Functional outcomes following surgical treatment of bilateral mandibular condylar fractures.

Debate continues regarding unilateral or bilateral treatment for mandibular condylar fractures. This retrospective study evaluates the functional outcomes of bilateral condylar process fractures after surgical intervention. From May 1994 to December 2004, 51 adult patients with bilateral mandibular condylar process fractures were studied. There were 33 cases of bilateral condylar fractures (type I); 12 cases of condylar-subcondylar fractures (type II); and six cases of bilateral subcondylar fractures (type III). All patients underwent open reduction and internal fixation. Four patients had chin deviation, six had malocclusion, three had poor chewing function and eight had limited mouth opening. Type I patients had a significantly higher incidence of limited mouth opening (P=0.039) and associated maxillary fractures (n=12) and psychiatric disease (n=6) which yielded significantly poor functional outcomes. Complications included transient facial paresis (n=4), fracture and loosening of postoperative plates (n=3) and surgical wound infections (n=2). Open reduction with rigid fixation for bilateral condylar fractures provided satisfactory functional outcomes in this study. Concomitant maxillary fractures and underlying psychiatric problems are poor outcome factors. Aggressive rehabilitation in the first 9 months is important for early functional recovery.

Analytical and biological considerations in the measurement of cell-associated CCR5 and CXCR4 mRNA and protein.

The accurate measurement of T cell-associated CC chemokine receptor type 5 (CCR5) and CXC chemokine receptor type 4 (CXCR4) expression, including expression of CCR5 and CXCR4 mRNA as an immune measure of immunologic response to highly active antiretroviral therapy (HAART) and newer agents, including entry inhibitors, is essential. Previous studies have reported alterations in lymphocyte cell membrane CCR5 expression that were related to blood collection and cell separation media. Clinical trials often require the transport of specimens to central laboratories for evaluation, resulting in significant time delays between specimen procurement and analysis. This study shows that CCR5 expression on naïve and memory T cells is influenced by blood collection media and specimen age. Peripheral blood collected in Streck Vacutainer tubes containing a cell stabilizer and fixative was found to improve detection of CCR5 expression compared to specimens collected in K2 EDTA anticoagulant. The selection of flow cytometry gating strategies for the identification of naïve and memory T-helper cells can also significantly influence the sensitivity of detection of CCR5 expression. Procedural methods are described that allow for the optimal measurement of naïve and memory T-helper cell CCR5 and CXCR4 expression as well as the quantitation of CCR5 and CXCR4 mRNA.

Metabolic syndrome, endothelial injury, and subclinical atherosclerosis in patients with systemic lupus erythematosus.

OBJECTIVES: To study the link between metabolic syndrome (MetS), endothelial injury, and atherosclerosis in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients without a history of arterial thrombosis were screened for atherosclerosis at the carotid and coronary arteries by B-mode ultrasound [intima-media thickness (IMT)] and multidetector computed tomography (MDCT) scan (Agatston calcium scores), respectively. Plasma levels of homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule (sVCAM)-1, P-selectin, and soluble thrombomodulin (sTM) were assayed. Patients were stratified according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria for MetS, using the Asian criteria for abdominal obesity. Risk factors for atherosclerosis were studied. RESULTS: Of the 123 SLE patients (93% women; age 47.9+/-11 years; SLE duration 10.9+/-7.0 years) studied, 20 (16.3%) had MetS. The prevalence of MetS in the SLE patients was significantly higher than in 492 age- and sex-matched healthy controls (9.6%; p=0.03). Coronary calcification and abnormal carotid IMT were detected in 38 (31%) and 72 (59%) of SLE patients, respectively. Patients with MetS had a significantly higher Agatston score (69.5+/-95 vs. 16.4+/-57; p=0.03) and a numerically higher carotid IMT (p=0.43) than those without. In a logistic regression model, the MetS [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.01-9.59, p=0.049] was associated with coronary atherosclerosis after adjustment for age and other risk factors. In addition, patients with MetS had significantly higher levels of hsCRP (p=0.002), homocysteine (p=0.03), and sTM (p=0.01). CONCLUSIONS: The MetS is more prevalent in SLE patients than the general population and is associated with endothelial injury and coronary atherosclerosis. More aggressive control of risk factors is justified in these patients.

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) as a molecular target in lung epithelial wound repair.

BACKGROUND AND PURPOSE: Epithelial injury contributes to lung pathogenesis. Our work and that of others have identified the phosphoinositide-3 kinase (PI3K)/Akt pathway as a vital component of survival in lung epithelia. Therefore, we hypothesized that pharmacological inhibition of PTEN, a major suppressor of this pathway, would enhance wound closure and restore lung epithelial monolayer integrity following injury. EXPERIMENTAL APPROACH: We evaluated the ability of two bisperoxovanadium derivatives, bpV(phen) and bpV(pic), in differentiated primary human airway epithelia and BEAS2B cultures for their ability to inhibit PTEN, activate the PI3K/Akt pathway and restore epithelial monolayer integrity following mechanical injury. KEY RESULTS: BpV(phen) and bpV(pic) induced Akt phosphorylation in primary and BEAS2B cells in a dose and time dependent manner. Minimal toxicity was observed as measured by lactate dehydrogenase (LDH) release. To verify that Akt phosphorylation is specifically induced by PTEN inhibition, the PTEN positive cell line, DU145, and two PTEN negative cell lines, LNCaP and PC3, were examined. PTEN positive cells demonstrated a dose responsive increase in Akt phosphorylation whereas PTEN negative cells showed no response indicating that bpV(phen) directly suppresses PTEN without affecting auxiliary pathways. Next, we observed that exposure to either compound resulted in accelerated wound closure following mechanical injury. Similar effects were observed after transfection with a dominant negative isoform of PTEN and PTEN specific siRNA. CONCLUSIONS AND IMPLICATIONS: From these studies, we conclude that PTEN is a valid target for future studies directed at restoring epithelial barrier function after lung injury.

Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation.

The substance P (SP)-preferring receptor neurokinin-1 receptor (NK-1R) has two forms: a full-length receptor consisting of 407 aa and a truncated receptor consisting of 311 aa. These two receptors differ in the length of the C terminus of NK-1R. We studied the undifferentiated and phorbol myristate acetate (PMA)-differentiated human monocyte/macrophage cell line THP-1 to investigate the expression and function of NK-1R. The expression of full-length and truncated NK-1R in this cell line was determined by using real-time PCR and immunofluorescence staining. Undifferentiated THP-1 cells expressed only truncated NK-1R. The differentiation of THP-1 cells with PMA to a macrophage-like phenotype resulted in the expression of full-length NK-1R, which was functionally accompanied by an SP (10(-6) M)-induced Ca2+ increase. In contrast, the addition of SP (10(-6) M) did not trigger Ca2+ response in undifferentiated THP-1 cells; however, SP did enhance the CCR5-preferring ligand RANTES (CCL5)-mediated Ca2+ increase. When a plasmid containing the full-length NK-1R was introduced into undifferentiated THP-1 cells, exposure to SP triggered Ca2+ increase, demonstrating that the full-length NK-1R is required for SP-induced Ca2+ increase. The NK-1R antagonist aprepitant (Emend, Merck) inhibited both the SP-induced Ca2+ increase in PMA-differentiated THP-1 cells and the SP priming effect on the CCL5-mediated Ca2+ increase, indicating that these effects are mediated through the full-length and truncated NK-1R, respectively. Taken together, these observations demonstrate that there are unique characteristics of NK-1R expression and NK-1R-mediated signaling between undifferentiated THP-1 cells and THP-1 cells differentiated to the macrophage phenotype.

Glycerol kinase deficiency presenting with hypodipsia, osmotic diuresis and severe hypernatraemia.

A Chinese boy with glycerol kinase deficiency is reported. His presentation with severe hypernatraemia secondary to hypodipsia and glycerol-induced osmotic diuresis is unusual and not previously described in the literature.

Macroprolactin-a cause of pseudohyperprolactinaemia.

Macroprolactin is a complex of immunoglobulin G and monomeric prolactin with little biological activity in vivo. Macroprolactin cross-reacts in modern commercial prolactin assays, however, leading to pseudohyperprolactinaemia. This report is of three patients with macroprolactinaemia and the untoward consequences if this benign condition is misdiagnosed as genuine hyperprolactinaemia are discussed. One adult and one child without symptoms of hyperprolactinaemia were incidentally found to have elevated serum prolactin levels, one of whom had a pituitary incidentaloma. Repeat prolactin measurement after polyethylene glycol precipitation showed that the majority of circulating prolactin was macroprolactin. The third patient had galactorrhoea and pituitary microadenoma. Polyethylene glycol study showed that macroprolactinaemia exists simultaneously with genuine hyperprolactinaemia leading to falsely high serum prolactin levels. The recognition of this relatively common and benign condition is important in order to avoid misdiagnosis and unnecessary investigations and treatment. Particular attention must be paid to patients in whom the clinical and radiological findings are incompatible.

Microinvasive Nd:YAG laser therapy of early glottic carcinoma and its effect on soluble interleukin-2 receptor, interleukin-2, and natural killer cells.

OBJECTIVE: To investigate the effectiveness of microinvasive Nd:YAG laser therapy in human glottic Tis and T1 carcinomas, as well as its effect on the cellular immune function of the tumor-bearing hosts. STUDY DESIGN: We treated 34 patients with microinvasive Nd:YAG laser therapy and evaluated its effect on the cellular immune function of the host. METHODS: Thirty-four patients with glottic Tis or T1 squamous cell carcinoma were treated with fiberoptic laryngoscopic Nd:YAG laser surgery. Both before and after therapy, serum levels of soluble interleukin-2 receptor (SIL-2R) and interleukin-2 (IL-2), as well as natural killer (NK) cell activity, were determined by means of double-antibody sandwich technique, tritiated thymidine-deoxyribonucleoside incorporation, and iodine 125-uridine-deoxyribonucleoside release technique, respectively. RESULTS: All 34 patients tolerated the procedure well. A 3- to 7-year follow-up in a subgroup of 27 patients resulted in an estimated cure rate of 85.2% (23 of 27 patients). In all 27 patients with a regular follow-up, a subjective improvement of phonation was noted after therapy to various degrees. In 74% (20 of 27 patients), voice and speech subjectively recovered to almost normal levels. The post-therapy serum levels of SIL-2R were significantly declined (P <.001), whereas those of IL-2 and the NK activity were significantly elevated (P <.001) as compared with those detected before therapy. CONCLUSIONS: Therapy with fiberoptic laryngoscopic Nd:YAG laser surgery is simple, safe, effective and only minimally invasive for patients with glottic Tis or T1 carcinoma. At the same time, it has an immunoenhancing effect on its host.

Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes.

Substance P (SP) is a potent modulator of neuroimmunoregulation. We recently reported that human immune cells express SP and its receptor. We have now investigated the possible role that SP and its receptor plays in HIV infection of human mononuclear phagocytes. SP enhanced HIV replication in human blood-isolated mononuclear phagocytes, whereas the nonpeptide SP antagonist (CP-96,345) potently inhibited HIV infectivity of these cells in a concentration-dependent fashion. CP-96,345 prevented the formation of typical giant syncytia induced by HIV Bal strain replication in these cells. This inhibitory effect of CP-96,345 was because of the antagonism of neurokinin-1 receptor, a primary SP receptor. Both CP-96,345 and anti-SP antibody inhibited SP-enhanced HIV replication in monocyte-derived macrophages (MDM). Among HIV strains tested (both prototype and primary isolates), only the R5 strains (Bal, ADA, BL-6, and CSF-6) that use the CCR5 coreceptor for entry into MDM were significantly inhibited by CP-96,345; in contrast, the X4 strain (UG024), which uses CXCR4 as its coreceptor, was not inhibited. In addition, the M-tropic ADA (CCR5-dependent)-pseudotyped HIV infection of MDM was markedly inhibited by CP-96,345, whereas murine leukemia virus-pseudotyped HIV was not affected, indicating that the major effect of CP-96,345 is regulated by Env-determined early events in HIV infection of MDM. CP-96,345 significantly down-regulated CCR5 expression in MDM at both protein and mRNA levels. Thus, SP-neurokinin-1 receptor interaction may play an important role in the regulation of CCR5 expression in MDM, affecting the R5 HIV strain infection of MDM.

The effect of shoulder-girdle loading by a school bag on lung volumes in Chinese primary school children.

BACKGROUND: Heavy loading of the spine may induce musculoskeletal problems in children. Local surveys reported frequent overloading of school bags carried by primary school children. The effect of an overweight school bag on the child's lung function has not been reported. AIMS: To investigate the effect of shoulder-girdle loading on forced expiratory lung volumes in primary school children and to compare this effect with that of an assumed kyphotic posture. STUDY DESIGN AND SUBJECTS: Forty-three primary school children, mean age 9.6 years underwent spirometry lung-function measurements, while adopting the following five conditions in random order: free standing; kyphotic standing; standing wearing a backpack weighing 10%, 20% and 30% of their body weight. OUTCOMES MEASURES: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEF). RESULTS: There were no significant differences in FEV1 and FVC between free standing and the 10% body weight load. However, both FEV1 and FVC decreased significantly when the student adopted the kyphotic posture and when the load in the backpack was increased to 20% and 30% of body weight. CONCLUSIONS: This study demonstrates a restrictive effect on lung volumes when a school-bag load is heavier than 10% of a child's body weight. Our results also confirm the detrimental effect of a kyphotic posture on pulmonary mechanics and the necessity for health-care professionals to advocate proper postural advice to school children, teachers and parents.

Detection of substance P and its receptor in human fetal microglia.

Substance P, the most abundant neurokinin in the CNS, is a major modulator of the immune system. We have examined the gene expression of substance P and its receptor in human fetal brain microglia. Using reverse transcription-polymerase chain reaction and Southern blotting assay, the four isoforms of preprotachykinin-A gene transcripts (alpha, beta, gamma and delta) were detected in the microglia. The human fetal microglia produced significantly higher levels of endogenous substance P protein (640-850 pg/10(6) cells) than did human peripheral blood monocyte-derived macrophages (25-50 pg/10(6) cells), as determined by an enzyme immunoassay. Using immunohistochemical staining with an anti-substance P antibody, cell membrane substance P immunoreactivity was observed. In addition, we identified the presence of messenger RNA for neurokinin-1 receptor, a primary receptor for substance P in human fetal microglia.From these data, we propose that substance P and its receptor are biologically involved in regulating the functions of microglia, and potentially play an important role in host defense of the central nervous system.

Acute life-threatening injuries in facial fracture patients: a review of 1,025 patients.

BACKGROUND: The literature on facial fractures has emphasized obstruction of the airway as the most common associated life-threatening problem. Other life-threatening injuries associated with facial fractures are not as well documented. For this reason, we conducted a retrospective study involving 1,025 patients with facial fractures admitted to the trauma center at Chang Gung Memorial Hospital in Taiwan from January 1995 through December 1998. METHODS: This study identifies the incidence of facial fractures and establishes a management plan. Life-threatening injuries associated with facial fractures were those that warranted immediate invasive rescue procedures. RESULTS: Sixty-four (6.2%) of the patients with facial fractures required life-saving intervention; 21 patients had cerebral trauma prompting craniotomy, 19 had hemorrhagic shock, 17 had airway compromise, and 7 had pulmonary injury grave enough to necessitate tube thoracostomy. There were five mortalities, three due to cerebral trauma and two credited to hemorrhagic shock not identified until long after admission. CONCLUSION: These findings illustrate the need for prompt identification and proper management of the associated life-threatening injuries in facial fracture patients. Clinical assessment should begin with evaluation of cerebral trauma, followed by hemorrhagic shock, airway compromise, and hemopneumothorax. Proper management may require a multidisciplinary and coordinated team approach.

Application of endoscope in zygomatic fracture repair.

The endoscope has been used to visualise the upper face and brow in aesthetic facial surgery which is performed without a coronal incision. We applied these principles to repair zygomatic fractures with the aid of a 4 mm, 30 degree telescope inserted through a small temporal incision. Fracture sites at the zygomatic arch and the zygomaticofrontal suture were exposed and fixed with miniplates under endoscopic control. This technique was used in 15 consecutive patients including 2 with isolated zygomatic arch comminuted fractures and 13 having displaced zygomatic fractures with segmental, displaced zygomatic arch fractures. Nine patients were men and six patients were women with a mean age of 35 years. Three patients had associated mandibular fractures. The periods of follow-up ranged from 3 to 22 months. Two patients developed transient frontal nerve palsy which recovered within 2 months. One patient had mild temporal hollowing on the side of the facial fracture. All patients achieved the adequate anatomic reduction and satisfactory malar symmetry. There has been no case of chewing problems, cheek numbness or progressive enophthalmos developing postoperatively. Application of the endoscope in zygomatic fracture repair minimises the scalp scar, avoids forehead numbness, provides a comfortable postoperative recovery and shortens hospital stay. Careful preoperative evaluation and proper surgical technique are mandatory for achieving optimal results in selected patients.

Management of carbon monoxide poisoning using oxygen therapy.

The management of carbon monoxide poisoning requires an accurate assessment of the extent of blood oxygenation. Measuring the fractional oxyhaemoglobin content by using co-oximetry gives a true picture of the oxygen-carrying capacity of blood in the presence of carboxyhaemoglobin. The use of readings from pulse oximetry or a standard blood gas analyser is insufficient and can be misleading. We report on a case of carbon monoxide poisoning to illustrate this potential pitfall.

Quantification of substance P mRNA in human mononuclear phagocytes and lymphocytes using a mimic-based RT-PCR.

We have recently demonstrated that human monocytes and lymphocytes express the substance P (SP) gene at both the mRNA and protein level [Ho, W.Z., Lai, J.P., Zhu, X.H., Uvaydova, M., Douglas S.D., 1997. Human monocytes and macrophages express substance P and neurokinin-1 receptor. Journal of Immunology, 159, p. 5654; Lai, J.P., Douglas, S. D., Ho, W.Z., 1998. Human lymphocytes express substance P and its receptor. Journal of Neuroimmunology, 86, p. 80; Lai, J.-P., Douglas, S.D., Rappaport, E., Wu, J., Ho, W.-Z., 1998. Identification of a delta isoform of preprotachykinin mRNA in human mononuclear phagocytes and lymphocytes. Journal of Neuroimmunology, 91, p. 121]. Using RT-PCR assay with several specific human SP primer pairs, we were able to differentiate four isoforms of preprotachykinin (PPT-A, the SP precursor) mRNA transcripts on ethidium bromide-stained agarose gels and clone the PCR amplified cDNA of the four isoforms (alpha, beta, gamma, and delta) of the PPT-A gene. In an effort to quantitatively measure PPT-A mRNA levels, we have developed a mimic-based RT-PCR assay to analyze total PPT-A mRNA levels in human monocytes and lymphocytes. We designed a specific human SP primer pair (HSP4/HSP3) to amplify a single fragment of cDNA derived from all four isoforms of PPT-A mRNA transcripts, with a sensitivity of 120 molecules per reaction. Thus the PPT-A mRNA transcripts in an unknown sample can be quantitatively analyzed using the mimic-based RT-PCR. The accuracy and reproducibility of this assay were confirmed by the plasmids containing alpha, beta, gamma and delta cDNA inserts and by in vitro synthesized mRNA from a plasmid containing beta isoform cDNA insert. Our data indicate that the SP mimic-based RT-PCR assay has potential advantages in studies of SP levels in a variety of human cells as well as in clinical specimens.

Interferon-gamma upregulates CCR5 expression in cord and adult blood mononuclear phagocytes.

The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-gamma (IFN-gamma) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-gamma showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta, confirming the functional relevance of IFN-gamma-induced CCR5 expression. However, IFN-gamma suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-gamma inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-gamma on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-gamma-induced secretion of C-C chemokines (RANTES, MIP-1alpha, and MIP-1beta) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

Endoscopically assisted reconstruction of orbital medial wall fractures.

Traditional surgical approaches to orbital medial wall fractures are either direct extraocular skin incisions or indirect bicoronal flap. However, these methods can leave remarkable orbital scars or scalp alopecia with the possible associated complications. A minimally invasive endoscopic technique with the assistance of a 2.7-mm, 30-degree telescope through a medial transconjunctival incision has been successfully used to reconstruct the orbital medial wall fractures. This technique was applied to four patients who had orbital medial wall fractures. Three patients also had concomitant orbital floor fractures. The other had associated superior orbital fissure syndrome. All patients were presented with limited eye movement, positive forced duction test, horizontal diplopia, and enophthalmos (3 mm to 6 mm) preoperatively. The entrapped periorbital tissues in the ethmoid sinus were completely reduced endoscopically. The bone defect of orbital medial wall was reconstructed with autogenous rib bone grafts under endoscopic control. The patients were followed up for 8 to 16 months with an average of 11 months. Three patients recovered completely without any residual eye symptoms after intervention. Clinically significant residual enophthalmos of 3 mm occurred in the patient with the superior orbital fissure syndrome. His eye movement limitation caused by entrapment of medial rectus muscle was relieved postoperatively. There was no donor-site morbidity or any complications related to the endoscopically assisted procedure. Endoscopically assisted medial transconjunctival approach to the orbital medial wall fractures is an excellent adjunct for the exposure and complete reduction of herniated periorbital tissue and bony reconstruction of the medial orbital wall.

Endoscopically assisted mandibular subcondylar fracture repair.

The endoscope has been widely used in aesthetic surgery in recent years, but rarely has it been used in cases of facial trauma. From July of 1996 to December of 1996, the endoscope was used successfully to assist in the repair of mandibular subcondylar fractures in eight patients (five men and three women). Their ages ranged from 15 to 60 years with an average age of 31 years. Six of the patients had other associated mandibular fractures including angular, parasymphyseal, and contralateral subcondylar fractures. A 4.0-mm, 30-degree telescope was introduced to visualize the fracture site by means of an intraoral incision over the ascending ramus. A miniplate was used to stabilize the fracture site with the help of a percutaneous trocar. Intermaxillary fixation was applied for 3 to 6 days. Functionally, all patients returned to normal range of motion within 8 weeks. A slight deviation to the trauma site was noted on maximal opening in three patients, but this condition returned to normal 3 months after surgery. There was no facial palsy or lip numbness. The benefits of the endoscopic approach include not only the provision of better visualization and precise anatomic alignment of bony segments but also the avoidance of large facial scars and facial nerve injuries.