A pediatric case of SAPHO-CNO syndrome with clinical correlation between cutaneous and osteoarticular features.

Synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic nonbacterial osteomyelitis (CNO) represent overlapping osteoarticular autoinflammatory syndromes, with a minority displaying neutrophilic skin features at the time of diagnosis. The pathophysiological link and chronological timeframe between skin and osteoarticular findings remain ambiguous, which in turn can manifest in diagnostic delay. We present a rare pediatric case of SAPHO-CNO with a clear association between cutaneous and osteoarticular symptoms, treated with nonsteroidal anti-inflammatory medications, corticosteroids, and intravenous pamidronate. By raising physician awareness of these syndromes, we hope that appropriate management will be initiated in a more timely fashion avoiding unnecessary investigations and treatment.

Public at risk: a survey of sunbed parlour operating practices in Northern Ireland.

BACKGROUND: The International Agency for Research on Cancer has identified artificial ultraviolet (UV) radiation as a class 1 carcinogen. The contribution of sunbeds to malignant melanoma has been estimated at 100 deaths per year in the U.K. The sunbed industry is growing and claims self-regulation. OBJECTIVES: To explore the standards of operation and client protection for sunbed users. METHODS: An observational study of tanning parlour practices was conducted by Environmental Health Practitioners who made unannounced visits to the majority of known commercial tanning parlours in Northern Ireland (population 1.77 million) during July/August 2007. Descriptive statistics were produced and comparisons between groups were made using chi(2) analysis. RESULTS: All 332 premises visited cooperated with the survey. The UV type in machines was unknown in 71.2% of premises while 15.6% reported using type 4, high-dose UV devices; 36.2% of premises did not regularly service sunbeds or were unsure. Unsupervised use of sunbeds was reported in 8.6% of parlours and 3.4% provided a home sunbed service. Eye protection was available in 97.6% of premises but 34.6% charged for the service and only 79.6% sanitized these between use. Of the responders 15.9% were members of the Sunbed Association. These were more likely to have maintenance records and operating manuals but were also more likely to provide a home sunbed service. CONCLUSIONS: This study highlights the need for improved standards of regulation of the sunbed industry to protect clients from excessive and dangerous levels of UV radiation in a population where the numbers of melanomas continue to rise.

Dynamics of Campylobacter colonization of a natural host, Sturnus vulgaris (European starling).

Wild European Starlings (Sturnus vulgaris) shed Campylobacter at high rates, suggesting that they may be a source of human and farm animal infection. A survey of Campylobacter shedding of 957 wild starlings was undertaken by culture of faecal specimens and genetic analysis of the campylobacters isolated: shedding rates were 30.6% for Campylobacter jejuni, 0.6% for C. coli and 6.3% for C. lari. Genotyping by multilocus sequence typing (MLST) and antigen sequence typing established that these bacteria were distinct from poultry or human disease isolates with the ST-177 and ST-682 clonal complexes possibly representing starling-adapted genotypes. There was seasonal variation in both shedding rate and genotypic diversity, both exhibiting a maximum during the late spring/early summer. Host age also affected Campylobacter shedding, which was higher in younger birds, and turnover was rapid with no evidence of cross-immunity among Campylobacter species or genotypes. In nestlings, C. jejuni shedding was evident from 9 days of age but siblings were not readily co-infected. The dynamics of Campylobacter infection of starlings differed from that observed in commercial poultry and consequently there was no evidence that wild starlings represent a major source of Campylobacter infections of food animals or humans.

Skin cancer trends in Northern Ireland and consequences for provision of dermatology services.

BACKGROUND: The incidence of skin cancer, both melanoma and nonmelanoma skin cancer (NMSC), is rising throughout the world. The evaluation of trends in skin cancer will allow better planning of the future development of skin cancer services. OBJECTIVES: Using data collected from the Northern Ireland Cancer Registry (NICR), the incidence of the three major cutaneous cancers, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM), was determined and the workload associated with their management assessed. METHODS: The records of patients with a first diagnosis of BCC, SCC or MM occurring between 1993 and 2002 were retrieved from the NICR database. The annual age- and sex-adjusted incidence rates of all three skin cancers were computed per 100 000 person-years by direct standardization according to the European Standard Population. Trends in incidence were estimated by calculating the estimated annual percentage change using Microsoft Excel. For patients registered with the NICR as having BCC, SCC or MM, the number of pathological reports where malignant samples had been examined was counted and then summed to provide the number of specimens examined each year between 1993 and 2004. RESULTS: For all three cancers the age-specific rates for both males and females increased with age, except for MM in men aged 75 years and over, where the rates were seen to decrease. Over the 12-year period there was a 62% increase in the overall number of skin cancer samples processed by local pathology laboratories and a 20% increase in the number of patients. These data highlight the fact that many patients will have more than one skin cancer, which reinforces the benefit in collecting data for both patient and sample numbers in order to obtain a true reflection of the workload. The data have also shown that more affluent men and women have higher rates of BCC and MM than their less affluent counterparts. CONCLUSIONS: In view of the data presented it is clear that management of NMSC and MM will impose significant demands on services in the years ahead. This will impact on the entire multidisciplinary team. Future planning, in terms of manpower and resources, will prove essential if we are to remain in a position to manage our patients with these malignant tumours appropriately.

Pregnancy and pregnancy outcome in hepatitis C type 1b.

A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

Social tactics of pigs in a competitive foraging task: the 'informed forager' paradigm.

Studies of the social dynamics in foraging groups have focused primarily on birds, rodents and nonhuman primates. We extended the study of animal social tactics to the domestic pig, Sus scrofa, by using an experimental analogue of natural foraging skills, the 'informed forager' paradigm. We investigated the behaviour of 16 pigs foraging in pairs in an arena in which food had been hidden in one of eight monopolizable buckets. Before each pair trial, one of the pigs, the 'informed' pig, was given privileged knowledge about the location of the food during a solitary search trial. The 'noninformed' pig was naïve about the location of the food during pair trials, but heavier than its informed partner and thus able to displace the latter from the baited bucket. By first focusing on the informed pigs' behaviour, we show that pigs are able to remember and relocate the food site. They found the food in relocation trials, using fewer bucket investigations than expected of a random searcher. Second, by focusing on the noninformed pigs, we show that pigs are able to exploit the knowledge of others by following them to a food source. They investigated more buckets immediately after their informed partners significantly more often than expected by chance and required fewer bucket investigations to find the food in pair trials than expected from a random searcher, but not in solitary search trials. We discuss these latter findings with reference to social foraging tactics. Copyright 2000 The Association for the Study of Animal Behaviour.

Potential acuity meter results in cataract patients.

PURPOSE: To determine the ability of the potential acuity meter (PAM) to predict potential visual acuity through lenticular opacities in a group of cataract patients without significant other ocular pathology. METHODS: This prospective study undertook PAM measurements on each eye of 84 subjects during preoperative hospital visits to either A Scan or Primary Care clinics. PAM results were compared to best corrected visual acuity findings obtained at least 6 weeks post-cataract extraction. RESULTS: Comparison of PAM result to visual outcome showed poor correlation (rho = 0.41, P = 0.0005). Using predictive estimates, 49% of subjects' PAM results underestimated visual outcome as determined by a difference of greater than 2 Snellen acuity lines in these results. Factors such as preoperative vision level, cataract type and pupil dilation did not significantly influence the predictive power of the PAM. Preoperative pinhole results were also correlated with visual outcome (rho = 0.42, P = 0.0006). Vison in the fellow eye of subjects with 6/9 or better was correlated to the PAM result indicating a moderate to good predictive power in 'normal' eyes. CONCLUSIONS: PAM results were considered to be poor for a clinical test. The results of this study indicate that this instrument has only a limited usefulness as part of the standard preoperatve examination in patients undergoing cataract extraction.

Preliminary investigations of ultraviolet-induced markings on domestic turkey chicks and a possible role in injurious pecking.

Several gallinaceous species including domestic turkeys have the capacity for ultraviolet (UV) vision. This might function in signalling between birds, for example in individual recognition, which would suggest the presence of plumage markings visible under UV radiation. Between 1 and 22 d of age, the plumage of 17 male turkey poults (BIG6) was examined. When viewed under a conventional fluorescent white luminaire (which emits minimal UV) the birds were a uniform yellow or white according to the stage of feather emergence. However, when viewed under a lamp emitting radiation with peaks in the UV spectrum, distinct fluorescent and non-fluorescent patches were observable on several parts of the body including the wings, tail, shoulders, thighs, neck, breast and dorsal surface. This paper describes the changes in incidence, size, location and qualitative aspects of these UV-visible markings. The age at which UV-visible markings were first observed on the wings and tail corresponded closely with the age at which injuries to these sites were first caused by pecking, as reported previously. It is suggested that the 'unnatural' appearance of these markings under conventional lighting, which emits minimal UV radiation, might attract or protract injurious pecking from conspecifics.

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis.

Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. METHODS--In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. RESULTS--Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. CONCLUSION--These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated.

T cell subsets and disease progression after total lymphoid irradiation in chronic progressive multiple sclerosis.

T lymphocyte subset percentages were determined in 16 total lymphoid irradiation (TLI) treated and 18 sham treated control patients with chronic progressive multiple sclerosis. During the first year after treatment, the ratio of T helper/inducer to T suppressor/cytotoxic cells (Th/Ts ratio) was significantly higher in sham treated multiple sclerosis patients who worsened clinically compared with TLI treated and sham treated multiple sclerosis patients who remained clinically stable. TLI caused a fall in the percentage of T helper cells in treated patients, while the percentage of T suppressor cells remained stable during the first year after treatment. In contrast, the percentage of T suppressor cells fell in sham treated multiple sclerosis patients who worsened clinically.

Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros.

To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.

Total lymphoid irradiation for multiple sclerosis.

Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one. Our data suggest that this modified TLI regimen has clinical efficacy and sufficiently low toxicity to make it suitable for investigative immunosuppressive treatment of patients with progressive MS or other non-malignant conditions.

Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course.

We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.