Plasma neurotransmitters, blood pressure, and heart rate during supine-resting, orthostasis, and moderate exercise conditions in major depressed patients.

Major depressed patients showed greater heart rate, noradrenaline, and free-serotonin values than normal. Conversely, platelet-serotonin values in major depressed patients were significantly lower than normal. Patients registered the normal differential blood pressure reduction during orthostasis. They also revealed progressive and significantly higher heart rate rises during orthostasis and exercise periods, when compared to normals. Whereas noradrenaline showed maximal rises during the two last periods, adrenaline only showed small but significant increase during exercise. The analysis of correlations, together with the above data, suggests that major depressed patients register maximal neural sympathetic activity as well as adrenal glands sympathetic hypoactivity. In addition, these patients show hyperparasympathetic activity, as reflected by the free-serotonin profile. Finally, the fact that both the Hamilton Depression Rating Scale and the self-rating Beck Depression Inventory correlated positively with noradrenaline/adrenaline ratio and free-serotonin values strongly suggests that both neural sympathetic and cholinergic mechanisms are involved in major depression.

Plasma neurotransmitters, blood pressure, and heart rate during supine resting, orthostasis, and moderate exercise in dysthymic depressed patients.

Dysthymic depressed patients showed platelet-serotonin (pS) + plasma-free serotonin values greater than normal as well as plasma noradrenaline values lower than normal during supine resting period (0'). Conversely, no significant differences were observed in the 0' values of any other of the measured parameters: systolic, diastolic and differential blood pressure (SBP, DBP, DP), heart rate (HR), adrenaline (Ad), dopamine (DA), cortisol, and platelet aggregability between patients and controls. Although patients showed then normal DP reduction at orthostasis (1'), this was not prevented by atropine as it does in controls. Patients but not normals showed significant rises of DBP at orthostasis and exercise (5') periods, which were positively correlated with NA rises. On the contrary, the abnormally raised resting fS values registered in patients showed progressive and significant reductions throughout the test that were negatively correlated with DBP-NA values. Adrenaline did not show the normal 5'-fS peak. The above findings suggest that dysthymics show hypoactivity of the two branches of the sympathetic system (neural + adrenal) along with hyperparasympathetic activity. Furthermore, their low NA + high pS values contrast with the high NA + low pS registered in major depressed subjects.

Neuropharmacologic treatment of bronchial asthma with the antidepressant tianeptine: a double-blind, crossover placebo-controlled study.

Studies have shown the levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic children with asthma correlates positively with clinical status and negatively with pulmonary function (forced expiratory volume in 1 second [FEV1]). Thus, reducing the concentration of free serotonin in plasma may be useful in treating children with asthma. We studied the effectiveness of tianeptine in treating these patients. Tianeptine is the only drug known to be able to reduce the level of free serotonin in plasma and to enhance the uptake by platelets. Sixty-nine of the 82 children with asthma initially enrolled participated in this study. Children were randomized to receive tianeptine or placebo or both in a double-blind crossover trial. The trial lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease of both clinical rating and free serotonin plasma levels and an increase in pulmonary function.

Pimozide therapy for trigeminal neuralgia.

Pimozide was compared with carbamazepine in a double-blind crossover trial in 48 patients with trigeminal neuralgia who were refractory to medical therapy. Pimozide treatment produced greater reduction in trigeminal neuralgia symptoms than carbamazepine treatment. All of the pimozide-treated patients improved, while only 56% of carbamazepine-treated patients were relieved of their pain. Although both drugs provoked some adverse effects, it was not necessary to interrupt the trial in any case. After this 24-week trial, all patients began receiving pimozide and were followed up according to an open-label study design. In all cases, the pimozide dosage was progressively reduced until the minimal effective dose was reached. Central and peripheral mechanisms that may underlie pimozide-induced improvement are discussed.

CPAP machine performance and altitude.

UNLABELLED: STUDY RATIONALE AND OBJECTIVE: Sleep-disordered breathing is commonly treated with nasally applied continuous positive airway pressure (CPAP). Typically, pressures are titrated to pneumatically splint the airway to prevent its collapse in response to negative inspiratory pressure. This investigation was prompted by several patient complaints of sleep-related breathing difficulty associated with travel to high altitudes. CPAP devices create pressure with fan-generated airflow; therefore, CPAP performance should behave according to collective fan laws. MEASUREMENTS AND RESULTS: In the present study, we examined the effect of simulated altitude change on four commercially available CPAP machines. Machines were tested using anatomic airway mannequins in an altitude chamber. We made three simulated ascents to 12,000 feet with machines set at 5, 10, and 12 cm H2O sea level pressure equivalents. We measured pressure using water manometers at 2,000-foot increments during ascent and descent. Mask pressures varied systematically with changing altitude in three machines. One machine, equipped with a pressure regulation feature, maintained pressure within 1 mm H2O at all pressure and altitude combinations. CONCLUSIONS: Altitude significantly alters delivered pressure according to predictions made by the fan laws, unless a unit has pressure-compensating features. Clinicians should consider this factor when CPAP is prescribed for patients who live or travel to places located at significantly higher or lower elevations than the titration site.

The serotonin uptake-enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind, crossover, placebo-controlled study.

Studies have shown that levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic patients with asthma correlates positively with clinical status and negatively with pulmonary function. Thus, reducing the concentration of free serotonin in plasma might be useful in treating patients with asthma. We studied the effectiveness of tianeptine in treating patients with asthma. Tianeptine is the only drug known to be able to reduce levels of free serotonin in plasma and to enhance uptake by platelets. In this study, 69 children with asthma were assigned in randomized fashion to receive tianeptine and/or placebo in a double-blind crossover trial that lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease in both clinical rating and free serotonin plasma levels and an increase in pulmonary function.

Treatment of ulcerative colitis with clonidine.

In the present 30-week, double-blind study of 45 ulcerative colitis (UC) patients treated with prednisone, sulfasalazine, clonidine, or placebo, we found that clonidine (an alpha 2 agonist) and prednisone were effective in treating idiopathic UC. Both drugs were more effective than sulfasalazine. Furthermore, clonidine potentiated prednisone and sulfasalazine effects. Clonidine was chosen because its effect on distal colon motility is similar to thioproperazine, an antipsychotic drug that, despite many adverse effects, possesses powerful anti-UC properties. Rating scales were outlined in order to evaluate clinical, endoscopic, histologic, and radiologic changes. Plasma cortisol levels, sedimentation rate, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, and other biochemical parameters were determined to assess the efficacy of each drug. Distal colon motility changes were also assessed. All our UC patients showed raised cortisol plasma levels and low sigmoidal tone during relapse periods. These parameters were reversed during remission periods. Peripheral and central mechanisms are discussed.

Peripheral blood immunological parameters in long-term benzodiazepine users.

Immunodeficiency is frequently invoked as an ethiopathogenetic factor for many somatic diseases. On the other hand, stress, depression, and psychotic disturbances are associated with severe immunological disorders. Taking into account that the benzodiazepines (BZ) are the psychoactive drugs more widely used than any other to treat psychological disturbances, it seems important to elucidate the immuno-enhancing or immunosuppressant potential of such drugs. Our goal was easily reached, since 69% of the outpatients visiting our Institute are chronic BZ consumers and because neurochemical, hormonal, immunological, and psychiatric investigations are routinely performed on all of our patients. In the present study, immune function was investigated on two occasions: while the patient was on active medication and 15 days after discontinuation. We concluded that chronic consumption of BZ provokes significant immunological disorders that should be further investigated. Said disorders could not be linked to a pre-existing affective disease or psychosis, since we only selected those BZ users in whom psychiatric investigations ruled out a past or present history of major psychiatric disease.

Treatment of bronchial asthma with tianeptine.

Although circulating catecholamines and free serotonin in the plasma (f-5-HT) were found to be increased during asthma attacks, only f-5-HT levels correlated positively with bronchoconstriction and clinical severity. Tianeptine, a drug that enhances serotonin uptake by platelets and serotonergic axons at the central nervous system (CNS), provoked an abrupt disappearance of asthma attacks. This fact explains why tianeptine has proven to be a powerful therapeutic tool in controlling asthma. Its success has been demonstrated not only in two double-blind placebo, cross-over trials, but through an open study lasting more than seven years that included over 25,000 asthmatic patients. In the present article, we discuss the peripheral and central nervous system mechanisms that may explain the therapeutic success of tianeptine. These are summarized below. F-5-HT is taken up by pulmonary endocrine cells (PNEC) located at the parasympathetic terminals. A presynaptic element, these cells release serotonin and potentiate acetylcholine (ACh)-induced contraction of bronchial muscle. This effect is mediated by 5-HT(3) and 5-HT(4) postsynaptic receptors located at the bronchial muscle. According to the above, the increased f-5-HT plasma level, triggered by both platelet aggregation and nocturnal and/or diurnal hyperparasympathetic activity, potentiates ACh-induced bronchoconstriction. The fact that serotonin released by medullary serotonergic axons stimulates the medullary vagal cardiorespiratory neurons obliges us to think that serotonin-induced CNS mechanisms are also involved. Furthermore, the finding that drugs that interfere with serotonin uptake, by both platelets and 5-HT-terminals, worsen asthma symptoms and are able to provoke asthma attacks gives additional support to the above peripheral and CNS mechanisms.

Adult respiratory distress syndrome (ARDS): the basics.

The term adult respiratory distress syndrome (ARDS) was first introduced by Ashbaugh and Petty more than two decades ago. Since then, our understanding of this clinicopathologic entity has increased significantly. However, little therapeutic progress has been achieved, and the mortality remains high. ARDS is characterized by diffuse pulmonary microvascular injury resulting in increased permeability and, thus, noncardiogenic pulmonary edema. Ventilation-perfusion lung studies have demonstrated that the predominant pathogenesis of hypoxemia in ARDS is related to intrapulmonary shunts. Common symptoms include dyspnea, tachypnea, dry cough, retrosternal discomfort, and moderate to severe respiratory distress. In most cases the diagnosis of ARDS is that of exclusion. The mainstay of therapy for this syndrome is the management of the underlying disorder causing it. To date, there are no specific pharmacologic interventions of proven value for the treatment of ARDS. Once the potentially treatable sources have been found and their therapy started, the main treatment for ARDS is supportive.

Candida lusitaniae catheter-related sepsis.

OBJECTIVE: To present a case describing Candida lusitaniae candidemia in an immunocompetent patient successfully treated with fluconazole antifungal therapy. Time-kill studies of the C. lusitaniae isolate using amphotericin B, and an extensive review of the literature are also presented. CASE SUMMARY: A 52-year-old immunocompetent Latin-American woman was admitted to the special care unit with severe sepsis. Her recent medical history included an exploratory laparotomy for gallstone pancreatitis, requiring cholecystectomy, segmental sigmoid colectomy, drainage of peritoneal abscesses, and a colostomy. In addition, the patient required a central venous catheter (CVC) placement for prolonged broad-spectrum antibiotic therapy and total parenteral nutrition therapy. Yeast was isolated from the abdominal abscess and blood cultures obtained on day 1, and from the catheter tip on day 5. The woman received initial empiric antifungal therapy with fluconazole, which was later changed to amphotericin B. After the yeast was identified as C. lusitaniae on day 8, this was changed to fluconazole for the duration of therapy. C. lusitaniae was not present in blood cultures taken two weeks after the CVC was removed, and the cultures remained negative thereafter. After a prolonged hospitalization, the patient was discharged home. DISCUSSION: Disseminated infections with C. lusitaniae usually occur in immunocompromised patients, although isolated reports of C. lusitaniae infections in immunocompetent patients have been described. Therapeutic challenges of C. lusitaniae treatment include its primary resistance to amphotericin B and species misidentification. Isolates recovered from our patient were submitted for fungus time--kill studies that suggested unique susceptibility patterns to amphotericin B, indicating a trend toward resistance. CONCLUSIONS: Based on variable susceptibility patterns of C. lusitaniae to amphotercin B and flucytosine, fluconazole is an appropriate choice as first-line therapy for C. lusitaniae candidemia.

Increased levels of free serotonin in plasma of symptomatic asthmatic patients.

BACKGROUND: Previous research has shown that symptomatic asthmatic patients have increased levels of norepinephrine, epinephrine, dopamine, free serotonin, and cortisol in plasma when compared with asymptomatic patients. OBJECTIVE: We investigated the relationship between plasma levels of catecholamines, free serotonin, and cortisol and clinical status and pulmonary function in symptomatic and asymptomatic patients with asthma. METHODS: We compared clinical severity, spirometry, and neuroendocrine factors at weeks 0, 1, 2, 3, and 4 in 57 symptomatic (forced expiratory volume in one second [FEV1] < 70%) and 72 asymptomatic (FEV1 > 80%) asthmatic patients. We used multiple analyses of variance (repeated measures) to interpret the data. In addition, we used the Pearson Product Moment Test to investigate correlations among the different variables. RESULTS: The clinical severity rating and levels of free serotonin, norepinephrine, epinephrine, dopamine, and cortisol were significantly higher in symptomatic asthmatic patients than those in asymptomatic patients (P < .001, in all cases). FEV1 was significantly lower in symptomatic patients than in asymptomatic patients. In symptomatic patients, the level of free serotonin correlated positively with the clinical severity rating (r = .564, P < .01) and negatively with FEV1 (r = -.959, P < .001). In addition, the clinical severity rating showed a negative correlation with FEV1 (r = -.359, P < .01). No significant correlations were found in asymptomatic patients. CONCLUSION: Our finding that free serotonin was the only neuroendocrine factor closely associated with clinical severity and pulmonary function suggests that this factor plays an important role in the pathophysiology of acute asthma.

Effects of clonidine on blood pressure, noradrenaline, cortisol, growth hormone, and prolactin plasma levels in high and low intestinal tone depressed patients.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE) plasma levels, cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 26 high intestinal tone (high-IT) and 24 low intestinal tone (low-IT) depressed patients, before and after the intramuscular injection of clonidine (2.5 micrograms/kg). A positive correlation was found between NE, DBP, and Hamilton Depression Rating Scale (HRS) values in low-IT depressed patients, while a negative correlation was found between HRS/IT and NE in high-IT depressed patients. Although clonidine induced significant reduction of SBP in both groups, the drug reduced DBP and NE in the low-IT group, only. CRT mean level was greater in the high-IT than in the low-IT depressed group. However, clonidine was unable to induce changes in CRT, GH, and PRL mean levels in any depressed group. Our results suggest that the clonidine-induced DBP reduction is a reliable index of sympathetic activity in depressed patients and that both parameters (DBP and IT) are useful physiological markers to differentiate two types of depressive syndromes.

Definite and sustained improvement with pimozide of two patients with severe trigeminal neuralgia. Some neurochemical, neurophysiological and neuroendocrinological findings.

In the present study we report two typical cases of trigeminal neuralgia in whom all conventional drug treatments were attempted without success, and in whom low doses of pimozide, a dopaminergic blocking agent, provoked a definite and sustained improvement. All biological markers used in these cases provided indirect evidence that a central serotonergic hypoactivity is an underlying mechanism in this disease. A low intestinal tone, raised levels of norepinephrine, dopamine, platelet serotonin and non-platelet plasma serotonin were registered during relapses and normalized during improvement periods. Pimozide was not able to improve the depressive state diagnosed in these two cases, nor in 13 other trigeminal neuralgia patients (not reported in this study).

Plasma neurotransmitters and cortisol in duodenal ulcer patients. Role of stress.

Levels of noradrenaline, adrenaline, dopamine, free serotonin, platelet serotonin, and cortisol were measured in the plasma of duodenal ulcer patients and controls. All subjects received antacids, and these substances were also measured. During relapse, all patients showed raised noradrenaline, adrenaline, dopamine, free serotonin, and cortisol values. In contrast, platelet serotonin showed very low values, which correlated negatively with all the former, except free serotonin. No correlations were found in parameters of the controls. After healing, significant reductions of noradrenaline, adrenaline, dopamine, free serotonin, and cortisol and significant increases of platelet serotonin values were observed. However, only dopamine, free serotonin, and cortisol reached normal values. Noradrenaline and adrenaline remained higher and platelet serotonin lower, both significantly more so than normals. These still-altered parameters showed similar correlations to those found during relapses. The present results demonstrate that some baseline autonomic system imbalance exists in patients, amplified and accentuated during relapse. We discuss the possibility that stress plays some role in triggering duodenal ulcer relapse.

Plasma neurotransmitters, blood pressure and heart rate during supine resting, orthostasis and moderate exercise in severely ill patients: a model of failing to cope with stress.

BACKGROUND: Previous clinical research has shown that severely ill (somatic) as well as many psychosomatic patients show raised noradrenaline (NA), adrenaline (AD), cortisol, free serotonin (f5HT) and platelet aggregability. Conversely, they show reduced NA/AD plasma ratio and platelet serotonin (p5HT). They also show adrenal hyperresponsiveness to an oral glucose load. These findings are opposed to those observed in depressed patients who show adrenal gland sympathetic hyporesponsiveness and neural sympathetic hyperactivity. OBJECTIVE: To investigate adrenal gland and neural sympathetic systems as well as the other parameters in nondrepressed severely ill patients through the orthostasis exercise stress test which in normals triggers NA but no AD rise. METHODS: We investigated 35 severely ill patients and their age- and sex-paired controls. Systolic, diastolic pulse pressure (PP), heart rate and neuroendocrine parameters were measured supine (0 min), at orthostasis (1 min) and exercise (5 min). A second test was performed 2 weeks later, after atropine injection. Multivariate analysis of variance, paired t test and Pearson product-moment test were employed. RESULTS: The normal PP orthostasis fall was not observed in patients. At this period, an abnormal AD peak substituted the normal NA peak. The normal p5HT-f5HT orthostasis-exercise peaks were absent in patients. Cortisol and platelet aggregability were raised in patients. CONCLUSIONS: Severely ill (somatic) patients responded to the orthostasis-exercise stress test with adrenal and corticosuprarenal but not neural sympathetic activity. They did not show the normal parasympathetic activity at orthostasis. This adrenal gland sympathetic hyperactivity registered in somatic patients is similar to that observed in mammals which fail to cope with stress and contrary to the profile registered in depressed subjects who show NA but not AD rise.