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BACKGROUND: Substance P (SP) is a neuropeptide known to enhance the swallow response. It likely acts as a neurotransmitter in the pharyngeal mucosa in response to local stimuli. It has been proposed that dysphagia after stroke may be related to reduced levels of SP, which therefore constitutes a therapeutic target. In the present pilot study, we evaluated whether electrical pharyngeal stimulation (EPS), a neuromodulation device to enhance cortical reorganization for the restoration of swallowing function after brain injury, is able to increase SP in saliva or serum. METHODS: In a randomized crossover study design, 20 healthy volunteers were treated with 10 min of real (0.2-ms pulses, 5 Hz, 280 V, stimulation intensity (mA) individually adjusted to tolerance level) or sham EPS on two separate sessions. Stimulation was delivered via a pair of bipolar ring electrodes mounted on an intraluminal catheter positioned in the pharynx. Blood and saliva samples were taken prior to, during, and up to 1 h after EPS and analyzed for their SP concentration by ELISA. KEY RESULTS: Following real EPS but not sham stimulation, SP levels in saliva increased immediately and significantly about 28% (p < 0.01) compared to baseline. Serum levels remained unchanged. CONCLUSIONS & INFERENCES: Electrical pharyngeal stimulation is able to induce pharyngeal SP release in healthy subjects.

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Osteoporotic fractures (OFs) are a major public health problem. Direct evidence of the importance and, particularly, the magnitude of genetic determination of OF per se is essentially nonexistent. Colles' fractures (CFs) are a common type of OF. In a metropolitan white female population in the midwestern United States, we found significant genetic determination of CF. The prevalence (K) of CF is, respectively, 11.8% (+/- SE 0.7%) in 2471 proband women aged 65.55 years (0.21), 4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers. The recurrence risk (K0), the probability that a woman will suffer CF if her mother has suffered CF is 0.155 (0.017). The recurrence risk (Ks), the probability that a sister of a proband woman will suffer CF given that her proband sister has suffered CF is 0.084 (0.012). The relative risk lambda (the ratio of the recurrence risk to K), which measures the degree of genetic determination of complex diseases such as CF, is 1.312 (0.145; lambda 0) for a woman with an affected mother and 1.885 (0.276; lambda s) for a woman with an affected sister. A lambda-value significantly greater than 1.0 indicates genetic determination of CF. The terms lambda 0 and lambda s are related to the genetic variances of CF. These parameters translate into a significant and moderately high heritability (0.254 [0.118]) for CF. These parameters were estimated by a maximum likelihood method that we developed, which provides a general tool for characterizing genetic determination of complex diseases. In addition, we found that women without CF had significantly higher bone mass (adjusted for important covariates such as age, weight, etc.) than women with CF.

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BACKGROUND: The annual decrease of daylight duration initiates a depressive phase in patients with seasonal affective disorder (SAD), and light therapy treats it. How much bright light exposure in winter and summer these patients actually receive may help understand the pathogenetic factors initiating SAD. METHODS: During a week in winter and summer, women with and without SAD kept daily logs of the time spent outdoors, subjective sleep, and self-ratings of mood and alertness. RESULTS: Compared with the winter depressive state, mood, alertness, and sleep of SAD patients improved in summer to control values, but did not correlate with the amount of light exposure. In summer, patients with SAD spent more time outdoors than controls. LIMITATION: Light logs--in comparison with light monitor measurements--may overestimate light exposure outdoors. CONCLUSION: Women with SAD do not spend less time outdoors in winter than controls, but spend more time outdoors in summer. CLINICAL RELEVANCE: Patients with SAD show a high amplitude seasonal difference in outdoor light exposure. The susceptibility to winter depression may arise not from behaviourally-related lack of sufficient light exposure, but an increased vulnerability to the amount of light received. They may require more light than controls to remain euthymic (higher light exposure in summer, light therapy in winter).

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The purpose of this paper is to report the linkage of a genetic locus (designated "HBM") in the human genome to a phenotype of very high spinal bone density, using a single extended pedigree. We measured spinal bone-mineral density, spinal Z(BMD), and collected blood from 22 members of this kindred. DNA was genotyped on an Applied Biosystems model 377 (ABI PRISM Linkage Mapping Sets; Perkin Elmer Applied Biosystems), by use of fluorescence-based marker sets that included 345 markers. Both two-point and multipoint linkage analyses were performed, by use of affected/unaffected and quantitative-trait models. Spinal Z(BMD) for affected individuals (N = 12) of the kindred was 5.54 +/- 1.40; and for unaffected individuals (N = 16) it was 0.41 +/- 0.81. The trait was present in affected individuals 18-86 years of age, suggesting that HBM influences peak bone mass. The only region of linkage was to a series of markers on chromosome 11 (11q12-13). The highest LOD score (5.21) obtained in two-point analysis, when a quantitative-trait model was used, was at D11S987. Multipoint analysis using a quantitative-trait model confirmed the linkage, with a LOD score of 5.74 near marker D11S987. HBM demonstrates the utility of spinal Z(BMD) as a quantitative bone phenotype that can be used for linkage analysis. Osteoporosis pseudoglioma syndrome also has been mapped to this region of chromosome 11. Identification of the causal gene for both traits will be required for determination of whether a single gene with different alleles that determine a wide range of peak bone densities exists in this region.

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A "QT"-interval driven rate responsive pacemaker can also be implanted on the occasion of pacemaker replacement. To evaluate the electrophysiological properties and limitations of chronic leads, in 30 patients the evoked intracardiac electrogram was recorded via the chronic lead during pacemaker replacement (14 different types, mean interval after implantation 111 (25-171 months). T-wave detectability was evaluated with different pulse amplitudes (2.5 and 5.0 V) and two pacemaker systems (TX 915, Rhythmyx) with different "fast recharge" mechanisms. In particular, the T-wave signal was influenced by capacitor discharge effects. At 2.5 V output T-wave amplitude was greater than or equal to 1.5 mV in all (19) patients, who could be paced at this voltage. However, at 5 V in 9/30 patients T-wave was less than 1 mV and detection was not possible in 6/30 cases. During pacing with the newly developed "QT"-interval driven, rate-responsive pacemaker (Rhythmyx) with two fast recharge pulses, in nine investigated patients the T-wave was markedly better discriminable compared to the TX 915 pacemaker. Accordingly, in 37 patients with implanted "QT"-controlled pacemakers (TX 911): n = 13; TX 915: n = 21; Rhythmyx: n = 3. Indication for pacemaker therapy: high degree AV block: n = 24, sick-sinus syndrome: n = 13) reliable T-wave sensing was possible at 2.5 V/0.2 ms output, whereas at 5 V/2 ms no T-wave sensing could be achieved in 8/37 cases. On the occasion of pacemaker replacement the "QT"-controlled pacemaker can be implanted without intraoperative measurements, whenever a pulse amplitude less than 2.5 V is sufficient for stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Thirteen patients with compensated (group 1) and six patients with decompensated hypertensive heart disease (group 2) were examined for ventricular late potentials using endocardial recording techniques. With endocardial catheter mapping, left ventricular late potentials could be recorded in six patients in group 2 (100%) but only in one patient from group 1 (8%); right ventricular late potentials could not be recorded in group 1 or in group 2 patients. The amplitudes of the late potentials were always in the microvolt range, with values ranging between 170 and 620 microV (with a mean of 349 +/- 152 microV). The coupling intervals of the late potentials--measured from the beginning of the preceding QRS complex to the beginning of the late potential--were found to be between 110 and 440 ms (with a mean of 311 +/- 122 ms). Late potentials could only be recorded in patients with reduced left ventricular pumping function--i.e., patients with an ejection fraction of less than 62% and a cardiac index of less than or equal to 2.9 L/min/m2, whereas patients with normal hemodynamic parameters had normal endocardial electrograms. Ventricular arrhythmias were recorded during 24-h, long-term electrocardiogram (ECG) in all patients in group 2 (100%) and in five patients from group 1 (38%). Ryan's class 2-4b malignant ventricular arrhythmias were only found in patients with demonstrable ventricular late potentials and reduced left ventricular pumping function. The present study shows that ventricular late potentials, and thus also ventricular arrhythmias, are found almost exclusively in patients with decompensated hypertensive heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

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To date, only commercially available cardioverters and standard electrode catheters have been used for closed-chest ablation of the atrioventricular conduction system; the latter are primarily designed for temporary pacing and electrophysiological examinations, both procedures requiring rather low voltages and currents. Therefore, the purpose of this experimental study was to assess the electrical charge when using high energies, for instance of 400 joules. A total of 7 different catheters with 2-4 electrodes produced by various manufacturers were tested. After discharging the capacitor (400 joules; commercially available cardioversion unit) the voltage and current were measured using an oscilloscope and the electrical flash was photographed. For temporary pacing previously used and newly sterilized catheters of varying sizes and numbers of electrodes tolerated only one single charge of 400 joules, a completely new catheter only a maximum of 3 discharges. Any additional test resulted in a non directional discharge, caused by an insulation defect. A Josephson catheter (USCI) and a newly developed catheter with modified insulation and electrode material (Cordis) had a higher stability. Both tolerated at least 5 charges per electrode, and in addition the Cordis probe tolerated another 20 charges of the 2nd lead without any non directional discharges. Thus, commercially available electrode catheters are of limited electrical stability when used for closed-chest ablation of the atrioventricular conduction system. For the protection of the patient and to prevent therapeutic failure, a maximum of 3 electrical discharges are possible when using a completely new catheter. As modified catheters demonstrate (currently only available in prototype), the electrical quality could be improved.(ABSTRACT TRUNCATED AT 250 WORDS)

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Left and right heart catheterization was conducted on 45 patients with a history of myocardial infarction in order to detect so-called ventricular late potentials by means of endocardiac mapping. The endocardiac signals were amplified 100 to 10,000 times at a low noise level using bipolar electrode catheters. The signals were stored unfiltered and visualized directly on an oscilloscope. Consistently recurring late potentials were recorded after QRS complexes in 32 patients (71%). They ranged in amplitude from 50 to 780 microV, while the coupling intervals were measured in the range of 80 to 620 ms from the beginning of the QRS complex to the beginning of the late potential. In some patients, the intracardially registered and/or Holter-monitored ventricular ectopic beats occurred with a delay, corresponding to the delayed occurrence of the ventricular late potentials.

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In 27 patients with myocardial infarction, late potentials were sought by means of diagnostic heart catheterization with endocardial left and right ventricular mapping. Signals of late potentials were amplified between 100 and 10,000 times at low noise level using bipolar electrode catheters. Late potentials were recorded reproducibly in 19 patients (70%). Their amplitudes ranged from 50 to 600 microV. The coupling interval in each individual patient was constant and in the total group ranged between 100 and 520 ms. There were no differences of amplitude, form, and coupling interval in patients with and without ventricular tachycardia. In conclusion, late potentials can be found by endocardial mapping in the majority of patients after myocardial infarction. Their clinical relevance, however, has not yet been sufficiently investigated.

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