A comparative evaluation of iliac crest bone graft with and without injectable and advanced platelet rich fibrin in secondary alveolar bone grafting for cleft alveolus in unilateral cleft lip and palate patients: A randomized prospective study.

PURPOSE: Platelet rich fibrin enhances bone healing and results in better graft intake and helps in faster periodontal healing. In this study we have used a combination of two newly developed forms of platelet rich fibrin: injectable and advanced along with iliac bone graft for secondary alveolar bone grafting and compared it with cases in which only iliac bone graft was used. METHODS: 30 patients with alveolar cleft, with age group of ≥7 years, having complete unilateral cleft alveolus were included and divided into 2 groups of 15 patients each randomly. In Group A, secondary alveolar bone grafting was done using iliac bone graft along with injectable and advanced palate rich fibrin and in Group B, secondary alveolar bone grafting was done only with iliac bone graft. Success of the treatment was assessed using radiographic and clinical methods which included: The bone resorption of the interalveolar septum height of the teeth adjacent to the cleft, evaluated as per Bergland classification, assessment of periodontal status of the teeth adjacent to cleft alveolus. RESULTS: After 3 months and 6 months postoperatively: study group had better overall scores as per Bergland criteria. Periodontal status improved in both groups but was more in study group compared to control group. For both evaluations the data was clinically favorable in the study group. CONCLUSION: On preliminary investigations it shows that combination of injectable and advanced platelet rich fibrin seems to enhance bone formation in alveolar clefts when admixed with autologous cancellous bone harvested from the iliac crest than using iliac bone graft alone. It also reduces the chances of bone resorption and show higher percentage of bone volume. Secondary alveolar grafting improves periodontal health around the cleft alveolus.

Genetic analysis of MRL-lpr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci.

In MRL mice, the mostly recessive lpr mutation results in both the accumulation of CD4-, CD8-, CD3+ T cells in lymphoid tissue and many features of generalized autoimmune disease, including immune complex glomerulonephritis. To positionally clone the lpr mutation and analyze the effects of background genes, backcross offspring were examined from the cross: (MRL/MpJ-lpr x CAST/Ei)F1 x MRL/MpJ-lpr. The lpr gene was found to be closely linked to a mouse chromosome 19 marker defined by a variation of a Fas gene restriction fragment. Our results identified differences in RNA expression and differences in the genomic organization of the Fas gene between normal and lpr mice, and confirm the recent report that a mutation in the Fas apoptosis gene is the lpr mutation. However, our results also indicate that the Fas gene is expressed in spleen cells from normal mice, and spleen and lymph node cells from mice with a second mutation at the lpr locus (lprcg). Together these results suggest that altered Fas transcription results in the failure of lymphocytes to undergo programmed cell death and may lead to an altered immune cell repertoire. This mechanism may explain certain central and peripheral defects in tolerance that are present in autoimmune disease. The current study also demonstrates the profound effect of background genes on the degree of nephritis, lymphadenopathy, and anti-DNA antibody production. Of major note, our studies suggest the identification of chromosomal positions for genes that modify nephritis. Analysis of the backcross mice for markers covering most of the mouse genome suggests that over 50% of the variance in renal disease is attributable to quantitative trait loci on mouse chromosomes 7 and 12. Moreover, this study provides a model for dissecting the complex genetic interactions that result in manifestations of autoimmune disease.

Comparison of efficacy of sodium hyaluronate and normal saline arthrocentesis in the management of internal derangement of temporomandibular joints - A prospective study.

PURPOSE: The aim of the present study was to evaluate the efficacy of arthrocentesis with and without sodium hyaluronate (SH) injection in the treatment of patients with temporomandibular joint (TMJ) internal derangement. MATERIALS AND METHODS: The study consisted of 20 patients with chief complaints of limited mouth opening, TMJ pain, and jaw deviation. Patients with disc displacement with reduction and closed lock were randomly divided into two groups. In Group 1, only arthrocentesis was performed, and in Group 2, arthrocentesis plus intra-articular injection of SH was performed. Arthrocentesis was performed under aseptic conditions using normal saline. Clinical evaluation was done for maximum mouth opening (MMO), TMJ pain, and jaw deviation before the procedure and 1 week, 2 weeks, 1 month, and 3 months following arthrocentesis. RESULTS: The mean visual analog scale (VAS) score change was statistically significant in Group 1 and Group 2 for within the group analysis. There was statistically significant difference in VAS score between Group 1 and Group 2 at all time intervals postoperatively. The increase in MMO from preoperative to 3 months postoperatively was statistically significant for within the group analysis. There was a reduction in mandibular deviation in both Group 1 and Group 2, but the difference was not statistically significant. There was no statistically significant difference in deviation between the two groups. CONCLUSION: Arthrocentesis with SH is superior to arthrocentesis alone in treating patients suffering with TMJ internal derangement, who are refractory to conservative treatment.

Evaluation of the Sternoclavicular Graft for the Reconstruction of Temporomandibular Joint After Gap Arthroplasty.

INTRODUCTION: Ankylosis may be defined as the fusion of the articular surfaces with bony or fibrous tissue. The treatment of temporomandibular joint ankylosis poses a significant challenge because of the high incidence of recurrence. A number of interpositional materials have been used including alloplastic materials (acrylic, proplast-teflon, silastic), and autogenous tissues (temporalis muscle flaps, buccal fat pad, dermis, costochondral grafts, metatarsal, fibula, tibia, iliac crest, cranial bone and Sternoclavicular graft SCG and cartilage). Literature suggests that rather than growth centre, we need adaptive centre. SCG is presumed to be a more suitable material for interpositional arthroplasty because Sternoclavicular Joint (SCJ) and TMJ are very similar developmentally, histologically and morphologically throughout the growth period. MATERIAL AND METHOD: Patients with TMJ ankylosis (8 males, 2 females) underwent release of the ankylosed joint by the senior author, between June 2013 and Novemeber 2015. The age of the patients ranged from 10 to 19 years. Pre- and post- operative assessment included a thorough history and physical examination to determine the cause of ankylosis, the maximal incisal opening, etiology and type of the ankylosis, recurrence rate. RESULT: MIO at 6 months follow up was 37.4±2.633 mm (range 32-40 mm), greater than MIO achieved in immediate postoperatively {34.4±2.22 mm (range 30-38 mm). After reconstruction of temporomandibular joint with sternoclavicular graft in the growing child there was a significant increase in the growth of mandible which was stunned due to ankylosis. And the ramal height also increased. CONCLUSION: The articular reconstruction with alloplastic or autogenous grafts, or gap arthroplasty for the treatment of ankylosis is shown to be efficient in relation to the post-operative maximal incisal opening, recurrence and articular function.

Evaluating the use of octyl-2-cyanoacrylate in unilateral cleft lip repair.

BACKGROUND: Facial cosmetic results are one of the most concerning issues for the parents who get their children operated for cleft lip. Moreover, the postoperative care of the surgical site, the discomfort associated with the suture removal, and additional visit for suture removal are other reasons which encourages one to use any new technologies that may replace the need for suture placement. In this study, we used octyl-2-cyanoacrylate, a tissue adhesive which offers a viable alternative to traditional techniques without compromising optimal wound closure. OBJECTIVE: To perform a comprehensive comparison of the outcomes from the use of Dermabond in patients undergoing primary repair of congenital cleft lip ± palate anomalies. MATERIALS AND METHODS: Twenty patients, in the age group of 3-18 months were treated surgically for unilateral cleft lip deformity using Millard rotation-advancement flap. Pre- and post-operative photographs of the patients were taken at 1 week, 2 week, 1 month, 6 months, and 1 year postoperatively and were evaluated using Vancouver scar scale which was given by Sullivan in 1990. Paired t-test was used for statistical analysis. RESULTS: Increased vascularity (hyperemia) was seen in the 1st and 2nd week in 35% and 30% patients, respectively which gradually reduced to normal in subsequent follow-ups. The scar was flat in 85% of patients in 1st week, and the number decreased to 10% at the end of 1 year. No wound dehiscence was found in any patients. Statistical analysis showed that among all the follow-ups, only the difference between the first and second follow-ups. Comparison of the results of 1 week with all other follow-ups yielded no significant results. CONCLUSION: Octyl-2-cyanoacrylate can be used for cleft lip closure effectively. The procedure is relatively painless and quick. Added to this are benefits of protection from wound infection since the material is bacteriostatic.

6-0 nylon versus 6-0 vicryl rapide in chieloplasty.

CONTEXT: Facial cosmetic result is one of the most concerning issues for the parents who get their children operated for cleft lip. Moreover, the discomfort associated with the suture removal encourages one to use any new technology that may replace the need for suture placement. The type of suture material used in surgery has been a long-standing debate among surgeons. In this study, we compared rapidly absorbable suture material (Vicryl Rapide™) with nonabsorbable suture material (nylon). AIMS: The aim of this study is to compare the appearance and course of scar, wound infection, and patient's parent perception using Vicryl Rapide and nylon in nonsyndromic congenital cleft lip repair. SETTINGS AND DESIGN: This was a randomized prospective controlled clinical trial. MATERIALS AND METHODS: Twenty patients, in the age group of 3-18 months treated for unilateral congenital cleft lip deformity, were included and randomly allocated to two groups with ten patients each. Skin suturing was done with 6-0 polyamide and 6-0 irradiated polyglactin in Groups A and B, respectively. Patients were evaluated at 1 week, 1, 3, 6 months, and 1 year postoperatively in person by the observer as well as by the patient's parent. STATISTICAL ANALYSIS USED: Descriptive statistical analysis was done using SPSS 20, and Student's t-test was applied. RESULTS: It was found that Vicryl Rapide showed more hypopigmented scars and raised scars than nylon at the end of 1 year though overall appearance was comparable between the groups. CONCLUSIONS: Vicryl Rapide showed poorer cosmetic outcomes in terms of height and pigmentation of car as compared to nylon suture of same thickness. However, since scars tend to improve with time, a bigger sample size and a longer follow-up are required to generalize this statement.

A conformational preference parameter to predict helices in integral membrane proteins.

Assignments were made for helical regions in several integral membrane proteins using an algorithm devised to delineate the transmembrane helices in bacteriorhodopsin (Eur. J. Biochem. 182 (1982) 565-575). A new conformational preference parameter for membrane-buried helices was obtained. The use of this parameter to predict helices in membrane proteins is discussed. When applied to the L and M subunits of Rhodopseudomonas sphaeroides, five helices were predicted, which is consistent with the three-dimensional X-ray crystal structure. Data on signal sequences and amino acid exchanges in membrane proteins are also analysed and discussed

Assessment of facial nerve injury with "House and Brackmann facial nerve grading system" in patients of temporomandibular joint ankylosis operated using deep subfascial approach.

BACKGROUND: Preservation of the functional integrity of the facial nerve (FN) is a critical measure of success in temporomandibular joint (TMJ) surgery. In spite of the development of a myriad of surgical approaches to the TMJ, FN remains at risk. The deep subfascial approach provides an additional layer of protection (the deep layer of the temporalis fascia and the superficial temporal fat pad) to the temporal and zygomatic branches of the FN and thus, is the safest method to avoid FN injury. OBJECTIVES: To assess FN injury following TMJ surgery using deep subfascial approach and measuring it on House and Brackman facial nerve grading system (HBFNGS). MATERIALS AND METHODS: Twenty TMJs in 18 patients were operated for TMJ ankylosis, using "the deep subfascial approach." FN function was assessed postoperatively at 24 h, 1 week, 1 month, 3 months, 6 months using HBFNGS. Statistical analysis was done using SPSS 16.0. RESULTS: Of 20 surgical sites 3 sites showed Grade III (moderate) FN injury and 17 sites showed Grade II (mild) FN injury at 24 h. The condition improved with time with full recovery of FN at all surgical sites at 6 months. CONCLUSION: The deep subfascial approach has a distinct advantage over the conventional approaches when dissecting the temporal region and is the safest method to avoid injury to FN.

Elucidation of the structure of retroviral proteases: a reminiscence.

Determinations of only a very few protein structures had consequences comparable to the impact exerted by the structure of the protease encoded by HIV-1, published just over 25 years ago. The structure of this relatively small protein and its cousins from other retroviruses provided a clear target for a spectacularly successful structure-assisted drug design effort that offered new hope for controlling the then-escalating AIDS epidemic. This reminiscence is limited primarily to work conducted at the National Cancer Institute, and is not meant to be a comprehensive history of the field, but is rather an attempt to provide a very personal account of how the structures of this most thoroughly studied crystallographic target were determined.

Crystal structure of a complex of HIV-1 protease with a dihydroxyethylene-containing inhibitor: comparisons with molecular modeling.

The structure of a crystal complex of recombinant human immunodeficiency virus type 1 (HIV-1) protease with a peptide-mimetic inhibitor containing a dihydroxyethylene isostere insert replacing the scissile bond has been determined. The inhibitor is Noa-His-Hch psi [CH(OH)CH(OH)]Vam-Ile-Amp (U-75875), and its Ki for inhibition of the HIV-1 protease is < 1.0 nM (Noa = 1-naphthoxyacetyl, Hch = a hydroxy-modified form of cyclohexylalanine, Vam = a hydroxy-modified form of valine, Amp = 2-pyridylmethylamine). The structure of the complex has been refined to a crystallographic R factor of 0.169 at 2.0 A resolution by using restrained least-squares procedures. Root mean square deviations from ideality are 0.02 A and 2.4 degrees, for bond lengths and angles, respectively. The bound inhibitor diastereomer has the R configurations at both of the hydroxyl chiral carbon atoms. One of the diol hydroxyl groups is positioned such that it forms hydrogen bonds with both the active site aspartates, whereas the other interacts with only one of them. Comparison of this X-ray structure with a model-built structure of the inhibitor, published earlier, reveals similar positioning of the backbone atoms and of the side-chain atoms in the P2-P2' region, where the interaction with the protein is strongest. However, the X-ray structure and the model differ considerably in the location of the P3 and P3' end groups, and also in the positioning of the second of the two central hydroxyl groups. Reconstruction of the central portion of the model revealed the source of the hydroxyl discrepancy, which, when corrected, provided a P1-P1' geometry very close to that seen in the X-ray structure.

Is the pseudo-dyad in retroviral proteinase monomers structural or evolutionary?

A pseudo-dyad was found to exist in the monomers of the crystal structures of the proteinases from Rous sarcoma virus and the human immunodeficiency virus. This dyad, also discovered earlier in pepsin-like aspartic proteinases and considered to be of probable evolutionary origin, has been shown to arise as a result of the topology and the folding of the proteinase monomers and may not therefore have much evolutionary significance.

Crystal structure of rabbit muscle creatine kinase.

The crystal structure of rabbit muscle creatine kinase, solved at 2.35 A resolution by X-ray diffraction methods, clearly identified the active site with bound sulfates surrounded by a constellation of arginine residues. The putative binding site of creatine, which is occupied by a sulfate group in this analysis, has been tentatively identified. The dimeric interface of the enzyme is held together by a small number of hydrogen bonds.

A left-handed crossover involved in amidohydrolase catalysis. Crystal structure of Erwinia chrysanthemi L-asparaginase with bound L-aspartate.

The crystal structure of L-asparaginase from Erwinia chrysanthemi in the presence and absence of L-aspartate was determined at 1.8 A resolution. Conserved residues in a left-handed crossover (a rare occurrence in protein structures) link pairs of dimers into the catalytically active tetrameric form of the enzyme. The structure of ErA containing bound aspartic acid shows that this unusual strand connectivity is an essential part of the active site architecture, responsible for releasing the product of the enzymatic hydrolysis. The orientation of the bound aspartate indicates for the first time a threonine residue as a catalytic nucleophile.

The oligomerization domain of p53: crystal structure of the trigonal form.

The structure of the oligomerization domain of the p53 tumor suppressor protein was determined in the trigonal crystal form, using a refined NMR structure as a model. A synthetic peptide comprising residues 319-360 of human p53 crystallized in the space group P3(1)21. There is one biologically relevant tetrameric domain in the crystallographic asymmetric unit. The structure was refined jointly with NMR data, only the third such case (the previous examples being IL-1beta (Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B., Davies, D.R. and Clore, G.M. (1992) Science 257, 961-964 [1]) and BPTI (Schiffer, C., Huber, R., Wuthrich, K. and Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588-599 [21)), to 2.5 A resolution with an R factor of 0.207. The distribution of tumor-derived mutations in the oligomerization region together with structural and biological data suggest a strategy for the design of antitumor therapeutics.

Distribution pattern of cell bodies and fibers with neurotensin-like immunoreactivity in the cat hypothalamus.

Neurotensin is widely distributed in the central and peripheral nervous systems. Extensive radioimmunoassay and immunohistochemical studies in rats show that the neurotensin immunoreactive perikarya and fibers are most prominent in the hypothalamus. Radioimmunoassay studies have suggested that the levels of neurotensin in the hypothalamus of cats may be six times higher than that of rats. We studied the distribution pattern of neurotensin immunoreactivity within the hypothalamus of the cat by avidin-biotin modification immunohistochemical methods: (1) to define its distribution pattern within the hypothalamus, and (2) to compare our findings with the patterns that have been described in rats. Results show that neurotensin immunoreactive cell bodies and fibers are most prominent in the rostral and intermediate regions of the cat hypothalamus. Cell bodies with neurotensin-like immunoreactivity are seen maximally in the medial preoptic region, the infundibular nucleus, and the lateral hypothalamus. The neurotensin positive fibers are dense in the periventricular regions of the entire rostro-caudal extent of the hypothalamus. This pattern of distribution of neurotensin immunoreactivity is similar to that described in rats. The suprachiasmatic nuclei of the cat hypothalamus, however, contained a significant number of neurotensin immunoreactive cell bodies, an observation not noted in the rat hypothalamus. The neurotensin immunoreactive neurons were more numerous in the lateral hypothalamus than has been reported in rats, but the paraventricular nucleus of the hypothalamus in cats contained fewer neurotensin immunoreactive perikarya. The presence of neurotensin immunoreactive perikarya in the suprachiasmatic nucleus and the apparent increase in the number of neurotensin immunoreactive neurons in the lateral hypothalamus may account for the increased levels of neurotensin reported in cats. Neurotensin has been speculated to play a role in nociception, thermoregulation, and control of arterial pressure by acting as a hormone or a neurotransmitter. Details of the pattern of colocalization of neurotensin with that of other neuropeptides and neurotransmitters will aid in our understanding of its role in these functions.

Invasion of human glioma: role of extracellular matrix proteins.

The invasion of glioma into normal brain tissue is a major challenge to clinical intervention because these tumors often highly infiltrate the surrounding brain tissue. Total surgical resection of gliomas is impossible, and recurrence of tumor growth is a common phenomenon; patients have a mean survival time of 8-12 months. Although in recent years substantial progress has been made toward understanding the invasive behavior of gliomas in vitro and in vivo, the factors responsible for the extensive infiltration are still poorly documented. This review focuses on recent research concerning the invasion of gliomas, as well as the extracellular matrix components, and the proteolytic enzymes involved. A better understanding of cell-matrix interactions will help in developing therapeutic strategies to decrease the invasion of gliomas.

Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy.

OBJECTIVE: To determine whether treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate hydrochloride or pemoline diminishes the response to growth hormone (GH) therapy in patients with idiopathic GH deficiency (IGHD) or idiopathic short stature (ISS). METHODS: The National Cooperative Growth Study database was used to identify patients between 3 and 20 years of age with IGHD or ISS and those within these groups who were treated with methylphenidate or pemoline for ADHD. Their growth in response to GH treatment (change in height standard deviation score [SDS]) was compared with that of patients with IGHD or ISS who were not treated for ADHD, by using a stepwise multiple regression analysis. RESULTS: In the IGHD cohort, there were 184 patients who were being treated for ADHD and 2313 who were not. In the ISS cohort there were 117 patients who were being treated for ADHD and 1283 who were not. There was a higher percentage of males being treated for ADHD in both cohorts. In the IGHD cohort, the change in height SDS was positively associated with the number of years of GH treatment, parents' heights, body mass index, and GH injection schedule, and was negatively associated with height SDS at the initiation of GH therapy, age, and maximum stimulated GH level. The use of methylphenidate or pemoline had a negative effect on the change in height SDS, but the magnitude of the effect was small. Similar effects were noted in the ISS cohort, but body mass index and the use of methylphenidate or pemoline had no effect on the change in height SDS. CONCLUSIONS: Concurrent ADHD therapy is associated with a slight decrease in the change in height SDS during GH treatment in patients with IGHD but not in those with ISS. Even in IGHD, the magnitude of the effect is small and should not deter the use of such concurrent therapy.

Implantable controlled delivery systems for proteins based on collagen--pHEMA hydrogels.

Co-polymeric hydrogels of collagen and poly(hydroxyethyl methacrylate) (pHEMA) were prepared using an ammonium persulphate-sodium metabisulphite redox initiation technique. Fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) was entrapped into these hydrogels. These gels were modified differently by external cross-linking and made highly porous by incorporation of ethylene glycol. The morphological characteristics of the gels containing FITC-BSA before and after release were studied. The in vitro release of FITC-labelled BSA was studied in phosphate buffer, pH 7.4, at 37 degrees C. The results clearly indicated that collagen-pHEMA hydrogels release FITC-BSA in a zero-order fashion. In the case of uncross-linked hydrogels, the release of FITC-BSA was about 81% within 8 d, compared to 49% for the same period in the case of cross-linked hydrogels. It was also observed that in the case of porous hydrogels the release was very fast (19% in the first hour) and lasted for about 12 h, releasing 76% of FITC-BSA. These results clearly indicated that collagen-pHEMA hydrogels released BSA in a zero-order fashion and that the release rate can be programmed by appropriate modification of the hydrogel matrices.

Systems for data analysis.

A system for data analysis is the end product of study planning, form design, data entry, data verification, and statistical analysis. This article reviews these steps and considers the fundamental choices in software for data entry and analysis. The appendix includes a listing of general and specialized software for data management and statistical analysis.

Localization of neuropeptide Y-like immunoreactivity in the cat hypothalamus.

The distribution pattern of neuropeptide Y-like immunoreactivity (NPY-Li) in cat hypothalamus was studied using avidin-biotin modification of immunocytochemical method. This study showed cell bodies containing NPY-Li in the periventricular and the infundibular nuclei and also a moderate number of neurons with NPY-Li in the ventromedial nucleus, an observation not reported in earlier studies. Fibers with NPY-Li were noted throughout the hypothalamus, but most prominently within the periventricular regions. The location of NPY cells within the hypothalamus suggests the possibility of an interaction with dopaminergic and other proopiomelanocortinergic neurons.