The pentoxifylline experience: exercise testing reconsidered

OBJECTIVE: This study provides the first objective assessment of a complete patient population undergoing laparoscopic cholecystectomy in the steady state. The authors determined the frequency of complications, particularly bile duct, bowel, vascular injuries, and deaths. SUMMARY BACKGROUND DATA: This retrospective study, conducted for the Department of Defense healthcare system by the Civilian External Peer Review Program, is the second complete audit of laparoscopic cholecystectomy. Data were collected on 9130 patients undergoing laparoscopic cholecystectomy between January 1993 and May 1994. METHODS: The study sample consisted of clinical data abstracted from the complete records of 9054 (99.2%) of the 9130 laparoscopic cholecystectomies performed at 94 military medical treatment facilities. RESULTS: Of 10,458 cholecystectomies performed in the Military Health Services System, 9130 (87.3%) were laparoscopic and 1328 (12.7%) were traditional open procedures. Seventy-six medical records were incomplete: however, there was sufficient data to determine mortality and bile duct injury rates. Of the remaining 9054 cases, 6.09% experienced complications, including bile duct (0.41%), bowel (0.32%), and vascular injuries (0.10 percent). The mortality rate was 0.13%. Access via Veress technique was used in 57.6% and Hasson technique in 42.4% of patients. Intraoperative cholangiograms were performed in 42.7% of the cases with a success rate of 86.2%. Eight hundred ninety-two (9.8%) patients were converted to open cholecystectomies. CONCLUSIONS: In the steady state, despite an increase in the percentage of laparoscopic cholecystectomies performed for nonmalignant gallbladder disease, there continues to be minimal complications and low mortality.     

The appearance of gallop rhythm after exercise stress testing

BACKGROUND AND HYPOTHESIS: Although it is generally assumed that the appearance of an early diastolic gallop, or third heart sound, appearing immediately after exercise during treadmill stress testing, indicates the presence of serious myocardial disease, no systemically collected data are available to test this hypothesis. METHODS: The author performed auscultation on 3,679 patients undergoing routine treadmill testing together with thallium-201 perfusion scans. Exercise-induced diastolic sounds were related to the available clinical information and electrocardiographic and nuclear test results. These findings were compared with those of 665 randomly selected patients undergoing stress testing in whom such sounds were absent. RESULTS: A total of 165 patients had audible third heart sounds (Group 1). In comparison with those patients lacking such sounds (Group 2), there was a considerably greater prevalence of myocardial scarring (68.5 vs. 26.9%), abnormal lung uptake of thallium (40 vs. 12.8%), diabetes mellitus (20.6 vs. 6.2%), and left bundle-branch block on the resting electrocardiogram (ECG) (15.1 vs. 1.2%). In addition, 65 patients (39.3%) had dilatation of the left ventricle after exercise; 31 (18.8%) of these were also dilated at rest, but only 2 (1.2%) had a drop in blood pressure during stress. In those individuals also subjected to nuclear ventriculography, the average resting ejection fraction was 35%. Estimated exercise capacity was generally reduced in Group 1 (average peak of 6.6 METs), but 29 (17.6%) exceeded 9 METs. Sensitivity and specificity of electrocardiographic ST depression were relatively poor in the detection of perfusion defects within this group (36 and 62%, respectively). Of the 39 patients in Group 1 with a normal resting ECG, 19 (48.7%) had scar (usually posterior or lateral) on nuclear scans. In an additional 10 of this group, nuclear evidence of ischemia (often extensive) was found. CONCLUSIONS: An early or mid-diastolic gallop sound developing after exercise virtually always signifies myocardial disease with reduced myocardial function. Common associated findings are prior infarction (with or without associated ischemia), diabetes, and left bundle-branch block. When found in the presence of a normal resting ECG, this sound commonly signals the presence an occult left ventricular scar and, less commonly, extensive myocardial ischemia. In those patients manifesting such sounds, electrocardiographic ST changes in response to exercise appear limited in the detection of coronary ischemia.     

The role of cardiopulmonary exercise testing in lung and heart-lung transplantation

Cardiopulmonary exercise testing in recipients of lung and heart-lung transplants demonstrates significant restoration of exercise tolerance to individuals severely disabled by their underlying cardiopulmonary disease. Recipients can perform moderate levels of activity compatible with a normal lifestyle. Considerable exercise limitation, however, remains in most recipients as measured by maximum oxygen uptake and work rate, despite substantial improvement and often normalization in resting cardiopulmonary function. The amount of exercise limitation observed in recipients of single-lung, bilateral-lung, and heart-lung transplants is interestingly similar, and the pattern of limitation is somewhat stereotyped. Ventilatory abnormalities are never limiting. Gas exchange abnormalities are sometimes seen (especially in single-lung transplant recipients) but generally are not limiting. Cardiac dysfunction is sometimes seen (particularly in heart-lung transplant recipients) but also does not appear to be limiting. Peripheral factors limiting exercise (which may include abnormalities in the peripheral circulation and peripheral neuromuscular structure and function) are almost universally seen and are probably the primary determinant of exercise limitation in these patients. At present, the relative contributions of various peripheral factors to exercise limitation are unclear. Further study may help elucidate these issues.     

The utility of exercise testing after cardiac transplantation in older patients

We studied here the effects of 8 kinds of kampo-hozais clinically used to treat atopic dermatitis (Shofu-san, Toki-inshi, Unsei-in, Oren-gedoku-to, Ji-zuso-ippo, Jumi-haidoku-to, Juzen-taiho-to, Hochu-ekki-to) on delayed-type hypersensitivity (DTH), using three types of murine models such as picryl chloride (PC)-induced (contact hypersensitivity), sheep red blood cell (SRBC)-induced (Jones-Mote's reaction) and tuberculin-induced DTH response, in order to clarify and to compare the immunopharmacological action of kampo-hozais. Most of the kampo-hozais investigated here suppressed PC-induced contact hypersensitivity, especially at the inductive phase. Comparing the efficacies of these kampo-hozais on the three types of DTH responses in mice, they were generally divided into 4 groups. Shofu-san significantly reduced PC-induced and tuberculin-induced DTH responses but not a SRBC-induced DTH response. On the other hand, Toki-inshi reduced contact hypersensitivity, tuberculin type DTH response and Jones-Mote's reaction. Ji-zuso-ippo and Juzen-taiho-to suppressed mainly Jones-Mote's reaction, and Unsei-in, Oren-gedoku-to and Jumi-haidoku-to intensively suppressed contact hypersensitivity. We thought that these findings could help us understand how to use these kampo-hozais properly.     

Value of exercise treadmill testing in women

OBJECTIVES: We sought to determine the ability of a treadmill score to provide accurate diagnostic and prognostic risk estimates in women. BACKGROUND: Treadmill testing has been reported to have a lower accuracy for diagnosis of chest pain in women. The diagnostic and prognostic value of the Duke Treadmill Score (DTS) in women is unknown. METHODS: We determined the diagnostic and prognostic value of the DTS in 976 women and 2,249 men who underwent both treadmill testing and cardiac catheterization in a single institution from 1984 to 1994. RESULTS: Women and men differed significantly in DTS (1.6 vs. -0.3, p < 0.0001), disease prevalence (32% vs. 72% significant coronary artery disease [CAD], p < 0.001), and 2-year mortality (1.9% vs. 4.9%, p < 0.0001). The DTS provided information beyond clinical predictors of both coronary disease and survival in women and men. Although overall women had better survival, the DTS performed equally well in stratifying both genders into prognostic categories. The DTS actually performed better in women than in men for excluding disease, with fewer low risk women having any significant coronary disease (> or = 1 vessel with > or =75% stenosis) (20% vs. 47%, p < 0.001), or severe disease (3-vessel disease or > or =75% left main stenosis) (3.5% vs. 11.4%, p < 0.001). CONCLUSIONS: By combining several aspects of treadmill testing, the DTS effectively stratifies women into diagnostic and prognostic risk categories.     

Cardiovascular responses to treadmill exercise testing in anemia

Gunshot wounds are rare in Japan because of few regulatory laws against the possession of guns. Nevertheless such wounds are increasing in prevalence these days. Reports on the microscopic findings concerning these intracerebral lesions are fewer than those on the macroscopic findings in the scalp, the skull and the intracranial cavity. In this study we evaluated computed tomographical and histopathological findings in craniocerebral gunshot injuries. CASES: Nine patients with gunshot wounds to the head were presented. All were male and the age ranged from 17 to 66 years. Four were suicides and four were attempted murders and the last one was of unknown etiology. Morphological examination was performed on 5 autopsy cases. The distance of the bullet from the cranial cavity was as follows: long distance, 4 cases; close contiguity, 5 cases. The calibers of the weapons were as follows: 38 mm in 6 cases, 45 mm in 1 case and unknown in 2 cases. RESULTS: CT scans were examined in six cases, which revealed a missile track, hemorrhagic contusion, traumatic subarachnoid hemorrhage and marked tension pneumocephalus. In some cases, CT scan also revealed bony and metallic fragments, some deep within the cranial cavity. In the histopathological study, we found marked swollen brain (brain weight over 1500 mg) and hemorrhagic contusion in the vicinity of the missile track and interhemispheric fissure, and widespread traumatic subarachnoid hemorrhage and intraventricular hematoma. We would like to emphasize especially the remote contusion seen in the distant part of the missile track as well as massive exsudation and hemorrhage around the nerve fiber bundles. Remote contusion was observed in the inferior surface of the fronto-temporal lobes, and bilateral hemorrhagic contusion was seen in the vicinity of the superior longitudinal fissure on CT scans and autopsy findings. In one case, the bullet rotated within the intracranial cavity. In conclusion, nine cases of craniocerebral gunshot injuries were examined, while we also reviewed the medical literature concerning the shearing injury produced by gunshot brain wounds. The head injuries were further delineated by the correlation between autopsy and computerized tomography findings.     

Special considerations in exercise testing. Protocols, equipment, and testing athletes

A growing number of physicians are performing exercise tests in their offices for the purposes of diagnosing cardiopulmonary disease and assessing exercise capacity in patients with heart disease. Methodology of testing is important in making the most effective use of the information gathered from the test. Selecting an approach that fits the objectives of the test and the individual being tested is essential for accurate and reproducible results. This article discusses the various exercise protocols and equipment used in exercise testing.     

The safety of treadmill exercise stress testing in patients with abdominal aortic aneurysms

We retrospectively compared patients with NF1 with and without optic pathway gliomas (OPG) to determine the incidence and range of orbital developmental abnormalities and compared the incidence of OPG in African-Americans and whites. From cranial MR scans, we manually measured 14 orbital dimensions, compared them to published standards of Waitzman et al, calculated orbital volumes, and determined the presence or absence of volumetric symmetry (delta v) (delta v < or = 3 cm3 was considered to be symmetrical). We compared the results of orbital configurational assessment between patients with (group I) and those without OPG (group II). The study population comprised 58 patients, 24 boys, 18 African-American, and one Hispanic. Median age at imaging was 7 years (range 0.5-25.5 years). Fifty-eight percent had conformational abnormalities, 16 of whom had more than one abnormality (28%), the most frequent being increased intertemporal distance (n=10), increased lateral orbital distance (n=8), increased medial wall length (n=6), and decreased medial wall length (n=6). The increased intertemporal and lateral orbital distances may contribute to the appearance of hypertelorism. Only two patients had sphenoid wing hypoplasia. We found a high incidence of orbital dimensional abnormalities in the total population but more often saw multiple abnormalities in patients with OPG. However, no pattern of configurational abnormality emerged. OPG is less frequent in African-Americans. Orbital volumetric disparity seems to be independent of the presence of OPG.     

Oxygen deficit during exercise testing in heart failure. Relation to submaximal exercise tolerance

Measurements of oxygen deficit during submaximal exercise were correlated with the anaerobic threshold (as measured by gas exchange analysis), peak work rate on a ramp protocol, and the ability to perform constant work rate exercise in 10 male patients with New York Heart Association class 2 congestive heart failure and 12 age- and gender-matched normal controls. All subjects performed a maximal ramp exercise test for measurement of the anaerobic threshold. In addition, several 15-min constant work rate exercise sessions were conducted to evaluate oxygen deficit, measured as the area between the "ideal" square curve of oxygen consumption at the onset of constant work rate exercise and the actual exponentially shaped curve. Since the oxygen deficit significantly correlated with the plateau oxygen consumption during the 25-W constant work rate exercise (r = 0.61, p = 0.002), the oxygen deficit was normalized by the rectangular area of 15-min oxygen consumption above baseline. This normalized value significantly correlated with the inverse of the anaerobic threshold (r = 0.81, p < 0.0001). The logarithm of the normalized oxygen deficit significantly correlated with the maximum ramp work rate (r = -0.86, p < 0.0001) and the highest constant work rate sustained for 15 min (r = -0.82, p < 0.0001). In addition, the time to reach plateau oxygen consumption for the 25-W exercise significantly correlated with the inverse of the anaerobic threshold (r = -0.78, p < 0.0001), the maximum ramp work rate (r = -0.76, p < 0.0001), and the highest constant work rate sustained for 15 min (r = -0.74, p < 0.0001). Thus, the oxygen deficit seen in patients with heart failure during constant work rate exercise results from abnormally slow oxygen uptake kinetics and correlates with exercise capacity as measured by anaerobic threshold (via gas exchange analysis) and maximal and submaximal exercise tolerance. Oxygen deficit warrants further evaluation as a submaximal index of functional capacity in patients with heart failure.     

Determinants of oxygen uptake. Implications for exercise testing

For exercise modalities such as cycling which recruit a substantial muscle mass, muscle oxygen uptake (VO2) is the primary determinant of pulmonary VO2. Indeed, the kinetic complexities of pulmonary VO2 associated with exercise onset and the non-steady state of heavy (> lactate threshold) and severe [> asymptote of power-time relationship for high intensity exercise (W)] exercise reproduce with close temporal and quantitative fidelity those occurring across the exercising muscles. For moderate (< lactate threshold) exercise and also rapidly incremental work tests, pulmonary (and muscle) VO2 increases as a linear function of work rate (approximately equal to 9 to 11 ml O2/W/min) in accordance with theoretical determinations of muscle efficiency (approximately equal to 30%). In contrast, for constant load exercise performed in the heavy and severe domains, a slow component of the VO2 response is manifest and pulmonary and muscle VO2 increase as a function of time as well as work rate beyond the initial transient associated with exercise onset. In these instances, muscle efficiency is reduced as the VO2 cost per unit of work becomes elevated, and in the severe domain, this VO2 slow component drives VO2 to its maximum and fatigue ensues rapidly. At pulmonary maximum oxygen uptake (VO2max) during cycling, the maximal cardiac output places a low limiting ceiling on peak muscle blood flow, O2 delivery and thus muscle VO2. However, when the exercise is designed to recruit a smaller muscle mass (e.g. leg extensors, 2 to 3kg), mass-specific muscle blood flow and VO2 at maximal exercise are 2 to 3 times higher than during conventional cycling. consequently, for any exercise which recruits more than approximately equal to 5 to 6kg of muscle at pulmonary VO2max, there exists a mitochondrial or VO2 reserve capacity within the exercising muscles which cannot be accessed due to oxygen delivery limitations. The implications of these latter findings relate to the design of exercise tests. Specifically, if the purpose of exercise testing is to evaluate the oxidative capacity of a small muscle mass (< 5 to 6kg), the testing procedure should be designed to restrict the exercise to those muscles so that a central (cardiac output, muscle O2 delivery) limitation is not invoked. It must be appreciated that exercise which recruits a greater muscle mass will not stress the maximum mass-specific muscle blood flow and VO2 but rather the integration of central (cardiorespiratory) and peripheral (muscle O2 diffusing capacity) limitations.     

The physiology of erection

The majority of contemporary knowledge on the physiology of erection was assembled during the past thirty years. Today we consider erection as a multifactorial process. Mechanically it can be compared to an electromechanically controlled hydraulic system. Its function is conditioned by a number of mutually coordinated processes. As to nervous processes they include autonomous (parasympathetic and sympathetic) innervation, as well as somatic innervation (sensory and motor pathways). The control function is exerted by spinal as well as cerebral centres. As to mediators, in particular acetylcholine, nitrous oxide (NO) released from the endothelium are involved, noradrenaline, VIP (vasoactive intestinal polypeptide), CGRP (calcitonin gene-related peptide) and prostaglandins. The most important roles in the phase of erection are played by nitrous oxide and VIP. Erection can be either reflex erection, psychogenic or nocturnal or morning. It usually takes place in six stages (at rest, latent, the tumescence stage, complete erection, rigid erection and subsequently the stage of detumescence). Except for neurohumoral mechanisms an essential prerequisite for the development of erection are the arterial supply of the genital and the so-called venoocclusive mechanism. Erection takes the following course (simplified): erotogenic stimuli lead to the stimulation of the parasympathetic nerve-->vasodilating substances are released-->the s inusoids are filled with blood (tumescence stage)-->the venoocclusive mechanism starts to work: thus complete erection occurs. Then the contractions of the musculature of the perineum compress the proximal portions of the corpora cavernosa: this leads to rigid erection. Detumescence which occurs as a rule after ejaculation) is due to released noradrenaline (active stage) and the reduced tonus of the smooth muscles of the blood vessels (released endothelin and neuropeptide Y). Knowledge of the physiological mechanisms of erection made clinical diagnosis of their disorders and successful treatment of some forms of impotence possible.     

The physiology of spasticity

The contractile effects of ATP and related purine compounds on the isolated rabbit detrusor were investigated. It was found that ATP produced an initial rapid, phasic contraction followed by a slowly developing and maintained increase in tension. ADP caused a contraction closely mimicking the tonic response to ATP. The ADP induced contraction and the tonic response to ATP could both be abolished by indomethacin. beta, gamma-methylene ATP (APPCP), which is not degraded to ADP, elicited a rapid, phasic response, which could be abolished by nifedipine. AMP, dibutyryl-cAMP, and adenosine in low concentrations had no contractile effects; high concentrations of adenosine and 2-chloroadenosine, which is resistant to adenosine deaminase, decreased tone and spontaneous activity. The amplitude of the ATP induced contraction was positively correlated to the Ca2+-concentration in the extracellular medium; removal of Ca2+ abolished the ATP contraction before the responses to high K+ and carbachol disappeared. Responses to electrical field stimulation, mediated by non-cholinergic, non-adrenergic mechanisms were abolished by nifedipine and significantly reduced by indomethacin. It is concluded that in isolated rabbit detrusor, a direct contractile response can be elicited only by tripolyphosphates (ATP and APPCP), and that the diphosphate moiety ADP stimulates synthesis of prostaglandins The similarity between the effects of stimulation of non-cholinergic, non-adrenergic neurones and the phasic response to ATP supports the view that in rabbit detrusor ATP may be involved in excitation.     

Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart. The effects of chronic hypoxaemia and Fontan procedure

BACKGROUND: Patients with univentricular hearts have decreased exercise tolerance and may demonstrate exertional dyspnoea. It is not known if chronic hypoxaemia exacerbates exercise intolerance and contributes to symptomatic limitation. The extent to which surgical correction of a right-to-left shunt by a Fontan-type procedure can increase exercise tolerance by reducing arterial deoxygenation is not well documented. The cardiopulmonary exercise responses and the symptomatic status in two groups of univentricular patients, those who are cyanotic and those who are acyanotic with Fontan-type circulation, were compared. METHODS AND FINDINGS: Cardiopulmonary exercise testing was performed in 10 univentricular patients with rest or stress-induced cyanosis (age 30.5 +/- 2.3 [SE] years; 5 men) who had palliative or no surgery and eight patients (age 29.4 +/- 1.5 years; 4 men) with Fontan-type circulation. Peak oxygen consumption was comparable in both groups of univentricular patients (21.7 +/- 2.5 vs 21.0 +/- 1.9 ml.kg-1.min-1, P = 0.85) but was less than an age-matched group of 10 healthy subjects (34.7 +/- 1.9 ml.kg-1.min-1, P < 0.001 for both). Arterial oxygen saturation was 90.6% at rest in the cyanotic patients compared with 95.1% in the Fontan patients (P < 0.001) and at peak exercise, 66.2% compared with 90.5% (P < 0.001). Using a modified Borg scale (0-10), the symptoms of dyspnoea and fatigue were also assessed during exercise in the patient groups. The Borg scores for dyspnoea in the cyanotic and the corrected univentricular patients were, respectively, as follows: Stage 1: 0.5 vs 1.7; P= 0.04; Stage 2: 1.8 vs 2.3, P = 0.5; Stage 3: 3.0 vs 3.5, P = 0.7; Peak Exercise: 4.9 vs 4.8, P = 0.9. In addition, the Borg scores for fatigue were: Stage 1: 0.4 vs 1.6, P = 0.08; Stage 2: 2.0 vs 2.2, P = 0.9; Stage 3: 3.0 vs 4.3, P = 0.5; Peak Exercise: 4.9 vs 5.4, P = 0.5. The major limiting symptom at peak exercise was dyspnoea in four cyanotic patients compared with one in the Fontan group (Chi-square 0.982, P > 0.10). The arterial oxygen desaturation at peak exercise in the cyanotic patients limited by dyspnoea was not different from those limited by fatigue (67.5 +/- 10.1% vs 66.7 +/- 13.7%, P = 0.92). Exercise tolerance was also not related to the arterial oxygen saturation at peak exercise (r = 0.47, P = 0.17) in these patients. CONCLUSIONS: Despite correction with Fontan-type surgery, the exercise tolerance and symptoms of these univentricular patients remained similar to those who were cyanosed. Cyanotic patients have adjusted to chronic hypoxaemia and it does not appear to determine the exercise tolerance or the genesis of dyspnoea in these patients. Further randomized prospective studies are required to investigate the long-term benefits of Fontan-type procedures in these patients on exercise tolerance, symptoms and prognosis.