Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.     

Modulation of glial cell signaling by adenosine and pharmacological reinforcement

In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative diseases, we investigated the underlying molecular signaling as a possible target for a pharmacological therapy. Here, we are particularly focusing on the endogenous modulation of the Ca²⁺ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the xanthine derivative propentofylline (PPF). As an experimental model, we used cultured rat microglial cells and astrocytes that are immature, show a high proliferation rate, and resemble in several aspects pathologically activated glial cells. A prolonged increase of the cellular cAMP level favored the differentiation of cultured astrocytes and associated properties required for the physiological nerve cell function. On the other hand, a strengthening of the cyclic nucleotide-dependent signaling inhibited potentially neurotoxic properties of cultured microglial cells. Similar effects were obtained by treatment with propentofylline, which mimicked modulatory adenosine effects and increased the intracellular level of cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by modifying the strength and the timing of these second messengers, may provide a therapy of neurodegenerative diseases in which a pathological activation of microglial cells and astrocytes is discussed to play a pathogenic role.     

Effect of minimizing preoperative fasting on perioperative blood glucose homeostasis in children

Two hundred healthy, unpremedicated children, ages 1–10 years, scheduled for elective outpatient surgery were studied in order to examine the effect of minimizing preoperative fasting on perioperative blood glucose concentrations in paediatric patients. None of the patients ingested solids after midnight. On the day of surgery, the children were assigned to one of two groups. Group A children (n= 113) were not allowed any liquids for at least 6 h prior to surgery (NPO). Children in Group B (n= 87) ingested 10 ml·kg^?1 of apple juice 2–4 h prior to the induction of anaesthesia. All patients received lactated Ringer's solution intraoperatively, unless BG at induction was < 50 mg·dl^?1 (2.8 m·mol·l^?1) in which case dextrose 2.5% in lactated Ringer's solution was administered. None of the patients who received apple juice was hypoglycaemic during induction of anaesthesia. However, two children in the NPO group had blood glucose values ± 50 mg·dl^?1 (2.8 m·mol·l^?1) at the time of induction of anaesthesia. Thirteen (11%) patients in Group A and 6 (7%) patients in Group B showed either no change or a further decrease in their postoperative BG concentration as compared with their induction values. Two of 43 patients in Group A and 2 of 41 patients in Group B had gastric fluid volumes > 0.4 ml/kg. All patients in both groups had gastric pH < 2.5. This study shows that gastric fluid volume and pH following a 2–4 h fast are not different from the values measured in children who were subjected to a traditional fasting period of 6 h or longer. Moreover, apple juice consumed 2–4 h prior to surgery neither buffers gastric pH nor does it modify intraoperative glucose homeostasis in children.     

Learning and sexual deficiencies in transgenic mice carrying a chimeric vasoactive intestinal peptide gene

The molecular mechanisms responsible for behavior are largely unknown. A state of the art model, paving the path from genes to behavior, is offered by transgenic animals. Candidate molecules are classic neuropeptides, such as vasoactive intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by the polyoma promoter were produced. Behavioral studies revealed learning impairment and prolonged retardation in memory acquisition in the genetically altered animals. Furthermore, reduced performance was observed when the male transgenic mice were tested for sexual activity in the presence of receptive females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP content of the transgenic mice brains. To directly assess genetically reduced VIP content as a cause for learning impairment, transgenic mice carrying diphtheria toxia-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and exhibited deficiencies in learning abilities, strongly supporting an important neurobiological function for VIP in vivo.     

Pseudotumoral appearance of small bowel strictureplasty for Crohn's disease

In two patients with Crohn's disease, strictureplasties had been marked operatively by a metal clip, so that definitive location on subsequent small bowel examination was possible. Each stricture-plasty presented radiologically as a short annular constriction with apparently shouldered edges and parallel lumen. Similar radiological features were found in five other patients with strictureplasties, suggesting that a pseudotumoral appearance is characteristic of strictureplasty. Attention is drawn to this finding to avoid confusion with malignancy.     

Amebic abscess of the liver manifested by “hemoptysis”: US,CT, and MRI findings

Ultrasonographic (US), computed tomographic (CT), and magnetic resonance imaging (MRI) findings of a patient suffering from an amebic abscess of the liver complicated by a bronchohepatic fistula are presented. Subsequent to US, CT provided the specific diagnosis. Multiplanar MRI was valuable to directly visualize the secondary diaphragmatic rupture and the bronchohepatic fistula.     

Renal vein renin analysis: Limitations of its use in predicting benefit from percutaneous angioplasty

Two hundred forty-four consecutive patients (mean age 61 years), including 123 who had technically valid renal vein renin (RVR) analysis and 121 without RVR data, underwent technically successful percutaneous renal artery angioplasty (PTRA). They were retrospectively examined to evaluate the utility of RVR analysis in identifying renal hypertension (RVH), predicting benefit from PTRA, and determining if the lack of knowledge of renin levels significantly affected clinical outcome after PTRA. Abnormal RVR values were associated with clinical benefit after PTRA in 62 of 93 patients (67% sensitivity, 20% specificity, 72% positive predictive value). Clinical improvement following PTRA occurred in 31 of 37 patients with normal pre-PTRA RVR values (16% negative predictive value). RVR analysis correctly identified 86 of 117 patients with renovascular hypertension (74% sensitivity, 16% negative predictive value). Improved blood pressure (BP) control occurred in 72% with abnormal RVR analysis and 66% of the 121 patients without RVR data (p>0.1). We conclude that the very low negative predictive value significantly limited the use of RVR analysis in this elderly (mean age 60 years) patient population with a high incidence of mild renal functional impairment (mean serum creatinine 1.4 mg/dl) and bilateral renal artery stenosis (38%). The lack of pre-PTRA renin data did not significantly affect clinical outcome. If RVR data were relied upon as the exclusive selection criterion in patients of this type, many would be prevented from having the benefit of cure or improvement by PTRA.     

CASE REPORT: Antibiotic-associated haemorrhagic colitis

Antibiotic-associated haemorrhagic colitis is an uncommon cause of bloody diarrhoea in patients taking penicillin or penicillin-related antibiotics. Symptoms of abdominal pain and bloody diarrhoea occur within 1 week of antibiotic use and resolve without specific therapy within days of discontinuing the offending antibiotic. There is an apparent increased incidence of the disease in patients of Oriental ethnicity. The pathogenesis is unknown. We present two cases of haemorrhagic colitis in patients taking penicillin-related antibiotics who presented within 4 months of each other. One of the patients was being treated for Helicobacter pylori infection. The published literature is reviewed with particular emphasis on the histology and pathogenesis of the condition.