Hippocampal volume and cingulum bundle fractional anisotropy are independently associated with verbal memory in older adults

The objective of this study was to investigate the relationship of medial temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as fractional anisotropy of the cingulum angular bundle (CAB) and the cingulum cingulate gyrus (CCG) bundle to performance on measures of verbal memory in non-demented older adults. The participants were 100 non-demented adults over the age of 70 years from the Einstein Aging Study. Volumetric data were estimated from T1-weighted images. The entire cingulum was reconstructed using diffusion tensor MRI and probabilistic tractography. Association between verbal episodic memory and MRI measures including volume of hippocampus (HIP), entorhinal cortex (ERC), PCC and fractional anisotropy of CAB and CCG bundle were modeled using linear regression. Relationships between atrophy of these structures and regional cingulum fractional anisotropy were also explored. Decreased HIP volume on the left and decreased fractional anisotropy of left CAB were associated with lower memory performance. Volume changes in ERC, PCC and CCG disruption were not associated with memory performance. In regression models, left HIP volume and left CAB-FA were each independently associated with episodic memory. The results suggest that microstructural changes in the left CAB and decreased left HIP volume independently influence episodic memory performance in older adults without dementia. The importance of these findings in age and illness-related memory decline require additional exploration.     

Fulminant hepatic failure from primary hepatic lymphoma: successful treatment with orthotopic liver transplantation and chemotherapy

Systemic lymphomas may involve the liver but rarely cause fulminant hepatic failure (FHF). Acute liver failure from primary hepatic lymphoma (PHL) is even less common with most patients succumbing to the sequelae of FHF before the correct diagnosis is made. We report a patient who underwent successful orthotopic liver transplant (OLT) and chemotherapy for FHF secondary to PHL. This previously-well male developed profound coagulopathy and encephalopathy 6 weeks after the onset of jaundice and fatigue. Workup failed to reveal the underlying cause of his liver failure and the patient soon required urgent OLT. Pathologic evaluation of his explanted liver revealed a malignant T-cell rich, large B-cell non-Hodgkin's lymphoma with widespread hepatocellular necrosis. The patient made an excellent clinical recovery and is undergoing CHOP-Rituxan chemotherapy. This scenario demonstrates that lymphoma should be considered in the differential diagnosis of FHF without clear etiology because of the potential for intervention with transplant and chemotherapy.     

Laparoscopy-assisted transperitoneal percutaneous nephrolithotomy for renal caliceal diverticular calculi

BACKGROUND AND PURPOSE: There are a variety of options for the management of symptomatic calculi in caliceal diverticula, each with utility in particular situations. Herein, we describe a laparoscopy-assisted transperitoneal percutaneous nephrolithotomy (PCNL) technique to address the unusual combination of an anterior caliceal diverticulum together with multiple branched calculi having segments both within and proximal to the diverticulum. TECHNIQUE: With the patient in a modified lithotomy position, standard transperitoneal laparoscopy was performed utilizing three 10-mm trocars. After mobilization of the colon medially, the cystic diverticulum was opened. An additional 12-mm trocar was placed to allow transperitoneal PCNL within the diverticulum. Rigid nephroscopy, holmium laser lithotripsy, and stone extraction were performed, including laser enlargement of the diverticular neck and removal of the stone burden proximal to the neck. A double-pigtail ureteral stent and Jackson-Pratt drain were placed. RESULTS: This procedure was successful in the only patient in whom it has been used to date. As far as we know, this is the first report of laparoscopy-assisted transperitoneal PCNL for the management of caliceal diverticular calculi. CONCLUSION: Laparoscopy-assisted transperitoneal PCNL is a safe and effective alternative for the management of symptomatic stones in anterior cystic caliceal diverticula with a narrow neck and complex branched calculi.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

MR of the cerebral operculum: abnormal opercular formation in infants and children.

PURPOSETo evaluate abnormalities of the cerebral operculum in infants and children and to propose the embryogenic basis of abnormal opercular formation as determined from MR imaging findings.METHODSEighty-six infants and children who had abnormally wide interopercular distances and/or distorted opercular topography seen on MR images were studied retrospectively. Clinically, patients presented with tonal abnormalities, macrocephaly, microcephaly, seizures, developmental delay, cerebral palsy, or facial dysmorphism. The abnormal opercula were compared with developing opercula at different stages of gestation.RESULTSAmong the 86 infants and children, two categories of opercular abnormalities were identified: an underdeveloped operculum (n = 64) and a malformed operculum (n = 22). The malformed operculum was further classified into three subtypes: nonformation of the operculum with lissencephaly (n = 1, 1%), abnormal opercular formation with pachygyria (n = 11, 13%), and nonformation or abnormal formation of the operculum without pachygyria or lissencephaly (n = 10, 12%). Two subtypes of the underdeveloped operculum were identified: an open operculum without a normal insula (n = 6, 7%) and an open operculum with a normal insula (n = 58, 67%). The five subtypes of abnormal opercular configuration showed a range of maturity that was comparable to the developing operculum at different ages.CONCLUSIONOpercular anomalies appear to follow sequentially predetermined normal steps in development. Arrest in opercular development or malformation may occur after an initial insult. MR imaging is the method of choice by which to identify these abnormalities.     

Specific uptake of 99mTc-NC100692, an αvβ3-targeted imaging probe,in subcutaneous and orthotopic tumors

IntroductionThe α_vβ₃ integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of α_vβ₃-targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with α_vβ₃-targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with ^99mTc. In an effort to begin to address this limitation, we evaluated the tumor uptake of ^99mTc-NC100692, a cyclic RGD peptide that binds to α_vβ₃ with ~ 1-nM affinity, in an α_vβ₃-positive tumor model as well as its in vivo specificity.MethodsMicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for α_vβ₃, to block and displace ^99mTc-NC100692 in an orthotopic U87 glioma tumor. The specificity of ^99mTc-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of ^99mTc-NC100692 with that of the non-specific structural analogue ^99mTc-AH-111744 and by blocking uptake of ^99mTc-NC100692 with excess unlabeled NC100692.ResultsMicroSPECT imaging studies demonstrated that uptake of ^99mTc-NC100692 in the intracranial tumor model was both blocked and displaced by the α_vβ₃-targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of ^99mTc-NC100692 at 1 h post-injection was 2.8 ± 0.7% ID/g compared to 0.38 ± 0.1% ID/g for ^99mTc-AH-111744 (p < 0.001). Blocking ^99mTc-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately five-fold, to 0.68 ± 0.3% ID/g (p = 0.01).ConclusionThese results confirm that ^99mTc-NC100692 does, in fact, target the α_vβ₃ integrin and may, therefore, be useful in identifying patients prior to anti-α_vβ₃ therapy as well as monitoring the response of these patients to therapy.     

Partial splenectomy for children with congenital hemolytic anemia and massive splenomegaly

Partial splenectomy is an alternative to total splenectomy for the treatment of congenital hemolytic anemias (CHAs) in children, although the feasibility of this technique in the setting of massive splenomegaly is unknown. This study was designed to evaluate the safety and efficacy of partial splenectomy in children with CHAs and massive splenomegaly. This retrospective study examined 29 children with CHAs who underwent partial splenectomy. Children were divided into 2 groups based on splenic size: 8 children had splenic volumes greater than 500 mL, whereas 21 children had splenic volumes less than 500 mL. Outcome variables included perioperative complications, transfusion requirements, hematocrits, reticulocyte counts, bilirubin levels, splenic sequestration, and splenic regrowth. All 29 children underwent successful partial splenectomy with 0.02 to 10 years of follow-up. After partial splenectomy, children overall had decreased transfusion requirements, increased hematocrits, decreased bilirubin levels, decreased reticulocyte counts, and elimination of splenic sequestration. Children with massive splenomegaly had similar outcomes compared with children without massive splenomegaly. Long-term complications included 3 mild infections, 4 cases of gallstones requiring cholecystectomy, and 1 child who required completion splenectomy. Partial splenectomy is a safe, effective, and technically feasible option for children with various CHAs, even in the setting of massive splenomegaly.     

Porcine wound healing in full-thickness skin defects using Integra? with and without fibrin glue with keratinocytes

BACKGROUND:

An artificial dermal matrix such as Integra (Integra Life Sciences Corporation, USA) provides a wound bed template for vascular and fibrocyte ingrowth as well as collagen remodelling. Dermal repair leads to epidermal and basement membrane regeneration. Burn wounds in particular have been shown to benefit from Integra by enhanced wound healing.

OBJECTIVE:

To evaluate the effect of fibrin glue to modify the integration of Integra in large excised cutaneous wounds. It was hypothesized that applying fibrin glue on a wound bed would reduce the time needed for matrix vascularization and incorporation of Integra and take of the cultured keratinocytes.

METHODS:

Four separate full-thickness wounds were created on the dorsum of two swine. Wound beds were randomly assigned to either application of fibrin glue or no application of fibrin glue before application of Integra. Full-thickness biopsies were performed at days 7, 14, 21, 29 and 35. On day 21, keratinocytes were applied either as sheets or aerosolized fibrin glue suspension.

RESULTS:

Histological analysis revealed a wave of inflammatory cells and early granulation tissue ingrowth into the Integra from the fascia below on day 7. Only this initial phase was augmented by application of fibrin glue to the wound bed. By day 14, most and by day 21, all of the Integra thickness was incorporated. Accelerated dermal repair proceeded from the base with new collagen deposition in Integra spaces. There was no evidence of keratinocyte engraftment, although re-epithelialization occurred at wound edges extending onto the incorporated Integra.

CONCLUSIONS:

It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension.