Whole-Genome Sequence of a Bordetella pertussis Brazilian Vaccine Strain.

Despite the reduction in incidence after vaccination, pertussis disease is still considered a public health problem worldwide, mainly due to recent and potential new outbreaks. We report here the complete genome of the Bordetella pertussis Butantan strain used in the Brazilian National Immunization Program as a whole-cell pertussis antigen to compose vaccines such as DTwP (diphtheria, tetanus, and whole-cell pertussis).

Treatment and long-term prognosis of myoclonic-astatic epilepsy of early childhood.

PURPOSE: We retrospectively studied patients with myoclonic-astatic epilepsy of early childhood (MAE) to investigate the most effective treatment and long-term seizure and intellectual prognosis. SUBJECTS: Eighty-one patients with MAE were recruited from among 3600 patients with childhood epilepsy according to the ILAE criteria of MAE. METHODS: We retrospectively investigated the clinical characteristics and ultimate prognosis of the patients with MAE from the medical records. The effects of various antiepileptic drugs, ketogenic diet and ACTH treatments on myoclonic-astatic seizures (MS/AS), apparently a hallmark of this unique epileptic syndrome, were also studied. RESULTS: MS/AS in 89 % of the patients disappeared within 1 to 3 years despite initial resistance, but generalized tonic-clonic or clonic seizures [G(T)CS] tended to continue. The most effective treatment for the MS/AS was ketogenic diet, followed by ACTH and ESM. At the last follow-up, 55 patients or 68 % of all the patients had remission of epilepsy, 11 patients or 14 % experienced a recurrence of GTCS after a long remission period but easily regained control, and the remaining 15 patients or 18 % continued to have seizures and intellectual outcomes were poor. In one half of these patients with poor outcomes, repeated minor epileptic status and nocturnal generalized tonic seizures persisted. A family history of epilepsy and a combination of minor epileptic status are risk factors for poor outcomes. CONCLUSION: MAE is considered to form a clinical spectrum ranging in its main seizure type from myoclonic to atonic, and in seizure and intellectual outcomes from benign to malignant. The overall prognosis, despite initial resistance to treatment, appears to be much better than originally thought when ILAE definitions excluding SME are followed.

Myoclonic-astatic epilepsy of early childhood--clinical and EEG analysis of myoclonic-astatic seizures, and discussions on the nosology of the syndrome.

PURPOSE: The aim of this study is to elucidate the clinical and neurophysiological characteristics of the myoclonic, myoclonic-astatic, or astatic seizures in patients with myoclonic-astatic epilepsy (MAE) of early childhood, and to discuss on the nosology of this unique epileptic syndrome. SUBJECTS: The subjects included 30 patients, who fulfilled the following modified International League Against Epilepsy (ILAE) criteria for MAE, and whose main seizures were captured by video-electroencephalographs (EEG) or polygraphs. The modified ILAE criteria includes: (1) normal development before onset of epilepsy and absence of organic cerebral abnormalities; (2) onset of myoclonic, myoclonic-astatic or astatic seizures between 7 months and 6 years of age; (3) presence of generalized spike- or polyspike-wave EEG discharges at 2-3 Hz, without focal spike discharges; and (4) exclusion of severe and benign myoclonic epilepsy (SME, BME) in infants and cryptogenic Lennox-Gastaut syndrome based on the ILAE definitions. RESULTS: The seizures were investigated precisely by video-EEG (n=5), polygraph (n=2), and video-polygraph (n=23), which identified myoclonic seizures in 16 cases (myoclonic group), atonic seizures, with or without preceding minor myoclonus, in 11 cases (atonic group), and myoclonic-atonic seizures in three cases. All patients had a history of drop attacks, apart from ten patients with myoclonic seizures. Myoclonic seizures, involving mainly the axial muscles were classified into those with mild intensity not sufficient to cause the patients to fall (n=10) and those that are stronger and sufficient to cause astatic falling due to flexion of the waist or extension of the trunk (n=6). Patients in the atonic group fell straight downward, landed on their buttocks, and recovered immediately. Analysis of the ictal EEGs showed that all attacks corresponded to the generalized spike or polyspikes-and-wave complexes. In the atonic form, the spike-and-wave morphology was characterized by a positive-negative-deep-positive wave followed by a large negative slow wave. In two patients, the intensity of the atonia appeared to correspond to the depth of the positive component of the spike-and-wave complexes. We did not detect any significant differences in the clinical and EEG features and prognosis, between the atonic and myoclonic groups. CONCLUSIONS: Although the determination of exact seizure type is a prerequisite for diagnosing an epileptic syndrome, the strict differentiation of seizure type into either a myoclonic or atonic form, does not appear to have a significant impact on the outcome or in delineating this unique epileptic syndrome. At present, we consider it better to follow the current International Classification of Epileptic Syndromes and Epilepsies until a more appropriate system than the clinico-electrical approach for classifying patients with MAE is available.

Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis correlation with disease activity.

To evaluate vascular endothelial growth factor (VEGF) levels in relation to disease activity in rheumatoid arthritis (RA), VEGF in the serum of 155 patients with RA and 75 healthy control subjects was quantified by our highly sensitive enzyme-linked immunosorbent assay. VEGF levels were found to correlate with the articular index (AI) and Lansbury's activity index (LI). Patients with RA had a mean serum VEGF concentration of 153.5+/-111.8 pg/ml, which was significantly higher than control subjects (104.8+/-65.7 pg/ml; P<0.01). VEGF concentration was elevated significantly according to disease progression as expressed by stages I to IV and correlated with AI (r=0.530, P<0.0001) and LI (r=0.688, P<0.0001) in stages I and II as well as with the conventional erythrocyte sedimentation rate or serum C-reactive protein concentration. Serum VEGF levels may therefore be valuable as a marker of disease activity in patients with early RA, and this cytokine may play a significant role in the pathophysiology of RA.

Adult T-cell leukemia with hypercalcemia-induced metastatic calcification in the lungs due to production of parathyroid hormone-related protein.

A 60-year-old man was diagnosed as adult T-cell leukemia with severe hypercalcemia because of production of parathyroid hormone-related protein. After admission, the patient had respiratory insufficiency with an infiltrative shadow in his lungs suggestive of pneumonia. However, neither improvement in respiratory function nor disappearance of the abnormal chest shadow was observed with administration of various antibiotics. An autopsy demonstrated the chest shadow had been caused by metastatic calcification associated with hypercalcemia due to production of parathyroid hormone-related protein. The possibility of metastatic calcification should be considered in patients with adult T-cell leukemia and hypercalcemia who have an abnormal chest shadow.

Kinematic approach to gait analysis in patients with rheumatoid arthritis involving the knee joint.

OBJECTIVE: To analyze abnormal gait patterns in patients with rheumatoid arthritis involving the knee joint. METHODS: In 2 patient groups with rheumatoid arthritis, changes in relevant angular parameters in the sagittal plane were analyzed by an electromagnetic tracking instrument. One group consisted of patients with knee joint involvement and severe inflammation without progressive destruction; the other group had knee joint involvement with progressive destruction and low disease activity. Knee angle was measured as the projected angle in the sagittal plane formed by 3 sensors (hip-knee-ankle); the changing mean angle, angular velocity, and angular acceleration were displayed. Furthermore, the angle formed by the vector element's endpoints for each sensor's displacement (designated alpha angle) was measured continuously. RESULTS: Compared with age-matched controls, patients with severe inflammatory knee joint involvement showed limitation of alpha angle change in the stance phase, and patients with knee joint destruction had shortened swing phase duration and decreased alpha angle change in the swing phase. A sharpened alpha angular velocity change curve was observed in the latter. Characteristic differences between groups with inflammation and destruction were more clearly evident from the alpha angle than from the knee angle itself. CONCLUSION: We observed gait differences between rheumatoid arthritis patients with active inflammatory arthritic knee joint involvement without progressive destruction and those with joint destruction and minimal inflammation. Features of gait disturbance in rheumatoid arthritis were not simple, even with a single major site. Therefore, techniques such as biokinetic gait analysis can provide practical information about functional joint integrity in this patient population that could aid in therapeutic decision making.

Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice.

Vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of inflammatory joint diseases, including rheumatoid arthritis (RA). To determine the importance of this cytokine in vivo, the effect of administering VEGF-neutralizing antibodies to mice with collagen-induced arthritis (CIA), which has many immunological and pathological similarities to human RA, has been investigated. Either saline, normal rabbit immunoglobulin or anti-human VEGF121 rabbit polyclonal antibody was administered to mice subcutaneously either before the onset of arthritis or after the establishment of clinical disease. Anti-VEGF antibody administered prior to disease onset significantly delayed the development of arthritis and decreased clinical score and paw thickness as well as histological severity. On the other hand, the frequency of occurrence of disease compared to either the control group administered saline or normal rabbit immunoglobulin was not altered. Anti-VEGF antibody also significantly ameliorated clinical and histological parameters even when administered after disease onset. These results indicate a possible therapeutical potential for anti-VEGF treatment in human arthritis.

[A case of progressive systemic sclerosis complicated by idiopathic portal hypertension with severe anemia].

A 44-year-old woman had been diagnosed with progressive systemic sclerosis (PSS) at the age of 39 years old and mild pancytopenia was noted at that time. At the age of 41 years symptoms of dry mouth appeared. In April 1997, anemia was in progress (Hb 5.8 g/dl) and severe esophageal varices were found by gastrointestinal fiber scope, and massive splenomegaly by abdominal CT. Serological examination was negative for hepatitis virus and for anti-mitochondrial antibody. In addition, Indocyanine Green test was normal and typical findings of liver cirrhosis were not demonstrated by CT scan. Also, the bone marrow result was normal. Therefore hypersplenism with idiopathic portal hypertension (IPH) was suggested and the patient was referred for splenectomy with the aim of improving the pancytopenia. The weight of the spleen was 2100 g and the pressure of the portal vein was measured at 390 mm H2O. The diagnosis of IPH was determined because pathologically there were no findings for liver cirrhosis. After splenectomy, pancytopenia was remarkably improved (Hb 9.6 g/dl). Consequently, this case was diagnosed as IPH complicated with PSS and Sjögren syndrome.

[Multiple cerebral infarction associated with cerebral vasculitis in rheumatoid arthritis].

A 64-year-old woman was suffering from rheumatoid arthritis since the age of 57. At the age of 62, she manifested episcleritis of the eyes and rheumatoid nodules in the skin, and rheumatoid factor in the blood became high. These findings indicated the presence of systemic vasculitis, and she was treated with prednisolone. At the age of 64, she suddenly became delirious, and T2-weighted and diffusion-weighted MR images revealed fresh infarctions in bilateral temporal and parietal lobes of the cerebrum. MR angiography failed to show any narrowing or obstruction of large cerebral arteries. She had also high fever and arthralgia, and her blood showed elevated levels of white blood cells, erythrocyte sedimentation rate, C-reactive protein, IgG-rheumatoid factor and immune complex. Lumbar puncture revealed an elevated protein level in CSF. A daily dose of 60 mg prednisolone ameliorated these clinical and laboratory findings as well as her consciousness, disclosing disturbances in higher cortical functions including Wernicke aphasia, disorientation, and ideomotor, ideational, and constructional apraxia. Previous 13 reported cases of cerebral infarction complicating rheumatoid vasculitis were mostly described as showing multiple infarctions in cerebral hemisphere, disturbance of consciousness, elevated protein in CSF, and effectiveness of steroid therapy. The present case had these characteristics, and the cerebral vasculitis mediated by IgG-rheumatoid factor and immune complex was indicated as a probable cause of multiple cerebral infarctions.

[Two cases of remitting seronegative symmetrical synovitis with pitting edema].

We report 2 elderly patients who present with a relatively acute onset of a severe symmetrical synovitis affecting the flexor digitorum tendon sheaths and wrist joints with pitting edema of the dorsum of both hands. These patients were seronegative for rheumatoid factor and responded to treatment with low dose predonisone (10 mg daily) without relapse. These presenting features were closely linked with the RS3PE syndrome originally described by McCarty.

The use of frozen inoculum and 0,2 por cento formaldehyde for inactivation of Pertussis vaccine production

The use of frozen seeds and the effect of the concentration of formaldehyde, and the removal of 2/3 of the supernatant were investigated in order to facilitate the production of pertussis cellular vaccine. Results indicated that is possible to replace fresh seeds by frozen ones, and the formaldehyde concentration can be increased to 0,2 por cento after the remotion of 2/3 of supernatant, resulting in a good vaccine preparation in a shorter time

Reduced muscle uptake of oxygen during exercise in patients with systemic lupus erythematosus.

OBJECTIVE: To assess the factors limiting aerobic exercise capacity in patients with systemic lupus erythematosus (SLE). METHODS: The anaerobic threshold (AT) and O2 pulse, i.e., VO2/heart rate (HR), were measured in 21 patients with SLE without cardiopulmonary complications by the analysis of expired gas during incremental work load in exercise testing. The relationships between work rate (WR) and VO2, HR and VO2/weight (Wt), and lupus activity index (LAI) and AT were analyzed. RESULTS: The AT of the patients with SLE was significantly lower than for a control group. Little increase in O2 pulse and very low delta VO2/delta WR and delta VO2/Wt@delta HR were found during work load in some patients with SLE, especially those with a low AT and high LAI. Patients with SLE with a high LAI tended to show a low AT. CONCLUSION: The low aerobic exercise capacity of patients with SLE appeared to be mainly due to a small increase in O2 pulse. This may have resulted from impaired oxygen diffusion in the inflamed peripheral muscles in patients with active SLE. Low AT may explain in part why patients with SLE become easily fatigued.

Sjögren's syndrome with hydronephrosis caused by pseudolymphoma.

A 67-year-old woman with Sjögren's syndrome was found to have left hydronephrosis and stenosis of the left ureter. Exploratory laparotomy disclosed a nodule at the ureteropelvic junction of the left ureter. Histopathological examinations of the biopsied specimen of this nodule showed lymphoid hyperplasia within the ureteral wall. Low dose prednisolone improved hydronephrosis and pseudolymphoma within several months. Hydronephrosis secondary to pseudo-lymphomatous infiltration of the ureter is a rare but, if properly treated, reversible complication of Sjögren's syndrome.

Progressive systemic sclerosis complicated with immune thrombocytopenia during D-penicillamine therapy.

Immune thrombocytopenia is a rare complication of progressive systemic sclerosis (PSS). A 47-year-old female with PSS treated with D-penicillamine developed immune thrombocytopenia, which promptly responded to prednisolone and withdrawal of D-penicillamine. Platelet-associated IgG was elevated and the bone marrow megakaryocyte count was normal. There was an inverse relationship between the level of platelet-associated IgG and the platelet count. A lymphocyte stimulation test sensitized by D-penicillamine was positive. The present case suggests that immune thrombocytopenia may be regarded as one of the D-penicillamine-related immune abnormalities. To our knowledge, its association with PSS has never been reported.

[Progress in laboratory tests of connective tissue diseases].

The presence of serum autoantibodies to nuclear antigens (ANA) and other antigens is a hallmark of connective tissue diseases. Antibodies to double-strand DNA were present in high titers in SLE patients. Antibodies to U1RNP correlated with Raynaud's phenomenon and finger erythema in SLE patients. Anticardiolipin antibody was present in 29% of 41 SLE patients. Antibody to Scl-70 was present in 52% of 21 PSS patients. Antibody to Jo-1 was present in patients with PM associated with pulmonary fibrosis. Two of our patients with PM had an autoantibody that precipitated 7SL RNA.

Ischemic heart disease in systemic lupus erythematosus. A retrospective study of 65 patients treated with prednisolone.

We studied the frequency of ST-T changes and ischemic heart disease (IHD) in prednisolone (PSL)-treated systemic lupus erythematosus (SLE) patients and compared them with the age-matched control of rheumatoid arthritis patients not receiving PSL. Twenty-five (38%) of the 65 SLE patients revealed ST-T changes as ST elevation (4%), ST depression (36%) and T wave flattening or inversion (60%). Among the control patients 4 (10%) had T wave flattening or inversion. The frequencies of ST-T changes in patients receiving total PSL dose of up to 5g and greater than 5g were 23% and 48%, respectively. Four patients developed IHD at an unusually young age during remission of SLE while receiving low dose of PSL and 2 of them later died of myocardial infarction (MI). The latter 2 patients had received PSL pulse therapy prior to MI. Regular ECG check up for SLE patients while they are on low dose PSL or pulse therapy may help reveal early ECG abnormalities and thus detect and treat one of the major risks of long-term effects of corticosteroid therapy.

[Aortocaval fistula secondary to rupture of abdominal aortic aneurysm; report of two cases].

Two cases of aortocaval fistula secondary to rupture of abdominal aortic aneurysm were presented. First case was 70 year old man who was admitted with pulsating abdominal mass. Prior to admission, he had been suffering from congestive heart failure. On physical examination, a pulsating mass, remarkable thrill and continuous bruit were recognized on his abdomen. Aortography showed abdominal aortic aneurysm and aortocaval fistula. The fistula (5mm X 3mm) was repaired within the aneurysm controlling the bleeding from the fistula by the direct digital compression. Aortic reconstruction was done with woven dacron bifurcation graft. Postoperative course was uneventful. Second case was 68 year old man who was admitted with the sudden onset of severe back pain. On admission, his physical status was already deteriorated. Diagnosis was made easily by the physical examination. Immediately after aortography, cardiac arrest occurred suddenly. After resuscitation, he was operated in the same manner of the first case. Large fistula (2 cm X 1cm) was noted. This patient died of renal failure and cerebral damage on 30th post operative day. Problems of pre- and post-operative patient management and surgical therapy for aortocaval fistula secondary to rupture of abdominal aortic aneurysm were discussed.