A graphical model framework for decoding in the visual ERP-based BCI speller.

We present a graphical model framework for decoding in the visual ERP-based speller system. The proposed framework allows researchers to build generative models from which the decoding rules are obtained in a straightforward manner. We suggest two models for generating brain signals conditioned on the stimulus events. Both models incorporate letter frequency information but assume different dependencies between brain signals and stimulus events. For both models, we derive decoding rules and perform a discriminative training. We show on real visual speller data how decoding performance improves by incorporating letter frequency information and using a more realistic graphical model for the dependencies between the brain signals and the stimulus events. Furthermore, we discuss how the standard approach to decoding can be seen as a special case of the graphical model framework. The letter also gives more insight into the discriminative approach for decoding in the visual speller system.

Factor analysis, including antihypertensive medication, of the outcome of pregnancy in pregnancy-associated hypertension.

AIM: To study the influence of different maternal factors, including antihypertensive medication, on the outcome of pregnancy in primi- and multiparas with pregnancy-associated hypertension. METHODS: A retrospective, multiple-variate analysis was undertaken of the influence of several maternal factors, including antihypertensive medication, on fetal death and Apgar scores and the correlation between the medication and the number of caesarean sections in 127 episodes of pregnancy-associated hypertension was studied for the whole group as well as for primi- and multiparas separately. Of the multiparas, 40.8% had a history of preeclampsia, 19.7% of chronic hypertension and 9.2% of diabetes mellitus. Antihypertensive treatment aimed at achieving a blood pressure of 140/90 mm Hg. Forty-one patients (32.3%) received intravenous hydralazine, 25 (19.7%) received nifedipine per os and 44 (34.6%) received labetalol per os. RESULTS: The maximum systolic and diastolic blood pressure in the patients given intravenous hydralazine, nifedipine per os or labetalol per os did not differ, whereas in the multiparas, the number of patients who reached the target blood pressure while using labetalol was higher than with the two other medications, especially in comparison with intravenous hydralazine. For the primiparas, the time of delivery was the only factor with a significant impact on the Apgar scores. In the multiparas, there was an additional negative influence of the use of intravenous hydralazine. This was not seen in the patients using nifedipine and labetalol. CONCLUSIONS: The results suggest that in multiparas, intravenous hydralazine is possibly associated with more fetal distress when compared to primiparas.

Non-typhoid Salmonella septicemia and visceral leishmaniasis in a renal transplant patient.

BACKGROUND: We report on a renal transplant patient with recurrent attacks of fever, in which Salmonella septicemia as well as visceral leishmaniasis were diagnosed. PATIENT: The patient was a 62-year-old man with diabetic nephropathy and a living related kidney transplantation. RESULTS: Nearly 2 years after the transplantation, the patient developed recurrent attacks of fever, which were initially diagnosed as non-typhoid salmonellosis and improved after treatment. Three months later, he had relapses of fever. As the patient developed pancytopenia, a bone marrow aspiration was done, showing Leishmania parasites. The patient responded well to treatment with sodium stibogluconate. CONCLUSIONS: A high index of suspicion, together with better diagnostic assays to detect visceral leishmaniasis, is warranted in the diagnostic work-up of any fever of unknown origin in immunocompromised patients, especially in endemic areas.

Regression of Post-transplant Kaposi's sarcoma after Replacing Cyclosporine with Mycophenolate Mofetil.

Kaposi's sarcoma (KS) has been recently linked with human herpes virus-8 (HHV-8) infection. Other risk factors include the use of cyclosporine and polyclonal anti-lymphocyte sera. Reduction of the immunosuppression, in particular cyclosporine, leads to regression or disappearance of the tumor in a significant number of patients. There are few publications about the response of the tumor to the newer immunosuppressive agent mycophenolate mofetil (MMF). We describe here a 52-year-old woman, who developed KS 22 months after living related transplantation. The sarcoma lesions disappeared after replacing cyclosporine and azathioprine by MMF, while the allograft function remained stable. This case suggests the importance of discontinuation of cyclosporine in the treatment of post-transplant KS. MMF, while maintaining allograft function in the absence of cyclosporine, apparently did not interfere with the regression of the tumor.

Hypertension in pregnancy: presentation, management and outcome - a retrospective analysis of 135 cases.

In view of continuous controversies regarding hypertension in pregnancy and lack of reports on this subject in Saudi Arabia, we retrospectively studied 135 episodes of hypertension in pregnancy in 123 patients over a 9-years period. Fifty-one (37.8%) were primiparas, the remaining were multiparas from 2 nd up to 14 11 pregnancy. Of the multiparas, 44% had a history of pregnancy induced hypertension, 26% of chronic hypertension, and 13% of diabetes mellitus. " HELLP"-syndrome occurred in nine and eclampsia in four pregnancies. There were 10 foetal deaths, eight of them presented on admission. Chronic hypertension and diabetes mellitus approached significance as risk factors for foetal death (logistic regression analysis). For the whole group, the time of delivery was the only factor with significant impact on the Apgar score (multiple regression analysis), with an additional negative influence of diabetes mellitus and intravenous hydralazine in the multiparas. When the patients with chronic hypertension and diabetes mellitus were not included, hydralazine lost its significance. The finding suggests that intravenous hydralazine should be given in multiparas with caution, particularly in the presence of chronic hypertension and diabetes mellitus. There was a significant relation of the birth weight to the time of delivery, the serum levels of total protein and, especially in multiparas, of uric acid, confirming the importance of these factors as markers of the severity of pregnancy induced hypertension. The hypertension persisted in patients not known to have chronic hypertension in 9.6% of pregnancies during a follow-up ranging from 2 months up to 9 years.

Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration.

To investigate the effect of glucose (Glc) infusion on endurance performance after beta-adrenoceptor blockade, eight healthy male volunteers performed four endurance cycle ergometer tests at 67% of maximal work load after 80 mg of propranolol (Pr) or placebo (Pl) were administered orally in combination with a continuous infusion of Glc (0.5 g/min) or saline (Sal). The order of the tests was randomized. Endurance times were 53 +/- 6 (SE), 64 +/- 7, 26 +/- 5, and 31 +/- 6 min after Pl+Sal, Pl+Glc, Pr+Sal, and Pr+Glc, respectively (P < 0.001). Glc infusion increased endurance after Pl (P < 0.05) but not after Pr. Glc infusion resulted in significantly higher plasma Glc concentrations during exercise compared with Sal infusion (P < 0.001). Glc infusion had no effect on cardiorespiratory or other metabolic variables. Plasma ammonia concentration was increased during the Pr tests (P < 0.001) but reached similar values at exhaustion in all tests and was not affected by Glc infusion. The maintenance of plasma Glc concentration during endurance exercise at or above preexercise levels did not improve the reduction of endurance performance after Pr, indicating that the availability of blood Glc is not a limiting factor in this process.

Observations in a Saudi-Arabian dialysis population over a 13-year period.

In contrast to Europe and the USA, data concerning dialysis treatment in Middle Eastern countries like Saudi Arabia are lacking. We therefore studied 325 patients (150 females and 175 males) in one dialysis centre over a 13-year period. The number of primary renal diseases of uncertain aetiology and of pyelo/interstital nephritis caused by renal stone disease was high (46% and 4.9% resp.), that of diabetic nephropathy (14.8%) not much different from EDTA figures, while adult polycystic kidney disease was seen in only four patients (1.2%, versus EDTA: 5.5%). Sixty-one percent needed antihypertensive medication to control the blood pressure, less than reported by the EDTA. Nineteen patients (5.8%) had pericarditis, 38% radiographic signs of renal bone disease and eight patients required parathyroidectomy. Only two patients had carpal tunnel syndrome. Over the 13-year period the number of HBsAg-positive patients was 14%, reflecting the high prevalence of this disease in the country, but in the last 4-5 years the incidence dropped markedly (3% in 1993). In 1993, 40% of the 67 patients on dialysis had hepatitis C (HCV) antibodies of which 19 (70%) were HCV-RNA positive. Although tuberculosis (mainly extra-pulmonary) was common (9.2%), no patient died because of this disease. Cardiovascular factors contributed in the same degree to the causes of death as in Europe: 63% versus 62%. One hundred and fourteen patients (35%) had a successful kidney transplant.

Cyclosporine in the treatment of lupus nephritis including two patients treated during pregnancy.

Although the combination of corticosteroids and intermittent pulse doses of cyclophosphamide has considerably improved the prognosis of lupus nephritis, there are still some unanswered questions about this regimen, in particular its use in pregnancy. As cyclosporine appeared to be effective in experimental models of lupus nephritis, some studies have been performed using this drug in patients with lupus nephritis. However, there was no mention of pregnancy in these patients. In view of the large experience with cyclosporine during pregnancy in renal transplant recipients and its established safety concerning teratogenicity, we decided to treat 5 young female patients having lupus nephritis with cyclosporine in combination with low-dose prednisone. Two of these patients were pregnant and both had successful delivery. During the follow-up period of 7-35 months there were no signs of flare-up of the lupus nephritis, except in one case where the patient accidentally discontinued the medication. In a second patient there was a slight increase of the serum creatinine level. Otherwise, the renal and immunological parameters improved or remained stable during the observation period. Hypertension developed in 3 cases. These preliminary results support the further evaluation of cyclosporine as an alternative to cyclophosphamide in the treatment of lupus nephritis, especially in young female patients with pregnancy or at high risk for pregnancy.

Nebivolol in hypertension: a double-blind placebo-controlled multicenter study assessing its antihypertensive efficacy and impact on quality of life.

Nebivolol is a selective beta 1-adrenoceptor antagonist with a particular hemodynamic profile, suggesting an ancillary vasodilating property. The nature of this ancillary property is still unknown. The present double-blind placebo-controlled multicenter study investigated the effect of 4 and 8 weeks treatment with nebivolol 5 mg once daily on blood pressure (BP), heart rate (HR), blood parameters, and ECG. The effect on quality of life perception and the adverse effect profile were also studied. Nebivolol 5 mg once daily had a good antihypertensive effect in supine (10/8 mm Hg) as well as in standing position (16/10 mm Hg). Of 114 patients studied, 65% had either normalization of or > 10% reduction in diastolic BP (DBP). No evidence of drug tolerance was observed during the 8-week treatment period. Quality of life perception, as measured with the Inventory of Subjective Health (ISH) and the perceived health rating scale, was not impaired with nebivolol during the entire 8-week study. Nebivolol showed a favorable adverse effect profile and appeared to be devoid of central nervous system (CNS) adverse effects. The total number of complaints with nebivolol treatment did not differ from the number of complaints with placebo treatment. ECG and blood analyses, also show that nebivolol is safe and well tolerated. This study also shows that absolute drug-induced changes in quality of life perception can be assessed only in a placebo-controlled study and that comparison with baseline might be incorrect and misleading.

Effect of increased plasma non-esterified fatty acid concentrations on endurance performance during beta-adrenoceptor blockade.

Inhibition of adipose tissue lipolysis, leading to a reduced availability of non-esterified fatty acids for energy production in the active skeletal muscles, may be involved in the impairment of endurance exercise capacity after administration of a beta-adrenoceptor blocking agent. The effect of increasing the availability of plasma NEFA during exercise after beta-blocker administration was studied. In a double-blind, randomized cross-over study 12 healthy volunteers were treated for 14 days with placebo, atenolol, and propranolol. On the 7th and 14th day of each treatment period an endurance exercise test at 70% of maximal aerobic power until exhaustion was performed while a continuous infusion of saline or triglycerides (Intralipid)+heparin was administered. Endurance time was reduced by 11% (n.s.) during atenolol and 40% (p < 0.01) during propranolol. Intralipid administration had no statistically significant effect on endurance in any treatment. Plasma NEFA and glycerol concentrations were elevated above control levels during Intralipid infusion, plasma glucose and lactate concentrations were unaffected. These results suggest that reduced availability of NEFA is not a major factor in the reduction of endurance performance during beta-adrenoceptor blockade, although an effect of beta-blockade on NEFA membrane transport cannot be excluded.

Exercise and the pharmacokinetics of propranolol, verapamil and atenolol.

The volumes of distribution of the beta-adrenoceptor blocking agents propranolol and atenolol, and the calcium antagonist verapamil, during exercise have been investigated. Changes in the plasma concentrations of atenolol and propranolol during exhaustive exercise at 70% of maximal aerobic power were compared after 1 week of oral treatment (propranolol 80 mg b.d. and atenolol 100 mg once daily) in 12 healthy volunteers. In a second study the effect of 10 min exercise at 50% of maximal aerobic power on steady state plasma concentrations of propranolol, atenolol and verapamil was compared in 7 healthy subjects. The drugs were administered by a continuous intravenous infusion. The plasma concentration of atenolol was not changed by exercise in either study, but the plasma concentrations of propranolol and verapamil were significantly increased in both studies. However, after correction for changes in plasma volume during exercise, the plasma propranolol concentration was not significantly elevated in the second study. From the results it is concluded that exercise led to a reduction in the volume of distribution of propranolol during prolonged exercise (25 min) at 70% Wmax, which was not clearly demonstrable during 10 min exercise at 50% Wmax. The volume of distribution of verapamil was reduced during 10 min exercise at 50% Wmax. No change in the volume of distribution of atenolol during exercise could be shown. The changes in the volumes of distribution of propranolol and verapamil during exercise may contribute to preventing an increase in the half-life of these drugs in patients performing prolonged physical exercise.

Submaximal endurance exercise performance during enalapril treatment in patients with essential hypertension.

In a double-blind randomized crossover study of 10 patients with mild essential hypertension, the influence of antihypertensive treatment with the angiotensin-I converting enzyme inhibitor enalapril (a single dose of 10 mg.day-1) on submaximal endurance exercise performance at a work rate eliciting a heart rate of 150 beats/min was studied. Resting and exercise blood pressure were significantly reduced during enalapril therapy. Heart rate was unaffected. Submaximal endurance exercise performance was reduced by 12% (p = 0.06). Plasma lactate concentrations were significantly increased and serum nonesterified fatty acid concentrations were decreased during exercise in patients receiving enalapril treatment. Plasma glucose and potassium levels and serum glycerol concentrations were not influenced by enalapril treatment. Because the impairment of endurance performance during enalapril treatment is relatively small compared with the reductions caused by other antihypertensive agents, such as beta-adrenoceptor blocking agents or diuretics, it is of minor clinical importance for most physically active patients with hypertension.

The influence of chronic treatment with verapamil on plasma atrial natriuretic peptide levels in young and elderly hypertensive patients.

In a double-blind, placebo-controlled cross-over study, the plasma atrial natriuretic peptide (ANP) levels of nine young and ten elderly hypertensive patients were compared after placebo and after treatment with 120 mg verapamil given three times daily over 4 weeks. During placebo, plasma ANP levels proved to be higher in elderly patients than in young subjects. Chronic treatment with verapamil induced a rise in ANP levels in both young and elderly patients with hypertension.

Verapamil and nebivolol improve carotid artery distensibility in hypertensive patients.

The effects of verapamil (a calcium antagonist) and nebivolol (a novel, selective beta 1-adrenoceptor blocker) on carotid artery distensibility and cross-sectional compliance were studied non-invasively in hypertensive patients with the use of a high-resolution multigate pulsed Doppler system. Arm blood pressure measurements were made with an automated device (Dinamap). After a 4-week washout period, 19 patients (aged 21-73 years) with essential hypertension entered a double-blind randomized placebo-controlled crossover study with 120 mg verapamil or placebo three times a day for 4 weeks. After the administration of verapamil, carotid artery distensibility and cross-sectional compliance were significantly larger (P less than 0.05) than after placebo. Using the same protocol, 29 patients (aged 25-70 years) were given 5 mg nebivolol or placebo once a day for 4 weeks. After the administration of nebivolol, carotid artery distensibility and cross-sectional compliance were significantly larger (P less than 0.05) than after placebo. In both studies no significant differences in diameter and pulse pressure were found between placebo and verapamil or nebivolol. Blood pressure was decreased similarly with both verapamil and nebivolol. These results indicate that both verapamil and nebivolol favourably influence carotid artery distensibility and cross-sectional compliance of the common carotid artery, resulting in a better management of the systolic pressure pulse. The improved carotid artery distensibility may help to protect the patient against atherosclerotic complications of hypertension.