Secondary hypogammaglobilinemia after use of carbamazepine: case report and review

Immunologic disorders related to anticonvulsant therapy have been described in the last three decades, including cellular and humoral alterations that result in recurrent infections; however, the physiopathologic mechanisms are not completely understood. This report describes a patient with complex partial epilepsy and hypogammaglobulinemia while in treatment with carbamazepine, with significant improvement in clinical signs and laboratory tests after substitution to sodium valproate. The authors stress the importance of clinical and laboratory evaluation of patients in continuous anticonvulsant therapy, including immunoglobulins levels and peripheral blood evaluations.

Immunoglobulin E-rheumatoid factor in juvenile rheumatoid arthritis

OBJECTIVES: To determine the presence of immunoglobulin E-rheumatoid factor in patients with juvenile rheumatoid arthritis and to correlate it with clinical and laboratory parameters. METHODS: A multicenter prospective study was carried out from January 1993 to January 1999 with the enrollment of 3 centers of pediatric rheumatology. Ninety-one children with juvenile rheumatoid arthritis diagnosed according to the American College of Rheumatology criteria were studied: 38 (42%) with systemic, 28 (31%) with pauciarticular, and 25 (27%) with polyarticular onset. Ages ranged from 2.1 years to 22.6 years (mean 10.5 ± 4.7), with 59 (65%) girls. The control group consisted of 45 healthy children. The detection of immunoglobulin E-rheumatoid factor was carried out utilizing an enzyme-linked immunosorbent assay. Associations of immunoglobulin E-rheumatoid factor with immunoglobulin M-rheumatoid factor (latex agglutination test), total serum immunoglobulin E, erythrocyte sedimentation rate, antinuclear antibody, and functional and radiological classes III or IV were analyzed. RESULTS: Positive immunoglobulin E-rheumatoid factor was found in 15 (16.5%) of the 91 children with juvenile rheumatoid arthritis: 7 (18.5%) with systemic, 5 (18%) with pauciarticular, and 3 (12%) with polyarticular onset. A significant correlation was observed between immunoglobulin E-rheumatoid factor and total serum immunoglobulin E in the juvenile rheumatoid arthritis patients. No correlation was found between immunoglobulin E-rheumatoid factor and positive latex agglutination slide test, erythrocyte sedimentation rate, antinuclear antibody, or the functional and radiological classes III or IV in any disease onset group. In 4 out of 45 control children (8.9%), immunoglobulin E-rheumatoid factor was positive but with no correlation with total serum immunoglobulin E levels. CONCLUSIONS: Immunoglobulin E-rheumatoid factor could be detected in 16.5% of juvenile rheumatoid arthritis patients, particularly in those with high levels of total serum immunoglobulin E, and immunoglobulin E-rheumatoid factor appears not to be associated with disease activity or severity.

Prevalence of antinuclear autoantibodies in the serum of normal blood dornors

OBJECTIVE:To examine the presence of serum antinuclear autoantibodies in a healthy population. METHODS: Serum of 500 normal blood donors between 18 and 60 years of age were tested for the presence of autoantibodies. Antinuclear antibodies were detected by indirect immunofluorescence technique using HEp-2 epithelial cells as the substrate. The presence of dnaN was detected by indirect immunofluorescence technique using Critidia lucillae as the substrate. Anti-SSA (RO), anti-SSB (LA), anti-Sm, and anti-RNP were determined by double radial immunodiffusion. RESULTS: In the evaluation of the presence of serum antibodies, antinuclear antibodies were detected in 22.6% of the sera. The presence of other antibodies was not significant. The majority of the titers were 1:40. CONCLUSION: The presence of autoantibodies is not necessarily pathologic and has to be related to the age group, gender, and clinical condition of the patient.

Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence

Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. PATIENTS AND METHODS: Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses). RESULTS: Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases. CONCLUSION: Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus follow-up, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.

Haematophagic behavior in laboratory of Lutzomyia cruzi (Mangabeira) (Diptera: Psychodidae) in relation to three mammalian blood sources in Manaus, Brazil

The sand fly Lutzomyia cruzi is considered as one of vectors of visceral leishmaniasis in Brazil. This work examined optimum feeding age, feeding time, host preference, fecundity rates, and female blood meal volume taken by single females from a closed colony of L. cruzi. Mean feeding time was longer on hamsters, 6.6 minutes, than on humans, 5.7 minutes. 49.1% of the 48h-old flies fed on humans and 43.3% of 72h-old flies fed on hamsters. Of a total of 120 females, 61% fed on humans and 25% fed on hamsters. Total fecundity was significantly higher in females fed on hamster than on human or opossum. Laboratory-reared L. cruzi females fed earlier, more promptly, and preferably on humans than on hamsters when offered these blood-meal sources simultaneously. The blood-meal volume is higher in females fed on hamsters than other hosts (human and opossum).

In vitro screening of Amazonian plants for hemolytic activity and inhibition of platelet aggregation in human blood

In the present study, different aerial parts from twelve Amazonian plant species found in the National Institute for Amazon Research's (INPA's) Adolpho Ducke Forest Reserve (in Manaus, Amazonas, Brazil) were collected. Separate portions of dried, ground plant materials were extracted with water (by infusion), methanol and chloroform (by continuous liquid-solid extraction) and solvents were removed first by rotary evaporation, and finally by freeze-drying which yielded a total of seventy-one freeze-dried extracts for evaluation. These extracts were evaluated initially at concentrations of 500 and 100 µg/mL for in vitro hemolytic activity and in vitro inhibition of platelet aggregation in human blood, respectively. Sixteen extracts (23 % of all extracts tested, 42 % of all plant species), representing the following plants: Chaunochiton kappleri (Olacaceae), Diclinanona calycina (Annonaceae), Paypayrola grandiflora (Violaceae), Pleurisanthes parviflora (Icacinaceae), Sarcaulus brasiliensis (Sapotaceae), exhibited significant inhibitory activity towards human platelet aggregation. A group of extracts with antiplatelet aggregation activity having no in vitro hemolytic activity has therefore been identified. Three extracts (4 %), all derived from Elaeoluma nuda (Sapotaceae), exhibited hemolytic activity. None of the plant species in this study has known use in traditional medicine. So, these data serve as a baseline or minimum of antiplatelet and hemolytic activities (and potential usefulness) of non-medicinal plants from the Amazon forest. Finally, in general, these are the first data on hemolytic and inhibitory activity on platelet aggregation for the genera which these plant species represent.

Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room

OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP) in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3%) complained of high BP, and 61 (76.3%) received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%). One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5%) were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits). Currently, the therapeutic approach is not recommended, even in specialized clinics.

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

Laboratory assessment of the hypertensive individual. Value of the main guidelines for high blood pressure

OBJECTIVE: To determine if abnormal laboratory findings are more common in individuals with hypertension and in those with other risk factors, such as obesity, smoking and alcohol ingestion. METHODS: A study was carried out in the general outpatient clinics of a university hospital (145 individuals without previous diagnosis of hypertension) and the following variables were assessed: high blood pressure (as defined by the VI Joint National Committee on Prevention, Detection and Treatment of High Blood Pressure - VI JNC), obesity [calculated using body mass index (BMI)], tobacco use, and alcoholic ingestion. The laboratory examinations consisted of the following tests: hemogram, glycemia, uric acid, potassium, total/HDL-fraction cholesterol, triglycerides, calcium and creatinine. RESULTS: High blood pressure was not associated with a higher number of abnormal laboratory tests. Hypertensive individuals with a BMI > or = 25kg/m² or normotensive obese individuals, however, had a higher frequency of diabetes (12X), hypertriglyceridemia (3X), and hypercholesterolemia (2X), as compared with hypertensive individuals with BMI <25kg/m² and preobese/normal weight normotensive individuals. CONCLUSION: High blood pressure is not associated with a higher frequency of abnormal laboratory tests. The association of high blood pressure and obesity, however, increases the detection of diabetes and dyslipidemias.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE: To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS: 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52±14 years). The average duration of the siesta was 118±58 minutes. RESULTS: (average ± standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138±16/85±11 vs 139±16/86±11 mmHg, p<0.05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION: The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.

End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the "transient arterial hypertension protocol" (TAH), and a quick and 10 min sustained elevation, the "sustained arterial hypertension protocol"(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it "transitory" or "sustained", did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

Influence of caffeine on blood pressure and platelet aggregation

OBJECTIVE: Studies have demonstrated that methylxanthines, such as caffeine, are A1 and A2 adenosine receptor antagonists found in the brain, heart, lungs, peripheral vessels, and platelets. Considering the high consumption of products with caffeine in their composition, in Brazil and throughout the rest of the world, the authors proposed to observe the effects of this substance on blood pressure and platelet aggregation. METHODS: Thirteen young adults, ranging from 21 to 27 years of age, participated in this study. Each individual took 750mg/day of caffeine (250mg tid), over a period of seven days. The effects on blood pressure were analyzed through the pressor test with handgrip, and platelet aggregation was analyzed using adenosine diphosphate, collagen, and adrenaline. RESULTS: Diastolic pressure showed a significant increase 24 hours after the first intake (p<0.05). This effect, however, disappeared in the subsequent days. The platelet aggregation tests did not reveal statistically significant alterations, at any time during the study. CONCLUSION: The data suggest that caffeine increases diastolic blood pressure at the beginning of caffeine intake. This hypertensive effect disappears with chronic use. The absence of alterations in platelet aggregation indicates the need for larger randomized studies.

Ambulatory blood pressure monitoring and microalbuminuria in normotensive subjects with insulin-dependent diabetes mellitus

OBJECTIVE: To assess the association between microalbuminuria with ambulatory blood pressure monitoring in normotensive individuals with insulin-dependent diabetes mellitus. METHODS: Thirty-seven patients underwent determination of the rate of urinary excretion of albumin through radioimmunoassay and ambulatory blood pressure monitoring. Their mean age was 26.5±6.7 years, and the mean duration of their disease was 8 (1-34) years. Microalbuminuria was defined as urinary excretion of albumin > or = 20 and <200µg/min in at least 2 out of 3 urine samples. RESULTS: Nine (24.3%) patients were microalbuminuric. Ambulatory blood pressure monitoring in the microalbuminuric patients had higher mean pressure values, mainly the systolic pressure, during sleep as compared with that in the normoalbuminuric patients (120.1±8.3 vs 110.8±7.1 mmHg; p=0.007). The pressure load was higher in the microalbuminuric individuals, mainly the systolic pressure load during wakefulness [6.3 (2.9-45.9) vs 1.6 (0-16%); p=0.001]. This was the variable that better correlated with the urinary excretion of albumin (rS=0.61; p<0.001). Systolic pressure load >50% and diastolic pressure load > 30% during sleep was associated with microalbuminuria (p=0.008). The pressure drop during sleep did not differ between the groups. CONCLUSION: Microalbuminuric normotensive insulin-dependent diabetic patients show greater mean pressure value and pressure load during ambulatory blood pressure monitoring, and these variables correlate with urinary excretion of albumin.

Response of blood pressure to maximum exercise in hypertensive patients under different therapeutic programs

OBJECTIVE: To evaluate the behavior of blood pressure during exercise in patients with hypertension controlled by frontline antihypertension drugs. METHODS: From 979ergometric tests we retrospectively selected 49 hipertensive patients (19 males). The age was 53±12 years old and normal range rest arterial pressure (<=140/90 mmHg) all on pharmacological monotherapy. There were 12 on beta blockers; 14 on calcium antagonists, 13 on diuretics and 10 on angiotensin converting enzyme inhibitor. Abnormal exercise behhavior of blood pressure was diagnosed if anyone of the following criteria was detected: peak systolic pressure above 220 mmHg, raising of systolic pressure > or = 10 mmHg/MET; or increase of diastolic pressure greater than 15 mmHg. RESULTS: Physiologic response of arterial blood pressure occurred in 50% of patients on beta blockers, the best one (p<0.05), in 36% and 31% on calcium antagonists and on diuretics, respectively, and in 20% on angiotensin converting enzyme inhibitor, the later the leastr one (p<0.05). CONCLUSION: Beta-blockers were more effective than calcium antagonists, diuretics and angiotensin-converting enzyme inhibitors in controlling blood pressure during exercise, and angiotensin converting enzyme inhibitors the least effective drugs.

Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: <=90 (n=6264); <=85 (n=6264); <=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure<=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure <=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of <=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of <=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels <=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure <=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.