Rabbit as an animal model for experimental research

Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. Though experimentation on rabbits seems to be easy there are many pitfalls. Our endeavor in this article is to integrate all the data about maintaining rabbits as a model and to critically analyze it on the basis of our experimentation.     

Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia

Background

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.

Design and Methods

Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.

Results

Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6–65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.

Conclusions

Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.     

Low-Dose Rituximab Therapy for Antibody-Mediated Rejection in a Highly Sensitized Heart-Transplant Recipient

Antibody-mediated rejection is the B-cell–mediated production of immunoglobulin G antibody against the transplanted heart. The currently available therapies for antibody-mediated rejection have had marginal success, and chronic manifestations of rejection can result in an increased risk of graft vasculopathy and perhaps require repeat transplantation. Rituximab, a monoclonal antibody directed against the CD20 receptor of B-lymphocytes and approved as therapy for lymphoma, can be used in heart-transplant patients for the management of antibody-mediated rejection.We present the case of a 52-year-old woman with high allosensitization (pre-transplantation panel reactive antibody level, 72%) who underwent successful orthotopic heart transplantation. Postoperatively, her acute antibody-mediated rejection with concomitant cellular rejection was successfully treated with low-dose rituximab. The patient died 5 months later because of multiple other medical problems. The present case suggests a role for low-dose rituximab as therapy for antibody-mediated rejection in heart-transplant patients.Key words: Antibodies, monoclonal/therapeutic use; antigens, CD20/immunology; B-lymphocytes/immunology; graft rejection/drug therapy; heart transplantation/pathology; HLA antigens/immunology; immunity, humoral/physiology/therapy; immunoglobulins, intravenous/metabolism; plasmapheresis; rituximab; time factorsAntibody-mediated rejection (AMR) in heart-transplant recipients is mediated by donor-specific antibodies and is histologically defined by linear deposits of immunoglobulin (Ig) and complement in the myocardial capillaries.¹ Antibody-mediated rejection is often accompanied by hemodynamic compromise and is associated with diminished graft survival. Standard immunosuppressive therapy, designed to target T-cell immune function, is largely ineffective against this B-cell–driven process. Various therapies for AMR, although available, can be of marginal use secondary to patients'' comorbidities.^2,3 We present the case of a woman with a history of ventricular assist device (VAD) implantation, dialysis dependence, and severe thrombocytopenia who responded well to the addition of anti-CD20 monoclonal antibody therapy with rituximab after heart transplantation.     

Bone Regeneration in Extraction Sockets with Autologous Platelet Rich Fibrin Gel

Aim

To evaluate the effects of autologous platelet rich fibrin gel (PRF gel) on bone regeneration following extraction.

Materials and Methods

The study design was approved by the Institutional Ethical Committee. Study sample consisting of a total of 22 patients requiring bilateral transalveolar third molar extractions were included after written informed consent. One side was randomly chosen as case and the other side was the control. Autologous PRF gel was prepared from Fresh blood obtained from the patient. The PRF gel was placed in the extraction site and primary closure was obtained. The patient was called for a follow up on the first post op day, 1st week, one month, three month and six months post op. Regeneration of bone was measured using serial radiographs (RVG) at immediate post op, one, three and six months. This was then compared with the bone regeneration seen in the control group, with the radiographs taken at same intervals, to estimate the difference in bone regeneration if any. RVGs were assessed for amount of radiologic bone filling by the method described by Matteo Chiapasco et al.

Results and Conclusion

Higher mean pixels was recorded in cases compared to controls at all the time intervals viz., immediate post op, 1 month post op, 3 months post op and 6 months post op. However, the difference in the mean pixels recorded between the two groups was not statistically significant (P > 0.05). For complete analysis, further follow up of the present patients and a larger sample size is required to obtain a conclusive result of the Bone Regeneration in extraction sockets with PRF gel.     

Le-fort I access osteotomy to nasopharyngeal tumor – A case-report

Removal of extensive central skull base and paranasal sinus tumors is a significant challenge that is often hampered by limited access and exposure. The safety and efficacy of the Le Fort I osteotomy approach to the skull base have been well established. The purpose of this article is to describe the use of Le fort-1I osteotomy as an access procedure to reach tumors in the nasopharyngeal region in a young patient. The large mass which he presented within the nasopharyngeal region, later diagnosed to be juvenile nasopharyngeal angiofibroma, posed a challenge for surgical access.     

Investigation of the urge-to-cough sensation in healthy volunteers

Background and objective: Recently, there has been interest in the sensation of irritation that precedes the motor act of coughing, which has been termed the urge‐to‐cough (UTC). The aim of this study was to perform the largest evaluation to date of the UTC threshold (C_u) in a healthy population. The specific aims were to investigate the relationship between C_u and cough reflex sensitivity, to evaluate gender differences in the UTC and to assess the reproducibility of measurements of C_u. Methods: Standard capsaicin cough challenge methodology was employed to measure cough reflex sensitivity in 100 healthy adult non‐smokers (50 females) with the additional measurement of C_u. A subgroup of 40 subjects (20 males) underwent repeat cough challenges after 1 week to examine the reproducibility of the measurements. Results: All 100 subjects demonstrated motor cough in response to capsaicin. Twenty‐one subjects (10 females) did not show a discernible C_u, as the motor cough event preceded a UTC sensation unaccompanied by cough. Although cough reflex sensitivity, as measured by the concentration of capsaicin inducing five or more coughs (C₅), was enhanced in women, there was no gender difference in C_u. Similar to standard cough reflex sensitivity measurements, the measurement of C_u was highly reproducible. Conclusions: These results demonstrate that the UTC threshold can be effectively and reproducibly measured using a modification of standard cough challenge methodology. Given its clinical significance as a prevalent symptom, UTC, as measured by C_u, represents an additional relevant end point for studies investigating the effects of pharmacological and other interventions in cough and cough reflex sensitivity.