Cell transplantation as a treatment for retinal disease.

It has been shown that photoreceptor degeneration can be limited in experimental animals by transplantation of fresh RPE to the subretinal space. There is also evidence that retinal cell transplants can be used to reconstruct retinal circuitry in dystrophic animals. Here we describe and review recent developments that highlight the necessary steps that should be taken prior to embarking on clinical trials in humans.

Schwann cell grafting into the retina of the dystrophic RCS rat limits functional deterioration. Royal College of Surgeons.

PURPOSE: To examine whether congenic Schwann cells grafted into the subretinal space of dystrophic Royal College of Surgeons (RCS) rats can prevent photoreceptor loss and maintain visual function. METHODS: Purified neonatal Schwann cells derived from congenic rats were grafted into the subretinal space of 3- to 4-week-old dystrophic RCS rats. Graft placement was confirmed using Schwann cells labeled in vitro with the fluorescent dye Hoechst 33342 or in grafted eyes processed for electron microscopy (48-hour to 1-month survival). At longer intervals, up to 9 months after surgery, animals were examined for photoreceptor survival; preservation of a visual reflex, head-tracking to moving stripes; and preservation of visual receptive fields associated with the region of graft placement. RESULTS: One week after the graft was performed, Schwann cells had integrated into the subretinal space with little evidence of a reactive response. When screened for head-tracking to moving stripes, Schwann cell-grafted animals performed better than sham-treated or control dystrophic animals. Threshold sensitivity measurements and visual field assessment made by recording from the superior colliculus also showed a significant level of preserved function compared with control animals. Functional rescue was correlated with photoreceptor survival and could be observed for at least 9 months after grafting. CONCLUSIONS: Schwann cells injected into the subretinal space limit functional deterioration and prolong photoreceptor survival. It is suggested that they act by local release of growth factors that either support photoreceptors directly and/or stimulate phagocytosis in RPE cells.

The role of 18F-fluorodeoxyglucose positron emission tomography in cancer screening - a preliminary report.

Positron emission tomography (PET) with 18F-fluoro-2 deoxy-D-glucose (FDG) is a non-invasive method for surveying the whole body and detecting various malignancy. A total of 299 subjects underwent whole-body FDG PET studies in our PET center over an 18-month period. FDG PET accurately detected malignant tumors in 7 (2.34%) subjects. False positive FDG PET studies in 3 (1%) subjects and false negative FDG PET studies in 2 (0.6%) subjects were found. Because of the high cost of FDG PET examination, it might not be suitable as a cancer screening test for the general population. However, it is a valuable supplemented tool for routine check-up, particularly for those at high-risk of developing cancer.

Lacrimal drainage surgery in Wegener's granulomatosis.

AIM: To examine the results of open lacrimal surgery in patients with Wegener's granulomatosis. METHODS: A retrospective review of patients with Wegener's granulomatosis who underwent lacrimal surgery over a 17 year period. RESULTS: 11 patients were identified and a total of 14 primary dacryocystorhinostomies (DCR) and one revisional DCR were performed; symptomatic relief was achieved in 13/14 operations and one patient required revisional surgery for persistent symptoms. There were no intraoperative and few postoperative complications. CONCLUSIONS: In contrast with some previous reports, open DCR appears to be a safe procedure and it is recommended as a treatment for lacrimal obstruction in patients with Wegener's granulomatosis, but an increase of perioperative immunosuppression is recommended in certain cases.

Differentiating benign and malignant pulmonary lesions with FDG-PET.

The purpose of this retrospective study was to evaluate the efficacy of positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG) to differentiate benign from malignant pulmonary lesions. Fifty-five patients, suspected of having primary pulmonary neoplasm based on chest radiographic findings, underwent FDG-PET scanning. Pathological diagnoses were obtained in 41 patients with a total of 43 pulmonary lesions. The other 14 patients (14 lesions) were followed-up clinically for at least four months. The standard uptake value (SUV) was determined in each patient. The SUV of the 15 benign and 40 malignant pulmonary lesions were 1.60+/-0.42 and 6.14+/-2.67, respectively. If SUV was > 2.50, the pulmonary lesion was considered as a malignant pulmonary lesion. FDG-PET could correctly detect 34 true-positive and 15 true-negative pulmonary lesions. However, 6 false-positive and one-false negative pulmonary lesions were misdiagnosed by FDG-PET. The sensitivity, specificity and accuracy of FDG-PET to differentiate between benign and malignant pulmonary lesions were 94%, 71% and 86%, respectively. FDG-PET can accurately detect malignant pulmonary lesions with a high sensitivity. However, false-positive FDG-PET findings caused by some inflammatory processes may decrease its specificity.

Intra-operative blood loss and operating time in orthognathic surgery using induced hypotensive general anaesthesia: prospective study.

We investigated the average operating time and extent of intra-operative blood loss in orthognathic surgeries performed using induced hypotensive general anaesthesia, with the intention of devising a practical guideline for blood unit preparation for these procedures. We prospectively studied 32 Chinese patients undergoing surgery to correct dentofacial deformities at a public hospital in Hong Kong from 1 December 1997 to 1 December 1998. Most patients (72. 4%) needed double-jaw surgery. The mean estimated blood loss was approximately 617.6 mL. The blood loss during simple Le Fort I osteotomies was about half that of multiple segmentalised osteotomies. For mandibular ramus osteotomies, the mean blood loss and operating time for were approximately 280 mL and 2 hours, respectively; for anterior mandibular osteotomies, the corresponding values were 171.3 mL and 1 hour 13 minutes. The average drop in the haematocrit value was 15.4%, and the crossmatch to transfusion ratio was 29. A bivariate correlation test between the blood loss and operating time gave a strong correlation (P<0.01), as did blood loss with a drop in haematocrit value (P<0.01). Orthognathic surgeries are thus safe and predictable in terms of intra-operative blood loss and operating time, and a 'type, screen, and save' policy for blood unit preparation is more appropriate than a 'crossmatch' policy.

A pilot randomised controlled trial comparing the post-operative pain experience following vitrectomy with a 20-gauge system and the 25-gauge transconjunctival system.

AIMS: To compare post-operative pain following 25-gauge (25G) and 20-gauge (20G) vitrectomy in the first week following surgery. METHODS: The study was a pilot randomised controlled trial with patients masked to the treatment allocation. Post-operative pain was assessed using both a visual scale and verbal pain scores for 1 week following surgery. Additional data collected included intraocular pressure (IOP), time taken to perform the surgical procedure, per-operative and post-operative complications, and dropout rates. RESULTS: Forty patients were recruited for the study: 21 randomised to 20G vitrectomy and 19 to 25G. In the first 12 h following surgery, presence of significant post-operative pain (defined as >1 cm on a visual analogue scale) was similar in both 20G (50%) and 25G (53%) patients. In the first week following surgery, 38 of the 527 scores (7.2%) were >1 (median 2.1, IQR 1.3-3) cm; however, there was evidence that "significant pain" was experienced more commonly in the 20G group. There was no statistical difference in the time taken to complete the surgical procedure, although in the 25G group the time from first incision to the start of vitrectomy was significantly shorter (p = 0.043) and in the 20G group the time taken to complete the vitrectomy was less (p = 0.047). Post-operative hypotony (IOP <6 mmHg) was observed in 25% of patients in the 25G group. No patients required additional surgery for hypotony. CONCLUSION: There was evidence that 25G resulted in less patient discomfort. However, pain was not a prominent feature in either group. We failed to find a significant advantage in 25G for patients or surgeons.

A new technique of combined retinal and choroidal biopsy.

AIMS: To evaluate a new technique in large retinal and choroidal biopsies in patients with uveitis of unknown aetiology and chorioretinal lesions or infiltrate. METHODS: Retrospective, non-comparative, consecutive interventional case series. Patients were identified from the computerised patient database and from histopathology records. RESULTS: A total of nine patients were included in the study. The commonest indication of biopsy was panuveitis of unknown aetiology. Positive histological diagnoses from the chorioretinal biopsies were made in five cases (55.6%). Complications included vitreous haemorrhages and one case of retinal detachment. CONCLUSION: The technique of large chorioretinal biopsy described appears to be safe. It produced good amounts of chorioretinal tissue for histopathological analysis. Positive histology results were seen in the majority of the sample and especially in those where vitreous biopsy alone proved to be inadequate.

Photoreceptor layer reconstruction in a rodent model of retinal degeneration.

We have examined the potential of retinal cell transplantation to dystrophic retinal degeneration mice as a way of replacing photoreceptors lost because of an intrinsic genetic defect. Early postnatal retinae which had been gently dissociated survived for at least 6 weeks after transplantation to the subretinal space. Over a significant area of distribution, transplanted cells formed outer segments which lay in close apposition to the host retinal pigment epithelial cell layer. The grafts integrated with the remaining host retina, sufficient at least to mediate a simple light-dark preference. A new synaptic layer was seen at the graft-host interface, which contained substantial numbers of photoreceptor synapses. This and the fact that the behavior could be elicited at low luminance levels argue for functional circuit reconstruction between grafted cells and host retina.

Review of the inverse Knapp procedure: indications, effectiveness and results.

PURPOSE: To evaluate the indications and results of inverse Knapp procedures performed at one institution over a 10 year period between 1987 and 1996. METHODS: The records of patients who had undergone inverse Knapp procedures were retrospectively reviewed. Demographic data were collected, pre- and post-operative orthoptic assessments were evaluated, and pre- and post-operative binocular single vision (BSV) charts and Hess charts were scored. RESULTS: Twenty-one patients were identified and records were available in 17. The main indication for the operation was orbital trauma. The mean vertical deviation in primary position and downgaze improved from 16.06 prism dioptres (PD) to 7.35 PD and 26.45 PD to 6.66 PD respectively. The pre-operative average score for BSV was 42%, increasing to 62% post-operatively. The Hess chart error scores improved on average from 848.8 pre-operatively to 296.4 post-operatively. Further operations were required for 8 patients. CONCLUSIONS: Inverse Knapp procedure is an uncommon strabismus operation but an extremely useful one in selected cases. We recommend it for the treatment of marked inferior rectus weakness, congenital or acquired, for post-traumatic inferior rectus underaction with or without orbital blow-out fracture and for residual large hypertropia in patients with poor binocular functions. The extent of inferior rectus underaction should be assessed very carefully to avoid overcorrecting.

Patient-controlled epidural analgesia: a prospective audit of epidural pethidine 4 mg/ml and ropivacaine 0.2% with fentanyl 2 micrograms/ml.

A prospective audit of one hundred and forty-seven (147) Acute Pain Service (APS) patients, who received postoperative patient-controlled epidural analgesia (PCEA) using pethidine 4 mg/ml or ropivacaine 0.2% with fentanyl 2 micrograms/ml in general surgical or orthopaedic wards over a twelve-month period, is presented. Data were collected from APS observation charts over a 48-hour period postoperatively. We found no significant difference in postoperative analgesia or side-effects between pethidine and ropivacaine with fentanyl in orthopaedic or general surgical patients.

Evolutionary driver scheduling with relief chains.

Public transport driver scheduling problems are well known to be NP-hard. Although some mathematically based methods are being used in the transport industry, there is room for improvement. A hybrid approach incorporating a genetic algorithm (GA) is presented. The role of the GA is to derive a small selection of good shifts to seed a greedy schedule construction heuristic. A group of shifts called a relief chain is identified and recorded. The relief chain is then inherited by the offspring and used by the GA for schedule construction. The new approach has been tested using real-life data sets, some of which represent very large problem instances. The results are generally better than those compiled by experienced schedulers and are comparable to solutions found by integer linear programming (ILP). In some cases, solutions were obtained when the ILP failed within practical computational limits.

Addition of meperidine to bupivacaine for spinal anaesthesia for Caesarean section.

BACKGROUND: In a prospective, randomized, double-blind, placebo-controlled trial, we investigated the effect of adding meperidine 10 mg to intrathecal bupivacaine on the duration of early postoperative analgesia in 40 patients having elective Caesarean section under spinal anaesthesia. METHODS: Patients received intrathecal injection of 0.5% hyperbaric bupivacaine 2.0 ml plus either normal saline 0.2 ml (saline group) or 5% meperidine 0.2 ml (meperidine group). After operation, all patients were given i.v. patient-controlled analgesia using morphine. RESULTS: The duration of effective analgesia, defined as the time from intrathecal injection to first patient-controlled analgesia demand, was greater in the meperidine group (mean 234 min, 95% confidence interval 200-269 min) compared with the saline group (mean 125 min, 95% confidence interval 111-138 min; P<0.001). The 24 h morphine requirement was similar in the two groups. The meperidine group had a greater incidence of intraoperative nausea or vomiting compared with the saline group (11 vs 3; P=0.02). CONCLUSION: Addition of meperidine 10 mg to intrathecal bupivacaine for Caesarean section is associated with prolonged postoperative analgesia but with greater intraoperative nausea and vomiting.

Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats.

Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RPE dysfunction.