γδT cells regulate chronic airway inflammation and development of airway remodelling.

BACKGROUND: γδT cells play a crucial immunoregulatory role in the lung, maintaining normal airway tone and preventing hyperresponsiveness to innocuous allergen. During acute inflammatory episodes, γδT cells promote resolution of acute inflammation. However, their contribution to inflammation-associated airway remodelling remains unexplored. Here we investigate the effects of γδT cell blockade on established allergic airway inflammation and development of remodelling. METHODS: Sensitised mice were exposed to prolonged ovalbumin challenge or continuous house-dust mite exposure to induce chronic inflammation and remodelling. Functional blocking anti-TCRδ antibody was administered therapeutically, and parameters of airway inflammation and remodelling were examined. RESULTS: Therapeutic blockade of γδT cells prevented the typical resolution of acute airway inflammation characterised by elevated eosinophil and Th2 cell numbers. Moreover, the lung displayed exacerbated airway remodelling, typified by excess peribronchiolar collagen deposition. CONCLUSIONS: These results demonstrate a unique role for γδT cells in constraining allergen-induced airway remodelling. Manipulating the γδT cell compartment may therefore contribute to strategies to prevent and treat remodelling.

Tolerizing allergic responses in the lung.

The absolute requirement of the pulmonary immune system is to limit the inflammatory consequences of inhaled infectious agents while maintaining tolerance to harmless aeroallergens. This tolerance is maintained by a complex network of cells and molecules interacting with lung stromal cells. However, in some individuals there is a breakdown in tolerance to particles such as pollens, animal dander, or dust, resulting in the development of allergic pathology. Emerging evidence suggests that this breakdown in tolerance is influenced by the genetic background of individuals as well as environmental considerations such as early exposure to respiratory pathogens. Further understanding of the mechanisms used by the pulmonary immune system to maintain tolerance might result in exploitation of novel avenues for therapy to treat the growing number of chronic asthmatic patients.

Inhaled house dust mite induces pulmonary T helper 2 cytokine production.

BACKGROUND: Inhaled house dust mite (HDM) results in T-helper (TH) 2 type pathology in unsensitized mice, in conjunction with airway hyperreactivity and airway remodelling. However, the pulmonary cytokine and chemokine profile has not been reported. METHODS: We have performed a time course analysis of the characteristic molecular mediators and cellular influx in the bronchoalveolar lavage (BAL) and lung in order to define the pulmonary inflammatory response to inhaled HDM extract. Mice were exposed five times a week to soluble HDM extract for 3 weeks. Lung function was measured in groups of mice at intervals following the final HDM challenge. Recruitment of inflammatory cells and inflammatory mediator production was then assessed in BAL and lungs of individual mice. RESULTS: We found that Th2 cytokines were significantly increased in BAL and lung after HDM challenge from as early as 2 h post-final challenge. The levels of cytokines and chemokines correlated with the influx of eosinophils and Th2 cells to the different compartments of the lung. However, the production of key cytokines such as IL-4, IL-5 and IL-13 preceded the increase in airways resistance. CONCLUSION: Inhaled HDM challenge induces a classical Th2 inflammatory mediator profile in the BAL and lung. These data are important for studies determining the efficacy of novel treatment strategies for allergic airways disease.

Oculoplastic reconstruction following Mohs surgery.

PURPOSE: Mohs micrographic surgery has been advocated as the optimal management of nonmelanoma skin cancer in the periocular region. It is a technique that is ideally suited to the removal of skin tumours with a contiguous growth pattern such as basal cell carcinoma and squamous cell carcinoma, allowing examination of 100% of the surgical margin. As a result of this total margin control, the technique offers an unsurpassed curve rate combined with maximal preservation of normal tissue. Following excision of a periocular tumour by a Mohs surgeon, the resulting defect usually requires reconstruction. Our objective was to determine whether the size of defect produced by Mohs surgery and the type of reconstruction required differed from the results we would have expected from standard surgery with a 3 mm excision margin. METHODS: A Mohs surgery service with a combined dermatological and oculoplastic approach was set up in Manchester in 1994. We reviewed 60 of our patients who underwent Mohs surgery and compared the size of defect produced as well as the type of reconstruction required with the results we would have predicted for standard excisional surgery with a 3 mm margin. RESULTS: Although a minority of patients required larger reconstructions than would have been anticipated (20%), many had smaller reconstructions than we had predicted (37%). This latter group often had important structures preserved, and therefore had the benefit of less extensive reconstructive surgery. CONCLUSIONS: Excision of a periocular tumour by Mohs surgery may occasionally identify extensive subclinical tumour extension and so produce an unexpectedly large defect for reconstruction. Many patients, however, require less extensive reconstructive surgery than would have been predicted. This produces benefits in terms not only of improved cosmesis and eyelid function, but also reduced operating theatre costs.

Autogenous labial mucous membrane and banked scleral patch grafting for exposed retinal explants.

Following retinal detachment surgery, exposure of the scleral explant is uncommon and usually requires its removal. In patients with a history of multiple retinal detachment procedures or continuing vitreoretinal traction removal of an explant can lead to retinal redetachment. In such patients it is preferable to cover and retain an exposed explant rather than remove it. Various techniques have been described to cover exposed explants. If the exposed area is small a conjunctivoplasty or conjunctival graft is usually adequate. The use of banked scleral patch grafts has been described in the management of exposed orbital implants. We describe the use of this technique in combination with a labial mucous membrane graft in four patients with an exposed silicone retinal explant. With a minimum follow-up period of 11 months the explant remains covered in all patients.

Recovery from mivacurium-induced neuromuscular blockade after neurosurgical procedures of long duration.

STUDY OBJECTIVE: To determine if recovery following prolonged (5 hours in length or greater) infusions of mivacurium is different from recovery after single bolus administration. DESIGN: open-labelled, controlled study. SETTING: Inpatient neurosurgical service at a university hospital. PATIENTS: 36 patients between the ages of 18 to 65 without significant history of renal, hepatic, cardiac, or metabolic disease undergoing neurosurgical procedures. 21 patients had craniotomies or skull base procedures of an estimated length of 5 hours or greater; 15 patients (control) underwent short neurosurgical operations (two hours or less). INTERVENTIONS: Intravenous (IV) mivacurium 0.15 mg/kg was given with stable general anesthesia with 70% nitrous oxide in oxygen, 0.2% to 0.3% end-tidal isoflurane, and continuous infusion of fentanyl. The control group was allowed to recover spontaneously after single bolus administration while neuromuscular blockade was maintained in the study group with a continuous infusion of mivacurium until 30 minutes before completion of surgery, at which time the infusion was discontinued and neuromuscular function was allowed to recover spontaneously. MEASUREMENTS AND MAIN RESULTS: The evoked compound electromyogram of the adductor pollicis brevis muscle was measured during stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. Measurements included time to 50% and 90% depression of twitch (T1 of the TOF response), time to T1 equal to 25% (T1(25)), 50% (T1(50)), and 75% (T1(75)) of baseline, and TOF ratio (TR) at 10%, 25%, 50%, and 75% recovery. Recovery index (RI), which is T1(75) minus T1(25), was also determined. All mivacurium infusion rates decreased during surgery. Recovery rates were significantly longer in the long infusion (LI) group than the control group. RI was also increased in the LI group compared with the single bolus control (11.3 +/- 1.2 minutes vs. 7.1 +/- 0.8 minutes p < 0.05). CONCLUSIONS: Recovery following mivacurium by prolonged continuous infusion was slower than that observed after single bolus administration in this patient population. Clinically, this increased time to recovery may be insignificant.

Propofol-based anesthesia as compared with standard anesthetic techniques for middle ear surgery.

STUDY OBJECTIVE: To determine if a total intravenous (i.v.) technique with propofol and fentanyl is superior to isoflurane anesthesia in patients undergoing middle ear surgery. DESIGN: Prospective, randomized study. SETTING: Inpatient otolaryngology service at a university medical center. PATIENTS: 102 ASA status I and II nonobese patients with no significant history of diabetes, chronic cholecystitis, neuropathy, or neuromuscular disorders that could produce delayed gastric emptying. INTERVENTIONS: Patients were admitted to the study and randomly divided into three equal groups. I.V. administration of thiopental sodium 5 mg/kg for induction of anesthesia followed by 60% air/oxygen (O2) with isoflurane 1% to 2% end-tidal for maintenance anesthesia (group 1). The same anesthetic was given as above, with the addition of droperidol 25 mcg/kg given after induction (group 2). I.V. administration of propofol 2 mg/kg for induction of anesthesia followed by propofol 50 to 250 mcg/kg/min for maintenance anesthesia. All groups received fentanyl 3 mcg/kg i.v. after induction. MEASUREMENTS AND MAIN RESULTS: Surgical duration, induction, maintenance, and total anesthesia times were recorded in addition to eye opening and extubation. Intergroup comparisons of postoperative nausea, vomiting, and pain were done, as were recovery scores using the Steward system. Patients receiving propofol had significantly less nausea than those receiving isoflurane only (4 of 34 versus 12 of 34, p < 0.05) as well as vomiting (2 of 34 versus 8 of 34, p < 0.05). Immediate recovery scores were significantly better for propofol compared with the isoflurane/droperidol group. Recovery at 30 minutes was also faster with propofol compared with isoflurane or isoflurane/droperidol (5.7 +/- 0.1 min versus 5.1 +/- 0.2 min and 5.2 +/- 0.2 min, p < 0.05). CONCLUSIONS: Propofol-fentanyl seems to be a better anesthetic than isoflurane-fentanyl in reducing the incidence of nausea and vomiting after middle ear surgery. Through the addition of droperidol to the isoflurane anesthetic seemed as effective, emergence from anesthesia was slower. For middle ear surgeries producing emesis, propofol-based anesthetics produced a rapid emergence with less nausea and vomiting.

Propofol-based anesthesia as compared with standard anesthetic techniques for middle ear surgery.

OBJECTIVE: To determine whether a totally intravenous technique with propofol and fentanyl is superior to isoflurane anesthesia in patients undergoing middle ear surgery. DESIGN: Prospective randomized study. SETTING: Inpatient otolaryngology service at a university medical center. PATIENTS: Physical status 1 and 2 nonobese patients with no significant history of diabetes, chronic cholecystitis, neuropathy, or neuromuscular disorders that could produce delayed gastric emptying. One hundred two patients were admitted to the study and randomly divided into three equal groups. INTERVENTIONS: Intravenous thiopental, 5 mg/kg, was administered for induction of anesthesia followed by 60% air/O2 with isoflurane, 1% to 2% end tidal, for maintenance anesthesia (group 1). The same anesthetic with the addition of droperidol, 25 micrograms/kg, was given after induction (group 2). Propofol, 2 mg/kg, was administered intravenously for induction of anesthesia and followed by propofol, 50 to 250 micrograms/kg/min, for maintenance anesthesia. All groups received fentanyl, 3 micrograms/kg intravenously, after induction. MEASUREMENTS AND MAIN RESULTS: Surgical duration, induction, maintenance, and total anesthesia times were recorded together with eye opening and extubation. Intergroup comparisons of postoperative nausea, vomiting, and pain, and recovery scores, we made by use of the Steward system. Patients receiving propofol, compared with the isoflurane-only group, had significantly less nausea (4/34 vs 12/34 patients, respectively; p < 0.05) and as vomiting (2/34 vs 8/34 patients, respectively; p < 0.05). Immediate recovery scores were significantly better for propofol compared with the isoflurane-droperidol group. Recovery scores at 30 minutes were also faster with propofol compared with isoflurane or isoflurane-droperidol (5.7 +/- 0.1 vs 5.1 +/- 0.2 and 5.2 +/- 0.2; p < 0.05).

Can a simple test of visual-motor skill predict the performance of microsurgeons?

A new test of manual dexterity and a test of spatial ability were administered to 37 participants of a microsurgery training course. Performance on microsurgical tasks undertaken by the trainees to assess their surgical skill correlated significantly (rho = -0.54, P < or = 0.01) with manual dexterity and (rho = 0.36, P < or = 0.05) spatial ability. The first of these findings is contrary to those of studies concerned with general surgery whereas the second confirms the results of reported research. Explanation for the results is given in terms of the specific nature of microsurgical skill compared with general surgery.

Is ophthalmic therapy often overlooked in hospital wards?

In a prospective study regarding the accuracy of ophthalmic drugs prescriptions of 55 inpatients in two general teaching hospitals, it was found that: only 27.3% of these patients had their ocular therapy correctly prescribed; 38.2% had their eye medications incorrectly prescribed; and 34.5% had no ophthalmic drugs prescribed. The authors conclude that more care during case history taking could prevent such errors.

The rate of visual field loss in untreated primary open angle glaucoma.

The mean rate of visual field loss in untreated primary open angle glaucoma was estimated by comparing the mean age at presentation of patients with early relative visual field loss with the mean age of those who presented with absolute field loss within five degrees of fixation. Analysis of the records of 177 patients indicated that the rate of field loss was related to the level of untreated intraocular pressure. For pressures of 21 to 25 mm Hg, untreated disease is likely to progress from early field changes to end stage in an average of 14.4 years. The same interval for pressures of 25 to 30 mm Hg was 6.5 years and for pressures over 30 mm Hg, 2.9 years. For untreated disease at pressures over 25 mm Hg the interval is estimated at 3.6 years and this is much shorter than the estimated period of 10 years under imperfect treatment and 38 years under optimum treatment identified in a prospective clinical trial of early trabeculectomy in patients with similar intraocular pressures at diagnosis.

The Purkinje vascular entoptic test: a halogen light gives better results.

The Purkinje vascular entoptic test is a test of macular function which employs a light directed through the sclera illuminating the fundus. This light casts shadows of retinal blood vessels on to posterior pole photoreceptors. When the light source is moved, a patient with a good macular function should be able to see a negative image of his or her retinal blood vessels. We evaluated the Purkinje test in eyes with clear ocular media. A bright 3.5 watt halogen rechargeable transilluminator was used instead of a pen torch as previously described. Sixty-eight patients (129 eyes) attending a diabetic eye clinic, were tested. The test correctly identified 91% of eyes with good macular function and 77% of eyes with poor macular function (visual acuity 6/24 or poorer). If a vascular pattern was seen, it was probable (0.89) that good macular function was present. If no vascular pattern was seen, it was probable (0.80) that the eye had poor macular function (chi 2 = 60.14, P = < 0.001). Our results were superior to those previously reported. We attribute the increased accuracy of our test to the brighter light source used.