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Many pathogenic bacteria produce extracellular DNase, but the benefit of this enzymatic activity is not understood. For example, all strains of the human bacterial pathogen group A Streptococcus (GAS) produce at least one extracellular DNase, and most strains make several distinct enzymes. Despite six decades of study, it is not known whether production of DNase by GAS enhances virulence. To test the hypothesis that extracellular DNase is required for normal progression of GAS infection, we generated seven isogenic mutant strains in which the three chromosomal- and prophage-encoded DNases made by a contemporary serotype M1 GAS strain were inactivated. Compared to the wild-type parental strain, the isogenic triple-mutant strain was significantly less virulent in two mouse models of invasive infection. The triple-mutant strain was cleared from the skin injection site significantly faster than the wild-type strain. Preferential clearance of the mutant strain was related to the differential extracellular killing of the mutant and wild-type strains, possibly through degradation of neutrophil extracellular traps, innate immune structures composed of chromatin and granule proteins. The triple-mutant strain was also significantly compromised in its ability to cause experimental pharyngeal disease in cynomolgus macaques. Comparative analysis of the seven DNase mutant strains strongly suggested that the prophage-encoded SdaD2 enzyme is the major DNase that contributes to virulence in this clone. We conclude that extracellular DNase activity made by GAS contributes to disease progression, thereby resolving a long-standing question in bacterial pathogenesis research.

Syndromic Hirschsprung disease has been associated with mutations in ZFHX1B, a Smad-interacting transcriptional repressor protein. Tissue in situ hybridization has demonstrated strong expression of ZFHX1B in the developing eye, suggesting that some mutations in this gene may cause visual loss. However, none of the reported mutations have been associated with an ocular phenotype. We describe a patient with Down syndrome and Hirschsprung disease with high myopia and ocular coloboma affecting the iris and retina. In addition to trisomy 21, a novel, de novo heterozygous A to G transition in exon 8 of the ZFHX1B gene was identified, which results in a R953G amino acid substitution. This abnormality was not seen in a screen of 200 chromosomes from ethnically matched, normal controls. The arginine residue at position 953 is an extremely conserved amino acid throughout evolution. This is the first report associating Hirschsprung disease and severe eye defects with a specific genetic mutation and is the first report of a mutation in ZFHX1B causing a developmental ocular anomaly., ((c) 2004 Wiley-Liss, Inc.)

In this article we reply to the recent critique by Punt et al. in Pediatric Rehabilitation. Our hypothesis about the pathogenesis of intracranial bleeding in infants has three important implications. First, in the case of an infant with a swollen brain, subdural and retinal haemorrhage but no objective evidence of trauma, the findings by themselves are not certain evidence of abuse; second, violence is not necessary to produce subdural and retinal haemorrhage; and lastly, non-traumatic events producing apnoea with a catastrophic rise in intracranial pressure could produce a clinical picture identical to that seen in trauma.

Background: We previously reported a pilot study of the use of subtenons lidocaine after primary, unilateral strabismus surgery in children. This study suggested an association between subtenons lidocaine administration at the conclusion of surgery and a reduction of pain in the immediate postoperative period. As a result of this pilot study we performed a full-scale prospective, randomized controlled trial to fully evaluate the efficacy of this intervention., Methods: Children undergoing primary surgery or reoperations for strabismus were recruited. If randomized to the treatment group, 1 ml of 2% lidocaine was injected into the subtenons space of each operated eye, just prior to conjunctival closure. The child's parents, who were masked to the intervention, assessed pain over 4 h postoperatively using an objective pain-scoring tool. Pain scores were recorded on return to the ward (0 h, approximately 20 to 30 min after the completion of surgery) and at 1, 2, and 4 h later., Results: One hundred eleven children were recruited, of whom 91 (82.0%) underwent unilateral and 20 (18.0%) underwent bilateral surgery. Ninety operations (81.1%) were primary procedures and 21 (18.9%) were reoperations. Fifty-four children (48.6%) were randomized to the treatment group and 57 (51.4%) were randomized to the control group. A subtenons lidocaine injection was associated with a significant reduction in pain at the 0 h observation (P = 0.0056), and the total pain score over the 4-h postoperative period was significantly lower in the treatment group compared to controls (P = 0.0381). There was no difference between the groups with respect to the need for additional systemic analgesia (P = 0.307)., Conclusion: This study showed that an intraoperative injection of subtenons lidocaine is associated with a significant reduction in postoperative pain during the first postoperative hour for all types of childhood strabismus surgery. There was no difference between the groups in the need for systemic analgesia.

Aims: To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry., Methods: Employees from 1981 to 1996 were traced through the Australian National Death Index and the National Cancer Statistics Clearing House. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate. Total follow up time was 176 598 person-years for males and 10 253 person-years for females., Results: A total of 692 of the 15 957 male subjects, and 16 of the 1206 female subjects had died by the cut off date, 31 December 1996. In males, the all-cause SMR and the SMRs for all major disease categories were significantly below unity. There was a non-significant increase of the all-cancer SIR (1.04, 95% CI 0.97 to 1.11). There was a significant increase of the incidence of melanoma (SIR 1.54, 95% CI 1.30 to 1.81), bladder cancer (SIR 1.37, 95% CI 1.00 to 1.83), and prostate cancer (SIR 1.19, 95% CI 1.00 to 1.40), and a marginally significant excess of pleural mesothelioma (SIR 1.80, 95% CI 0.90 to 3.22), leukaemia (SIR 1.39, 95%CI 0.91 to 2.02), and multiple myeloma (SIR 1.72, 95% CI 0.96 to 2.84)., Conclusions: Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. The melanoma excess may be the result of early diagnosis. The excess bladder cancer has not been observed previously in this industry and is not readily explained. The divergence between cancer incidence and cancer mortality suggests that the "healthy worker effect" may be related to early reporting of curable cancers, leading to increased likelihood of cure and prolonged mean survival time.

Aim: To investigate the relationship of postoperative pain to three different medicaments placed in the root canal after a complete biomechanical debridement of the root canal system in patients presenting for emergency relief of pain., Methodology: Two hundred and twenty-three teeth belonging to 221 patients presenting as emergencies to the Royal Dental Hospital of Melbourne were included in the study. Inclusion was limited to patients with a diagnosis of pulp necrosis and acute apical periodontitis. All teeth underwent conventional root canal treatment, which involved the instrumentation to the apices of each canal at the first visit. Canals were instrumented using a stepback technique and hand-files along with irrigants using Milton's (1% sodium hypochlorite) solution followed by 15% EDTAC. The canals were dried and one of the following three medicaments was inserted into the canal in random sequence: Group 1: Ledermix paste (Lederle Pharmaceuticals, Division of Cyanamid, Wolfratshausen, Germany); Group 2: calcium hydroxide paste (Calcipulpe, Septodont, France); and Group 3: no dressing. Before dismissal, the preoperative pain experienced on the previous night was recorded using a visual analogue pain scale. Patients were then instructed to record the degree of pain experienced 4 h after treatment and daily for a further 4 days., Results: The mean score pain for all three groups was between 42 and 48 prior to treatment being commenced. After 4 days, the pain score for Group 2 was 10, for Group 3 was 7 and for Group 1 was 4. Mean preoperative pain level was 44.4 (of a maximum 100) for all groups, and declined by 50% (to 22.1) after 24 h. Patients in Group 1 (Ledermix) experienced significantly less (P = 0.04) postoperative pain than those in the other two groups. There was no significant difference between Group 2 (calcium hydroxide) and Group 3 (no dressing)., Conclusion: Under the conditions of this study, painful teeth with acute apical periodontitis that had been dressed with Ledermix paste gave rise to less pain than that experienced by patients who had a dressing of calcium hydroxide or no dressing at all. Ledermix is an effective intracanal medicament for the control of postoperative pain associated with acute apical periodontitis, with a rapid onset of pain reduction.

Background: Men who were part of an Australian petroleum industry cohort had previously been found to have an excess of lympho-hematopoietic cancer. Occupational benzene exposure is a possible cause of this excess., Methods: We conducted a case-control study of lympho-hematopoietic cancer nested within the existing cohort study to examine the role of benzene exposure. Cases identified between 1981 and 1999 (N = 79) were age-matched to 5 control subjects from the cohort. We estimated each subject's benzene exposure using occupational histories, local site-specific information, and an algorithm using Australian petroleum industry monitoring data., Results: Matched analyses showed that the risk of leukemia was increased at cumulative exposures above 2 ppm-years and with intensity of exposure of highest exposed job over 0.8 ppm. Risk increased with higher exposures; for the 13 case-sets with greater than 8 ppm-years cumulative exposure, the odds ratio was 11.3 (95% confidence interval = 2.85-45.1). The risk of leukemia was not associated with start date or duration of employment. The association with type of workplace was explained by cumulative exposure. There is limited evidence that short-term high exposures carry more risk than the same amount of exposure spread over a longer period. The risks for acute nonlymphocytic leukemia and chronic lymphocytic leukemia were raised for the highest exposed workers. No association was found between non-Hodgkin lymphoma or multiple myeloma and benzene exposure, nor between tobacco or alcohol consumption and any of the cancers., Conclusions: We found an excess risk of leukemia associated with cumulative benzene exposures and benzene exposure intensities that were considerably lower than reported in previous studies. No evidence was found of a threshold cumulative exposure below which there was no risk.

Endoscopic orbital decompression may be used to treat disfiguring proptosis or sight threatening optic nerve compression in patients with thyroid eye disease. Strabismus is common in thyroid eye disease and frequently follows decompression surgery. We retrospectively reviewed patients undergoing endoscopic decompression for thyroid eye disease, by a single surgeon, from 1994 to 2000. Twenty-three patients (21 female, 2 male) were identified with a mean age of 47.5 years. At presentation, 21 patients had proptosis, 8 optic nerve compression (2 without proptosis) and 11 strabismus (9 complained of diplopia) with a mean BSV score of 24.5 before decompression. Forty orbits were decompressed with a mean decrease in proptosis of 3.3 mm. Following decompression, the mean BSV score was 25, and 17 patients had manifest strabismus in primary gaze (3 at near only) of whom 10 had pre-existing strabismus. Five patients had new diplopia (22%). Eleven patients ultimately required strabismus surgery of whom 8 had manifest strabismus before decompression. Following strabismus surgery, the mean BSV score was 37. The final BSV score for those not requiring strabismus surgery was 29. Mean follow-up was 28 months. Endoscopic orbital decompression can effectively treat disfiguring proptosis. Diplopia is a common complication, but pre-existing diplopia may improve.

The aim of this 2-year prospective cohort study was to determine whether food-level sugar-starch combinations are predictors of dental caries in a low-risk adolescent population. A total of 645 subjects, aged 12-13 yr at baseline, were recruited from 25 secondary colleges in the north-west region of metropolitan Melbourne, Australia. Examinations to record dental caries status were conducted annually. Dental caries was diagnosed according to the criteria of the World Health Organization. Dietary information was collected by four, continuous 4-d records. Demographic data was collected by parental self-administered questionnaire. A total of 504 subjects provided complete information for analysis. Approximately 37% of subjects experienced an increment in caries. In the multivariate model, only the low sugar-high starch food group was a significant predictor of caries increment on all surfaces and pit and fissure surfaces. For both these surfaces, significant interactions with starch at low sugar and across those clusters with a maximum proportion of sugar and/or starch (that is, high sugar-low starch, medium sugar-medium starch and high sugar-low starch) were found. Sugar-starch interactions may be predictive of caries risk in a low-risk adolescent population. Changing patterns of food consumption and the widespread exposure to various fluoride vehicles are possibly altering the diet-dental caries dynamic that once existed.

A histological review of dura mater taken from a post-mortem series of 50 paediatric cases aged up to 5 months revealed fresh bleeding in the dura in 36/50, the bleeding ranging from small perivascular haemorrhages to extensive haemorrhage which had ruptured onto the surface of the dura. Severe hypoxia had been documented clinically in 27 of the 36 cases (75%). In a similar review of three infants presenting with classical 'shaken baby syndrome', intradural haemorrhage was also found, in addition to subdural bleeding, and we believe that our findings may have relevance to the pathogenesis of some infantile subdural haemorrhage. Recent work has shown that, in a proportion of infants with fatal head injury, there is little traumatic brain damage and that the significant finding is craniocervical injury, which causes respiratory abnormalities, severe global hypoxia and brain swelling, with raised intracranial pressure. We propose that, in such infants, a combination of severe hypoxia, brain swelling and raised central venous pressure causes blood to leak from intracranial veins into the subdural space, and that the cause of the subdural bleeding in some cases of infant head injury is therefore not traumatic rupture of bridging veins, but a phenomenon of immaturity. Hypoxia with brain swelling would also account for retinal haemorrhages, and so provide a unified hypothesis for the clinical and neuropathological findings in cases of infant head injury, without impact or considerable force being necessary.

Purpose: To quantify the effect of a fadenoperation to a vertical rectus muscle on the field of binocular single vision (BSV)., Patients and Methods: BSV was assessed quantitatively in 32 patients before and after a fadenoperation to a single vertical rectus muscle by measuring the vertical extent of single vision in the midline and a score for the total field of BSV. Patients were aged from 14 to 72 years. All patients had diplopia in either downgaze or upgaze before surgery. In 11 patients, this was due to a fourth cranial nerve palsy, and in 8 patients it followed an orbital floor fracture., Results: The 15 patients who had an inferior rectus fadenoperation alone showed a significant mean increase in downward and total vertical extent of BSV and in their field of BSV. The 9 patients who underwent a superior rectus fadenoperation alone showed a significant increase in total vertical extent of BSV and field of BSV score. Three of the 8 who underwent a fadenoperation combined with another strabismus procedure at the same time had a substantial improvement in their score, but after the other 5 showed little change. Patients with a paretic deficit showed substantially more improvement than those with an upgaze deficit after a blowout fracture., Conclusion: The fadenoperation to a vertical rectus muscle produced a significant functional expansion in the field of BSV in approximately two thirds of patients. The procedure was more effective in incomitant squints of paretic rather than mechanical etiology.

Unlabelled: Poster at College Congress, Birmingham 2001. Oral presentation at European Strabismus Association, Florence 2001., Purpose: Anisometropia of more than one dioptre during the sensitive visual period may cause amblyopia. Its management requires refractive correction, and occlusion. Compliance with treatment is critical if visual improvement is to obtained. High anisometropia, poor initial acuity and mixed strabismic/anisometropia amblyopia are predictive factors for a poor outcome. We evaluated contact lens use in the management of high anisometropic amblyopia., Methods: Retrospective analysis of anisometropic amblyopia managed in a paediatric contact lens clinic (July 1996-July 2000), after standard amblyopia therapy of spectacles and occlusion therapy had been tried. Presenting age, acuity and refraction, duration of lens wear and occlusion, and final visual outcomes were noted., Results: Seven children (four male, three female) presented at age 3.5-6 years (mean 4.5). Six had myopic anisometropia 6.0-18.4 dioptres (mean 10.4 dioptres) and one 6.75 dioptres hypermetropic anisometropia. The initial corrected acuities of the amblyopic eyes were 6/18 to 1/60. Five patients used contact lenses with a range from 5 months to 4 years. Final acuities were 6/12-1/60. Two myopes with 6 dioptres anisometropia improved three to four Snellen lines, one with 8.8 dioptres improved one line. Three with >10 dioptres anisometropia did not improve. The hypermetropic patient improved part of one Snellen line., Conclusions: High anisometropic amblyopia is challenging to treat. In our study contact lenses improved visual acuity in myopic anisometropia of up to 9 dioptres.

Purpose: Thyroid eye disease (TED) can be a functionally disabling condition if ocular muscle involvement causes diplopia. The extraocular muscle restriction creates a reduced or eccentric field of binocular single vision (BSV). Orbital radiotherapy is now widely used in the treatment of TED, and although it has been reported as improving ocular motility, there have been few quantitative studies of the effect of treatment on ocular motor function., Methods: Retrospective case note review of patients undergoing orbital radiotherapy for TED between 1992-1998 identified 79 case records. A total of 27 patients had diplopia in primary position or a significantly reduced binocular field before undergoing radiotherapy. The fields of BSV were analyzed pretreatment and at 3, 12, and 24 months after therapy to assess any improvement in function. We used the field of BSV as an outcome measure because it can be quantified and is a good indicator of functional ability., Results: None of the 12 patients with double vision in primary position pretreatment regained a central binocular field with radiotherapy alone. Of the 15 patients with a central but reduced binocular field, 8 (53%) remained unchanged with treatment. In 4 patients (26.6%), there was an improvement in the field, while in 3 (20%) the field deteriorated. In all, 12 patients (44%) went on to require strabismus surgery., Conclusions: Orbital radiotherapy alone is ineffective in treating restrictive thyroid myopathy and improving binocular function.

We report a new model of community-based secondary vision screening and demonstrate that a high proportion of children can be effectively managed in such a clinic without referral to the hospital eye service (HES). We performed a 64-month retrospective study of a secondary vision screening clinic providing the combined skills of an optometrist and orthoptist in a community setting. Particular attention was given to the diagnosis and management of children not referred to the HES. During this period, 1755 children were sent appointments and 74% (1300) attended the clinic. The community orthoptist and school nurses referred 53% of the patients and health visitors, general practitioners and community medical officers made 32% of the clinic referrals. Spectacles were prescribed for 41% of the children and 8% were prescribed patching. Sixteen per cent of the children were referred on to the HES. This model of care using the combined expertise of the orthoptist and optometrist is able to diagnose and manage the majority of children who have failed primary vision screening and avoids unnecessary referrals to the HES.

Aims: To study binocular function in patients with longstanding asymmetric keratoconus., Methods: In 20 adult patients with longstanding asymmetric keratoconus managed with a scleral contact lens a full clinical and orthoptic assessment was performed with and without the scleral contact lens in the poorer eye., Results: All 20 patients had a corrected acuity of at least 6/9 in their better eye. With the scleral lens in situ the acuity of the poorer eye ranged from 6/6 to 6/60 and without the lens from 6/18 to hand movements. Patients were aged from 18 to 68 years and had worn a scleral contact lens for between 3 and 106 months. Without the contact lens in their poorer eye all patients had a small exotropia and all showed suppression, with the exception of one patient who had a right hypertropia with diplopia. With the scleral lens in situ 12 patients had an exophoria or esophoria, six a microexotropia, and two a manifest exotropia with suppression., Conclusions: Binocular function breaks down in some adult patients with longstanding asymmetric keratoconus. This is probably caused by longstanding unilateral visual deprivation. There are similarities to the breakdown of binocular function seen in some patients with a longstanding dense unilateral adult onset cataract who can develop intractable diplopia following cataract surgery.

A nested case-control study was undertaken to investigate whether an excess of lympho-haematopoietic cancers in the Australian petroleum industry was associated with benzene exposure. The benzene exposures of the cases and controls were estimated using a quantitative algorithm based largely on exposures measured in the Australian petroleum industry. The algorithm was used to estimate, for each subject, the benzene exposure in parts per million (ppm) for each job held in the industry, and the cumulative exposure in ppm years. Because of the critical importance of the exposure assessment in this design of epidemiological study, particular attention was paid to the reliability of the inputs to the algorithm. The inputs [base estimates (BEs) of exposure and technology-specific exposure modifiers (EMs)] were compared to data from other sources including the occupational hygiene literature. Where such comparison data were available, they were generally found to confirm the values used in the algorithm, although four input values were changed as a result of the validation exercise. The integrity of the task-based algorithm was validated by employing it to calculate the exposures of the tanker drivers in the study and comparing these with measured daily exposure for tanker drivers in the Australian petroleum industry and exposure values found in the occupational hygiene literature. After adjustment for the mix of products carried by the Australian tanker drivers, the estimates from the algorithm were found to be comparable to the measured and literature values. This exercise provided evidence that the exposure assessment for the epidemiological study was reliable and that the results of the study can be used as the basis for evaluating the relationship between exposure to benzene and the risk of lympho-haematopoietic cancer.

Aim: To study the effects of supervised inpatient occlusion treatment for amblyopia in children who had failed to respond to outpatient treatment., Methods: A retrospective study of 39 children admitted to a paediatric ophthalmic ward for 5 days of supervised intensive occlusion therapy having previously failed to respond to outpatient occlusion. Visual acuity of amblyopic and fellow eyes was recorded at each clinic visit before admission, daily during admission, and at each outpatient visit after discharge., Results: There was no significant overall improvement in visual acuity during a mean of 9 months of attempted outpatient occlusion before admission. During the 5 days of admission 26 children (67%) gained at least one line of acuity in their amblyopic eye and five (13%) gained three or more lines (mean gain 1.03 Snellen lines). The acuities of both the amblyopic and fellow eyes subsequently improved with continuing part time patching as an outpatient, including in nine of the children who did not respond during admission. At the last recorded visit, at a median time of 14 months after discharge, 13 (33%) of the patients had an acuity of at least 6/12 in their amblyopic eye., Conclusions: The acuity of amblyopic eyes did not improve without effective treatment. Subsequent supervised inpatient occlusion therapy was effective in the majority of the children.

Group A Streptococcus (GAS) expresses cell surface proteins that mediate important biological functions such as resistance to phagocytosis, adherence to plasma and extracellular matrix proteins, and degradation of host proteins. An open reading frame encoding a protein of 348 amino acid residues was identified by analysis of the genome sequence available for a serotype M1 strain. The protein has an LPATGE sequence located near the carboxy terminus that matches the consensus sequence (LPXTGX) present in many gram-positive cell wall-anchored molecules. Importantly, the central region of this protein contains 50 contiguous Gly-X-X triplet amino acid motifs characteristic of the structure of human collagen. The structural gene (designated scl for streptococcal collagen-like) was present in all 50 GAS isolates tested, which together express 21 different M protein types and represent the breadth of genomic diversity in the species. DNA sequence analysis of the gene in these 50 isolates found that the number of contiguous Gly-X-X motifs ranged from 14 in serotype M6 isolates to 62 in a serotype M41 organism. M1 and M18 organisms had the identical allele, which indicates very recent horizontal gene transfer. The gene was transcribed abundantly in the logarithmic but not stationary phase of growth, a result consistent with the occurrence of a DNA sequence with substantial homology with a consensus Mga binding site immediately upstream of the scl open reading frame. Two isogenic mutant M1 strains created by nonpolar mutagenesis of the scl structural gene were not attenuated for mouse virulence as assessed by intraperitoneal inoculation. In contrast, the isogenic mutant derivative made from the M1 strain representative of the subclone most frequently causing human infections was significantly less virulent when inoculated subcutaneously into mice. In addition, both isogenic mutant strains had significantly reduced adherence to human A549 epithelial cells grown in culture. These studies identify a new extracellular GAS virulence factor that is widely distributed in the species and participates in adherence to host cells and soft tissue pathology.

Background: The use of recombinant tissue plasminogen activator (r-TPA) has been advocated in the treatment of postsurgical fibrinous membrane formation following cataract surgery in adults. Its use in paediatric cases is not well documented., Method: A retrospective review of paediatric cataract extractions performed at Moorfields Eye Hospital between 1 January 1997 and 4 April 1999 was carried out., Results: Cataract extractions were performed in 37 patients, 22 in males 15 in females. Four (9.2%) underwent intracameral injection of 25 microg r-TPA. They were all females of Afro-Caribbean origin. The time to injection varied from 4-14 days, mean 7.2 days. Complete resolution of the fibrinous membrane was seen in all cases. There were no complications by the 3 month follow up., Conclusion: r-TPA may be used safely and effectively at a dose of 25 microg for the treatment of severe fibrinous membranes following paediatric cataract extraction. It aided the visual recovery of the children and also allowed a reduced regimen of topical steroid therapy to be used postoperatively.

An excess of lympho-haematopoietic (LH) cancers has been identified in the Australian petroleum industry through the Health Watch surveillance programme. A nested case-control study is being conducted to investigate this excess. This paper describes the methods used to provide quantitative estimates of benzene exposure for each of the subjects in the case-control study. Job histories were compiled for each subject from interviews and company employment records. Site visits and telephone interviews were used to identify the tasks included in each job title. Details about the tasks such as their frequency, the technology in use and about changes that had taken place over the years were also gathered. Exposure dated back to the late 1940s for a few subjects. Collaborating petroleum companies provided recent benzene exposure monitoring data. These were used to generate Base Estimates of exposure for each task, augmented with data from the literature where necessary. Past exposures were estimated from the Base Estimates by means of an exposure algorithm. The modifying effects of technological changes and changes to the product were used in the algorithm. The algorithm was then computed to give, for each job, for each subject, an estimate of average benzene exposure in ppm in the workplace atmosphere (Workplace Estimate). This value was multiplied by the years for which the job was held and these values summed to give an estimate of Cumulative Estimate of benzene in ppm-years. The occupational hygienists performing the exposure assessment did so without knowledge of the case or control status of subjects. Overall exposures to benzene in the Australian petroleum industry were low, and virtually all activities and jobs were below a time-weighted average of 5 ppm. Exposures in terminals were generally higher than at refineries. Exposures in upstream areas were extremely low. Estimates of Cumulative Estimate to benzene ranged from 0.005 to 50.9 ppm-years.

Background/aims: A recent report has highlighted the decreasing prevalence in recent years of severe intraventricular haemorrhage (IVH) in very low birthweight (VLBW) infants (<1500 g). This study attempted to identify the severity of the grade of IVH in infants with stage 3 retinopathy of prematurity (ROP), and to re-examine the association between threshold ROP and IVH., Methods: This was a retrospective study carried out over 3 years, between December 1995 and December 1998 of neonates admitted to a single neonatal intensive care unit. 28 infants with stage 3 ROP were identified from the ROP screening database. Cranial ultrasound scans were available on 24 of these infants. The scans were reviewed and the severity of IVH was graded from grade 1 to grade 4. The birth weight, sex, ethnic origin, and gestational age of the babies were recorded. The number of infants progressing to threshold disease and the treatment provided was documented., Results: The 24 infants had a median gestational age of 26 weeks (range 24-28 weeks) and a median birth weight of 762.5 g (range 540-1010 g). 17 infants were treated for threshold disease. 13 infants (54.2%) had IVH, of these eight (61.5%) had grade 1, two (15.4%) had grade 2, one (7.7%) had grade 3, and two (15.4%) had grade 4. 12 of the 13 infants (92.3%) with IVH had treatment with laser or cryotherapy for ROP compared with five of the remaining 11 infants (p = 0.023, Fisher's exact test). These data provide little evidence of any association between IVH and each of ethnic origin (p = 0.856), sex (p = 1), birth weight, or gestational age (p = 0.56 and p = 0.06 respectively) in infants with stage 3 ROP., Conclusions: These data provide strong evidence (p = 0. 023) of an association between the presence of IVH and treatment of threshold ROP. Although the numbers in this study are small the majority of infants with stage 3 ROP had grade 1 IVH, which heralds a more favourable neurological outcome. An association between the severity of ROP and severity of IVH was not demonstrated. With improvements in neonatal care and a reduction in the prevalence of severe IVH, there appears to be a weakening of the previously reported association between severe IVH and severe ROP. However, the presence of even a minor grade of IVH may be a significant risk factor for threshold ROP once stage 3 disease is encountered.

Purpose: To re-examine the risk of children born by assisted conception developing stage 3 retinopathy of prematurity (ROP) and to define whether the risk of ROP varies with the method of assisted conception., Methods: This was a retrospective study carried out between December 1995 and December 1998 of infants in a single neonatal unit serving the Brent and Harrow area of North West Thames requiring screening and treatment of ROP. The infants screened were identified from the ROP screening database. Those conceived by in vitro fertilisation (IVF) and other forms of assisted conception were identified by reviewing the neonatal notes and the maternal obstetric records. Birth weight, gestational age and the type of assisted conception were recorded. The presence or absence of any stage of ROP, its location and severity and the cases requiring treatment were recorded., Results: One hundred and seventy-nine infants fulfilled the screening criteria during this period. Acute ROP was detected in 32.4% (58 infants) and stage 3 ROP developed in 15.6% (28 infants). Twenty-one infants (11.7%) were born after assisted conception, with 12 (6.7%) being conceived by IVF. The others were conceived on clomiphene (8) or after intrauterine insemination (1). Assisted conception accounted for 21.4% of all those reaching stage 3 disease and 28.6% of those infants requiring treatment. Of the 12 infants conceived by IVF, 41.6% (5 infants) developed acute ROP which progressed to threshold ROP in all infants (100%). Of the assisted conception babies requiring treatment for ROP, 83.3% were conceived by IVF. The other child had been conceived on clomiphene. The gestational age and birth weight of the IVF infants reaching stage 3 ROP were 26.6 +/- 0.89 weeks and 937 +/- 170.2 g. The gestational age and birth weight in the rest of the infants reaching stage 3 ROP were lower than in those conceived by assisted conception (25.739 +/- 1.13 weeks and 735.29 +/- 117.70 g); however, this did not approach statistical significance (p = 0.35 and p = 0.13, respectively)., Conclusions: In this study 11.7% of the group requiring screening were conceived by assisted conception. Of all babies requiring treatment for ROP, 28.6% were born after assisted conception. Of the assisted conception group, 83.3% were conceived by IVF. Assisted conception using IVF rather than other techniques appears to be the major risk factor for the development of threshold ROP. We would advise increased vigilance when screening babies conceived by the IVF methods of assisted conception.

Group A Streptococcus (GAS) is a human pathogen that commonly infects the upper respiratory tract. GAS serotype M1 strains are frequently isolated from human infections and contain the gene encoding the hypervariable streptococcal inhibitor of complement protein (Sic). It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves caused by M1 strains, an observation suggesting that Sic participates in host-pathogen interactions on the mucosal surface (N. P. Hoe, K. Nakashima, S. Lukomski, D. Grigsby, M. Liu, P. Kordari, S.-J. Dou, X. Pan, J. Vuopio-Varkila, S. Salmelinna, A. McGeer, D. E. Low, B. Schwartz, A. Schuchat, S. Naidich, D. De Lorenzo, Y.-X. Fu, and J. M. Musser, Nat. Med. 5:924-929, 1999). To test this idea, a new nonpolar mutagenesis method employing a spectinomycin resistance cassette was used to inactivate the sic gene in an M1 GAS strain. The isogenic Sic-negative mutant strain was significantly (P < 0.019) impaired in ability to colonize the mouse mucosal surface after intranasal infection. These results support the hypothesis that the predominance of M1 strains in human infections is related, in part, to a Sic-mediated enhanced colonization ability.

Bioassays (7-day early life stage and 96 h acute bioassays) were conducted with the sheepshead minnow, Cyprinodon variegatus, to determine the toxicity of the dispersant Omni-Clean by itself and in combination with fuel oil no. 2. Performance characteristics of both bioassay types were also compared. Bioassays used oil by itself, dispersant by itself, and oil and dispersant in various ratios. Omni-Clean was less toxic than many other dispersants, and had a relatively small effect on individual biomass. Toxicities of the oil/dispersant combinations were generally higher than expected from the toxicities of the oil and dispersant by themselves, indicating a more-than-additive effect on toxicity. The comparison of performance characteristics between the 7-day and the 96-hour bioassays showed that the early life stage test is generally more sensitive, and has the added advantage of an additional and sensitive endpoint (fish biomass).

Objective: To establish the effectiveness of botulinum toxin A (BTXA) in the treatment of patients with acute acquired concomitant esotropia., Design: Retrospective, interventional, noncomparative case series., Participants: Fourteen patients presenting to the Strabismus and Pediatric Service at Moorfields Eye Hospital with acute-onset esotropia over a 6-year period (1991-1997)., Intervention: 2.5 units of BTXA injected into the unilateral medial rectus muscle of the deviating eye under electromyographic control., Main Outcome Measures: Pre- and postinjection angle of deviation, pre- and postinjection stereopsis, final level of stereopsis achieved, and whether corrective squint surgery was later required., Results: Fourteen patients were identified, of whom eight were male and six female. The mean age at presentation was 5.4 years, and the average time from onset to attending the clinic was 18 weeks. The mean time from onset of acute esotropia to injection was 32.5 weeks. All patients, except one, showed considerable improvement in their manifest deviation after one injection of BTXA. Eight patients (57%) maintained high-grade stereopsis of 120 seconds of arc or better and long-term ocular alignment with toxin treatment alone. In total, 11 patients (79%) gained improved stereopsis and maintained satisfactory ocular alignment with toxin therapy and did not require squint surgery. Two patients (14%) did not maintain a stable ocular position after toxin treatment and later required squint surgery, gaining good ocular alignment and high-grade stereopsis. The one patient who did not respond to the initial BTXA injection refused all further treatment. The mean follow-up time was 22 months., Conclusions: Botulinum toxin therapy has a definite role in the treatment of children with acute-onset esotropia. It may well obviate the need for squint surgery. The safety and ease of administration of this treatment add to its merits.

The finding of retinal or vitreous hemorrhage in a child under age 3 years may cause significant controversy with regard to the etiology, because it raises the suspicion of nonaccidental injury. Blood dyscrasias have been documented to cause retinal and vitreous hemorrhages in adults and children, but they have rarely been reported to be the cause of retinal hemorrhages in neonates. We report on a patient with a low plasma fibrinogen level who had bilateral retinal hemorrhage that proceeded to vitreous hemorrhage. This subtle abnormality of the blood clotting cascade caused significant retinal and vitreous hemorrhage in a child without risk factors for abuse.

The purpose of this study was to establish if a community based model using a Hospital Optometrist and Community Orthoptist can provide a practical secondary vision screening service for children. These professionals working in an Inner London Health Centre, assessed children who had failed primary vision screening. In total 483 new patients were seen between April 1994 and March 1996 with the largest referral source being the school nurse screening programme. The majority were managed by the team with a total onward referral rate to the Hospital Eye Service of 14%. In 78% of these cases the consultant's diagnosis agreed with the reason for referral. Where the consultant's diagnosis differed the children were identified as normal or a variant of normal. This model of care provides a 'one stop service' where a child identified as having a potential visual problem at primary screening can be assessed, refracted and provided with spectacles in a local setting without hospital referral. Referrals to the Hospital Eye Service are considerably reduced and a convenient service is provided for parents and children.

We report on a 5-year-old boy who was born with a unilateral complete ptosis secondary to a lid hematoma sustained at birth, which resolved spontaneously over the course of 6 weeks. Visual acuity and binocularity have developed normally. This case adds evidence to the proposal of a latent period before the onset of a sensitive period in visual development.

Objective: To determine the efficacy and effectiveness of a primary preventive dental programme., Design: A field trial comparing an intervention and control group over three years. The intervention group received a preventive programme which consisted of a weekly fluoride mouthrinse (0.2% neutral NaF), an annual application, replacement or repair of pit and fissure sealants, and an annual oral hygiene education programme. The control group received the oral hygiene education programme only. Examinations to record dental caries status were conducted annually for both study groups., Setting: Five secondary colleges in two non-fluoridated regions of Victoria, Australia., Subjects: 522 subjects aged 12-13 years and considered at high risk of developing dental caries were recruited for the study; 256 received the preventive programme and 266 acted as controls., Outcome Measures: Dental caries was diagnosed according to World Health Organization criteria., Results: Subjects in the intervention group who completed the three-year preventive programme (efficacy) incurred an average of 1.49 fewer decayed, missing or filled tooth surfaces than the control group. The difference was highly statistically significant. The programme also had a statistically significant impact when analysed by intention-to-treat (effectiveness), even when it was assumed that subjects lost to follow-up received minimal future benefit. Approximately 70% of the improvement in oral health was in the pit and fissure surfaces, with the remainder in the smooth surfaces., Conclusion: A comprehensive preventive dental programme introduced into adolescent populations at high risk of developing dental caries can result in significant improvements in their dental health. Further research is required to clarify the public health impact of school-based fluoride mouth rinsing.

Background: Cycloplegia is a traumatic experience for most children, as guttae cyclopentolate stings on instillation into the conjunctival sac. This may result in inadequate cycloplegia, difficulty in further examination and a child who is scared of both the doctor and the ophthalmology department. Guttae proxymetacaine hydrochloride 0.5% (Ophthaine, Proparacaine) is a topical local anaesthetic that does not sting on instillation., Methods: Eighty-eight consecutive children in the paediatric clinic were assessed. The response of the patient to previous use of cyclopentolate alone was assessed by the parents of the child using a grading scheme. The use of proxymetacaine prior to instillation of cyclopentolate was then assessed using the same grading system., Results: Seventy per cent of the children who received cyclopentolate alone were assessed to have cried and been unhappy. Ninety-one per cent of the children who received cyclopentolate after proxymetacaine were assessed to have shown no adverse reaction to the cycloplegia and remained happy., Conclusion: This study shows that use of proxymetacaine prior to cyclopentolate results in atraumatic cycloplegia in children. This can confer multiple benefits on the doctor-patient relationship.

This study investigated the effect of pretreatment with topical diclofenac 0.1% on the changes in intraocular pressure (IOP) associated with use of an external ocular compression device. The IOP reduction in eyes receiving pretreatment was significantly greater than in controls after 40 minutes of compression, and the recovery in IOP after removal of the compression device was significantly reduced. We conclude that the IOP rise after such compression is largely prostaglandin mediated, and suggest that use of ocular compression devices is associated with marked intraocular prostaglandin release.

We describe the case of a patient with carotico-cavernous fistula who had botulinum toxin A to induce a protective ptosis 4.5 days before death. The levator palpebrae superioris muscle from both sides and the superior rectus muscle from the injected side were obtained for examination. The preserved samples were stained with haematoxylin and eosin, Martius scarlet blue, Glees, S100, dehydrogenase, ATPase, and toluidine blue as well as being examined by electron microscopy. Inflammation and oedema were found that were probably due to the carotico-cavernous fistula. Axonal and some myelin sheath damage were also seen.

One hundred and forty acute corneal rejection episodes in 94 patients were studied retrospectively. Sixteen episodes in 15 eyes were associated with raised intraocular pressure (IOP) on admission, three of whom had had previously elevated IOP. At six weeks, six (37.5%) still required hypotensive therapy. Five eyes with raised IOP at rejection had lost vision at six weeks. Five of the six eyes with graft failure at review had raised IOP either pre-graft, at rejection or at follow-up. Eyes grafted for herpes simplex keratitis with hypertensive rejection episodes had a higher mean admission IOP, with a more short-lived rise than other eyes.

A modification of Patterson's external antro-ethmoidectomy operation is described which provides a more direct and simpler approach than the transantral operation for decompression of the orbit.

The technique for obtaining and processing conjunctival impression cytology is described. The method of grading the stained samples is outlined. Our findings in various ocular conditions with particular emphasis on; alkali burns, uveitis, hypopyon ulcer and Botulinum toxin protective ptosis are shown. Cytology from severely damaged eyes is highly abnormal, improving as the ocular disease settles. In alkali burns a return to normal cytology does not correlate with return of corneal clarity. Loss of goblet cells is a common finding in the ocular diseases demonstrated, and appears to be a non-specific indicator of ocular problems.