γδT Cells Are Essential for Orthodontic Tooth Movement.

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αßT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αß T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)-17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor-κß ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.

Solid-state electron spin lifetime limited by phononic vacuum modes.

Longitudinal relaxation is the process by which an excited spin ensemble decays into its thermal equilibrium with the environment. In solid-state spin systems, relaxation into the phonon bath usually dominates over the coupling to the electromagnetic vacuum1-9. In the quantum limit, the spin lifetime is determined by phononic vacuum fluctuations 10 . However, this limit was not observed in previous studies due to thermal phonon contributions11-13 or phonon-bottleneck processes10, 14,15. Here we use a dispersive detection scheme16,17 based on cavity quantum electrodynamics18-21 to observe this quantum limit of spin relaxation of the negatively charged nitrogen vacancy (NV-) centre 22 in diamond. Diamond possesses high thermal conductivity even at low temperatures 23 , which eliminates phonon-bottleneck processes. We observe exceptionally long longitudinal relaxation times T1 of up to 8 h. To understand the fundamental mechanism of spin-phonon coupling in this system we develop a theoretical model and calculate the relaxation time ab initio. The calculations confirm that the low phononic density of states at the NV- transition frequency enables the spin polarization to survive over macroscopic timescales.

Manual Ability Measure (MAM-16): a preliminary report on a new patient-centred and task-oriented outcome measure of hand function.

The purpose of this study was to develop an easy-to-use and psychometrically sound outcome instrument that is task-oriented and patient-centred. One hundred fifteen patients with a variety of hand impairments completed a rating scale of perceived manual ability (i.e., the Manual Ability Measure). The first 70 patients also completed two other questionnaires about physical health and psychological well-being. Rasch Analyses were conducted to transform the ordinal ratings into linear measures; Rasch statistics were used to evaluate its measurement properties at both scale and item levels. Eighty-three original items were reduced to 16 common tasks; Rasch reliabilities were good; the easy-to-difficult item hierarchy makes sense clinically. Moderate correlations were found between manual ability, physical function and general sense of well-being. The results of this preliminary study suggest that the MAM is a promising outcome measure that has adequate psychometric properties and can be used to complement other objective clinical measurements.

Experience with the Arndt paediatric bronchial blocker.

Previously reported techniques for single lung ventilation in children have failed to provide consistent, single lung ventilation with relative ease and reliability. We report our experience with the use of a new device, the Arndt 5 French (Fr) paediatric endobronchial blocker, for single lung ventilation in a series of 24 children. We were able to achieve single lung ventilation in 23 of the 24 patients (aged 2-16 yr). Placement required approximately 5-15 min. Attempts at placement were aborted in one patient who was unable to tolerate even short periods of apnoea because of lung pathology. Although it has some limitations, our experience suggests that the paediatric bronchial blocker can be used as a consistent, safe method of single lung ventilation in most young children.

Jaundice caused by a clinically undetectable T-cell lymphoma infiltrating the sphincter of Oddi.

Malignant lymphoma rarely presents with jaundice. We describe a patient who had a unique etiology for painless jaundice, dilated ducts, and a normal ampulla of Vater. A Whipple's procedure was performed for the suspicion of pancreatic cancer, and initial pathological review detected only mild focal chronic pancreatitis. Seven months later, the patient developed ascites, retroperitoneal mass, and splenomegaly caused by a T-cell lymphoma. Reevaluation of the Whipple's specimen revealed previously unrecognized microscopic infiltration and fibrosis of the sphincter of Oddi by atypical T-lymphocytes. Obstructive jaundice caused by a clinically undetectable primary duodenal T-cell lymphoma has not been previously reported and is contrasted with other causes of jaundice associated with malignant lymphoma and ampullary lesions.

A new lithium alkoxide accelerated diastereoselective cyanation of ketones.

[reaction: see text] A remarkably general lithium heteroatom assisted TMSCN or TBSCN addition to aldehydes and ketones has been discovered. The process provides excellent selectivities and high rates. Conformationally constrained ketones such as camphor, fenchone, and nopinone give excellent diastereoselectivities with TMSCN. Reduction of 2 provided diastereopure amino alcohol 3 in good yield. alpha- and beta-Methyl cyclohexanones with TBSCN-LiOR afford high diastereoselectivities and yields.

Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells.

OBJECTIVE: Recent experimental data have shown that dietary soy isoflavones such as genistein can significantly suppress invasiveness and growth of a number of human malignancies. In this study we examined whether genistein, at a concentration typical of plasma levels following soy formula intake, in combination with cisplatin or vincristine exhibited an additive or synergistic inhibitory effect on the growth of medulloblastoma cells. METHODS: Three human medulloblastomas cell lines (HTB-186, CRL-8805 and MED-1) were treated with genistein at 6 microM, the maximum reported dietary plasma level in children, combined with cisplatin (0-10 microM) or vincristine (0-1 microM). Monolayer cell growth and cytotoxicity, as measured by colonigenic survival in soft agarose, were then compared in control and drug-treated cultures. Presence of apoptosis, using the DNA ladder assay and laser scanning cytometry, was investigated in all cell lines at those concentrations at which an enhancement of antiproliferative effect of cisplatin and vincristine in presence of genistein was observed. RESULTS: Genistein at 6 microM led to a 2.8-fold increase in the monolayer growth inhibitory effect of cisplatin (0.05 microM) in HTB-186 cells (p = 4.5 x 10(-4) by one-tailed t test). Genistein increased colonigenic survival inhibition of HTB-186 2.6-fold at the same cisplatin concentration (p = 1.5 x 10(-4)). Genistein caused a 1. 3-fold increase in antiproliferative effect of cisplatin (0.5 microM) in CRL-8805 cells (p = 3.1 x 10(-4)). Similarly the inhibition of colonigenic survival was enhanced 2.0-fold in CRL-8805 (p = 1.22 x 10(-5)). The addition of genistein to 0.5 microM cisplatin led to a 1.7-fold increase in monolayer growth inhibition and 2.4-fold increase in colonigenic survival inhibition of MED-1 cells (p = 8.3 x 10(-4) and p = 1.1 x 10(-4) respectively). These effects were primarily synergistic but also additive in nature. The combination of genistein and vincristine, as compared to vincristine alone, caused a minimal-to-modest increase in antiproliferative effect on medulloblastoma cells studied here. We were unable to detect apoptosis by two methodologies in any of the medulloblastoma lines when genistein was combined with cisplatin or vincristine. CONCLUSION: These results indicate that genistein at typical dietary plasma levels can significantly enhance the antiproliferative and cytotoxic action of cisplatin and, to a lesser extent, vincristine. The implication for treatment of medulloblastomas of early childhood may be a reduction in the chemotherapeutic dose recommendations of these agents and subsequently a decrease in the risk of treatment sequelae for these patients.

Pediatric blunt carotid injury: a review of the National Pediatric Trauma Registry.

Blunt carotid injury (BCI) is an uncommon yet potentially devastating entity which has received little attention in the pediatric literature. In an attempt to better characterize pediatric BCI, a review of the National Pediatric Trauma Registry was performed. Records were obtained from all children diagnosed with internal or common carotid injury associated with blunt trauma. The incidence of BCI was 0.03% (15 of 57,659 blunt trauma patients). Variables examined included: age, gender, mechanism of injury, associated injuries, various injury severity scores, and outcome. Various injuries were associated with an increase in BCI incidence including chest trauma (4-fold), combined head and chest trauma (6-fold), basilar skull fractures (4-fold), intracranial hemorrhage (6-fold), and clavicle fractures (8-fold). Thirty-three percent of the patients diagnosed with BCI suffered neurological complications directly attributable to their carotid injuries. Current practices regarding screening, diagnosis, and treatment are reviewed.

Computed tomographic angiography as a screening modality for blunt cervical arterial injuries: preliminary results.

BACKGROUND: The diagnosis of blunt cervical arterial injury (CAI) is made difficult by its infrequent occurrence and delayed presentation. Beginning in January of 1995, we used computed tomographic angiography (CTA) of the neck to screen for CAI. We hypothesized that CTA could be incorporated into the workup of patients sustaining blunt neck injury as a screening modality for CAI and that CTA would increase the early detection of CAI. METHODS: Retrospective review of all CAI for the years January of 1988 to June of 1997 at a Level I trauma center. CAI diagnosed before introduction of CTA (pre-CTA; January of 1988 to December of 1994) were compared with those after (post-CTA; January of 1995 to June of 1997). RESULTS: The overall incidence of CAI for the entire time period was 0.11%. Motor vehicle crash (53%) was the most common mechanism, with focal neurologic deficit (23%) or seizures (17.6%) the most common presenting clinical symptoms. CTA added only a few additional minutes to the time required for the workup of patients sustaining blunt neck injury in whom CAI was suspected. The incidence of CAI increased from 0.06% pre-CTA to 0.19% post-CTA (p = 0.02; Fisher exact test). CTA was associated with a decrease in mean time to make the diagnosis of CAI (156 hours pre-CTA vs. 5.9 hours post-CTA). In addition, CTA was associated with a decrease in the incidence of permanent neurologic sequelae from CAI (50% pre-CTA vs. 0% post-CTA; p = 0.07; Fisher exact test). CONCLUSION: We conclude that CTA does not significantly increase the time of the diagnostic workup of the patient with injuries caused by blunt trauma. The introduction of CTA at our institution was associated with an increase in the detection rate of CAI. Earlier detection of CAI may allow for more timely therapeutic intervention and potentially prevent permanent neurologic sequelae.

Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial.

BACKGROUND: Experimental and clinical work has suggested that hypertonic saline (HTS) would be better than lactated Ringer's solution (LRS) for the resuscitation of patients with head injuries. No clinical study has examined the effect of HTS infusion on intracranial pressure (ICP) and outcome in patients with head injuries. We hypothesized that HTS infusion would result in a lower ICP and fewer medical interventions to lower ICP compared with LRS. METHODS/DESIGN: Prospective, randomized clinical trial at two teaching hospitals. RESULTS: Thirty-four patients were enrolled and were similar in age and Injury Severity Score. HTS patients had a lower admission Glasgow Coma Scale score (HTS: 4.7+/-0.7; LRS: 6.7+/-0.7; p = 0.057), a higher initial ICP (HTS: 16+/-2; LRS: 11+/-2; p = 0.06), and a higher initial mean maximum ICP (HTS: 31+/-3; LRS: 18+/-2; p < 0.01). Treatment effectively lowered ICP in both groups, and there was no significant difference between the groups in ICP at any time after entry. HTS patients required significantly more interventions (HTS: 31+/-4; LRS: 11+/-3; p < 0.01). During the study, the change in maximum ICP was positive in the LRS group but negative in the HTS group (LRS: +2+/-3; HTS: -9+/-4; p < 0.05). CONCLUSION: As a group, HTS patients had more severe head injuries. HTS and LRS used with other therapies effectively controlled the ICP. The widely held conviction that sodium administration will lead to a sustained increase in ICP is not supported by this work.

Multiple intradural spinal lipomata with intracranial extension.

An intradural, intramedullary lipoma originating within the upper cervical cord with significant extension into the posterior fossa is reported in an infant. Two additional lipomas were found in the lumbar region. This constellation of findings represents the first description of multiple intradural, intramedullary spinal lipomas with extensive intracranial involvement.

Spinal anesthesia for repair of meningomyelocele in neonates.

The use of spinal anesthesia for meningomyelocele repair in neonates has received minimal attention. Spinal anesthesia may lessen the stress response to surgery and decrease postoperative respiratory complications. We therefore examined the efficacy of spinal anesthesia in 14 neonates requiring repair of lumbar or sacral meningomyelocele. All neonates were positioned prone with a small chest roll. Hyperbaric 0.5% tetracaine with epinephrine was injected into the caudal end of the meningomyelocele sac. If necessary, supplemental tetracaine was administered directly into the intrathecal space by the surgeon during the operation. Blood pressure, heart rate, and oxyhemoglobin saturation were measured throughout surgery. Neonates were monitored with transthoracic impedance apnea monitors, electrocardiogram (ECG), and pulse oximetry for 36 h after surgery. Spinal anesthesia was successful in all cases. Seven patients received one supplemental tetracaine injection; one patient received two supplemental injections. Arterial blood pressure decreased an average of 5 mm Hg with the largest decrease being 10 mm Hg. Two postoperative respiratory events occurred in the first 8 h after surgery. Both neonates had received intraoperative midazolam for sedation. Neurologic function was assessed pre- and postoperatively. Twelve patients had no change in neurologic function after surgery, while two infants demonstrated improved function. We conclude that spinal anesthesia can be safely used for meningomyelocele repair.

Advances in the early management of patients with head injury.

The last decade has seen continual improvement in our skills of visualizing and diagnosing the many types of human head injury. As we continue to unravel the complex biochemistry and molecular changes caused by trauma, we expect to find new methods and agents to enhance the extracellular milieu of injured but salvageable neurons and supporting cells, resulting in continued improvement in outcome for patients with severe head injury.

Primary diffuse chiasmatic germinomas: differentiation from optic chiasm gliomas.

Primary germ cell tumors confined to the optic nerves and chiasm without suprasellar extension are uncommon. These tumors appear similar to chiasmatic gliomas on both computed tomography and magnetic resonance imaging, potentially resulting in treatment errors if the diagnosis is based on radiologic criteria alone. Unlike chiasmatic gliomas, suprasellar germinomas characteristically present with a clinical triad of endocrine abnormalities, diabetes insipidus, and visual complaints. We report the case of a 9-year-old boy who presented with a 5-month history of fatigue, 16-pound weight gain, polydipsia, polyuria, visual complaints, and intermittent headache. Imaging studies demonstrated findings consistent with a glioma of the chiasm with infiltration into the optic tracts. At surgery, the chiasm and optic tracts were diffusely enlarged with no other suprasellar abnormalities. Biopsy specimens were characteristic of germ cell tumor. Based on this result, the patient received a treatment regimen different from that used at our institution for chiasmatic gliomas. We feel it is imperative to biopsy chiasmatic lesions that radiologically appear to be gliomas if symptoms do not adhere to the classical clinical presentation.

Prophylactic vena cava filter insertion in patients with traumatic spinal cord injury: preliminary results.

Pulmonary embolism (PE) is a devastating complication in patients with traumatic spinal cord injury (SCI). Prophylactic measures such as venous compression hose or low-dose heparin are only partially protective in reducing the risk of venous thromboembolism and are contraindicated in some patients. Because of extended perturbations in fibrinolytic activity, catecholamine effects on platelet aggregation, increased activity of complement and acute phase reactants, abnormally high factor VIII concentrations, and persistent venous stasis with ongoing endothelial damage, the patient with an SCI remains at prolonged risk for venous thromboembolism. A retrospective 5-year review at the Medical Center Hospital of Vermont revealed seven patients with eight documented PEs (three fatal; 2.7%) in 111 SCI patients (6.3%). Six PEs (75%) occurred after discharge from the acute care facility. Median time to PE after injury was 78 days (range, 9-5993). Although comprising only 4% of all trauma admissions, SCI accounted for 31% of all PEs in the total trauma population (2525 patients). Beginning in July 1991, a new prophylaxis protocol was instituted, which included the percutaneous insertion of vena cava filters under local anesthesia in all SCI patients with paraplegia or quadriplegia. Fifteen patients have undergone the insertion of titanium filters. Impedance plethysmography was performed weekly to detect deep venous thrombosis. No complications were associated with vena cava filter insertion. No patients developed deep venous thrombosis during their acute hospitalization (median, 22 d), and no patients have developed PE after filter insertion.(ABSTRACT TRUNCATED AT 250 WORDS)

The epidemiology of injury in a rural state: 5,322 cases over 6 years.

Presently, descriptions of rural trauma are complications of national sample statistics and local data from states projected to rural areas. This study reviews all hospital discharges (36,866) for children (aged 0 to 18 years) from January 1985 through December 1990 in an entirely rural state. Fourteen percent of admissions (5,322) were due to traumatic injury and 63% of these occurred in boys. Injury rates were age dependent with children 15 to 18 years experiencing an incidence of 110/10,000; 10 to 14 years 55/10,000; 5 to 9 years 39/10,000; 1 to 4 years 35/10,000; and < 1 year 39.5/10,000. Mean age for the entire population was 11.4 +/- 5.7 years. Thirty-five percent of children had more than one major site of injury. Sixty-three percent of admissions were for blunt trauma and only 4.8% were penetrating. The remainder were due to burns, hanging, ingestion, and other toxic agents. Falls constituted the most prevalent cause of injury in this population occurring in 25.9%, motor vehicle accidents 22.9%, struck by an object 9.6%, suicide attempts 8.5%, poisoning 4.7%, fire 1.2%, drowning 0.7%, and farm machinery 0.3%. The vast majority of motor vehicle accidents involved the child as an operator or occupant of the vehicle. Less than 10% involved a pedestrian being struck and less than 5% involved a child being struck while on a bicycle. Less than 6% of all injuries involved a bicycle. Child maltreatment was recorded in less than 2% of this population. Only 3.3% of injured children required transfer to another acute care facility (1/3 because of a motor vehicle accident and 1/4 because of a fall).(ABSTRACT TRUNCATED AT 250 WORDS)