Presentation and outcome of patients with intracranial tuberculoma in a high HIV prevalence setting.

SETTING: A referral hospital in South Africa.OBJECTIVE: To describe the clinical presentation, serial brain imaging findings during treatment and outcome of patients with intracranial tuberculoma in a high human immunodeficiency virus (HIV) prevalence setting.DESIGN: This was a retrospective observational study conducted over a 12.5-year period. Records of adults (age ≥18 years) who presented with neurological TB were screened. We included patients with tuberculoma in whom sequential brain imaging was performed.RESULTS: Of 66 patients enrolled, HIV status was known in 61; 47 (71%) were HIV-infected and 14 (21%) were non-HIV-infected. Clinical and imaging findings and outcomes were similar between these groups. Persistent tuberculoma was present at 18 months follow-up in 20/41 (49%) patients who underwent repeat imaging at that timepoint; those with persistent tuberculoma were more likely to have persisting neurological abnormalities (85% vs. 52%; P = 0.043). Larger tuberculoma size at presentation (≥3 cm) was the only factor significantly associated with tuberculoma persistence (multivariable logistic regression, OR 19.9, 95%CI 1.27-309.68; P = 0.033).CONCLUSION: Tuberculoma is a severely disabling TB manifestation regardless of HIV coinfection, with half of patients showing radiologically persistent lesions at 18 months follow-up. Large size of tuberculoma at presentation heralds lower chance of its resolution within 18 months.

Update on the subcutaneous administration of rituximab in Canadian cancer centres.

Results of studies comparing subcutaneous (sc) with intravenous (iv) rituximab indicate that the two formulations are comparable in efficacy, but most patients and health care professionals prefer the sc route, commonly because of shorter chair time and reduced risk of infusion-related reactions. Recent Canadian data, including those from the scuba study reported here, support the results of earlier international studies showing a reduction in preparation and administration time with the sc formulation, lower cost of administration, and reduced drug wastage because of the fixed sc dosing. Given the significant time and cost savings of the sc formulation, that formulation is generally preferred over the iv formulation for the treatment of follicular lymphoma, diffuse large B cell lymphoma, and chronic lymphocytic leukemia.

Does Increasing Packing Density Using Larger Caliber Coils Improve Angiographic Results of Embolization of Intracranial Aneurysms at 1 Year: A Randomized Trial.

BACKGROUND AND PURPOSE: The impact of increased aneurysm packing density on angiographic outcomes has not been studied in a randomized trial. We sought to determine the potential for larger caliber coils to achieve higher packing densities and to improve the angiographic results of embolization of intracranial aneurysms at 1 year. MATERIALS AND METHODS: Does Embolization with Larger Coils Lead to Better Treatment of Aneurysms (DELTA) was an investigator-initiated multicenter prospective, parallel, randomized, controlled clinical trial. Patients had 4- to 12-mm unruptured aneurysms. Treatment allocation to either 15- (experimental) or 10-caliber coils (control group) was randomized 1:1 using a Web-based platform. The primary efficacy outcome was a major recurrence or a residual aneurysm at follow-up angiography at 12 ± 2 months adjudicated by an independent core lab blinded to the treatment allocation. Secondary outcomes included indices of treatment success and standard safety outcomes. Recruitment of 564 patients was judged necessary to show a decrease in poor outcomes from 33% to 20% with 15-caliber coils. RESULTS: Funding was interrupted and the trial was stopped after 210 patients were recruited between November 2013 and June 2017. On an intent-to-treat analysis, the primary outcome was reached in 37 patients allocated to 15-caliber coils and 36 patients allocated to 10-caliber coils (OR = 0.931; 95% CI, 0.528-1.644; P = .885). Safety and other clinical outcomes were similar. The 15-caliber coil group had a higher mean packing density (37.0% versus 26.9%, P = .0001). Packing density had no effect on the primary outcome when adjusted for initial angiographic results (OR = 1.001; 95% CI, 0.981-1.022; P = .879). CONCLUSIONS: Coiling of aneurysms randomized to 15-caliber coils achieved higher packing densities compared with 10-caliber coils, but this had no impact on the angiographic outcomes at 1 year, which were primarily driven by aneurysm size and initial angiographic results.

A review of patients with glutaric aciduria type 1 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Glutaric aciduria type 1 (GA1) is an organic acidaemia. The objective of this study was to describe the profile of patients diagnosed with GA1 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 2007 to 2015. We identified 6 children (4 girls, 2 boys) in a retrospective review. The mean age at diagnosis was 12 months. Clinical findings on presentation were encephalopathic crises (n=4), hypotonia (n=4) and macrocephaly (n=5). Other complications included seizures (n=4), dystonia (n=3) and bulbar dysfunction (n=4). Urine organic acid screens showed elevated glutaric acid levels (n=6). Five patients tested positive for the A293T mutation on the glutarylco-enzyme A (CoA) dehydrogenase gene. Abnormalities on magnetic resonance imaging screening included hyperintense basal ganglia (n=6), widened perisylvian fissures (n=6), and an abnormal signal in the cerebral peduncles (n=5) and central tegmental tract (n=4). All patients were treated with L-carnitine and dietary modification. Two patients had a static clinical course, 1 patient gained milestones, and 3 have shown further neuroregression.

Balloon valvuloplasty versus closed commissurotomy for pliable mitral stenosis: a prospective hemodynamic study.

Closed surgical mitral valvotomy is the procedure of choice in most patients with symptomatic pliable mitral stenosis in developing countries. The procedure is efficacious and safe. Mitral valvotomy performed with a balloon has shown similar good results, with infrequent complications in selected subjects. Because there is a paucity of studies comparing the two techniques, this study was undertaken to compare the results of percutaneous balloon mitral valvuloplasty with those of closed commissurotomy as determined by catheterization studies. Forty-five patients with tight pliable mitral stenosis were randomly assigned to one of two groups: 23 patients had balloon valvuloplasty by the single catheter technique (group I) and 22 underwent closed surgical valvotomy (group II). The two groups were similar with regard to clinical and hemodynamic findings before intervention. Mitral valve area increased from 0.8 +/- 0.3 to 2.1 +/- 0.7 cm2 in group I (p less than 0.001) and from 0.7 +/- 0.2 to 1.3 +/- 0.3 cm2 in group II (p less than 0.001). Pulmonary artery pressure and pulmonary vascular resistance decreased in both groups, but these changes did not reach statistical significance in group II. Treadmill exercise time increased from 3.8 +/- 2.3 to 7.3 +/- 2.6 min in group I (p less than 0.001) and from 4 +/- 2.6 to 5.6 +/- 2.6 min in group II (p less than 0.001). There were no deaths. One patient in each group developed moderate (3+) mitral regurgitation. A small interatrial shunt (less than 1.5:1) was detected in three patients in group I immediately after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy.

A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe calcification of glutaraldehyde-preserved porcine xenografts in children.

Despite the widespread use of glutaraldehyde-preserved porcine xenografts, severe short-term calcification of these valves has been infrequently reported. This report describes four cases of glutaraldehyde-preserved porcine xenografts in the mitral valve position in which severe calcification occurred within 17 to 25 months of implantation. All four patients were children, aged 13 to 15 years. The clinical presentation in all four cases occurred at a late stage when there was severe xenograft obstruction, with acute symptoms of cardiac decompensation in the presence of pulmonary hypertension and right heart failure. There was rapid cardiac deterioration resulting in a low output state and episodic pulmonary edema necessitating urgent mitral valve replacement. In only one case was there clear auscultatory evidence of severe mitral stenosis. Calcification of these xenografts occurred in the presence of normal serum calcium levels and was not related to infective endocarditis. Histologic examination of the calcified xenografts strongly suggested dystrophic calcification resulting from primary collagen degeneration. The exact cause is unclear, but it appears that glutaraldehyde-preserved porcine xenografts may produce severe short-term calcification with acute hemodynamic deterioration necessitating urgent valve replacement and that this accelerated calcification may be a complication in young persons,

Gacyclidine (Beaufour-Ipsen).

Beaufour-Ipsen is developing gacyclidine (GK-11) for the potential treatment of traumatic brain injury. Phase II clinical trials of the compound for this indication had been completed as of October 1999 and the company is looking for a partnership before undertaking further clinical development for this and, possibly, other indications [344879], [346265], [386763]. Phase II trials for acute spinal cord injury gave disappointing results and development for this indication has been discontinued [344879].

Congenital aneurysms adjacent to the anuli of the aortic and/or mitral valves.

The unusual occurrence of non-infected submitral and aortic aneurysms developing sequentially in an adult prompted us to review the pathogenesis of congenital aneurysms adjacent to the aortic and mitral valves. The findings support the suggestion that subvalvular aneurysms, like aortic sinus aneurysms, are a result of a congenital defect at the valve anulus. Submitral aneurysms occur only subjacent to the posterior leaflet. Whereas aortic sinus aneurysms may arise from any of the three sinuses, subaortic aneurysms occur only under the intermediate portion of the left aortic sinus. In the absence of rupture, the clinical presentation of these aneurysms results from valvular insufficiency or compression of the left coronary artery or of the conduction system.

Subpulmonic stenosis as a result of noncalcific constrictive pericarditis.

The clinical, electrocardiographic, and radiologic features in a patient with a pericardial band which produced an unusual form of infundibular pulmonary stenosis are presented. The findings are unique in that the band was not calcified and, therefore, not visualized roentgenographically and developed without a previous history of pericarditis or pericardial surgery. The diagnostic value of cineangiography is stressed and illustrated.

Clinical experience with the Lillehei-Kaster cardiac valve prosthesis.

This paper reviews our experience with the Lillehei-Kaster pivoting disc prosthesis in 155 patients with aortic and mitral valve disease. We employed 189 valves during the period 1971 to 1974. The early surgical mortality rates for isolated mitral, isolated aortic, and combined mitral and aortic valve replacements were 9 per cent, 14 per cent, and 3 per cent, respectively. Postoperatively, there was no evidence of significant hemolysis, and the gradients across the prostheses were satisfactory. Clinical evaluation of prosthetic function was made difficult by the infrequency of an opening click and the common occurrence of mid-diastolic murmurs even with minimal gradients. The most disturbing complication, which has led to our abandoning use of this valve, was thrombosis, which occurred in at least 10 per cent of the mitral and 5 per cent of the aortic valves. The cause is thought to be late prosthetic disproportion as the heart shrinks in size.

Pulmonary edema following pulmonary valvulotomy.

A previously unreported combination of critical pulmonary valve stenosis and mitral stenosis is described. The initial clinical presentation was one of right ventricular failure that obscured the evidence of pulmonary venous hypertension. Following pulmonary valvulotomy, pulmonary edema ensued because of the increased pulmonary blood flow. The importance of urgent cardiac catheterization postoperatively following an operation that increases pulmonary blood flow is discussed.

Post-treatment with nicotinamide (vitamin B(3)) reduces the infarct volume following permanent focal cerebral ischemia in female Sprague-Dawley and Wistar rats.

Delayed treatment with nicotinamide (NAm) protects male rats against cerebral ischemia. Since the preponderant use of male animals in stroke research may produce results not applicable to female stroke patients due to gender-related differences, we examined whether delayed NAm treatment could protect female rats against focal cerebral ischemia using a model of permanent middle cerebral artery occlusion (MCAo). NAm (500 mg/kg) given intravenously, 2 h after MCAo, significantly reduced the infarct volume of female Sprague-Dawley (55%, P<0.05) and Wistar rats (60%, P<0.05) rats when compared with saline-injected controls. These studies confirm that NAm is neuroprotective specifically at the dose of 500 mg/kg in rats. The novel findings are that this neuroprotection occurs in female, as well as male rats, and that the neuroprotection observed is more robust when administered as an intravenous bolus compared with intraperitoneal administration.

Multifunctional polymeric nanoplexes for anticancer co-delivery of p53 and mitoxantrone.

Co-delivery of the anticancer drug, mitoxantrone (MTO) and the gene encoding tumor suppressor protein p53 was evaluated towards anticancer combinatorial therapy. The nanoplatforms developed herein are assembled by coupling ß-cyclodextrin and the cationic polymer, polyethyleneimine to a hydrophilic polymer, pullulan (PPEICD). The ß-cyclodextrin serves as a nanocontainer for the drug MTO, while the cationic moiety can condense pDNA. Acid base titrations provided insight into the buffering capacity of the PPEICD conjugate. Cytotoxicity studies by MTT assay in HepG2 and C6 cell lines and hemocompatibility studies confirmed the conjugate to be nontoxic and hemocompatible. In vitro release studies of MTO in phosphate buffered saline pH 7.4 showed an initial burst effect followed by a slow drug release. The released data fitted with the Korsmeyer-Peppas model and their diffusional exponents suggest that the drug release from the polymeric system followed diffusion and non-Fickian transport. Combined drug and gene loaded nanoplexes have a more apoptotic effect than either the drug or gene individually as confirmed by MTT assay and live dead assay. This indicated the significance of the combined drug and gene delivery system and the ability of the nanoplatform to overcome the multidrug resistance (MDR) of MTO. Moreover, preference of asialoglycoprotein receptor (ASGPR) mediated internalization for nanoparticle cellular uptake in HepG2 cell lines was identified by treating with the inhibitor asialofetuin. Cell studies in both HepG2 and C6 cell lines demonstrated that the nanoplatform PPEICD can efficiently and selectively deliver both p53 and MTO to cancer cells inducing high cell death.

Mechanical thrombectomy with the Solitaire stent: is there a learning curve in achieving rapid recanalization times?

METHODS: In acute ischemic stroke, good outcome following successful recanalization is time dependent. In patients undergoing endovascular therapy at our institution, recanalization times with the Solitaire stent were retrospectively evaluated to assess for the presence of a learning curve in achieving rapid recanalization. METHODS: We reviewed patients who presented to our stroke center and achieved successful recanalization with the Solitaire stent exclusively. Time intervals were calculated (CT to angiography arrival, angiography arrival to groin puncture, groin puncture to first deployment, and deployment to recanalization) from time stamped images and angiography records. Patients were divided into three sequential groups, with overall CT to recanalization time and subdivided time intervals compared. RESULTS: 83 patients were treated with the Solitaire stent from May 2009 to February 2012. Recanalization (Thrombolyis in Cerebral Infarction score 2A) occurred in 75 (90.4%) patients. CT to recanalization demonstrated significant improvement over time, which was greatest between the first 25 and the most recent 25 cases (161-94 min; p<0.01). The maximal contribution to this was from improvements in first stent deployment to recanalization time (p=0.001 between the first and third groups), with modest contributions from moving patients from CT to the angiography suite faster (p=0.02 between the first and third groups) and from groin puncture to first stent deployment (p=0.02 between the first and third groups). CONCLUSIONS: There is a learning curve involved in the efficient use of the Solitaire stent in endovascular acute stroke therapy. Along with improvements in patient transfer to angiography and improved efficiency with intracranial access, mastering this device contributed significantly towards reducing recanalization times.

Temporal resolution of dynamic angiography using flat panel volume CT: in vivo evaluation of time-dependent vascular pathologies.

BACKGROUND AND PURPOSE: Recently introduced fpVCT scanners can capture volumetric (4D) time-varying projections enabling whole-organ dynamic CTA imaging. The main objective of this study was to assess the temporal resolution of dynamic CTA in discriminating various phases of rapid and slow time-dependent neurovascular pathologies in animal models. MATERIALS AND METHODS: Animal models were created to assess phasic blood flow, subclavian steal phenomena, saccular aneurysms, and neuroperfusion under protocols approved by the SRAC. Animals with progressively increasing heart rate-Macaca sylvanus (~100 bpm), Oryctolagus cuniculus (NZW rabbit) (~150 bpm), Rattus norvegicus (~300 bpm), Mus musculus (~500 bpm)-were imaged to challenge the temporal resolution of the system. FpVCT, a research prototype with a 25 × 25 × 18 cm coverage, was used for dynamic imaging with the gantry rotation time varying from 3 to 5 seconds. Volumetric datasets with 50% temporal overlap were reconstructed; 4D datasets were analyzed by using the Leonardo workstation. RESULTS: Dynamic imaging by using fpVCT was capable of demonstrating the following phenomena: 1) subclavian steal in rabbits (ΔT ≅ 3-4 seconds); 2) arterial, parenchymal, and venous phases of blood flow in mice (ΔT ≅ 2 seconds), rabbits (ΔT ≅ 3-4 seconds), and Macaca sylvanus (ΔT ≅ 3-4 seconds); 3) sequential enhancement of the right and left side of the heart in Macaca sylvanus and white rabbits (ΔT ≅ 2 seconds); and 4) different times of the peak opacification of cervical and intracranial arteries, venous sinuses, and the jugular veins in these animals (smallest, ΔT ≅ 1.5-2 seconds). The perfusion imaging in all animals tested was limited due to the fast transit time through the brain and the low contrast resolution of fpVCT. CONCLUSIONS: Dynamic imaging by using fpVCT can distinguish temporal processes separated by >1.5 seconds. Neurovascular pathologies with a time constant >1.5 seconds can be evaluated noninvasively by using fpVCT.