Outcome after decompressive craniectomy in patients with dominant middle cerebral artery infarction: A preliminary report

Introduction:

Life-threatening, space occupying, infarction develops in 10-15% of patients after middle cerebral artery infarction (MCAI). Though decompressive craniectomy (DC) is now standard of care in patients with non-dominant stroke, its role in dominant MCAI (DMCAI) is largely undefined. This may reflect the ethical dilemma of saving life of a patient who may then remain hemiplegic and dysphasic. This study specifically addresses this issue.

Materials and Methods:

This retrospective analysis studied patients with DMCAI undergoing DC. Patient records, operation notes, radiology, and out-patient files were scrutinized to collate data. Glasgow outcome scale (GOS), Barthel index (BI) and improvement in language and motor function were evaluated to determine functional outcome.

Results:

Eighteen patients between 22 years and 72 years of age were included. 6 week, 3 month, 6 month and overall survival rates were 66.6% (12/18), 64% (11/17), 62.5% (10/16) and 62.5% (10/16) respectively. Amongst ten surviving patients with long-term follow-up, 60% showed improvement in GOS, 70% achieved BI score >60 while 30% achieved full functional independence. In this group, motor power and language function improved in 9 and 8 patients respectively. At last follow-up, 8 of 10 surviving patients were ambulatory with (3/8) or without (5/8) support. Age <50 years corresponded with better functional outcome amongst survivors (P value –0.0068).

Conclusion:

Language and motor outcomes after DC in patients with DMCAI are not as dismal as commonly perceived. Perhaps young patients (<50 years) with DMCAI should be treated with the same aggressiveness that non-DMCAI is currently dealt with.Key Words: Craniectomy, dominant, middle cerebral artery, outcome, stroke     

Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons

The regulation of metal ion transport within neurons is critical for normal brain function. Of particular importance is the regulation of redox metals such as iron (Fe), where excess levels can contribute to oxidative stress and protein aggregation, leading to neuronal death. The divalent metal transporter 1 (DMT1) plays a central role in the regulation of Fe as well as other metals; hence, failure of DMT1 regulation is linked to human brain pathology. However, it remains unclear how DMT1 is regulated in the brain. Here, we show that DMT1 is regulated by Ndfip1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins. Using human neurons we show the Ndfip1 is upregulated and binds to DMT1 in response to Fe and cobalt (Co) exposure. This interaction results in the ubiquitination and degradation of DMT1, resulting in reduced metal entry. Induction of Ndfip1 expression protects neurons from metal toxicity, and removal of Ndfip1 by shRNAi results in hypersensitivity to metals. We identify Nedd4–2 as an E3 ligase recruited by Ndfip1 for the ubiquitination of DMT1 within human neurons. Comparison of brains from Ndfip1^−/− with Ndfip1^+/+ mice exposed to Fe reveals that Ndfip1^−/− brains accumulate Fe within neurons. Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons.     

Viscoexpression of anterior chamber cysticercus cellulosae

We report a case of anterior chamber Cysticercus cellulosae that was removed by viscoexpression.     

Genetic and immunological comparison of anti-botulinum type A antibodies from immune and non-immune human phage libraries

Understanding the antibody response in botulinum intoxication is important for vaccine design and passive prophylaxis. To investigate this activity, we have studied the immune response to BoNT/A (botulinum neurotoxin serotype A) binding domain (HC) at the molecular level using phage display. The scFv antibodies were isolated from V-gene repertoires prepared from (a) human volunteer immunized with pentavalent botulinum toxoid and (b) non-immune human peripheral blood lymphocytes and spleenocytes. A large panel of serotype specific phage expressing botulinum binding scFv could be selected from both libraries. Epitope mapping of immune scFv binders towards BoNT/A HC revealed surprisingly a limited number of scFv recognizing conformational epitopes that corresponded to two distinct groups, clusters I and II. Only scFv from cluster I exhibited neutralizing activity in the mouse hemidiaphragm assay. Anti- BoNT/A HC clones derived from a non-immune library could be conveniently grouped into clusters III-XI and appeared to share no overlapping epitopes with cluster I or II. In addition they showed no neutralization of toxin at biologically significant concentrations. We therefore suggest that a vaccine based on the pentavalent botulinum toxoid directs the humoral immune response to a limited number of immunodominant epitopes exposed on the binding domain HC.     

Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.

We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using these biomarkers, in this study we examined the anticarcinogenic mechanisms of these chemopreventive agents. Rats were maintained on AIN-76A chow or supplemented with 0.4% UDCA or F(6)-D(3) (2.5 nmol/kg chow) and treated weekly with AOM 20 mg i.p./kg wt or saline x 2 weeks. F(6)-D(3) was continued for an additional 2 weeks and UDCA for the duration of the study. At 40 weeks, animals received bromodeoxyuridine (BrdUrd) i.p. 2 h before sacrifice. A portion of each tumor was fixed in formalin and the remainder flash frozen. Colons were divided longitudinally and half-fixed in formalin and half in ethanol. The size and location of methylene blue-stained ACF were recorded. Cell proliferation (BrdUrd labeling) and apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay) were measured in colonic crypts and tumors. Protein expression levels of several regulators of cell proliferation were analyzed by immunostaining and Western blotting. Colonic crypt cyclin D1 and E-cadherin mRNA levels were measured by real-time PCR. In saline injected controls, neither UDCA nor F(6)-D(3) alone had any effect on cytokinetic parameters or on the expression of mitogenic regulators. AOM significantly increased the proliferation (percentage of BrdUrd-positive cells) of both ACF (23.1 +/- 1.7%) and non-ACF crypts (17.6 +/- 1.6%), compared with normal colonic crypts (4.5 +/- 0.8%; P < 0.05). This hyperproliferation was accompanied by a 5-fold increase in cyclin D1 and >50% decrease in E-cadherin protein (P < 0.05) in ACF, both of which are predicted to be growth-enhancing alterations. UDCA and F(6)-D(3) significantly (P < 0.05) inhibited AOM-induced crypt cell hyperproliferation, ACF development, and tumor burden. These chemopreventive agents also significantly blocked AOM-induced alterations in cyclin D1 and E-cadherin protein in ACF and tumors. In ACF, changes in mRNA levels of cyclin D1, but not E-cadherin, paralleled alterations in protein expression. Cyclooxygenase-2 and inducible nitric oxide synthase were increased in AOM tumors but not in ACF, and these changes were blocked by UDCA and F(6)-D(3). UDCA and F(6)-D(3) significantly inhibited ACF development and hyperproliferation, in part, by preventing carcinogen-induced alterations in cyclin D1 and E-cadherin. In established tumors, UDCA and F(6)-D(3) also limited inductions of cyclooxygenase-2 and inducible nitric oxide synthase, which together with their effects on cyclin D1 and E-cadherin, contribute to their chemopreventive actions.     

Bilateral lacrimal sac mucocele with punctal and canalicular atresia

Congenital absence of lacrimal puncta may be an isolated finding or associated with other developmental abnormality. Nasolacrirnal ducts can be absent thus predisposing to the formation of a congenital lacrimal mucocele. Punctal and canalicular agenesis is very rare. Four percent of new patients attending the lacrimal clinic at Moorfields Eye Hospital, London, UK. from 1981 to 1990 inclusive were diagnosed to have this condition. We describe a case of bilateral congenital absence of lacrimal puncta with lacrimal mucocele. Combined surgery was carried out by Ophthalmologist and Otolaryngologist with successful results.     

Safety of oral iron chelator deferiprone in young thalassaemics

Deferiprone is now widely used for iron chelation in patients with thalassaemia. Studies on its efficacy and safety have largely included older children and adults. OBJECTIVE: To assess the safety of deferiprone in children <6 yr of age. METHODS: The study is based on scrutiny of follow-up data of 44 patients of age <6 yr receiving deferiprone for a variable period of time. Occurrence of various side effects including gastrointestinal, osteoarticular were noticed and complete blood counts were performed every 2-4 wk. RESULTS: Nausea and vomiting were noticed in 12 (27.2%), joint symptoms were reported by four (9.1%) and neutropenia was observed in only two patients (4.5%). None of the patient had agranulocytosis. Thrombocytopenia was observed in 20 patients (45.45%), which occurred 3 months to 1 yr after deferiprone therapy. Interruption of deferiprone for 2-4 wk led to reversal of symptoms in all but two patients. CONCLUSION: Thrombocytopenia is one of the major side effects in young thalassaemics and necessitates frequent close monitoring of blood counts but its resolution after discontinuation and absence of clinical evidence of bleeding does not preclude its use.     

Spinal myelopathy induced by subarachnoid batrachotoxin: Ultrastructure and electrophysiology

A combined structural and electrophysiologic analysis on the effects of subarachnoid injections of batrachotoxin was conducted in rats. Swelling of neuronal perikarya, accompanied by areas of clearing, satellitosis, fatty metamorphosis and central chromatolysis were demonstrated in the spinal anterior horns. Studies on isolated extensor digitorum longus (fast) and soleus (slow) muscles showed membrane depolarization in the extensor 24 h after injection, with progressive augmentation of this phenomenon in animals given multiple injections of the toxin. Differential sensitivity of fast and slow muscles was evident: soleus was only slightly affected. Subarachnoid injections of batrachotoxin, which induced swelling of neuronal perikarya and axonal processes, also caused signs of denervation in the extensor muscle 7 days after injection, while spontaneous transmitter release was still present. Some structural and most electrophysiologic alterations after batrachotoxin injections were reversible.     

A prospective randomized comparison of type of nephrostomy drainage following percutaneous nephrostolithotomy: large bore versus small bore versus tubeless

PURPOSE: We compared postoperative outcomes among tubeless, conventional large bore nephrostomy drainage and small bore nephrostomy drainage following percutaneous nephrostolithotomy (PCNL) in a prospective randomized fashion. MATERIALS AND METHODS: Between January and June 2001, 30 patients undergoing PCNL were randomized to receive conventional large bore (20Fr) nephrostomy drainage (group 1, 10 patients), small bore (9Fr) nephrostomy drainage (group 2, 10 patients) or no nephrostomy drainage (group 3, 10 patients). Inclusion criteria included a single subcostal tract, uncomplicated procedure, normal preoperative renal function and complete stone clearance. Factors compared among the 3 groups were postoperative analgesia requirement, urinary extravasation, duration of hematuria, duration of urinary leak, decrease in hematocrit and hospital stay. RESULTS: The postoperative analgesic requirement was significantly higher in group 1 (217 mg) compared to groups 2 (140 mg, p <0.05) and 3 (87.5 mg, p <0.0001). Patients in group 3 had a significantly shorter duration (4.8 hours) of urinary leak through the percutaneous renal tract compared to patients in groups 1 (21.4 hours, p <0.05) and 2 (13.2 hours, p <0.05). Hospital stay was significantly shorter in group 3 (3.4 days) compared to groups 1 (4.4 days, p <0.05) and 2 (4.3 days, p <0.05). All 3 groups were similar in terms of operative time, duration of hematuria and decrease in hematocrit. Postoperative ultrasound did not reveal significant urinary extravasation in any case. CONCLUSIONS: Tubeless PCNL is associated with the least postoperative pain, urinary leakage and hospital stay. Small bore nephrostomy drainage may be a reasonable option in patients in whom the incidence of stent dysuria is likely to be higher.