Does cone beam CT actually ameliorate stab wound analysis in bone?

This study aims at verifying the potential of a recent radiological technology, cone beam CT (CBCT), for the reproduction of digital 3D models which may allow the user to verify the inner morphology of sharp force wounds within the bone tissue. Several sharp force wounds were produced by both single and double cutting edge weapons on cancellous and cortical bone, and then acquired by cone beam CT scan. The lesions were analysed by different software (a DICOM file viewer and reverse engineering software). Results verified the limited performances of such technology for lesions made on cortical bone, whereas on cancellous bone reliable models were obtained, and the precise morphology within the bone tissues was visible. On the basis of such results, a method for differential diagnosis between cutmarks by sharp tools with a single and two cutting edges can be proposed. On the other hand, the metrical computerised analysis of lesions highlights a clear increase of error range for measurements under 3 mm. Metric data taken by different operators shows a strong dispersion (% relative standard deviation). This pilot study shows that the use of CBCT technology can improve the investigation of morphological stab wounds on cancellous bone. Conversely metric analysis of the lesions as well as morphological analysis of wound dimension under 3 mm do not seem to be reliable.

Modulation of the platelet serotonin transporter by thermal balneotherapy: a study in healthy subjects.

BACKGROUND: Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. AIM: The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 30 healthy volunteers before (t0) and 30 minutes after (t1) thermal balneotherapy with ozonized water, as compared with a similar group who underwent a bath in non-mineral water. MATERIALS AN METHODS: The SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. RESULTS: The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. CONCLUSIONS: The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of 3H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.

Retrograde approach for revascularization of coronary chronic total occlusion.

Retrograde approach via collateral channels in coronary angioplasty for chronic total occlusion (CTO) can improve recanalization success rate. Most interventionalists will meet few cases where the retrograde approach will provide unequaled advantages, but many are held back from taking retrograde approach by lack of proper equipment and expertise. In this article, we give detailed description of all techniques to traverse the collateral channels, and to cross the CTO by retrograde approach. We also illustrate the difficulties in collateral channel crossing with different examples providing a basic guide for case selection purposes.

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

Clinical significance of FGF-23 measurement in dialysis patients.

AIMS: Considering the growing relevance of fibroblast growth factor-23 (FGF-23) in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD-MBD), an analysis was performed to determine the relative importance of C-terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the first place and the relationship between FGF-23 and mortality as a secondary aim. METHODS: In 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D, FGF-23 (C-terminal and intact molecule) were measured and their correlations were analyzed. The relationship between FGF-23 levels and patient survival was also analyzed. RESULTS: A significant correlation was found between cFGF-23 and 1,25D, PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23 independent predictors were phosphate and 25D. No significant relationship was found between FGF-23 and mortality. CONCLUSIONS: C-terminal or intact FGF-23 levels are weakly correlated and thus not clearly indicative of FGF-23 effects on PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF-23 showed a good correlation, but the intact molecule was not superior in defining interactions with CKD-MBD molecules. Measuring FGF-23 on a regular basis with the current assays in CKD and dialysis patients does not yet seem clinically useful.

Impaired brachial artery endothelial flow-mediated dilation and orthostatic stress in hemodialysis patients.

PURPOSE: Chronic kidney disease (CKD) is associated with an impaired endothelial function, which may contribute to cardiovascular events. Whether impairment in endothelial function is involved in the circulatory response to orthostatic stress is unknown. We assessed endothelial function via brachial artery flow-mediated dilation (BAFMD), an index of endothelial-dependent vasodilation. METHODS: We measured changes in brachial artery diameter (BAD) and blood flow by Doppler ultrasound in 35 CKD patients on hemodialysis, 37 young healthy controls (HC) and 50 non-uremic matched controls (MC), in the supine position and after 60 degrees head-up tilting (HUT). RESULTS: In the supine position, endothelial flow-mediated BAD was significantly increased in HC (p<0.001) and MC (p<0.01) while no significant changes were detected in CKD. Mean percent blood flow changes were HC+323.5%, MC+195.1% and CKD+158.8% (HC vs. CKD p<0.001; HC vs. MC p<0.001; MC vs. CKD p=0.04). Similarly, during HUT mean BAD and blood flow increases were significantly impaired in CKD patients. CONCLUSION: In CKD patients, an impaired response in the physiologic vascular reactivity, suggesting endothelial dysfunction, was found in the supine position and after orthostasis by BAFMD. Our results are in favor of a possible adjunctive role of uremia in the abnormal brachial artery response.

The Kenya cancer research and control stakeholder program: Evaluating a bilateral partnership to strengthen national cancer efforts.

Background: In response to a growing cancer burden and need for improved coordination among stakeholders in Kenya, the US National Cancer Institute and the Kenya Ministry of Health collaboratively hosted a stakeholder meeting in 2014 which identified four priority areas of need (research capacity building, pathology and cancer registries, cancer awareness and education, and health system strengthening) and developed corresponding action plans. Methods: Surveys were conducted with participants to collect input on the progress and impact of the 2014 stakeholder meeting. Findings: Of 69 eligible participants, 45 responded from academia, healthcare institutions, civil society, government, and international agencies. Of the four technical focus areas, three have continued to conduct working group meetings and two have conducted in-person meetings to review and update their respective action plans. Accomplishments linked to or enhanced by t meeting include: Kenyan and international support for expansion of population-based cancer registries, increased availability of prioritized diagnostic tests in selected regional referral hospitals, a greater focus on development of a national cancer research agenda, strategic planning for a community education strategy for cancer awareness, and improved coordination of partners through in-country technical assistance. Interpretation: The Stakeholder Program has successfully united individuals and organizations to improve cancer control planning in Kenya, and has enhanced existing efforts and programs across the country. This model of partners working in parallel on prioritized track activities has supported development of long term coordination of cancer research and control activities sustainable by the Kenyan government and Kenyan institutions.

Left ventricular hypercontractility and ST segment depression in patients with syndrome X.

OBJECTIVES: This study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X. BACKGROUND: Clinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise. METHODS: The pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise. RESULTS: Left ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients. CONCLUSIONS: These findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.

Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X)

The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of epicardial coronary artery tone and reactivity in Prinzmetal's variant angina and chronic stable angina pectoris.

It has been suggested that a generalized coronary vasomotion disorder is present in variant angina and that evaluation of baseline coronary artery tone may be useful for predicting the occurrence of coronary artery spasm. The vasomotor response of angiographically normal proximal and distal coronary artery segments was studied in 9 patients with atypical chest pain and normal coronary arteriograms (control group), 13 patients with active variant angina and 41 patients with chronic stable angina. Ergonovine (intravenous, 100 to 300 micrograms, or intracoronary, 8 to 20 micrograms, was administered to all 22 patients in the control and variant angina groups and to 11 of the 41 patients with chronic stable angina. All patients also received intracoronary isosorbide dinitrate (1 to 2 mg). Computerized coronary artery diameter measurement of angiographically normal segments was carried out before and after ergonovine and nitrate administration. Mean baseline intraluminal diameter of proximal and distal coronary segments was not significantly different in control patients and those with variant angina (nonspastic segments only) or coronary artery disease (proximal 2.89 +/- 0.15, 2.83 +/- 0.14 and 2.82 +/- 0.09 mm; distal 1.60 +/- 0.08, 1.63 +/- 0.07 and 1.62 +/- 0.06 mm, respectively). After ergonovine, proximal segments constricted by 10 +/- 2%, 15 +/- 3% and 11 +/- 4% and distal segments by 11 +/- 3%, 11 +/- 2% and 14 +/- 3% in control, variant angina and coronary artery disease groups, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Predictive and prognostic markers in a series of patients with head and neck squamous cell invasive carcinoma treated with concurrent chemoradiation therapy.

It has been proposed that diverse anticancer drugs and radiation therapy may induce a mode of cell death with the characteristics of apoptosis. Since apoptosis is under the control of several oncogenes, we analyzed the expression of the protein encoded by the proto-oncogenes bcl-2 and p53. Furthermore, we studied cell proliferation [using PC-10 mAb to proliferating cell nuclear antigen (PCNA)] and vascularization [using the CD-31 mAb and by counting intratumoral microvessel density (IMD)] using immunocytochemistry. A series of 73 patients with clinical stage II-IV squamous cell invasive carcinoma of the head and neck (H&N) were treated with concurrent chemoradiation therapy (cisplatin, 80 mg/m2, versus carboplatin, 375 mg/m2, three times every 3 weeks and a total dose of radiation therapy of 64 Gy in 6-8 weeks). We correlated the expression of these markers, determined prior to treatment, with response to the therapy and prognosis. Bcl-2 protein was expressed in 37.4% of the carcinomas (25/67 evaluable), and it was not significantly associated with any other feature studied. Forty (56. 4%) of the 71 carcinomas evaluable for p53 were p53 positive; the median IMD was 38 microvessels/field at the hot spot (range, 18-80), and the median percentage of nuclei labeled by the PC-10 mAb was 50% (range, 0-95%). In the univariate analysis, regional lymph node negativity (P = 0.016), good performance status (PS) (PS >/= 90; P = 0.044), bcl-2 positivity (P = 0.070), and low vascularization (P = 0. 085) were significantly associated with a higher probability of complete remission. In the multivariate analysis (final model), only IMD (continuous variable; P = 0.045) and PS (P = 0.017) retained significance. As far as prognosis is concerned, in the univariate analysis, patients with tumors with low histological grading (grades 1-2; P = 0.006), p53 negative (P = 0.09), bcl-2 positive (P = 0.08), and high PCNA labeling (P = 0.06) had a significantly better disease-free survival. In the multivariate analysis, only grading (P = 0.003) and p53 (P = 0.04) retained significance for disease-free survival. For overall survival, in the univariate analysis, the following markers were significantly prognostic when only deaths due to progression are considered: response to therapy (P = 0.00001), PS (P = 0.04), nodal status (P = 0.028), PCNA (P = 0.04), p53 (P = 0. 08), and grading (P = 0.01). In the multivariate analysis, only patients who achieved complete response (P = 0.00002), high PCNA values (P = 0.002), and low histological grading (P = 0.01) retained a statistically significant probability of better overall survival. Our results suggest that in this series of H&N cancer patients the markers capable of predicting response to therapy are distinct from those associated with prognosis, once the remission has been achieved. This information is potentially useful to the clinician for developing a more rational therapeutic approach for H&N cancer patients eligible for concurrent chemoradiation therapy.

Facial changes in adult uremic patients on chronic dialysis: possible role of hyperparathyroidism.

BACKGROUND: Uremic patients on regular dialytic treatment (RDT) are often affected by a complex metabolic syndrome leading to osteodystrophy. Bone changes are primarily due to high bone turnover, often combined with a mineralization defect leading to increased bone fractures and bone deformities. Although rarely considered, the craniofacial skeleton represents one of the peculiar targets of this complex metabolic disease whose more dramatic pattern is a form of leontiasis ossea. This complication, although described, has never been evaluated in depth nor quantitatively assessed. In order to assess facial deformities in uremic conditions and to understand the possible relation with hyperparathyroidism, we undertook a quantitative evaluation of soft facial structures in a cohort of uremic patients undergoing RDT. METHODS: The three-dimensional coordinates of 50 soft-tissue facial landmarks were obtained by an electromagnetic digitizer in 10 male and 10 female patients with chronic renal insufficiency aged 53-81 years, and in 34 healthy individuals of the same age, ethnicity and sex. Uremic patients were enrolled according to hyperparathyroid status (PTH < 300 pg/mL and PTH > 500 pg/mL). From the landmarks, facial distances, angles and volumes were calculated according to a geometrical face model. RESULTS: Overall, the uremic patients had significantly larger facial volumes than the reference subjects. The effect was particularly evident in the facial middle third (maxilla), leading to an inversion of the mandibular-maxillary ratio. Facial dimensions were increased in all three spatial directions: width (skull base, mandible, nose), length (nose, mandible), and depth (mid face, mandible). The larger maxilla was accompanied by a tendency to more prominent lips (reduced interlabial angle). Some of the facial modifications (nose, lips, mandible) were significantly related to the clinical characteristics of the patients (age, duration of renal insufficiency and PTH levels). CONCLUSIONS: This report, the first in the literature, shows that facial structures of uremic patients are enlarged in comparison with matched normal subjects and that increased bone turnover could be responsible--at least in part--for facial bone changes.

[Prevention of extraskeletal calcifications in uremia]. / Prevenzione delle calcificazioni extrascheletriche nel paziente uremico.

Secondary hyperparathyroidism (HPTH) is a common feature in end-stage renal disease (ESRD) patients. The three main factors involved in secondary HPTH pathogenesis are high phosphate levels, hypocalcemia and vitamin D deficiency. Recently, many studies demonstrated a strong association between bone disease and cardiovascular events in chronic kidney disease patients. In addition, cardiovascular events are the most frequent cause of death in patients with chronic renal failure. Increased levels of serum phosphorus and calcium-phosphate product are directly involved in the pathogenesis of extraskeletal calcifications (blood vessels, soft tissues, etc) in dialyzed patients compared to the non-uremic population. Recent studies suggested that vascular calcification is due not only to a passive calcium-phosphate deposition on atherosclerotic arteries, but also to active mechanisms regulated by bone-associated genes. In particular, fetuin and matrix Gla-protein are two 'protective' proteins associated with reduced vascular calcification and could be the regulatory keys in preventing this process in renal failure. The limitations of calcium salts as phosphate-binders in patients with advanced renal failure have been thoroughly evaluated in the last 5 yrs. New phosphate binders, which do not contain aluminum or calcium, have been developed to reduce the risk of extraskeletal calcifications in ESRD.

[New insights in the pathogenesis of secondary hyperparathyroidism]. / Nuove acquisizioni nella patogenesi dell'iperparatiroidismo secondario.

Parathyroid gland growth is a major cause of secondary hyperparathyroidism in renal failure. It is well known that high serum phosphate levels, low serum calcium levels and vitamin D deficiency are the three promoters of parathyroid hyperplasia in renal failure. Recent studies have investigated in depth the potential role of growth factors (transforming growth factor alpha) and their receptors (epidermal growth factor receptor) in the pathogenesis of parathyroid cell hyperplasia in chronic renal failure. The identification of molecular mechanisms involved in calcium, phosphate and vitamin D manipulations in an experimental renal failure model could help design more effective therapy for secondary hyperparathyroidism in uremic patients.

Phosphate balance in ESRD: diet, dialysis and binders against the low evident masked pool.

Phosphate metabolism is crucial in the pathophysiology of secondary hyperparathyroidism and vascular calcification. High phosphate levels have been consistently associated with unfavorable outcomes in dialysis patients, but several limitations are still hampering a resolutive definition of the optimal targets of phosphate serum levels to be achieved in this cohort. Nonetheless, hyperphosphatemia is a late marker of phosphate overload in humans. Clinical nephrologists routinely counteract the positive phosphate balance in dialysis patients through nutritional counseling, stronger phosphate removal by dialysis and prescription of phosphate binders. However, the superiority against placebo of phosphate control by diet, dialysis or binders in terms of survival has never been tested in dedicated randomized controlled trials. The present review discusses this conundrum with particular emphasis on the rationale supporting the value of a simultaneous intervention against phosphate overload in dialysis patients via the improvement of dietary intakes, dialysis efficiency and an individualized choice of phosphate binders.

Comparison of rest-redistribution thallium-201 imaging and reinjection after stress-redistribution for the assessment of myocardial viability in patients with left ventricular dysfunction secondary to coronary artery disease.

Thallium (Tl)-201 reinjection after stress-redistribution (RI) imaging has been proven to accurately identify ischemic and viable myocardium. Quantitative Tl-201 analysis after stress has also shown viable myocardium in most mild to moderate (51% to 85% of normal uptake) irreversible Tl-201 defects. However, if the main clinical question is whether a region is viable, and not whether there is inducible ischemia, a resting protocol may be more appropriate. The aim of this study was to determine whether rest-redistribution (RD) quantitative Tl-201 single-photon emission tomographic imaging provides the same information on viable myocardium as Tl-201 RI. Thus, 15 patients (mean age 58 +/- 9 years) with chronic coronary artery disease and left ventricular dysfunction (ejection fraction 35 +/- 8%) were studied by both RI and RD Tl-201 single-photon emission tomography. Regional Tl-201 uptake was assessed quantitatively using a 16-segment model. When Tl-201 images were classified as normal/reversible (viable) or irreversible (nonviable), RI showed viable myocardium in 145 of 240 myocardial regions (60%), whereas RD showed it in 103 of 240 myocardial regions (43%). The 2 imaging protocols provided concordant information in 176 of 240 myocardial regions (73%). Among the 64 (27%) discordant regions, 53 (22%) were viable by RI and nonviable by RD, whereas 11 (5%) were viable by RD and nonviable by RI (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Reactivity of proximal and distal angiographically normal and stenotic coronary segments in chronic stable angina pectoris.

To assess whether vasoreactivity of significant coronary stenosis (greater than 50% intraluminal diameter reduction) and that of angiographically normal coronary segments differs in proximal and distal locations, 53 patients (40 men, 13 women, mean +/- standard deviation age 55 +/- 11 years) with chronic stable angina and angiographically documented coronary artery disease were studied. While abstaining from antianginal therapy, all 53 patients underwent coronary arteriography before and after 1 mg of intracoronary isosorbide dinitrate and 21 of the 53 also before and after 20 to 30 micrograms intracoronary ergonovine. Computerized quantitative angiography was used to assess changes in the intraluminal diameter of 126 normal coronary segments (63 proximal, 63 distal) and 43 significant coronary stenoses. Nitrates dilated proximal normal coronary segments by 7.4 +/- 1.2% and distal normal coronary segments by 15 +/- 1.7% (p less than 0.01). Significant proximal coronary stenoses dilated by 11 +/- 2.5% and distal stenoses by 23 +/- 2.8% (p less than 0.01) after nitrates. Ergonovine reduced the diameter of proximal normal coronary segments by 9.3 +/- 1.7% and that of normal distal segments by 15.5 +/- 1.4% (p less than 0.01). Proximal stenoses constricted by 11 +/- 2.2% and distal stenoses by 18.4 +/- 2.8% (p = 0.06). Analysis of segments showed that nitrates dilated 19 of 63 (30%) proximal normal segments by (greater than or equal to 10%), 31 of 63 (49%) distal (p less than 0.05) and 21 of 43 (49%) stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Pain threshold and tolerance in women with syndrome X and women with stable angina pectoris.

A recent report showed that during Holter monitoring of patients with syndrome X (typical anginal pain, positive exercise test response [at least 0.1 mV of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries), 50% of episodes of ischemic ST-segment depression were painful. This proportion is considerably higher than that in patients with chronic stable angina, which is about 30%. A significantly lower threshold and tolerance to painful stimuli was seen in a group of patients with chronic stable angina in whom 50% of episodes were painful compared with a group in whom only 5% of episodes were silent. Hence, patients with syndrome X may have enhanced sensitivity to painful stimuli. To investigate whether this difference was due to a lower threshold for painful stimuli in general, 12 patients with syndrome X and 10 (age- and sex-matched) with chronic stable angina were studied using the same battery of painful stimuli. Patients with syndrome X had a significantly lower threshold and tolerance for forearm ischemia (-36%, p less than 0.05, and -40%, p less than 0.001) and electrical skin stimulation (-37%, p less than 0.01, and -35%, p less than 0.001); the cold pressor test did not show significant differences (-7%, p = 0.391, and -1%, p = 0.818). Thus, patients with syndrome X in this study had significantly lower threshold and tolerance values for forearm ischemia and for electrical skin stimulation. These differences in sensitivity to pain may partly explain a higher incidence of painful ischemic episodes detected by ambulatory electrocardiographic monitoring during unrestricted daily life.

Lack of evidence for alpha-adrenergic receptor-mediated mechanisms in the genesis of ischemia in syndrome X.

Patients with syndrome X (typical angina pectoris, positive exercise tests [greater than or equal to 1 mm of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries) have a reduced coronary flow reserve due to inappropriate dilatation of small resistive vessels. To assess whether alpha-adrenergic mechanisms play a role in the genesis of ST-ischemic changes in syndrome X, 12 patients with this syndrome (2 men and 10 women, mean age 50 +/- 6 years) underwent exercise testing and 24-hour ambulatory electrocardiographic monitoring. They were done off treatment and after alpha blockade with prazosin and clonidine on 2 separate weeks. Despite treatment, all exercise tests remained positive and patients were stopped because of progressive angina pain. Compared to the off-treatment tests, exercise duration and heart rate-blood pressure product at 1 mm of ST-segment depression did not change significantly after prazosin (617 +/- 203 vs 663 +/- 203 seconds and 23,857 +/- 6,125 vs 22,098 +/- 4,816 beats/min X mm Hg, respectively) and clonidine (684 +/- 148 vs 649 +/- 80 seconds and 25,514 +/- 2,386 vs 24,567 +/- 2,001 beats/min X mm Hg, respectively). Ambulatory monitoring showed similar results regarding number of episodes of ST-segment depression greater than or equal to 0.1 mV during control and after prazosin (39 vs 38) or clonidine (26 vs 23) treatment. None of the 8 patients who also underwent provocative testing with phenylephrine had ischemic electrocardiographic changes; only 2 experienced chest pain during the test.(ABSTRACT TRUNCATED AT 250 WORDS)