Clinical and epidemiological features of 123 cases of cryptococcosis in Mato Grosso do Sul, Brazil

To identify the clinical and epidemiological profile of cryptococcosis diagnosed at the University Hospital of the Federal University of Mato Grosso do Sul, Brazil, medical records of 123 patients admitted from January 1995 to December 2005 were analyzed. One hundred and four cases (84.5%) had HIV infection, six (4.9%) had other predisposing conditions and 13 (10.6%) were immunocompetent. Male patients predominated (68.3%) and their age ranged from 19 to 69 years (mean: 35.9). Most patients (73.2%) were born and lived lifelong in the state of Mato Grosso do Sul. Involvement of the central nervous system occurred in 103 patients (83.7%) and headache and vomiting were the most frequent symptoms. In 77 cases it was possible to identify the Cryptococcus species: 69 (89.6%) C. neoformans and eight (10.4%) C. gattii. Amphotericin B was the drug of choice for treatment (106/123), followed by fluconazole in 60% of cases. The overall lethality rate was 49.6%, being 51% among the HIV infected patients and 41.2% among the non-HIV infected (p > 0.05). Although cryptococcosis exhibited in our region a similar behavior to that described in the literature, the detection of an important rate of immunocompetent individuals and five C. gattii cryptococcosis in HIV-infected patients is noteworthy.     

The α₂β₁ integrin is a metastasis suppressor in mouse models and human cancer

Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles in tumor progression and metastasis. Although work in preclinical models suggests that β1 integrins may stimulate metastasis of a number of cancers, expression of the β1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the α2β1 integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of α2β1 integrin in normal breast epithelium and loss of α2β1 in poorly differentiated breast cancer. They are also consistent with our systematic analysis of microarray databases of human breast and prostate cancer, which revealed that decreased expression of the gene encoding α2 integrin, but not genes encoding α1, α3, or β1 integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of α2 expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the α2β1 integrin functionally inhibits breast tumor metastasis, and α2 expression may serve as an important biomarker of metastatic potential and patient survival.     

Prevalence of the white-coat effect at multiple visits before and during treatment

OBJECTIVE: To investigate the prevalence and persistence of the white-coat effect (WCE) and white-coat hypertension (WCH) on multiple blood pressure measurement occasions in hypertensive patients with and without treatment. DESIGN: Essential hypertensive patients in whom we took office blood pressure measurements (OBPM) at eight visits (three readings per visit) performed self blood pressure measurements (SBPM) for 1 week prior to each visit (42 readings per week) over a period of 1 year. All measurements were performed with the same automatic device (Omron 705CP). In addition, 24-h ambulatory blood pressure monitoring (ABPM) was performed at the start and at the end of the study. At the start, patients did not use any medication but on subsequent visits they were treated on the basis of their SBPM values. WCH was defined as an OBPM-value > or = 140 and/or 90 mmHg and a SBPM or daytime ABPM value < 135/85 mmHg. This definition was used irrespective of treatment. We also determined the prevalence of a substantial WCE (OBPM 20 mmHg systolic or 10 mmHg diastolic higher than SBPM or daytime ABPM). SETTING: Patients were recruited at hospital or general practice. PATIENTS: A total of 163 mild-to-moderate essential hypertensive patients with a mean age of 56 years (56% males). RESULTS: At eight blood pressure (BP) measurement occasions, 75% of all patients had a substantial WCE at least once, while 57% had WCH at least once. One-third of the patients consistently had a substantial WCE and 14% consistently had WCH on three or more occasions The magnitude of the WCE was significantly related to the height of blood pressure in treated but not in untreated patients. CONCLUSION: In some patients, WCH or a substantial WCE occurs consistently on multiple OBPM visits. Especially in untreated patients, the magnitude of the WCE varies widely among individuals. These results support the incorporation of SBPM and/or ABPM into optimal management of hypertension, not only to prevent misdiagnosis in untreated patients but also to determine the need for adjusting antihypertensive therapy in treated subjects.     

Effects of amlodipine and lisinopril on intima-media thickness in previously untreated, elderly hypertensive patients (the ELVERA trial)

OBJECTIVE: To compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor lisinopril on intima-media thickness (IMT) in elderly, previously untreated hypertensive individuals. DESIGN: A double-blind randomized parallel-group trial (the ELVERA trial). PATIENTS: The study population comprised 166 newly diagnosed hypertensive individuals (aged 60-75 years) with diastolic blood pressure between 95 and 115 mmHg or systolic blood pressure between 160 and 220 mmHg, or both. INTERVENTION: Patients were allocated randomly to groups to receive amlodipine 5-10 mg or lisinopril 10-20 mg for 2 years. MAIN OUTCOME MEASURES: Before and after 1 and 2 years of treatment, IMT was measured in three carotid and two femoral arterial sites by B-mode ultrasound. The primary endpoint was the change from baseline of the combined mean maximum far wall IMT of carotid and femoral arteries, evaluated by repeated measurement analysis of the treatment effect in an intention-to-treat analysis. RESULTS: After 2 years of treatment, amlodipine decreased IMT by 0.089 mm [95% confidence interval (CI) 0.144 to 0.037]. Lisinopril decreased IMT by 0.065 mm (95% CI 0.124 to 0.010). No differences between the two drugs were found (P = 0.18). Both treatment regimens achieved the greatest reduction of IMT after 1 year, with a slight increase after the second year, whereas the reduction in blood pressure was maintained. Comparing the carotid and femoral arteries, a significant treatment difference in the change from baseline in favour of amlodipine was observed in the IMT of the elastic common carotid artery (P < 0.05). The effects of the two drugs on the muscular common femoral artery were not different. CONCLUSION: In a long-term study, amlodipine and lisinopril reduce IMT to a similar extent in newly diagnosed elderly hypertensive patients. It is suggested that the two drugs have different effects on arteries that are not prone to atherosclerosis.     

No effects of bosentan on microvasculature in patients with limited cutaneous systemic sclerosis

The endothelium-derived vasoconstrictor molecule endothelin-1 (ET-1) has been suggested to play a role in the pathogenesis of Raynaud’s phenomenon (RP) and systemic sclerosis (SSc). We studied the effect of bosentan on microvascular structure and function in patients with RP secondary to limited cutaneous SSc in a mechanistic pilot study. In this single center, open study, 15 patients with limited cutaneous SSc were treated with bosentan for 16 weeks with a follow-up period of 4 weeks. Changes in microvascular structure and function were studied with assessment of vasodilatory microvascular responses using laser Doppler fluxmetry combined with iontophoresis, capillary permeability using fluorescence videomicroscopy, nailfold capillary microscopy, and serological markers of endothelial activation. No significant changes were seen in vasodilator responses to acetylcholine and sodium nitroprusside following bosentan treatment. No effect was noted on capillary permeability during treatment. The number of nailfold capillaries remained unchanged. The endothelial activation marker vascular cell adhesion molecule did not change during treatment, but levels of thrombomodulin significantly decreased after 12 weeks of treatment. Bosentan did not induce significant changes in vasodilator responses, capillary permeability, and capillary density during treatment, so no evidence was obtained for structural improvement of microvascular structure and function in this short-time mechanistic pilot study in patients with lcSSc.     

Neck pounding during sinus rhythm: a new clinical manifestation of dual atrioventricular nodal pathways

Objective—To determine the clinical and electrophysiological characteristics of patients with paroxysmal palpitations and neck pounding during sinus rhythm.
Methods—Clinical, electrocardiographic, and electrophysiological characteristics of six patients with paroxysmal palpitations and neck pounding during sinus rhythm were studied in basal conditions and when symptomatic. Response to treatment was observed.
Results—Baseline ECGs were normal (four patients) or had first degree atrioventricular block with intermittent PR shortening. During symptoms, narrow QRS rhythms were seen without visible P waves (three patients) or with P waves partially hidden in the QRS complex (three patients). Dual atrioventricular nodal pathways were found in all five patients who had electrophysiological studies. In these patients the slow pathway conduction time was long enough (mean (SD), 425 (121) ms) for ventricular activation after slow pathway conduction during sinus rhythm to coincide with the next atrial depolarisation, causing neck pounding during exercise (four patients) or at rest (two patients). Tachycardia was not induced in any patient. Medical treatment aggravated symptoms in three patients. A pacemaker was successfully used in two.
Conclusions—Neck pounding during sinus rhythm is a clinical manifestation of dual atrioventricular nodal pathways. Medical treatment may aggravate symptoms but a pacemaker may offer definitive relief.

Keywords: neck pounding;  nodal conduction;  palpitations