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Background: Procedures combining a short scar with superficial musculoaponeurotic system (SMAS) manipulation are increasingly popular for patients with early signs of mid- and lower-facial laxity seeking rhytidectomy. We present the senior author's experience with a short scar volumetric malar imbrication rhytidectomy, which avoids post-auricular incisions and sub-SMAS dissection., Patients and Methods: Between January 2004 and April 2007, 54 patients underwent a short scar volumetric rhytidectomy (9.6% of all facelifts). These procedures were primary in 38 and secondary in 16 patients, at a mean age of 49 years (range 35-77 years). Average operating time was 90 min. Resultant vertical and horizontal skin movement at the helical root was recorded. Concurrent procedures included blepharoplasty, canthoplasty, endoscopic forehead rejuvenation and fat grafting. Minimum follow up was 3 months. Pre- and 3 month postoperative photographs of 25 randomly selected patients were rated by three independent surgeons. A seven-point scale was used to grade the improvement in the malar eminence, melolabial fold, jowls and cervicomental angle. The overall aesthetic result was assessed using the MDACS grading system. Statistical analysis was performed using Student's t-tests and general estimation equations where appropriate., Results: There were no significant complications. Three patients developed minor cheek swellings which all settled with antibiotics. Mean postoperative aesthetic outcomes were rated as 'Good' using the MDACS scale (mean score 0.64), with no 'Poor' results. Vertical skin lifting was significantly greater than the horizontal skin lifting (P<0.001). Mild postoperative improvements were noted in the malar eminence soft tissue volume, nasolabial fold diminishment, jowl diminishment and cervicomental angle., Conclusion: In the appropriately selected face, short scar volumetric malar imbrication rhytidectomy is a straightforward, safe and effective procedure for improving the early signs of ageing.

Bodylifting is often considered a high-risk surgical procedure. There is a widely held perception is that the operation is both time consuming and physically demanding for the surgeon, with, potentially, a long recovery and high complication rate for the patient. The senior author's experience of 16 consecutive bodylift procedures does not reflect this. Fourteen female patients and two male patients underwent Lockwood-type bodylifting procedures at two different hospitals over a 5 year period. Patients studied were unsuitable for a standard abdominoplasty either because of excess lateral abdominal tissue, or had undergone significant weight loss and developed redundant folds of skin in a circumferential pattern around the waistline. The average Body Mass Index (BMI) prior to surgery was 26.7. Mean surgical time and hospital stay was 4.2 hrs and 3.5 days respectively. No patient required blood transfusion. The follow up period was between 3 and 24 months. Levels of patient satisfaction were high and complications few. Only one patient required minor revisional surgery. No major complications were recorded. The commonest problem, seroma, developed in 4 out of 16 patients and was managed by simple aspiration. This study supports the effectiveness of the lower body lift as a procedure with the potential to produce an outcome unachievable by other means with a low incidence of minor complications.

Six pigeons were trained in a delayed matching-to-sample task involving bright- and dim-yellow samples on a central key, a five-peck response requirement to either sample, a constant 1.5-s delay, and the presentation of comparison stimuli composed of red on the left key and green on the right key or vice versa. Green-key responses were occasionally reinforced following the dimmer-yellow sample, and red-key responses were occasionally reinforced following the brighter-yellow sample. Reinforcer delivery was controlled such that the distribution of reinforcers across both comparison-stimulus color and comparison-stimulus location could be varied systematically and independently across conditions. Matching accuracy was high throughout. The ratio of left to right side-key responses increased as the ratio of left to right reinforcers increased, the ratio of red to green responses increased as the ratio of red to green reinforcers increased, and there was no interaction between these variables. However, side-key biases were more sensitive to the distribution of reinforcers across key location than were comparison-color biases to the distribution of reinforcers across key color. An extension of Davison and Tustin's (1978) model of DMTS performance fit the data well, but the results were also consistent with an alternative theory of conditional discrimination performance (Jones, 2003) that calls for a conceptually distinct quantitative model.

Background: Craniofacial dysostosis syndromes produce multisutural synostoses combined with severe midfacial retrusion. This may cause serious functional problems, including airway obstruction, exposure of the eyes, visual pathway dysfunction, and raised intracranial pressure. Early midface advancement may be necessary to address these issues. Distraction osteogenesis has provided the facility to achieve significant advances safely and is often in excess of that which is achievable by conventional means., Methods: A retrospective study of 20 patients with craniofacial dysostosis and severe midface hypoplasia who underwent monobloc advancement osteotomies using the rigid external distractor system principally for functional reasons was undertaken. The multidisciplinary management and outcome measures of these patients were recorded., Results: The midface was distracted an average of 16.4 mm, with a range of 12 to 22 mm. Ocular protection was achieved in all patients with preoperative exposure keratopathy and/or globe subluxation. Improvements in optic disc swelling and pattern visually evoked potentials were seen in those patients with threatened visual impairment. Improvement in airway obstruction was seen in those patients with abnormal polysomnography. Decannulation was achieved in five of the seven patients with tracheostomies. Fifty percent had a reduction in hyponasality, and the visual appearance of speech was improved. Complications included persistent cerebrospinal fluid leakage, acquired hypernasality in 25 percent, cranial bone loss, and sinus formation requiring surgical revision., Conclusions: Monobloc distraction osteogenesis results in good aesthetic and functional outcomes. The relatively high rate of complications remains a concern, and further adaptations of technique are needed to reduce the risks of this procedure.

Multisutural synostosis may result in frontofacial hypoplasia. The aesthetic and function problems arising from this can be corrected by frontofacial advancement, either by monobloc or bipartition osteotomy. Significantly larger, safer advancements can be achieved using distraction osteogenesis when compared to conventional osteotomy. However, the stability of this technique has been questioned. A retrospective study of 21 patients with craniofacial dysostosis who underwent frontofacial advancement osteotomies using the rigid external distractor system was undertaken. Twelve were distracted on protocol 1 (24 hours after surgery at 1.5 mm/d). Nine were distracted on protocol 2 (7 days after surgery at 1 mm/d). A 6-week consolidation period was used. Changes in frontofacial advancement in the sagittal plane were measured preoperatively, immediately, at 6 months, and where possible thereafter annually using lateral cephalograms and three-dimensional computed tomography scans. The midface was distracted an average of 16.4 mm with a range of 12 to 22 mm as measured in the sagittal plain. Relapse was seen only in 3 of 21 patients, and all of these patients were distracted using protocol 1. Distraction osteogenesis of the frontofacial skeleton using the rigid external distractor frame is generally stable. In this series, a longer latency period and reduced distraction rate resulted in greater stability. Overdistraction in the growing infant is recommended to allow for completion of growth. Overdistraction is not needed to compensate for potential relapse.

Background: Postoperative drainage is often used instinctively in face lifting on the assumption that it may reduce the likelihood of complications. This potential benefit should be balanced against cost, discomfort, and the possibility of provoking bleeding and hematoma on removal. Evidence-based decisions on drainage are problematic, since no prospective studies have examined its role. This study was designed to address this issue directly., Methods: Fifty consecutive patients undergoing face lift over a 3-month period were randomized to drainage of one side of the face only, with the contralateral side serving as a paired control. Bruising, swelling, and hematoma or seroma were assessed objectively, independently of the operating surgeon and subjectively by the patients., Results: Postoperative hematoma and edema were not influenced by the use of drains (p > 0.5). Patients reported no difference between the two sides with respect to swelling (p = 0.6) or discomfort (p = 0.5). However, drains produced a statistically significant reduction in postoperative bruising both on clinical assessment (p = 0.005) and patient assessment (p = 0.002)., Conclusions: This article represents the first prospective, randomized, controlled trial assessing the use of postoperative drainage in facial rejuvenation surgery. Surgical drains do not influence postoperative complications, but they do significantly reduce bruising and so may facilitate the patient's return to normal activity.

Solids retention time (SRT), biological scum trapping and recycle, and the dynamic equilibrium between Nocardioform populations in the foam and the mixed liquor are the controlling factors in activated sludge foaming events caused by Nocardioform bacteria. For the operating modes described in this paper, a cured mixed liquor foaming condition (filament counts of approximately 10(5) intersections/g volatile suspended solids) was only achieved when SRT control, selective wasting, and polymer addition were in effect. Solids retention time control, with the SRT remaining below 1.5 days, and selective wasting will cure a severely foaming mixed liquor, but effects will only be observed after 3 or 4 months after implementation. The combined wastage of Nocardioform bacteria from selective wasting and SRT control can ensure long-term foam control to the operation of a pure-oxygen activated sludge system with foam-trapping features. An SRT of 0.3 days will result in the complete washout of Nocardioform bacteria from the activated sludge system, which can then operate at an SRT of 3 days free of Nocardioform. Polymer addition to mixed liquor is only effective for foam control when a large portion of the system biomass exists as a heavy layer of foam above the mixed liquor.

The case notes of 278 consecutive patients who underwent abdominoplasty, during a five-year period, in one institution under the care of four surgeons were reviewed. Patient details, early and late complications and revision procedures were noted. Seventy-five percent of patients had a 'full' abdominoplasty with undermining to costal cartilage and repositioning of the umbilicus and 23% had 'mini abdominoplasties', 2% were revision operations. Eighteen percent of patients suffered from early complications the most common of which were seroma (5%), haematoma (3%), infection (3%), skin or fat necrosis (2.5%) and delayed healing (2%). Twenty-five percent of patients had late complications which were often relatively minor. These included 'dog ears' (12%), localised fatty excess (10%) and unsatisfactory scars (8%). Twenty-four percent of patients underwent revision surgery. Most commonly further liposuction (12%), dog ear revision (10%) and scar revision (5%). Analysis failed to reveal significant risk factors. Despite an apparently high complication and revision rate the subjective impression is of a satisfied patient cohort.

The chin is an important and often neglected feature of facial balance. Genioplasty is a useful procedure in aesthetic surgery and often can be combined with other procedures to obtain an optimal aesthetic outcome. A retrospective case note review of the senior author's (BMJ) experience of aesthetic genioplasty over an 11-year period was undertaken. Cases with non-aesthetic indications for genioplasty were excluded and overall 64 patients were included in this study. Our technique of intraoral osseous genioplasty is described and discussed. A total of 54 patients underwent osseous genioplasty, eight underwent alloplastic genioplasty and two underwent removal of a chin prosthesis only. Most of the patients who had an osseous genioplasty had a sliding advancement correction. Four of these patients required secondary surgery, five had additional minor complications and there were seven cases of transient numbness. Nine patients had a genioplasty alone, 26 had one additional procedure and 19 had more than one, with an average of 2.9 additional procedures. Twenty-four patients had a simultaneous rhinoplasty and 18 had a facelift. Osseous genioplasty is our preferred technique for its versatility and long-term stability compared to alloplastic methods. If performed correctly it provides excellent results with a high degree of patient satisfaction and few long-term complications.

Objective: The incidence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in a cohort of Chinese patients with juvenile idiopathic arthritis (JIA) and adults with rheumatoid arthritis (RA) were studied., Methods: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 59 patients with JIA, 129 adult RA patients, 48 children with diseases other than JIA, 68 adult patients with rheumatic diseases other than RA, and 60 normal adults. Associations between anti-CCP antibodies and clinical and laboratory parameters were determined by Fisher's exact test., Results: Six of 59 (10.2%) patients with JIA and 71 of 129 (55%) patients with RA were positive for anti-CCP. Four of five RF-positive JIA patients and two of 54 RF-negative JIA patients were positive (p<0.001). One paediatric patient with allergy (0.9%) and two adult patients with rheumatic diseases other than RA (2.3%) were positive. All healthy controls were negative for anti-CCP. The specificity was 99.1% for JIA and 98.4% for RA. The sensitivity was 10.2% for JIA and 55% for RA. Positive predictive values were 85.7% for JIA and 97.3% for RA and negative predictive values were 66.9% for JIA and 68.5% for RA., Conclusion: The anti-CCP antibody assay is a valuable tool for the diagnosis of RA and a subset of JIA in Chinese patients. It could be a useful predictive test for joint erosion in JIA of the polyarticular RF-positive subset and may be influential in the choice of the best therapeutic strategy in patients with recent-onset arthritis.

The spontaneous development of self-injurious behavior (SIB) in singly housed monkeys poses a challenge for their management and well-being in captivity. Relatively little information is available on effective treatments for SIB. This study examined the effects of diazepam (Valium) on self-wounding and other abnormal behaviors in eight individually housed male rhesus monkeys (Macaca mulatta). Each monkey's response to an anxiolytic dose of diazepam (1 mg/kg or greater orally) was compared with the animal's behavior during drug-free periods. When examined across all animals, treatment with diazepam did not significantly alter wounding frequency or rates of self-directed biting without wounding. However, closer examination of the data revealed that four of the animals showed significant decreases in self-biting and wounding frequency (positive responders, PR group), whereas the remaining monkeys showed a trend towards increased wounding frequency (negative responders, NR group). Subsequent examination of colony and veterinary records demonstrated that compared with NR monkeys, PR monkeys had spent significantly more years in individual cage housing and had experienced a greater number of minor veterinary procedures. PR animals also were significantly less likely to have a documented history of self-biting behavior. Our findings suggest that SIB is not a homogeneous disorder in rhesus monkeys; rather, distinct subtypes exist that require different treatment approaches.

Context: There have been few longitudinal studies of cytokine production in neonatally acquired HIV-1 infection and none in Asian or Chinese children., Objective: To determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV-1 infection., Setting: Clinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong., Patients: Ten Asian and 2 Eurasian children infected with HIV-1 by mother-to-child transmission were followed for up to 5 years while on treatment with highly active antiretroviral therapy (HAART)., Main Outcome Measures: Numbers of unstimulated and mitogen-activated cytokine-secreting cells (IFN-gamma, interleukin [IL]-2, IL-4, IL-6, IL-10, IL-12, and TNF-alpha) were measured by ELISPOT assay at frequent intervals, and correlations were sought with CD4+ and CD8+ cell counts and viral loads., Results: Mitogen-stimulated IL-2-secreting cells were directly associated with recovery of CD4+ cells. Correlations with viral load were found for Con A-induced IFN-gamma, Con A-induced IL-4, and unstimulated IL-10, suggesting that these cytokines were either suppressed by high virus levels or that higher cytokine levels suppressed virus. IFN-gamma, IL-2-, IL-4-, and IL-12-secreting cells induced by PHA, Con A, and/or SAC tended to increase for the first 3-4 years of treatment but declined thereafter., Conclusions: Alterations in cytokine profiles were not associated with adverse clinical events and there was little evidence to indicate that monitoring cytokine enzyme-linked immunospots (ELISPOTs) could contribute to pediatric patient management.

Accelerated apoptosis of erythroid progenitors in beta-thalassemia is a significant barrier to definitive therapy because the beneficial effects of fetal globin-inducing agents on globin chain balance may not be inducible in cells in which programmed cell death is established early. Accordingly, our objectives have been to identify methods to decrease cellular apoptosis and to identify orally tolerable fetal globin gene inducers. A pilot clinical trial was conducted to determine whether combined use of a fetal globin gene inducer (butyrate) and rhu-erythropoietin (EPO), the hematopoietic growth factor that prolongs erythroid cell survival and stimulates erythroid proliferation, would produce additive hematologic responses in any thalassemia subjects. Butyrate and EPO were administered in 10 patients. Novel fetal globin gene inducers that also stimulate erythroid proliferation were evaluated for pharmacokinetic profiles. Patients with beta+-thalassemia had relatively low levels of endogenous EPO (<145 mU/mL) and had additive responses to administered EPO and butyrate. Patients with at least one beta 0-globin mutation had higher baseline HbF levels (>60%) and EPO levels (>160 mU/mL), and three-fourths of these subjects responded to the fetal globin gene inducer alone. A few select fetal globin-inducing short-chain fatty acid derivatives that stimulated cell proliferation also had favorable pharmacokinetics. These studies identify a significant subset of thalassemia patients who appear to require exogenous EPO to respond optimally to any HbF inducer, as well as new therapeutic candidates that act on both cellular and molecular pathologies of beta-thalassemia. Both approaches now offer excellent potential for tolerable, definitive treatment of beta-thalassemia.

Since the introduction of endoscopic brow lifting in the mid-1990s, it has become widely accepted as a method for rejuvenation of the upper third of the face. Despite the multitude of brow fixation techniques, there are few long-term studies providing accurate analysis of outcome. The aims of this investigation were to evaluate the long-term objective results of endoscopic brow lifting and to establish whether the technique of fixation altered the longevity of aesthetic outcome. The outcome of endoscopic brow lifts carried out on 538 consecutive patients over a 6-year period was assessed. For each patient, midpupil-to-brow distance was measured preoperatively and at intervals postoperatively. Two different fixation methods were compared: fibrin glue (n = 189, group 1; 104 records available) and polydioxanone sutures tied through bone tunnels (n = 349, group 2; 220 records available). In 214 patients, an upper lid blepharoplasty was performed simultaneously (85 in group 1 and 129 in group 2). At 1 month postoperatively, each fixation technique had produced a significant change in mean pupil to brow height (5.93 mm in group 1 and 6.21 mm in group 2, with no significant difference between the two methods; p = 0.17). However, when measurements were compared more than 3 months postoperatively (mean, 9.4 months), there was a significant difference, with some relapse in the patients treated with fibrin glue (p < 0.01). However, in group 2 (tunnel fixation), measurements remained stable, with 6.21 mm at 1 month compared with 6.16 mm long term (no significant difference, p = 0.34). In contrast, in group 1 (fibrin glue), measurements showed significant reduction, with a 1-month result of 5.93 mm and a long-term outcome of 3.79 mm (p < 0.01). Upper lid blepharoplasty had no effect on the long-term outcome of either group (p > 0.3 in group 1, p > 0.4 in group 2). Complications were few in both groups. In group 1, there was one infection, two instances of significant alopecia (both temporary), and one reoperation for relapse. In group 2, four patients required minor surgical revision of a lateral port scar and three minor areas of temporal alopecia, which recovered in less than 3 months. One patient had a paresis of the frontal branch that had recovered after 4 months. The endoscopic brow lift is therefore a safe and effective technique for increasing mean pupil to brow height. Fixation with polydioxanone sutures tied through bone tunnels produces a significantly more stable result than fibrin glue, without greater risk. This lends weight to experimental evidence that periosteal fixation must be maintained for at least 6 weeks to be secure.

Severe acute respiratory syndrome (SARS) is a new disease which has spread rapidly and widely. We wished to know whether evaluation of in vitro cytokine production could contribute to improved understanding of disease pathogenesis and to better patient management. Numbers of unstimulated and mitogen-stimulated cytokine-secreting peripheral blood mononuclear cells were measured repeatedly during and after hospitalization in 13 patients with SARS using enzyme-linked immunospot technology. Numbers of interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and IL-12 secreting cells induced by T cell activators were below normal in many or most patients before and during treatment with corticosteroids and ribavirin but returned essentially to normal after completion of treatment. Staphylococcus aureus Cowan 1 (SAC)-stimulated IL-10 secreting cells were increased in early SARS but fell during treatment. SAC-induced IL-12 secreting cells were deficient before, during and long after treatment. Numbers of cells induced to produce IL-6 and tumour necrosis factor-alpha by T cell or monocyte activators were higher than normal in many early SARS patients and were still increased in some during and after treatment. We conclude that prolonged dysregulated cytokine production occurs in SARS and that future studies should be directed at improving anti-inflammatory and antiviral therapies in order to limit cytokine impairment.

Tumescent infiltration has been widely used in body-contouring surgery to facilitate dissection and reduce blood loss. Although its use in facial surgery has been suggested, there are presently no comparative studies of its efficacy. The aim of this study was to investigate the long-term outcome in a large series of consecutive face lifts performed with and without tumescence. During a 6-year period, 678 consecutive face lifts were performed: 449 without tumescence and 229 with tumescent infiltration using 200 ml on each side of the face. The spectrum of techniques included the extended superficial musculoaponeurotic system (SMAS) procedure, the lateral SMASectomy, the extended supraplatysmal plane lift, and the cutaneous face lift. Complications, such as hematoma, skin necrosis, alopecia, and scar quality, were compared between groups using Fisher's exact test. The use of tumescent infiltration facilitated dissection, particularly in the neck. Postoperative swelling and bruising were reduced in the tumescent group. In comparisons of major complications between groups, no difference was seen in hematoma rate (p > 0.5), although the incidence of other complications was significantly reduced by tumescent infiltration. Significant reduction was observed in the rate of skin necrosis (p = 0.03), alopecia (p = 0.006), hypertrophic scarring (p = 0.001), stretched scarring (p = 0.003), and scar revision (p < 0.001). This is the first comparative study of tumescent infiltration in facial rejuvenation surgery. Tumescence made dissection easier and significantly reduced the incidence of troublesome complications. The surgical technique and aesthetic implications for rejuvenation surgery are discussed.

Facial bipartition is amongst the most radical craniofacial surgery undertaken but is performed rarely. There is little published information on its anaesthetic management. We undertook a retrospective case-note review of 22 consecutive patients undergoing bipartition surgery by the same surgical team in one centre in the period 1993-2001. There were incomplete data for two cases and these were therefore excluded. Patients were aged 2 months to 19 years. Conditions treated were facial cleft (n = 5), frontonasal dysplasia (n = 7) and facial dysostosis (n = 8).Intra-operative complications included major haemorrhage (n = 4), bradycardia (n = 3) and unintentional tracheal extubation (n = 1). There were no peri-operative deaths. All patients required intra-operative blood transfusion and 15% of them had a postoperative haemoglobin concentration > 115% of their pre-operative value. In this series, four patients required postoperative lung ventilation for a median duration of 3 days. Infants < 14 months old were significantly more likely to receive a massive blood transfusion (p = 0.0002), to have an excessively high postoperative haematocrit (p = 0.008) and to require postoperative lung ventilation (p = 0.0002) compared with older patients. We conclude that patients in this age group have a significantly increased risk of postoperative complications.

Hematoma remains the most common complication of rhytidectomy and can lead to prolonged facial edema and skin necrosis. A number of ancillary procedures have been suggested to reduce hematoma, including dressings, drains, fibrin glue, tumescence, and adrenaline. The aim of this study was to investigate the statistical effect of these parameters on hematoma incidence in a large series of face lifts. Over an initial 6-year period, 678 consecutive face lifts were performed and included in the first part of the study. The effect of dressings, drains, fibrin glue, and tumescence on hematoma rate was investigated retrospectively. In the second part of the study, the specific effect of adrenaline was analyzed while all other parameters were kept constant. The 229 patients with adrenaline-containing infiltrations were compared with the 232 patients whose infiltration had no adrenaline. Retrospective analysis of both groups was performed using Fisher's exact test. In the first part of the study investigating 678 consecutive face lifts, no difference in hematoma rate (4.4 percent overall) was observed with the use of dressings (p > 0.5), drains (p > 0.4), fibrin glue (p > 0.6), or tumescence (p > 0.5). In the second part of the study, the specific effect of withdrawing adrenaline in a comparative group of 461 face lifts significantly reduced the incidence of hematoma requiring surgical evacuation (p < 0.0001). There was also a significant reduction in the incidence of minor hematoma requiring only aspiration (p = 0.02). There was no change in the incidence of any other face lift complications observed during this part of the study. This study found a significant reduction in the incidence of hematoma following face lifting. Although many of the suggested ancillary methods used to reduce hematoma did not produce any statistical reduction in the incidence of this complication, the exclusion of adrenaline had a profound effect. The technique and implications with respect to safety and outcome are described.

A biomechanical model of a one-month old baby was designed and tested by Duhaime and co-workers in 1987 in an attempt to assess the biomechanics of the shaken baby syndrome (SBS). The study implied that pure shaking alone cannot cause fatal head injuries, a factor which has been applied in criminal courts. In an attempt to test the validity of the model a preliminary study was undertaken in which a replica was constructed and tested. The broad description of the design and construction of the Duhaime model allowed for variations and therefore uncertainties in its reproduction. It was postulated therefore that differences in certain parameters may increase angular head accelerations. To further investigate this observation, an adjustable replica model was developed and tested. The results indicated that certain parameter changes in the model did in fact lead to an increase in angular head acceleration. When these parameter changes were combined and an injurious shake pattern was employed, using maximum physical effort, the angular head acceleration results exceeded the original Duhaime et al. (1987) results and spanned two scaled tolerance limits for concussion. Additionally, literature suggests that the tolerance limits used to assess the shaking simulation results in the original study may not be reliable. Results from our study were closer to the internal head injury, subdural haematoma, tolerance limits. A series of end point impacts were identified in the shake cycles, therefore, an impact-based head injury measure (Head Injury Criterion - HIC) was utilized to assess their severity. Seven out of ten tests conducted resulted in HIC values exceeding the tolerance limits (critical load value, Stürtz, 1980) suggested for children. At this present stage the authors conclude that it cannot be categorically stated, from a biomechanical perspective, that pure shaking cannot cause fatal head injuries in an infant. Parameters identified in this study require further investigation to assess the accuracy of simulation and increase the biofidelity of the models before further conclusions can be drawn. There must now be sufficient doubt in the reliability of the Duhaime et al. (1987) biomechanical study to warrant the exclusion of such testimony in cases of suspected shaken baby syndrome.

Six pigeons performed a simultaneous matching-to-sample (MTS) task involving patterns of dots on a liquid-crystal display. Two samples and two comparisons differed in terms of the density of pixels visible through pecking keys mounted in front of the display. Selections of Comparison 1 after Sample 1, and of Comparison 2 after Sample 2, produced intermittent access to food, and errors always produced a time-out. The disparity between the samples and between the comparisons varied across sets of conditions. The ratio of food deliveries for the two correct responses varied over a wide range within each set of conditions, and one condition arranged extinction for correct responses following Sample 1. The quantitative models proposed by Davison and Tustin (1978), Alsop (1991), and Davison (1991) failed to predict performance in some extreme reinforcer-ratio conditions because comparison choice approached indifference (and strong position biases emerged) when the sample clearly signaled a low (or zero) rate of reinforcement. An alternative conceptualization of the reinforcement contingencies operating in MTS tasks is advanced and was supported by further analyses of the data. This model relates the differential responding between the comparisons following each sample to the differential reinforcement for correct responses following that sample.

Objective: To assess the efficacy of 2% clindamycin vaginal cream (CVC) to treat bacterial vaginosis (BV) in pregnancy., Methods: A prospective, randomized, double-blind, placebo-controlled, tricenter study. Four hundred and four women with BV on Gram stain at their first antenatal clinic visit were randomized to receive a 3-day course of 2% CVC or placebo. The outcome was assessed using an intention to treat analysis at 3 weeks and 6 weeks post-treatment according to three different diagnostic methods based on five criteria (Gram stain and all four elements of clinical composite criteria: vaginal discharge, abnormal vaginal pH, clue cells, amine odor), three criteria (vaginal pH, clue cells, amine odor) or two criteria (clue cells and amine odor) to reflect stringency of diagnosis, historical precedence and government agency recommendations respectively., Results: Using five diagnostic criteria, 18% of CVC patients were cured and 70.8% either cured and/or improved compared to 1.6% and 12% of placebo patients respectively (p < 0.0001). Using three diagnostic criteria, 44.8% of CVC patients were cured and 77.3% were either cured and/or improved compared to 9.3% and 28.8% of placebo patients respectively (p < 0.000 1). Using two diagnostic criteria, 75.0% of CVC patients were cured compared to 18.0% of placebo patients (p < 0.0001 ). Recurrence rates in those CVC patients successfully treated were approximately 6% at 6 weeks post baseline and 10% at 28 to 34 weeks gestation., Conclusions: A 3-day course of CVC appears to be well tolerated by the mother and statistically significantly more efficacious than placebo in the treatment of BV during the second trimester of pregnancy.

This study set out to detect specific classes of potentially genotoxic aldehydes resulting from soybean-oil peroxidation in oil samples from 51 Trilucent implants in 26 patients and two factory-retained prostheses. The chemical analysis was performed independently of AEI inc. All of the implants showed evidence of shell deterioration suggestive of lipid absorption, and of lipid bleed throughout the implant shell. The mean implant weight loss was found to be almost 2% per year. Although none of the implants had actually ruptured in-situ, we identified specific problems with anterior and posterior patch delaminations, making the implant prone to rupture. Our data suggest that the soybean oil in all the explanted Trilucent implants and the two factory-retained prostheses had undergone peroxidation, yielding aldehyde by-products in millimolar concentrations. These concentrations are over 1000 times that thought to be potentially genotoxic. The clinical implications of these findings remain unclear. Capsular tissue was submitted to AEI Inc for histological and chemical analysis, but the data have not been forthcoming, which is disappointing as this may provide further evidence for the risks of long-term complications in these patients.

CT scanning is accepted as a regular component of the investigation of patients with simple craniosynostosis. In a series of 109 cases with simple craniosynostoses treated at Great Ormond Street Hospital for Children, a correct diagnosis on the basis of clinical findings was made in 100% of cases by an experienced clinician. CT scans with 3D reconstructions provided diagnostic confirmation in 100% of the patients when performed, but 91% of patients had already had sufficient confirmation of diagnosis by radiography. The clinical use of the scans for purposes other than diagnosis was examined. CT scanning in simple craniosynostosis in this series did not provide any additional clinical benefit as a screening method for the detection of intracranial abnormalities or for surgical planning. We propose that it may be appropriate to limit CT scanning, both axial images and three dimensional reconstructions, to selected cases where diagnostic uncertainty exists or where, it is used in surgical planning.

Objective: Critical cellular events at the palatal medial edge epithelium (MEE) occur in unperturbed mammalian palatogenesis, the molecular control of which involves a number of growth factors including transforming growth factor beta 3 (TGF beta 3). Apert syndrome is a monogenic human disorder in which cleft palate has been significantly correlated to the fibroblast growth factor receptor (FGFR) 2-Ser252Trp mutation. We report the relative expression of these genes in human palatogenesis., Methods: The expression of the IgIIIa/b and IgIIIa/c transcript isoforms of FGFR2 and the proteins FGFR1, FGFR2, and FGFR3 was studied in situ throughout the temporospatial sequence of human palatal shelf fusion and correlated with the expression of TGF beta 3. In addition, the immunolocalization of the ligand FGFs 2, 4, and 7 was undertaken together with the intracellular transcription factor STAT1, which is activated by FGFR signaling., Results: FGFRs are differentially expressed in the mesenchyme and epithelia of fusing palatal shelves, in domains overlapping those of their ligands FGF4 and FGF2 but not FGF7. Coexpression is seen with TGF beta 3, which is implicated in MEE dynamics and FGF and FGFR upregulation, and STAT1, an intracellular transcription factor that mediates apoptosis., Conclusions: The coregulation of molecules of the FGFR signaling pathway with TGF beta 3 throughout the stages of human palatal fusion suggests their controlling influence on apoptosis and epitheliomesenchymal transdifferentiation at the MEE. Experimental evidence links FGFR2-IgIIIa/b loss of function with palatal clefting, and these correlated data suggest a unique pathological mechanism for Apert cleft palate.

Globally, energy demand is projected to continue to increase well into the future. As a result, global NOx emissions are projected to continue on an upward trend for the foreseeable future as developing countries increase their standards of living. While the US has experienced improvements in reducing NOx emissions from stationary and mobile sources to reduce ozone, further progress is needed to reduce the health and ecosystem impacts associated with NOx emissions. In other parts of the world, (in developing countries in particular) NOx emissions have been increasing steadily with the growth in demand for electricity and transportation. Advancements in energy and transportation technologies may help avoid this increase in emissions if appropriate policies are implemented. This paper evaluates commercially available power generation and transportation technologies that produce fewer NOx emissions than conventional technologies, and advanced technologies that are on the 10-year commercialization horizon. Various policy approaches will be evaluated which can be implemented on the regional, national and international levels to promote these advanced technologies and ultimately reduce NOx emissions. The concept of the technology leap is offered as a possibility for the developing world to avoid the projected increases in NOx emissions.

Mutations in the fibroblast growth factor receptor (FGFR) genes 1, 2, and 3 are causal in a number of craniofacial dysostosis syndromes featuring craniosynostosis with basicranial and midfacial deformity. Great clinical variability is displayed in the pathologic phenotypes encountered. To investigate the influence of developmental genetics on clinical diversity in these syndromes, the expression of several genes implicated in their pathology was studied at sequential stages of normal human embryo-fetal cranial base and facial ossification (n = 6). At 8 weeks of gestation, FGFR1, FGFR2, and FGFR3 are equally expressed throughout the predifferentiated mesenchyme of the cranium, the endochondral skull base, and midfacial mesenchyme. Both clinically significant isoforms of FGFR2, IgIIIa/c and IgIIIa/b, are coexpressed in maxillary and basicranial ossification. By 10 to 13 weeks, FGFR1 and FGFR2 are broadly expressed in epithelia, osteogenic, and chondrogenic cell lineages. FGFR3, however, is maximally expressed in dental epithelia and proliferating chondrocytes of the skull base, but poorly expressed in the osteogenic tissues of the midface. FGF2 and FGF4, but not FGF7, and TGFbeta1 and TGFbeta3 are expressed throughout both osteogenic and chondrogenic tissues in early human craniofacial skeletogenesis. Maximal FGFR expression in the skull base proposes a pivotal role for syndromic growth dysplasia at this site. Paucity of FGFR3 expression in human midfacial development correlates with the relatively benign human mutant FGFR3 midfacial phenotypes. The regulation of FGFR expression in human craniofacial skeletogenesis against background excess ligand and selected cofactors may therefore play a profound role in the pathologic craniofacial development of children bearing FGFR mutations.

Steroids are often administered to paediatric craniomaxillofacial patients perioperatively to reduce postoperative facial swelling, although there is little evidence of their efficacy. Preoperative tumescent infiltration using 7 ml x kg(-1) of a solution consisting of 0.1 mg x ml(-1) triamcinolone acetate, 0.0125% bupivacaine, 0.025% lignocaine, 3 units x ml(-1) hyaluronidase and 1:1000000 adrenaline in Hartmann's solution was evaluated from a retrospective case controlled study of patients undergoing standard fronto-orbital remodelling for simple craniosynostosis (n = 20). Eye closure (i.e. inability to open the eyes) was used as a marker for severe facial swelling. Patients receiving the tumescent infiltration demonstrated significantly less eye closure (P < 0.005), implying that the tumescent infiltration had a significant effect on facial swelling. The avoidance of eye closure allowed more effective monitoring for neurological and ophthalmological complications, which is a significant clinical benefit. The infiltration solution has the advantage of a lower corticosteroid dose than previously reported dexamethasone-based perioperative regimens, thereby minimising any unwanted metabolic effects. The technique is advocated for the reduction of postoperative facial swelling in craniomaxillofacial surgical patients., (Copyright 2001 The British Association of Plastic Surgeons.)

Object: Heterogeneous mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of FGFR2. In contrast, a broad range of mutations throughout the extracellular domain of FGFR2 causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses., Methods: In this paper the expression of FGFR1, the IgIIIa/c and IgIIIa/b isoforms of FGFR2, and FGFR3 is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues. Both FGFR1 and FGFR3 are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of FGFR2, which widely include preosseous cranial mesenchyme. Expression of FGFR2, however, is restricted to domains of advanced osseous differentiation in both Apert syndrome- and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of FGF4 or FGF7. Whereas expression of the FGFR2-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome-affected cranial osteogenesis., Conclusions: Contraction of the FGFR2-IgIIIa/c (BEK) expression domain in cases of Apert syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.

Haematoma remains the most common complication of rhytidectomy and can lead to prolonged facial oedema or skin necrosis. The factors leading to haematoma formation remain unclear, and studies establishing causal relationships are lacking. The aim of this study was to determine which parameters were significantly associated with haematoma formation in a consecutive series of facelifts performed by two high-volume operators. The records of 1078 patients who underwent facelifting between 1994 and 1999 were reviewed and the parameters associated with haematoma formation were investigated using multivariate statistical analysis. In this series of 1078 patients, 45 haematomas occurred (4.2%). Analysis revealed significant associations between haematoma formation and anterior platysmaplasty (P= 0.009), systolic pressure (P= 0.02), gender (P= 0.03), aspirin or non-steroidal anti-inflammatory intake (P= 0.04) and smoking (P= 0.049). In addition the relative risk of each parameter was calculated. This allowed the haematoma risk for individual patients to be calculated and haematoma-prone patients were identified preoperatively. This is the first study to establish independent statistical risk factors for haematoma after rhytidectomy and to present a scoring system that calculates the haematoma risk preoperatively. The implications of these findings and possible measures for the prevention of haematoma are also presented., (Copyright 2001 The British Association of Plastic Surgeons.)

Cells programmed to traffic through lymph nodes dominate initial increases in total CD4(+) T cell numbers after highly active antiretroviral therapy (HAART) is begun for human immunodeficiency virus type 1 (HIV-1) infection. However, it is unknown whether this dominance continues throughout the first year of treatment. To examine this question, 10 subjects who had a positive response to HAART for 1 year were selected from a cohort of 20 who were receiving this treatment. Flow cytometry, which was used to characterize CD4(+) T cell subsets by immunophenotype, demonstrated that cells programmed to traffic through lymph nodes, irrespective of their memory or naive phenotype, continued to best account for increases in CD4(+) T cells, even 1 year after starting HAART. This suggests that, although this pool is preferentially depleted during HIV-1 infection, HAART allows for reaccumulation of these cells for at least 1 year. Furthermore, it suggests that phenotypic differences based on markers of lymphocyte trafficking may be more relevant for understanding HIV-1 pathogenesis than are naive and memory markers alone.

The Apert hand is characterized by metaphyseal fusions of the metacarpals and distal phalanges, symphalangism, and soft-tissue syndactyly. More subtle skeletal anomalies of the limb characterize Pfeiffer and Crouzon syndromes. Different mutations in the fibroblast growth factor receptor 2 (FGFR2) gene cause these syndromes, and offer the opportunity to relate genotype to phenotype. The expression of FGFR1 and of the Bek and KGFR isoforms of FGFR2 has, therefore, been studied in human hand development at 12 weeks by in situ hybridization. FGFRs are differentially expressed in the mesenchyme and skeletal elements during endochondral ossification of the developing human hand. KGFR expression characterizes the metaphyseal periosteum and interphalangeal joints. FGFR1 is preferentially expressed in the diaphyses, whereas FGFR2-Bek expression characterizes metaphyseal and diaphyseal elements, and the interdigital mesenchyme. Apert metaphyseal synostosis and symphalangism reflect KGFR expression, which has independently been quantitatively related ex vivo to the severity of clinical digital presentations in these syndromes. Studies in avian development implicate FGF signaling in preventing interdigital apoptosis and maintaining the interdigital mesenchyme. Herein is proposed that in human FGFR syndromes the balance of signaling by means of KGFR and Bek in digital development determines the clinical severity of soft-tissue and bony syndactyly.

Object: In this study the authors investigated whether patterns of intracranial venous drainage in children with complex craniosynostosis associated with raised intracranial pressure (ICP) were abnormal and, thus, could support the theory that venous hypertension is a major contributor to raised ICP that can lead to impaired visual function or even blindness in these patients., Methods: The authors analyzed the anatomy of intracranial venous drainage as demonstrated in the results of 24 angiography studies obtained in 23 patients, all of whom had either a craniosynostosis-related syndrome (18 patients) or a nonsyndromic multisutural synostosis (five patients). Twenty-one patients had experienced raised ICP (in 19 patients diagnosis was based on invasive ICP monitoring and in two patients on clinical grounds alone) 1 to 6 weeks before undergoing angiography. Of the two remaining patients (both with Apert syndrome) whose ICP monitoring was normal immediately before angiography, each had undergone two previous cranial vault expansion procedures. On results of 18 angiography studies a 51 to 99% stenosis or no flow at all could be observed in the sigmoid-jugular sinus complex either bilaterally (11 patients) or unilaterally (seven patients). In 11 of these patients a florid collateral circulation through the stylomastoid emissary venous plexus was also seen. Two angiography studies were performed in one patient with Crouzon syndrome. A comparison of the two studies demonstrated a progression of the abnormal venous anatomy in that case. The authors found no obvious correlation between each patient's baseline ICP and the degree of abnormality of their venous anatomy, as judged on the basis of a venous-phase angiography severity score., Conclusions: Based on their findings, the authors assert that in children with complex forms of craniosynostosis in whom other factors, such as hydrocephalus, are absent, abnormalities of venous drainage that particularly affect the sigmoid-jugular sinus complex produce a state of venous hypertension that, in turn, is responsible for the majority of cases of raised ICP. The incidence of these changes is unknown, but an analysis of the ages of the children in this study indicated that the period of particular vulnerability to the effects of venous hypertension lasts until the affected child is approximately 6 years old. After that age the collateral venous drainage through the stylomastoid plexus will likely become sufficient to allow ICP to normalize.

Background: Guolin Qigong is a combination of meditation, controlled breathing and physical movement designed to control the vital energy (qi) of the body and consequently to improve spiritual, physical and mental health. Practice of Qigong has been reported to alter immunological function, but there have been few studies of its effects on cytokines, the key regulators of immunity., Methods: Numbers of peripheral blood cytokine-secreting cells were determined by ELISPOT in 19 healthy volunteers aged 27 - 55, before they were taught the practice of Qigong and after 3, 7 and 14 weeks of daily practice. The effect of Qigong on blood cortisol was also examined., Results: Numbers of IL4 and IL12-secreting cells remained stable. IL6 increased at 7 weeks and TNFalpha increased in unstimulated cultures at 3 and 7 weeks but decreased at these times in LPS and SAC-stimulated cultures. Of particular interest, IFNgamma-secreting cells increased and IL10-secreting cells decreased in PHA-stimulated cultures, resulting in significant increases in the IFNgamma:IL10 ratio. Cortisol, a known inhibitor of type 1 cytokine production, was reduced by practicing Qigong., Conclusion: These preliminary studies in healthy subjects, although not necessarily representative of a randomized healthy population and not including a separate control group, have indicated that blood levels of the stress-related hormone cortisol may be lowered by short-term practice of Qigong and that there are concomitant changes in numbers of cytokine-secreting cells. Further studies of the effect of Qigong in patients with clinical diseases known to be associated with type 2 cytokine predominance are merited.

It has been postulated that certain organic acids produced by the anaerobes associated with bacterial vaginosis (BV) could prevent a purulent response in this infection. Varying concentrations of pure succinic, acetic and lactic acids were incubated in vitro with a monocytic cell line (MonoMac 6). High inhibition of chemotaxis was produced by succinic acid; lower inhibition and no inhibition was shown by acetic acid and lactic acid respectively. Succinic and acetic acids were detected in high concentrations in the vaginal fluid of women with BV and in culture supernates of Prevotella and Mobiluncus spp.; these acids impaired chemotaxis of MonoMac 6 cells in vitro. The vaginal fluids of normal women and the culture supernates of Lactobacillus spp. had no effect on chemotaxis.

We report our findings in a retrospective study of patient satisfaction with soybean oil-filled mammary implants. Sixty-two women who had breast augmentation with Trilucent breast implants were sent a questionnaire to assess their satisfaction with implant placement; 19 of the 62 attended for clinical examination. Overall satisfaction with triglyceride implant placement was high: very pleased 45% (18/40), pleased 32.5% (13/40), content 12.5% (5/40). The majority of women felt that it had enhanced their body image and lifestyle (82.5%).

In order to investigate the role of type 1 and type 2 cytokines in the remission of Graves' disease (GD) during pregnancy, spontaneous and mitogen-stimulated production of interleukin (IL)-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunospot assay of peripheral blood mononuclear cells from 10 pregnant women with GD, 8 healthy pregnant women, and 10 healthy nonpregnant women. Tests were performed in the first, second, and third trimesters of pregnancy and 10-17 weeks after delivery. IL-4 production was not affected greatly by normal or GD pregnancy, whereas IFN-gamma production was suppressed throughout pregnancy but returned to normal levels after delivery in both controls and patients. IL-6 and TNF-alpha tended to be higher in GD pregnancy than normal pregnancy, especially in the second and third trimesters. Controls had raised IL-10 in the first trimester with a return to normal levels by the third trimester, whereas patients had raised levels throughout pregnancy. IL-12 levels were suppressed to a greater extent in control than Graves' pregnancy, especially during the second and third trimesters. Ratios of IL10:IL12 in phytohemaglutinin (PHA)-stimulated cultures were much lower in GD than normal pregnancy and cross-regulation of IL-10 and IL-12 may be deficient in GD.

Spontaneous and mitogen-stimulated production of interleukin-4 (IL-4), IL-6, IL-10, IL-12, interferon-gamma (IFNgamma), and tumor necrosis factor-alpha were evaluated by enzyme-linked immunospot assay of peripheral blood mononuclear cells from patients with Graves' disease immediately before and at 4, 17, and 59 days after treatment with radioactive iodine. Patients had significantly reduced IL-4 and IFNgamma production before treatment compared with healthy controls. Both cytokines were increased to normal levels by day 17 after treatment, and IFNgamma remained at normal levels on day 59, whereas IL-4 returned to subnormal levels at this time. IL-12 production was initially normal and was not significantly altered by therapy. IL-6, IL-10, and tumor necrosis factor-alpha were also normal before radiotherapy, but increased significantly on day 17, returning to pretreatment levels by day 59. Thus, radioiodine treatment induced a transient increase in both proinflammatory and antiinflammatory cytokines and a more prolonged increase in IFNgamma production, the latter representing a definite shift toward a type 1 cytokine profile.

Production of cytokines in unstimulated and mitogen-stimulated cultures were evaluated by ELISPOT in 34 SLE patients with low to moderate disease activity and 23 healthy controls. Significantly reduced production of IFN gamma, IL4 and IL12 and significantly increased production of IL6, IL10 and TNF alpha were found in patients with SLE. Regression analysis revealed that production of all six cytokines tended to decrease with increasing disease activity, but negative correlation with SLEDAI was significant (p < 0.05) only for PHA-stimulated IL4, unstimulated and PHA-stimulated IL10 and SAC-stimulated IL6. Negative correlation of stimulated and unstimulated IL6 and TNF alpha production with anti-DNA antibody levels were also significant.

A total of 76 extracts from 35 plants available in the Turkish flora were assayed for their in vitro antibacterial activities against five pathogenic bacteria and a yeast. Sixteen crude extracts from eight plant species were found to possess an activity against at least one or more test microorganisms. Bioassay-guided fractionation of the most active crude extracts was also carried out with the most active extracts. Activity against Staphylococcus aureus, Bacillus cereus, Branhamella catarrhalis, Escherichia coli, Clostridium perfringens and Candida albicans (yeast) is discussed.

Interleukin 12 (IL-12) is a heterodimer comprising p35 and p40 subunits which are encoded and regulated separately. The authors previously demonstrated deficient IL-12 production in SLE which correlates negatively with disease activity. The present study was designed to determine whether deficiency of IL-12 and excess production of IL-10 and IL-6 in systemic lupus erythematosus (SLE) are due to aberrant regulation at the gene level. Using semiquantitative RT-PCR assay, it was shown that constitutive expression of IL-12 p35 gene is somewhat impaired in SLE compared with controls and that IL-12 p40 mRNA, which was present at low levels in controls, was undetectable in unstimulated SLE peripheral blood mononuclear cells (PBMC). Gene expression of IL-12 p35 and p40 was significantly increased in response to SAC, with significantly lower SAC-induced expression of p40 in SLE patients than controls. SAC-stimulated IL-12 p35 and p40 mRNAs were significantly augmented by interferon gamma (IFN-gamma). Exogenous IL-12 or IFN-gamma significantly inhibited IL-10 gene expression, without affecting IL-6 mRNA or other proinflammatory cytokine mRNA levels. These observations were further confirmed by studies of protein production at the single cell level using ELISPOT assay. Downregulation of IL-12 p40 expression appears to be the cause of IL12 p70 deficiency in SLE. If this defect could be repaired, normalization of IL-12 and IFN-gamma production should reduce excessive IL-10 and prevent pathology., (Copyright 1999 Academic Press.)

In HIV-1 infection, the abrupt rise in CD4 T cells after effective antiretroviral therapy has been viewed as a measure of HIV-1-related CD4 T cell turnover in the steady state. The early (2-4 wk) response is reportedly dominated by CD4 T cells with a memory (CD45RO) phenotype. It is controversial whether the measurement of steady-state kinetics identifies cells that otherwise would have been recruited into a short-lived, virus-producing pool or reflects lymphoid redistribution/sequestration. We performed detailed phenotypic and kinetic analysis of CD4 T cell subsets in 14 patients. Turnover occurs in memory (CD45RO) as well as naive (CD45RA) cells, if the latter are present at baseline. Most of the turnover occurs in those memory (CD45RO) and naive (CD45RA) cells that are programmed for recirculation through lymphoid organs (CD62L+ and CD44low), whereas very little turnover occurs in memory cells (CD45RO) destined for recirculation from blood to tissue (CD62L- and CD44high). Turnover occurs in both activated (CD25+ and HLA-DR+) and nonactivated populations, although it is restricted to CD38-positive cells, indicating that turnover does not measure cells that are already infected. More likely, turnover occurs in cells that replace infected cells or are on their way to becoming infected. Taken together, markers of lymphocyte trafficking better describe cell turnover related to virus replication than do naive and memory markers per se, and lymph organs, not tissue-destined cells or peripheral blood cells, appear to be the important site of virus replication and CD4 T cell turnover, destruction, and redistribution.

Apert's syndrome (acrocephalosyndactyly type 1) is characterised by anomalies of the cranium, hands, and feet. The cranial and hand anomalies have been investigated, and the management of these is well established. In contrast, the anomalies affecting the feet and their management has previously received little attention. Forty-three children with Apert's syndrome underwent investigation of the anomalies affecting their feet. This consisted of history, clinical examination, and where possible, radiographic examination to establish the anomalies present, how these altered during development, and their clinical significance. The conclusion of the study is that there are widespread anomalies of the feet, with defects including both predictable dysmorphic changes and progressive fusions of the skeletal components during skeletal maturity. These fusions and their effect on growth combine to produce increasing deformity during childhood. The clinical significance of the anomalies is that walking is often delayed, and the increasing deformity results in difficulty obtaining footwear. This is the most common reason for surgery to the feet being undertaken during childhood to improve the shape of the feet to facilitate the provision of footwear. The unexpectedly high incidence of surgery in this study suggests that the management of foot deformities may require surgery more frequently than current literature would suggest.

Twenty-four callus, and eleven cell suspension, cultures were established from Turkish medicinal plants, and crude extracts prepared from them tested against microorganisms to assess their antimicrobial activities in vitro. Of the extracts tested, those belonging to the cell cultures of five of the plant species showed antibacterial activity against mainly three bacteria and a yeast. No activity was observed against herpes simplex viruses, HSV-I and II, but an extract from Hypericum capitatum showed a slight anti-retroviral activity against HIV-I.

New therapeutic regimens have dramatically altered morbidity and mortality attributed to HIV-1 infection. Changes in lymphocyte subsets after treatment may mirror salutary clinical changes. Over 4 months we analyzed lymphocyte subsets in 20 patients starting new HIV-1 therapy. Absolute numbers of lymphocytes, CD4+ T cells, CD8+ T cells, and B cells increased significantly by 4 months, but CD8+ T cell and B cell increases were restricted to late-stage patients. Subset analysis revealed that the magnitude of recovering naive-phenotype CD4+ T cells (slope) correlated with the number of these cells present at baseline, equaling or exceeding the memory-phenotype slope within days if these naive cells were abundant at baseline. Five of 10 patients in whom naive-phenotype CD4+ T cells were absent at baseline partially repopulated these cells by 4 months. These findings have important implications for the origin and mechanisms of renewal of naive-phenotype CD4+ T cells following effective treatment for HIV-1 infection.

We report on 3 male and 2 female infants with acromelic frontonasal dysostosis. All 5 had a frontonasal malformation of the face and nasal clefting associated with striking symmetrical preaxial polysyndactyly of the feet and variable tibial hypoplasia. In contrast, the upper limbs were normal. This rare variant of frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We suggest that the molecular basis of this condition may be a perturbation of the Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the development of the midline central nervous system/craniofacial region and the limbs.