Head and neck pilomatricoma: an analysis of 201 cases.

We report our experience with 201 pilomatricomas of the head and neck. They occurred over a wide age range (2-93 years, mean 29.5) and were most common in the first and second decades. Almost half (49%) presented in people over 40 years of age and there was no sex predilection (male:female ratio 1:1.1). The most common presentation was as a slowly enlarging, asymptomatic, subcutaneous mass, although nearly 25% were symptomatic, and 12% had a reddish blue skin discolouration. Most lesions were solitary; only 9 patients (5%) had multiple lesions. The most commonly affected sites were the cheek (23%), neck (22%), eyebrow (18%), and scalp (14%). Tumours were often mistaken for other lesions and a correct preoperative diagnosis was made in only 28% of cases. Preoperative investigations were done only occasionally and were not always helpful. All lesions were excised and excision was reported to have been incomplete in 22%. Two patients (1%) had a recurrence after incomplete excision. We highlight the condition to raise awareness among clinicians, and we support conservative excision as the most appropriate method of treatment.

GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility.

There is an urgent clinical need for a safe, efficacious stimulant of gastric emptying; current therapies include erythromycin (an antibiotic with additional properties which preclude chronic use) and metoclopramide (a 5-hydroxytryptamine type 4 receptor agonist and an antagonist at brain D2 receptors, associated with movement disorders). To move away from the complex motilide structure of erythromycin, a small molecule motilin receptor agonist, GSK962040, was identified and characterized. The compound was evaluated using recombinant human receptors, rabbit and human isolated stomach preparations known to respond to motilin and in vivo, by measuring its ability to increase defecation in conscious rabbits. At the human motilin receptor, the pEC50 (the negative logarithm to base 10 of the EC50 value, the concentration of agonist that produces 50% of the maximal response) values for GSK962040 and erythromycin as agonists were, respectively, 7.9 and 7.3; GSK962040 had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, GSK962040 300 nmol L(-1)-10 micromol L(-1) caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 +/- 47% at 3 micromol L(-1). In human-isolated stomach, GSK962040 10 micromol L(-1), erythromycin 10 micromol L(-1) and [Nle13]-motilin 100 nmol L(-1), each caused muscle contraction of similar amplitude. In conscious rabbits, intravenous doses of 5 mg kg(-1) GSK962040 or 10 mg kg(-1) erythromycin significantly increased faecal output over a 2-h period. Together, these data show that GSK962040, a non-motilide structure, selectively activates the motilin receptor. Simplification of the structural requirements to activate this receptor greatly facilitates the design of potentially new medicines for gastroparesis.

Factors influencing the occurrence of multicentric and 'recurrent' Warthin's tumour: a cross sectional study.

The multicentric nature of Warthin's tumour has been well recognised, though the factors predicting its occurrence and its influence on management remain speculative. In this cross sectional study, the authors analysed the presentation, management and outcome of solitary and multicentric Warthin's tumour, treated in the maxillofacial unit and investigated factors that could influence the occurrence of multicentric and recurrent tumours. Warthin's tumour was found in 24% (150/628) of patients presenting with parotid neoplasms and multicentric tumours were found in 13% (21/ 161) of parotidectomy specimens. Age, sex, side, site and smoking history were not predictors of multicentricity (P>0.40). Clinical examination (19%), imaging investigations (28%) and intra-operative palpation (33%) were poor at detecting multicentric tumours. Superficial parotidectomy was the most commonly performed operation. The recurrence rate was 0% in the solitary and 10% in the multicentric tumour group. Intra-operative rupture was not uncommon (11%), but was not associated with tumour recurrence (P= or >0.999). Incomplete excision (P=0.007) and multicentricity (P=0.026) were predictors of recurrence.

The sero-prevalence of antibodies to trypanosoma cruzi in Latin American refugees and immigrants to Canada.

BACKGROUND: Chagas' disease is caused by infection with the protozoan agent Trypanosoma cruzi. An estimated sixteen to eighteen million people are infected in Latin America. Outside of endemic regions, Chagas' disease may be transmitted through the transfusion of infected blood components, congenital infection and organ transplantation. We sought to determine the sero-prevalence of antibodies to T. cruzi in a community sample of Latin American refugees and immigrants to Canada. METHODS: This was a sero-prevalence study in Latin American refugees and immigrants living in Canada. Eligible subjects were born in South America, Central America or in Mexico. Participants were recruited from a variety of community settings, as well as from medical clinics. Serum was tested by enzyme-linked immunoassay for antibodies to T. cruzi. RESULTS: A total of 102 participants were enrolled. One sample tested positive for antibodies for T. cruzi. The seroprevalence in our sample was 1.0% (95% CI: 0.2%- 5.3%). INTERPRETATION: We found a low sero-prevalence of Chagas' disease in a community sample of Latin American immigrants and refugees. Physicians who treat Latin American immigrants should consider the risk profile and clinical status of the individual in their decision to screen for Chagas' disease.

Pharmacokinetics, metabolism, excretion and plasma protein binding of 14C-levofloxacin after a single oral administration in the Rhesus monkey.

Levofloxacin's metabolism, excretion, and in vitro plasma protein binding, together with its pharmacokinetics, were studied in the Rhesus monkey in support of an anthrax efficacy study in this species. Three males and three female Rhesus monkeys were dosed with a single oral dose of 14C-levofloxacin at 15 mg kg-1 (2 MBq kg-1). Following dose administration, blood samples were collected up to 48 h post-dose, and urine and faeces were quantitatively collected up to 168 h post-dose. Blood, plasma, urine, and faeces were analysed for total radioactivity. Metabolite profiling and identification was performed using radio-high-performance liquid chromatography (HPLC) and liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS). Additionally, the plasma protein binding of levofloxacin was determined in vitro by means of equilibrium dialysis. Peak plasma levels of total radioactivity and levofloxacin were rapidly reached after oral administration with a total radioactivity blood: plasma ratio close to unity. The elimination half-life of levofloxacin was estimated at about 2 h. Total radioactivity was mainly excreted in urine (about 57-86% of the dose) with faecal excretion accounting for only a minor fraction of the total amount of excreted radioactivity (about 7.4-14.7%). In the plasma, the majority of total radioactivity was accounted for by levofloxacin. In addition, two minor metabolites, i.e. levofloxacin n-oxide and presumably a glucuronide conjugate of levofloxacin, were detected. In the urine, five components were found, with levofloxacin being the major component. Minor metabolites included desmethyl levofloxacin, levofloxacin n-oxide, and a glucuronide conjugate of levofloxacin. In the faeces, the major analyte was a polar metabolite, tentatively identified as a levofloxacin glucuronide. The in vitro plasma protein binding was low (on average 11.2%) and independent of concentration (1.0-10.0 microg ml-1). No sex differences were noted in any of the investigations. The present data indicated that the metabolism and excretion pattern, and also the in vitro plasma protein binding of levofloxacin in the Rhesus monkey, were comparable with those previously reported in man, hereby supporting the use of this animal species in the efficacy evaluation of levofloxacin against inhalation anthrax. The shorter half-life of levofloxacin in the Rhesus monkey relative to man (2 versus 7 h) prompted the development of an alternative dosing strategy for use in the efficacy study.

Balancing prevention and screening among international migrants with tuberculosis: population mobility as the major epidemiological influence in low-incidence nations.

BACKGROUND: Tuberculosis infection and disease remain a significant cause of global morbidity and mortality. The burden of tuberculosis disease is greatest in the developing nations of the world, although the effect of imported disease is observed in low-incidence tuberculosis regions, represented predominantly by high-income countries. In these regions, national tuberculosis control and elimination programmes are increasingly challenged to address disease in foreign-born residents. Immigration policies and shifting migration patterns over the past 5 decades have brought larger numbers of permanent and temporary residency migrants from high-prevalence regions of the world into low tuberculosis incidence environments. As a consequence, both national immigration policies and global health strategies for the control of tuberculosis share common interest in mobile populations moving from high-to-low prevalence regions. Existing immigration medical screening practices in major immigrant-receiving nations were often designed to prevent and manage the importation of contagious, active pulmonary tuberculosis disease. Such programmes may be limited in addressing the long-term consequences of latent tuberculosis infection in foreign-born residents. In nations with a low incidence of tuberculosis, a direct link can be found between the globalization of health factors related to international population movements, as observed with tuberculosis and immigration policies and practices. Continued migration from high-endemic tuberculosis regions will increasingly influence the disease burden in low-endemic areas, and challenge local tuberculosis control and elimination programmes. Evidence-based approaches to meeting those challenges will allow for the effective use of resources and support ongoing programme evaluation.

Multiple synchronous and metachronous neoplasms of the parotid gland: the Chichester experience.

Parotid neoplasms are usually solitary and multiple tumours occurring in an individual are uncommon. The incidence and implications of multiple synchronous and metachronous tumours remains relatively unknown. We reviewed the case notes of 606 patients who had parotidectomies for neoplastic lesions over a 30 year period and identified 30 patients (5%) with multiple primary tumours. There were 24 patients with synchronous tumours and 6 with metachronous tumours. Sixteen of the synchronous tumours (67%) were ipsilateral, whereas all six metachronous tumours were contralateral. Preoperative examination was effective at detecting bilateral tumours but poor at detecting multiple ipsilateral tumours. Multiple tumours were likely to be of the same histology (n=24, 80%) and Warthin's was by far the most common multiple tumour. Ipsilateral tumours of differing histological types and identical tumours other than Wartin's were uncommon. All but one patient had superficial parotidectomies and there were no recurrences.

Immigration medical screening and HIV infection in Canada.

HIV infection, particularly associated with AIDS, is often used by migrant screening nations to exclude entry into the country. The unique feature of the Canadian immigration HIV screening programme is that it was not primarily for determining inadmissibility of HIV-positive applicants, but for health promotion and disease prevention purposes. All applicants over 15 years of age for permanent residency or temporary residency from designated countries are HIV antibody tested. This includes persons seeking asylum from within Canada. The highest rates of HIV infection were found in migrant applicants from high prevalence areas of the world and reflected the demographic profile of the source region (predominately women). The majorities of HIV-positive persons are exempt from exclusion from Canada due to class of application (refugee, family) or are already in Canada (refugee claimant). Significant issues in notification, reporting and programme management have been identified as a consequence of this programme.

Surgical management of incompletely excised basal cell carcinomas of the head and neck.

We made a retrospective audit of all basal cell carcinomas excised in the Maxillofacial Units at St. Richard's Hospital, Chichester and the Worthing and Southlands NHS Trust between 1990 and 1999. A total of 3795 BCCs were excised. Of these, 3560 were completely excised (93.8%) and 235 were incompletely excised (6.2%), which compares favourably with other series. Of these, 84 patients had further excision, 11 had radiotherapy, and 140 were kept under review. Residual tumour was present in 45% of the re-excised specimens. Of the 140 cases managed by observation, 21% recurred. Notably, 31% of patients in the observation cohort died of other causes without recurrence. Incomplete excision was significantly more likely (P < 0.001) if multiple lesions were excised at the time of operation. Involvement of multiple margins was not a significant risk factor for recurrence in the 'observed' cohort. This study shows that a flexible strategy, which balances observation, further excision and radiotherapy, is superior to any single approach.

Meningoencephalitis associated with an unidentified apicomplexan protozoan in a Pacific harbor seal.

A Pacific harbor seal (Phoca vitulina richardsii) was found on the central California coast with neurologic signs and labored breathing, which were unresponsive to treatment. Necropsy revealed a nonsuppurative necrotizing meningoencephalitis, a multilocular thymic cyst, and nonsuppurative cystitis and renal pyelitis. Microscopic examination revealed protozoans in the brain, thymic cyst, and bladder mucosa. Ultrastructurally, the protozoal tachyzoites were different from those of Neospora caninum, Toxoplasma gondii, and Sarcocystis neurona; the rhoptries were small and had electron-dense contents, and the organism divided by endodyogeny. Specific antibodies were not detected in serum using agglutination (N. caninum, T. gondii) and immunoblot assays (S. neurona). Immunohistochemistry for these organisms was negative. Polymerase chain reaction on brain tissue using specific primers did not amplify T. gondii deoxyribonucleic acid. The meningoencephalitis in this seal thus appears to have been caused by a novel protozoan.

Parotid neoplasms in children: experience of diagnosis and management in a district general hospital.

Parotid neoplasms are uncommon in children and the available literature is predominantly from specialized centres. This paper highlights our experience at a district general hospital, in the diagnosis and management of parotid neoplasms in children. The case records of all parotidectomies performed in a 26-year period between 1974-1999 were scrutinized and patients aged 18 years and below identified. The demographic data, histology, presentation, investigations, treatment, outcomes and complications were analysed. 545 parotidectomies were performed in 536 patients, in whom 569 neoplasms were diagnosed. Only 12 patients aged 18 and under were identified (2.2%). The relative frequency of individual tumours differed markedly from that in adults. 75% of the tumours were benign. Pleomorphic adenoma and mucoepidermoid carcinoma were the most common tumours. A painless mass was the most frequent clinical presentation and CT sialogram was the most common investigation. Parotidectomy with preservation of the facial nerve was performed in all cases, and adjuvant radiotherapy employed in the case of malignant tumours. All patients were alive and well at the time of last follow up. Transient facial nerve palsy and hypertrophic scars were the most common complications.

Conditional mutation of Rb causes cell cycle defects without apoptosis in the central nervous system.

Targeted disruption of the retinoblastoma gene in mice leads to embryonic lethality in midgestation accompanied by defective erythropoiesis. Rb(-/-) embryos also exhibit inappropriate cell cycle activity and apoptosis in the central nervous system (CNS), peripheral nervous system (PNS), and ocular lens. Loss of p53 can prevent the apoptosis in the CNS and lens; however, the specific signals leading to p53 activation have not been determined. Here we test the hypothesis that hypoxia caused by defective erythropoiesis in Rb-null embryos contributes to p53-dependent apoptosis. We show evidence of hypoxia in CNS tissue from Rb(-/-) embryos. The Cre-loxP system was then used to generate embryos in which Rb was deleted in the CNS, PNS and lens, in the presence of normal erythropoiesis. In contrast to the massive CNS apoptosis in Rb-null embryos at embryonic day 13.5 (E13.5), conditional mutants did not have elevated apoptosis in this tissue. There was still significant apoptosis in the PNS and lens, however. Rb(-/-) cells in the CNS, PNS, and lens underwent inappropriate S-phase entry in the conditional mutants at E13.5. By E18.5, conditional mutants had increased brain size and weight as well as defects in skeletal muscle development. These data support a model in which hypoxia is a necessary cofactor in the death of CNS neurons in the developing Rb mutant embryo.

Changing frequency of parotid gland neoplasms--analysis of 560 tumours treated in a district general hospital.

An analysis of all parotidectomies performed for neoplastic lesions in the maxillofacial unit at a district general hospital during a 26-year period between 1974-1999 was undertaken. The details analysed were age, sex, histology and temporal variations in the frequency of specific tumour types during the study period. A total of 538 parotidectomies performed on 529 patients in whom 560 tumours were present, formed the basis of this study. Marked variations were present in the age and sex distribution and relative frequency of specific tumour types in this study, when compared to previous reports. There were also differences in the age and sex distribution of pleomorphic adenoma and adenolymphoma (P <0.0001) in this study. The relative frequency of benign tumours and adenolymphoma increased, whereas that of pleomorphic adenoma decreased during the study period. In addition, there was a statistically significant decrease in the relative frequency of pleomorphic adenoma (P <0.0001) and an increase in adenolymphoma (P <0.0001) when comparisons were made with previous studies. This study from a defined population may be more representative of the true proportion of specific tumours in this population. The potential implications of the results on the investigation and treatment of parotid neoplasms is highlighted.

Randomised, blinded, placebo controlled trial of doxycycline for chronic seronegative arthritis.

OBJECTIVE: To determine whether long term doxycycline improves symptoms in patients with chronic seronegative or reactive arthritis. METHODS: A randomised, triple blind, controlled clinical trial of three months' treatment with doxycycline or placebo of patients with chronic reactive or seronegative arthritis was conducted. The primary study end points were three month pain and functional status measured by a self administered Arthritis Impact Measurement Scales version 2 (AIMS2) quality of life questionnaire. Secondary end points were pain and functional status at 6-12 months, three month rheumatologist assessed joint count, pain, and arthritis activity, and treatment efficacy in those with previous exposure to chlamydia. RESULTS: Of 60 patients randomly allocated to receive doxycycline or placebo, results from 37 were evaluable at three months. Groups were well balanced for major prognostic variables. Doxycycline had no detectable effect at three months on pain change scores (mean difference 1.5, 95% CI -1.2 to 4.2, p=0.25) or composite functional change scores (mean difference 0.8, 95% CI -5.6 to 7.1, p=0.81). Furthermore, there were no differences in secondary study end points, and no apparent treatment effect in patients with previous chlamydia infection. CONCLUSION: Three months' treatment with doxycycline did not improve pain or functional status in patients with chronic reactive or seronegative arthritis.