 74% of the patients. Compared with literature data the reduced overall dose of 20 Gy in 10 fractions led to a reduction of CRs by approximately 50% while the overall response rate remained equal. The success of radiotherapy for the nodular component of Kaposi's sarcoma can be improved, if a dose exceeding 20 Gy in 10 fractions is applied but at the cost of increasing side-effects in case that non-conventional fractionation schemes are used.