Primary External Ventricular Drains in the Management of Open Myelomeningocele Repairs in the Neonatal Setting in Ireland

Aim The aim of this study is to outline the role of primary external ventricular drains (EVD) in the management of open myelomeningoceles in the neonatal setting in Ireland. Methods Retrospective cohort study involving all infants who underwent open myelomeningocele repair in a teritary centre in Ireland between January 2009 and April 2016. Medical charts and laboratory data was reviewed on all infants meeting the inclusion criteria. Results One hundred and forty-three neonates underwent open myelomeningocele repair in the 6.5 year period. EVD were inserted at the time of primary wound closure in 19 cases (13%). EVD were used to aid in wound closure and as a primary method of cerebrospinal fluid (CSF) diversion. They remained in place for a median of 8 days, ranging from 1-22 days. All EVD, apart from one, in our series were replaced by a ventricular-peritoneal (VP) shunt at some stage. Conclusion EVD were used in 13% of cases of open myelomeningocele repairs from Jan 2009-Apr 2016 as a primary measure to aid in management. Compared to the cohort in whom an EVD was not inserted at the time of surgery, there was a decrease in the rate of infections. However, there was an increased rate of wound dehiscence/leak and a later need for VP shunt insertion.

The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

AIM: To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative. METHOD: One-hundred and fifty-three patients with a T3/T4 and/or a node-positive rectal cancer underwent neoadjuvant 5-fluorouracil-based CRT followed by surgical resection. RESULTS: Thirty-six (23.5%) patients achieving complete pathological response (ypCR) had a 5-year disease-free survival (DFS) rate of 100% compared with a DFS rate of 74% for 117 (76.5%) patients without ypCR (P = 0.003). The Royal College of Pathologists (RCPath) TRG best condenses the Mandard five-point TRG by stratifying patients into three groups with distinct 5-year DFS rates of 100%, 86% and 67%, respectively (P = 0.001). In multivariate analysis, pathological nodal status and circumferential resection margin (CRM) status, but not TRG, remained significant predictors of DFS (P = 0.002, P = 0.035 and P = 0.310, respectively). CONCLUSION: Our findings support the notion that ypCR status, nodal status after neoadjuvant CRT and CRM status, but not TRG, are predictors of long-term survival in patients with locally advanced rectal cancer.

Phylogenetically associated residues within the VH3 subgroup of several mammalian species. Evidence for a "pauci-gene" basis for antibody diversity.

Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the V(HIII) subgroup on the basis of homology with known human heavy chain sequences. The mammals studied could be divided into three distinct categories on the basis of the distribution of the V(HIII) subgroup. In several species the V(HIII) subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the V(HIII) subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar V(HIII) subgroup distribution. Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.

Glutamate activates a K+ conductance increase in Aplysia neurons that appears to be independent of G proteins.

A study was made of the role of G proteins in the K+ conductance increases elicited by cholinergic and glutamatergic agonists in identified Aplysia neurons. The cholinergic response, previously shown to be G protein mediated, was occluded by dialysis with either nonhydrolyzable GTP analogs (GTP gamma S or Gpp(NH)p) or beryllium fluoride and was blocked by pertussis toxin as well as by dialysis with a nonhydrolyzable GDP analog (GDP beta S). In contrast, the glutamatergic response, studied simultaneously in the same cell, persisted throughout all of the above manipulations and hence does not appear to depend upon G protein activation. This characteristic differentiates the glutamatergic response from most other transmitter- or hormone-induced increases in K+ conductance elicited in either neurons or other cell types, whether vertebrate or invertebrate.

Synaptically triggered action potentials in dendrites.

We tested the hypothesis that action potentials originate in apical dendrites of pyramidal cells. Layer V somata were voltage clamped in thin slices of rat motor cortex. Fibers synapsing in unclamped regions far out on the apical dendrite caused small, slow synaptic currents, as recorded at the soma, and sometimes elicited complex, multicomponent current spikes, beginning with a small first spike. Hyperpolarization, or tetrodotoxin applied to basal dendrites and soma, blocked the later spike components without affecting the synaptic current and the first component, which was a synaptically triggered Na+ spike in the apical dendrite. Similar spikes followed voltage steps or direct stimulation. We conclude that Na+ action potentials are initiated in the apical dendrite in response to synaptic input.

Alteration of chemotherapy toxicity using a chemically defined liquid diet in rats.

Controversy exists as to whether administration of a chemically defined diet alters toxicity to chemotherapy. The purpose of this study was to evaluate toxicity to methotrexate in rats fed a chemically defined liquid diet or a regular chow diet. In the first study, 48 adult rats were randomized to be fed a chemically defined liquid diet or a regular diet for 14 days when methotrexate (25 or 50 mg/kg) was given. All liquid diet rats became anorexic and died within 96 h, while no deaths were observed in rats fed regular diet. When 20 liquid diet and regular diet rats were pair-fed to equalize caloric intake before and after methotrexate administration, similar mortality results occurred. In a second study, methotrexate (50 mg/kg) or saline was given and 60 h later all animals were sacrificed to obtain small bowel luminal cultures and tissue sections for histological evaluation. Administration of the liquid diet altered small bowel flora to predominantly Escherichia coli and Pseudomonas sp. and histology showed severe small bowel mucosal enteritis in comparison with regular diet rats. To evaluate whether the changes in intestinal flora or alterations in drug pharmacokinetics were responsible for the increased mortality, two additional studies were done. Gentamicin (4.8 mg/kg/day) was given p.o. or i.m. to the rats on the chemically defined liquid diet. A significant reduction of intraluminal bacteria occurred, but survival time was not improved in animals receiving antibiotics. When mean serum methotrexate levels were analyzed in non-antibiotic-treated rats, drug concentrations were significantly increased at 24, 36, and 48 h after methotrexate injection in the elemental liquid diet rats compared with chow diet rats. Administration of a chemically defined liquid diet to rats receiving methotrexate increased the occurrence and severity of intestinal enteritis, altered intraluminal bowel flora, and decreased clearance of methotrexate from the serum.

Independence of and interactions between GABA-, glutamate-, and acetylcholine-activated Cl conductances in Aplysia neurons.

In certain Aplysia neurons, glutamate, GABA, and acetylcholine (ACh) all elicit desensitizing Cl-dependent responses. This fact and the finding that the glutamate and GABA responses "cross-desensitize" led to the suggestion (Swann and Carpenter, 1975; King and Carpenter, 1987) that the responses to these transmitters were mediated by the same receptor-channel complex. This hypothesis is incompatible with the demonstration given here that the GABA- and glutamate-gated channels are clearly distinct; the GABA channel, but not the glutamate channel, shows outward rectification (Matsumoto, 1982; King and Carpenter, 1987, 1989) and is selectively blocked by intracellular sulfate. Exploiting these distinctive characteristics and the independent expression of the receptors in some cells, we have been able to reevaluate the so-called cross-desensitization by analyzing the ability of GABA, glutamate, and other agonists to interact with each of the receptor molecules. The cross-desensitization was found to be exclusively attributable to the ability of GABA to interact with the glutamate receptor (Oyama et al., 1990). The GABA receptor is unaffected by glutamate. Nevertheless, in cells expressing both receptors, glutamate can reduce the GABA response by auto-desensitizing the part of the response that is mediated by the glutamate receptor. No interactions were observed between ACh-induced responses and either of the responses elicited by the amino acids. The invertebrate glutamate-gated Cl channels that have been cloned resemble the vertebrate glycine receptor (Vassilatis et al., 1997). Our pharmacological evaluation of the molluscan glutamate receptor points in the same direction.

Tyrosine sulfation: a modulator of extracellular protein-protein interactions.

Tyrosine sulfation is a post-translational modification of many secreted and membrane-bound proteins. Its biological roles have been unclear. Recent work has implicated tyrosine sulfate as a determinant of protein-protein interactions involved in leukocyte adhesion, hemostasis and chemokine signaling.

High levels of X-linked Inhibitor-of-Apoptosis Protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer.

BACKGROUND: The mainstay of treatment in rectal cancer is neoadjuvant radio chemotherapy prior to surgery, in an attempt to downstage the tumour, allowing for more complete removal during surgery. In 40 % of cases however, this neoadjuvant radio chemotherapy fails to achieve tumour regression, partly due insufficient apoptosis signaling. X-linked Inhibitor of Apoptosis Protein (XIAP) is an anti-apoptotic protein that has been reported to contribute to disease progression and chemotherapy resistance. METHODS: We obtained rectal biopsy normal and matched tumour tissue from 29 rectal cancer patients with varying degrees of tumour regression, and using Western blot, examined anti-apoptotic XIAP and pro-apoptotic Smac protein levels in these tissues, with the aim to examine whether disturbed XIAP/Smac levels may be an indicator of neoadjuvant radio chemotherapy resistance. Expression of inhibitor of apoptosis proteins cIAP-1 and cIAP-2 was also examined. RESULTS: We found that levels of XIAP increased in accordance with the degree of radio chemotherapy resistance of the tissue. Levels of this protein were also significantly higher in tumour tissue, compared to matched normal tissue in highly resistant tissue. In contrast, Smac protein levels did not increase with radio chemotherapy resistance, and the protein was similarly expressed in normal and tumour tissue, indicating a shift in the balance of these proteins. Post treatment surgical resection tissue was available for 8 patients. When we compared matched tissue pre- and post- radio chemotherapy we found that XIAP levels increased significantly during treatment in both normal and tumour tissue, while Smac levels did not change. cIAP-1 and cIAP-2 levels were not differentially expressed in varying degrees of radio chemotherapy resistance, and neoadjuvant therapy did not alter expression of these proteins. CONCLUSION: These data indicate that disturbance of the XIAP/Smac balance may be a driver of radio chemotherapy resistance, and hence high levels of XIAP may be a useful indicator of neoadjuvant radio chemotherapy resistance in rectal cancer. Moreover, as XIAP levels increase with radio chemotherapy it is possible that a subset of more resistant tumour cells survive this treatment and may be resistant to further adjuvant treatment. Patients with resistant tumours highly expressing XIAP may benefit from alternative treatment strategies, such as Smac mimetics post neoadjuvant radio chemotherapy.

BCL2 protein signalling determines acute responses to neoadjuvant chemoradiotherapy in rectal cancer.

UNLABELLED: In locally advanced rectal cancer, neoadjuvant chemoradiotherapy is performed prior to surgery to downstage the tumour. Thirty to 40 % of patients do not respond. Defects in apoptotic machinery lead to therapy resistance; however, to date, no study quantitatively assessed whether B cell lymphoma 2 (BCL2)-dependent regulation of mitochondrial apoptosis, effector caspase activation downstream of mitochondria or a combination of both predicts patient responses. In a cohort of 20 rectal cancer patients, we performed protein profiling of tumour tissue and employed validated ordinary differential equation-based systems models of apoptosis signalling to calculate the ability of cancer cells to undergo apoptosis. Model outputs were compared to clinical responses. Systems modelling of BCL2-signalling predicted patients in the poor response group (p = 0.0049). Systems modelling also demonstrated that rectal cancers depended on BCL2 rather than B cell lymphoma-extra large (BCL(X)L) or myeloid cell leukemia 1 (MCL1) for survival, suggesting that poor responders may benefit from therapy with selective BCL2 antagonists. Dynamic modelling of effector caspase activation could not stratify patients with poor response and did not further improve predictive power. We deliver a powerful patient stratification tool identifying patients who will likely not benefit from neoadjuvant chemoradiotherapy and should be prioritised for surgical resection or treatment with BCL2 antagonists. KEY MESSAGES: Modelling BCL2-family proteins identifies patients unresponsive to therapy. Caspase activation downstream of mitochondria cannot identify these patients. Rectal tumours of poor responders are BCL2- but not BCL-XL-dependent. DR_MOMP allows clinicians to identify patients who would not benefit from therapy. DR_MOMP is also a useful patient stratification tool for BCL2 antagonists.

CYP1A2 is expressed along with CYP1A1 in the human lung.

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S(9) fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S(9) fractions from the tissues catalyzed the bioactivation of benzo[a]pyrene (B[a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.

CYP1A2 is expressed along with CYP1A1 in the human lung.

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S9 fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S9 fractions from the tissues catalyzed the bioactivation of benzo[a]pyrene (B[a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.

Effects of postoperative infusion of branched chain amino acids on nitrogen balance and forearm muscle substrate flux.

A branched chain amino acid (45% BCAA)--enriched solution was compared with a standard amino acid (25% BCAA) solution in a randomized blinded study in eight patients undergoing cystectomy and ileal loop diversion. Solution administration rates were designed to provide 20 kcal/kg/day and 0.26 gm nitrogen/kg/day postoperatively from days 1 to 8. Daily urine creatinine and nitrogen levels were measured. On day 4 during infusion, forearm blood flow was measured by capacitance plethysmography. Arterial and antecubital deep venous blood samples were drawn simultaneously for determinations of glucose, lactate, pyruvate, and amino acids; substrate flux was calculated (mumol/ml/min, uptake = +, release = -). The mean total amino acid flux was significantly improved In the 45% BCAA group (+1.7 +/- 0.4) versus the 25% BCAA group (-0.03 +/- 0.2, P less than 0.05). The mean total BCAA flux was significantly improved in the 45% BCAA group (+1.1 +/- 0.4) compared with the 25% BCAA group (-0.03 +/- 0.2) (P less than 0.02). There were no significant differences between groups in alanine, glutamine, glucose, lactate, or pyruvate forearm flux. The cumulative adjusted 7-day nitrogen balance was -1.4 +/- 7 gm in the 45% BCAA group and -14.2 +/- 4 gm in the 25% BCAA group (NS). the 45% BCAA solution resulted in significant uptake of total amino acid and BCAA into forearm muscle, which was not significantly demonstrated in whole body nitrogen balance studies. Sixty-six percent of the increase in total amino acid forearm flux with use of the 45% BCAA solution was due to the uptake of BCAA even though less leucine was given compared with the 25% BCAA solution.

Effects of alpha-toxins from Bungarus multicinctus and Bungarus caeruleus on cholinergic responses in Aplysia neurons.

The effects of alpha-bungarotoxin from Bungarus multicinctus and Bungarus caeruleus were studied on three types of cholinergic response in Aplysia central neurones. These responses are the result of three distinct changes in ionic permeability: selective increases in permeabiliyt to Na, Cl and K, respectively. It was shown that 10(-5) M alpha-bungarotoxin from B. multicinctus completely blocks the response resulting from an increase in Cl permeability, while having no effect on either of the other two responses types (even when the toxin concentration was increased to 5 X 10(-5) M). The block of the Cl-dependent response by alpha-bungarotoxin is reversible. None of the three response types were affected by similar concentrations of alpha-toxin from B. caeruleus. Higher concentrations were not systematically tested. These results contradict reports of other authors on the action of alpha-bungarotoxin on molluscan acetylcholine (ACh) responses. Possible reasons for the discrepancies between our findings and those published by other authors are discussed.

The genetic control of antibody formation.

Studies of the molecular biology of lymphoid cells have markedly increased our understanding of how millions of different antibodies can be synthesized by a single animal. To date, the most detailed understanding has been achieved for the mouse, primarily because of the relatively greater experimental availability of this species. These studies, as well as those involving other species, have shown that the complete genes for antibody polypeptide chains are assembled from disparate genetic elements which are originally widely separated in the genome. The assembly process itself, together with the coding information present in the germ line genetic elements, contributes to the diversity of structure (and thus combining specificities) shown by mature antibody molecules. Specifically, the diversity of structure characteristic of antibody variable regions is due to three distinct mechanisms: innate variability of germ line genes; mismatching of individual gene segments during their somatic rearrangement leading to junctional diversity; and somatic mutation in variable region genetic material during or after the rearrangement. These processes lead to the wide array of combining specificities that permit the humoral immune system of a mature animal to interact with essentially any non-self antigen which it encounters. Complex genetic rearrangements are also responsible for the class switching phenomenon long known to be characteristic of the humoral immune response. A form of homologous recombination between constant region genes, possibly mediated by specific "switching" enzymes, is now believed to be involved in this phenomenon. It is also currently believed that the restriction of gene rearrangement processes to one of the two possible chromosomes of a diploid pair in each cell is responsible for the phenomenon of allelic exclusion that has long been associated with the normal functioning of mammalian B-cells.

Characterization of a homogeneous paraprotein from a horse with spontaneous multiple myeloma syndrome.

A novel myeloma paraprotein has been isolated from a horse with a lymphoid tumor. The protein was a euglobulin and consequently was readily isolated from serum in pure form and high yield by simple dilution in distilled water. The purified intact protein had a molecular weight of 150,000 and was composed of heavy and light chains, both of which had blocked amino-termini and were thus not susceptible to amino-terminal sequence analysis. The amino acid compositions of these respective chains corresponded to those of comparable chains from immunoglobulins of other species. Peptide maps of paraprotein light chains prepared by high pressure liquid chromatography corresponded in part to those of normal pooled equine light chains. The identification of this paraprotein as an equine AI (aggregating immunoglobulin) protein was confirmed by serological analysis using a specific antiserum. The relationship of this particular protein to other members of the immunoglobulin family was further demonstrated by the production of an anti-idiotypic antiserum individually specific for this molecule.

Vaginal prostaglandins for the ripe cervix.

OBJECTIVES: To assess the efficacy of vaginal prostaglandin (PGE2) tablets for induction of labor in the presence of a ripe cervix. METHODS: A randomized controlled trial was performed. Two hundred and nine consecutive women undergoing induction of labor with a Bishop Score > or = 5 were randomly assigned to (a). Study group receiving PGE2 tablets (n = 106) and (b). Control group having artificial rupture of membranes only (n = 103). The duration of labor, oxytocin and analgesia requirements, the mode of delivery, complications and duration of confinement were recorded. RESULTS: Mean duration of first stage of labor was shorter in parous patients in the study group (194 min v. 319 min), as was the mean induction delivery interval in primigravidas. Oxytocin was used in 75% of primiparas and 40% multiparas in the study group compared with 100% and 80%, respectively, in the controls. Epidural analgesics and instrumental delivery rates were also reduced. CONCLUSIONS: The use of vaginal PGE2 tablets for induction of labor with a ripe cervix is associated with a shorter first stage of labor and with reduced requirements for oxytocin, analgesia and instrumental delivery.

Update on delivery following prior cesarean section: a 15-year review 1972-1987.

Fear of true rupture remains the main indication for repeat section. Between 1972 and 1987 there were 2434 patients with one or more prior section and 1350 (55%) were permitted trial of labor, the remainder, having had two or more previous sections (maximum number, 10), had repeat surgery. Induction was employed in 31% and oxytocin for induction or acceleration in 32% patients. The first period (1972-1982) had 844 and the second period (1982-1987) had 506 trial of labor patients. Improved management resulted in the true rupture rate falling from 0.6% (1:169) to 0.2% (1:506) and the elimination of procedure-related perinatal death. There were two maternal deaths with repeat section and none with trial of labor. We have achieved a plateau for cesarean section (10-11%) and a continuing fall in the uncorrected hospital perinatal mortality, which has averaged 10.6/1000 for the years 1982-1986 inclusive.

True rupture/scar dehiscence in delivery following prior section.

Fear of uterine rupture has led to the widespread practice of 'Once a section, always a section'. Between 1972 and 1982, 1498 patients with one or more previous cesarean sections were delivered at University College Hospital, Galway. Trial of labor was undertaken in 844 patients, while the remaining 654 patients underwent repeat elective section because they had two or more prior sections. Eight true ruptures and 22 scar dehiscences were found. Regional analgesia and oxytocin did not significantly affect the rate of true rupture. The mean parity with uterine rupture was five, and it occurred most frequently in the initial trial of labor. There were four perinatal deaths associated with true rupture. Failure to detect the already compromised fetus before labor and delivery, rather than the method of delivery, was responsible for fetal demise in some instances. Five true ruptures were found in the trial of labor group (i.e. a ratio of 1:169), with the loss of three babies. A further baby was stillborn in a mother who ruptured a classical scar before labor. There were no maternal deaths in trial-of-labor patients and one in the elective section group. Two patients with true rupture had their uterus repaired, and were subsequently delivered by section. Another two patients with bloodless dehiscence and no repair, had two subsequent elective repeat sections each, and the unrepaired scar dehiscence was not evident.

Splinting and replantation after traumatic avulsion.

A rational approach can be taken in the dental office to avulsion and replantation. Consideration must be given to: Extraoral time. During this critical time, the prognosis for successful replantation noticeably decreases as the out-of-mouth time increases. Transport. Preferably the tooth will be transported in the socket, but milk or water may be used to keep the tooth moist. The buccal vestibule may be recommended for adults and teenagers but not for young children. Root surface. The root surface must not be handled, scraped, brushed, or have any part removed; it can be rinsed with sterile water, saline, or tap water but not with caustic solutions, disinfectants, or medicaments to clean the surface. Endodontic treatment. A tooth with an open apex should be evaluated bimonthly for revitalization. A tooth with a fully formed apex should have the pulp removed in 7 to 14 days after avulsion. Status of the alveolar process. Alveolar fractures may require a modified splint design to provide additional strength for a longer splinting duration. Obturation materials. Calcium hydroxide paste is used for a minimum of 6 to 24 months before filling permanently with gutta-percha. Selection of a splint. Each case is different and should be treated as such. Special consideration must be given to splint design, which will directly influence the desired result. Although any number of splints may be effective, inherent advantages and disadvantages of each should be understood fully by the clinician. This is where the art, the clinical experience, and the common sense of endodontic therapy dictate the proper splint and appropriate duration of splinting for the patient.(ABSTRACT TRUNCATED AT 250 WORDS)