Fanconi-Bickel syndrome

We present here the first case of Fanconi-Bickel syndrome, a rare type of glycogen storage disease, from India. A 17-month-old female child presented with severe growth retardation and abdominal distention. Clinical examination revealed a "doll-like" face, massive hepatomegaly, and rickets. Laboratory investigations confirmed severe hypophosphatemic rickets and proximal renal tubular dysfunction. Liver biopsy showed glycogen accumulation in the hepatocytes.     

Prognostic value of direct bilirubin in neonatal hyperbilirubinemia

Objective To determine the prognostic value of indirect and direct hyperbilirubinemia in neonates with jaundice. Methods A cohort of 92 consecutive neonates reporting with hyperbilirubinemia to a tertiary care center were followed up till well and discharged, or, till death to assess risk and rate of mortality. Results The baseline median values of total, direct and indirect bilirubin in the cohort of 21.8, 1.6 and 18.6 mg/dl, respectively, were used as cut-offs for high and low levels. Using survival analyses i.e. Kaplan-Meier plots, logrank tests and multivariate Cox proportional hazards regression models to adjust for other strong predictors such as receipt of breastfeeding, being small for gestational age (SGA) and exchange transfusion, high direct bilirubin (≥ median value of 1.6 mg/dl) was independently associated with a higher and faster mortality. Conclusion This study showed that direct bilirubin has independent and additive prognostic value and due attention should be given to newborns with raised levels.     

Complications of AlphaCor keratoprosthesis: a clinicopathologic report

PURPOSE: To describe the clinical and histopathologic features of intractable secondary glaucoma induced by AlphaCor keratoprosthesis. METHODS: An elderly woman with pseudoexfoliation glaucoma and pseudophakic bullous keratopathy in the right eye had graft failures after penetrating keratoplasty. Her best-corrected visual acuity at presentation was counting fingers in the right eye and 20/30 in the left eye. Examination showed severe corneal neovascularization. Chirila keratoprosthesis type II was implanted in 2 stages. Ten months later, the patient developed dense retrocorneal membrane, 360 degrees occlusion of angles, intractable glaucoma, no light perception, and nasal stromal melting associated with partial extrusion of the keratoprosthesis. RESULTS: Histopathology revealed invasion of the porous material of the keratoprosthesis by reactive fibroblasts and multinucleated foreign-body giant cells. In the area of dehiscence, we noted thinning and lysis of the collagen fibers, infiltration of lymphocytes, and plasma cells with a sheet of fibroinflammatory tissue extending into the anterior chamber. CONCLUSIONS: Corneal stromal melting and retrocorneal prosthetic membrane formation after AlphaCor keratoprosthesis implantation led to intractable glaucoma and extrusion of the implant.     

The implication of compromised renal function at presentation in myeloma

The purpose of the study was to determine the role of sequential therapy (ST) in new patients with myeloma presenting with renal dysfunction (RD): serum creatinine >140 μmol/L (1.6 mg/dL). Between April 1985 and June 1998, 251 patients, 59 (23%) with RD were entered into a ST program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP (vincristine, doxorubicin, and methylprednisolone with/without cyclophosphamide) followed by autologous transplantation and interferon maintenance. The median overall survival (OS) of 251 patients from the start of IC was 4.2 yr with the RD group faring significantly poorer (median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6 yr; p=0.0025). Mortality during the first 100 d of IC was significantly higher in patients with RD (11/59; p=0.01) compared to patients with NRD. In patients consolidated with high-dose therapy, the OS and event-free survival (EFS) were not significantly different between the two groups. Cox analysis of the variables at presentation failed to show RD as a factor influencing outcome, but it showed that patients with beta-2-microglobulin (β₂M)≥3.7 (p<0.0001), age ≥52.5 yr (p=0.002), performance status (PS) ≥2 (p=0.005) and patients with light-chain myeloma (p=0.03) had a significantly shorter OS, β₂M≥3.7, PS≥2, and light-chain myeloma were predictive of shorter EFS. The study shows that with modern intensive schedules of treatment, renal disease at presentation in isolation does not compromise outcome.     

Cellulose acetate microspheres prepared by o/w emulsification and solvent evaporation method.

The study is concerned with the development of cellulose acetate microspheres by the o/w emulsification and solvent evaporation method in the presence of polyvinyl alcohol as an emulsifying agent. The influence of process parameters such as solvent mixture (acetone + dichloromethane) composition, concentration of the emulsifying agent and speed of stirring has been examined. The microspheres have been analysed for their size, drug loading capacity and release kinetics. Spherical and smooth surfaced microspheres with encapsulation efficiencies ranging between 73-98%, were obtained. Use of acetone in the oil phase drastically reduced the particle size. Slow drug release from microspheres occurred up to approximately 8 h and the release was found to be non-Fickian. An optimization procedure was employed to investigate and identify the key parameters affecting the properties of the microspheres. A 33 randomized full factorial design was used in the analyses of the data. A linear model with interactive terms was generated using a multiple linear regression approach. The statistical analysis confirms the significant effect of solvent composition and concentration of emulsifying agent on the drug release characteristics.     

Possible involvement of prostaglandins in haloperidol-induced orofacial dyskinesia in rats

Dopaminergic abnormality is one of the pathological mechanisms involved in the pathophysiology of tardive dyskinesia, a late complication of neuroleptic treatment. Prostaglandins modulate the dopamine release in the striatum, the principle area involved in the pathophysiology of tardive dyskinesia. Rats were chronically treated with haloperidol (HPD) (1.5 mg/kg) for a period of 21 days, to induce orofacial dyskinesia. Behavioural assessment of orofacial dyskinesia was done 24 h after the last dose of haloperidol. Catalepsy was induced in rats by acute treatment with haloperidol (1 mg/kg), and catalepsy was scored for the next 4 h. Chronic haloperidol treatment induced profound vacuous chewing movements in rats. Indomethacin, a nonselective cyclooxygenase inhibitor dose-dependently (5–20 mg/kg) suppressed the vacuous chewing movements count in haloperidol-treated animals. In conclusion, the results of the present study infer that prostaglandins might play a significant role in the haloperidol-induced vacuous chewing movements, and prostaglandin synthesis inhibitors can serve as novel drug candidates for the treatment of tardive dyskinesia.     

D1/D2 dopamine and N-methyl-d-aspartate (NMDA) receptor participation in experimental catalepsy in rats

Mixed D₁/D₂ dopamine (DA) antagonists, perphenazine (5 mg/kg) and haloperidol (2 mg/kg) induced catalepsy in rats. SCH 23390 (1 mg/kg), a D₁ DA antagonist, also produced catalepsy. Co-administration of perphenazine (0.5 mg/kg) and SCH 23390 (0.1 mg/kg), at low doses, produced a marked increase in cataleptic response. B-HT 920, a D₂ agonist, reversed the cataleptogenic effects of perphenazine, haloperidol and SCH 23390. SKF 38893 (5 mg/kg) reduced the cataleptogenic effect of SCH 23390 but failed to reverse haloperidol- or perphenazine-induced catalepsy. SKF 38393 (10 mg/kg), however, protected the animals against perphenazine- induced catalepsy. Combined administration of B-HT 920 (0.1 mg/kg) and SKF 38393 (5 mg/kg) enhanced the protective effect of B-HT 920 in SCH 23390-treated animals but not in animals treated with haloperidol or perphenazine. MK-801 (0.025–0.5 mg/kg), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reduced the cataleptogenic effects of perphenazine, haloperidol as well as SCH 23390. The anticataleptic action of MK-801 was enhanced by scopolamine (0.1 mg/kg) but not by bromocriptine (1 mg/kg) or clonidine (0.05 mg/kg) in perphenazine-treated rats. Unlike B-HT 920 (0.1 mg/kg), SKF 38393 (5 mg/kg) potentiated the anticataleptic effect of MK-801 (0.01 mg/kg) against SCH 23390-induced catalepsy. The above data suggests D₁/D₂ interdependence in catalepsy and a modulatory role of D₁ and D₂ DA receptor stimulation on the anticataleptic effect of MK-801.     

DTI at long diffusion time improves fiber tracking

While diffusion‐tensor‐imaging tractography provides remarkable in vivo anatomical connectivity of the central nervous system, the majority of DTI studies to date are predominantly limited to tracking large white‐matter fibers. This study investigated DTI tractography using long diffusion time (t_diff) to improve tracking of thinner fibers in fixed rhesus monkey brains. Stimulated Echo Acquisition Mode (STEAM) sequence on a 3T Siemens TRIO was modified to include a diffusion module. DTI was acquired using STEAM with t_diff of 48 and 192 ms with matched signal‐to‐noise ratios (SNR). Comparisons were also made with the conventional double‐spin echo (DSE) at a short t_diff of 45 ms. Not only did the fractional anisotropy increase significantly with the use of long diffusion time, but directional entropy measures indicated that there was an increased coherence amongst neighboring tensors. Further, the magnitude of the major eigenvector was larger at the t_diff = 192 ms as compared to the short t_diff. Probabilistic connectivity maps at long t_diff showed larger areas of connectivity with the use of long diffusion time, which traversed deeper into areas of low anisotropy. With tractography, it was found that the length of the fibers, increased by almost 10% in the callosal fibers that branch into the paracentral gyrus, the precentral gyrus and the post central gyrus. A similar increase of about 20% was observed in the fibers of the internal capsule. These findings offer encouraging data that DTI at long diffusion time could improve tract tracing of small fibers in areas of low fractional anisotropy (FA), such as at the interfaces of white matter and grey matter. Copyright © 2010 John Wiley & Sons, Ltd.