Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.

Trichodysplasia spinulosa (TS) is a rare dermatological disease caused by TS-associated polyomavirus (TSPyV) in immunosuppressed patients. The seroprevalence of TSPyV in immunocompetent adults is high and the number of immunosuppressed patients developing TS remains low, suggesting that TS is underdiagnosed and/or that additional unknown factors are needed in order to develop TS. There is no well-established treatment for TS, and to date a majority of reported cases have consequently received ineffective therapies, likely due to the unavailability of reviews and recommendations of treatments for TS. The few treatments reported in case reports to be effective include topical cidofovir 3%, reduction of immunosuppression and oral valganciclovir. In this comprehensive review, we present all published cases to date, together with a summary of all treatments for TS categorized by overall clinical efficacy, thus addressing this rare disease and what appears to be its clinically efficacious treatment.

A global epidemic increase of an HPV-induced tonsil and tongue base cancer - potential benefit from a pan-gender use of HPV vaccine.

In 2007, human papillomavirus (HPV) type 16 was finally recognized as a risk factor, besides smoking and alcohol, for oropharyngeal squamous cell carcinoma (OPSCC), including tonsillar squamous cell carcinoma (TSCC), by the International Agency for Research against Cancer. Just before, in 2006, the Food and Drug Administration had approved Gardasil, the first vaccine against HPV16, 18, 6 and 11, for preventive vaccination women against cervical cancer. Concurrently, some Western countries, where smoking was decreasing, disclosed an epidemic increase in the incidence of OPSCC, especially of TSCC and base of tongue cancer (BOTSCC), together accounting for 80-90% of all OPSCCs, and mainly affecting men. The epidemic was later revealed to be due to a rise in HPV-positive cases, and scientists in the field suggested HPV vaccination also of boys. Globally, there are roughly 96 000 incident OPSCC cases/year of which 20-24% are caused by HPV, thereby accounting for around 22 000 OPSCC cases annually. Of these cases, 80-90% are due to HPV16 infection and would be prevented with the presently registered HPV vaccines. In Western countries, such as Sweden (with almost 400 TSCC and BOTSCC cases per year) and the United States, HPV prevalence in OPSCC is higher and around 70%. HPV vaccination of girls has been initiated in many countries, and the vaccines have been efficient and their side effects limited. HPV vaccination of boys has, however, been the exception, but should definitely not be delayed any further. It would benefit both girls and boys directly, and result in better and more robust herd immunity. Today, we have the possibility to eliminate several high-risk HPV types in the younger generations and avoid more than 600 000 cancer cases annually worldwide, and this possibility should be embraced by offering global pan-gender HPV vaccination.

Stathmin and EGFR correlates to HPV status and clinical outcome in sinonasal inverted papilloma.

BACKGROUND: Inverted papilloma (IP) is a locally destructive benign tumour of the sinonasal mucosa with a tendency for malignant transformation. Stathmin and epidermal growth factor receptor (EGFR) are important markers in cancer prognosis. Here we investigate if expression of stathmin and EGFR correlate to dysplasia, recurrence and HPV in IP. METHODS: 98 patients with IP diagnosed 2000-2010 were analyzed for stathmin and EGFR by immunohistochemistry (IHC) and HPV by polymerase chain reaction assay (PCR). RESULTS: All IPs expressed stathmin while its expression was absent or weak in normal mucosa. Dysplasia was present in 26,7% of IPs with high stathmin expression while only 7.4% of IPs with low stathmin expression showed dysplasia. Stathmin positive IPs showed a trend towards earlier recurrences. 57.1% of IP expressed EGFR but no significant association was seen between EGFR-positivity and recurrence or dysplasia. EGFR was expressed by 91.7% of the HPV-positive IPs compared to 52,3% of the HPV negative IPs. CONCLUSIONS: EGFR expression is significantly higher in HPV positive IP. Stathmin is expressed by all IP tumour cells. Stathmin was also associated with dysplasia and a trend towards a correlation between stathmin positivity and recurrence was found. Stathmin and EGFR might therefore be considered therapeutic targets.

Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer.

BACKGROUND: The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer has increased rapidly during the past decades. HPV is typically associated with a favourable outcome; however, a need exists for new and more effective prognostic and predictive markers for this disease. Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumour suppressor protein that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers, including cervical cancer, where HPV is a key aetiological agent. METHODS: The prognostic value of LRIG1 and LRIG2 immunoreactivity was investigated in tumour specimens from a Swedish cohort of patients with tonsillar and base of tongue oropharyngeal cancers, including 278 patients. RESULTS: LRIG1 immunoreactivity correlated with disease-free survival and overall survival in univariate and multivariate analyses. Notably, patients with HPV-positive tumours with high LRIG1 staining intensity or a high percentage of LRIG1-positive cells showed a very good prognosis. Furthermore, LRIG1 expression correlated with HPV status, whereas LRIG2 expression inversely correlated with HPV status. CONCLUSIONS: Taken together, the results suggest that LRIG1 immunoreactivity could be a clinically important prognostic marker in HPV-associated oropharyngeal cancer.

Medical diagnostic X-ray radiation--an evaluation from medical records and dentist cards in a case-control study of thyroid cancer in the northern medical region of Sweden.

The aim of this study was to evaluate the association between thyroid cancer and diagnostic X-ray radiation based on medical records. By using the Swedish Cancer Registry, 187 living cases with thyroid cancer (81%), aged 20-70 years at the time of their diagnosis in 1980-1989 were identified in the Northern Health Care Region of Sweden. Seven cases were reclassified as having a disease other than thyroid cancer and were excluded. The investigation included 180 living cases and 360 controls from the National Population Registry. In 132 cases and 251 controls data from X-ray records on earlier investigations > 5 years prior to diagnosis and corresponding years for the controls were analysed. The mean calculated thyroid dose for the cases was 7.0 mGy (median 1.1) and for the controls 7.4 mGy (median 1.0). This study showed no difference in the total material between calculated absorbed thyroid dose of medical diagnostic X-ray in cases versus controls. In younger women (< or = 50 years at diagnosis) with papillary thyroid cancer an association was found, however it was not significant. The results could be related to selective bias and should be treated with caution. Future studies require analysis of diagnostic medical X-ray investigations involving the thyroid gland including more specific data on sex and age of exposure in the whole study group.

Treatment of snoring and obstructive sleep apnea with a mandibular protruding device: an open-label study.

The study objectives were to describe the changes in signs and symptoms of obstructive sleep apnea (OSA) and snoring using a mandibular protruding device (MPD) and to define the group of responders. The design of the study was a nonrandomized, open-labeled, prospective clinical study with a duration of 6 months. The setting was a hospital sleep laboratory and an ear, nose, and throat and dental outpatient clinic. Patients included 35 individuals treated: 22 with a diagnosis of OSA and 13 who snored without apnea. The intervention before MPD prescription entailed a medical examination, a one-night somnographic registration, a questionnaire, and a clinical jaw function examination. All procedures were iterated at the 6-month follow-up. When the patients used the MPD, the subjective symptoms decreased significantly (p < 0.001). Twenty-four of the 35 patients were classified as responders, i.e., reduced their symptoms > or = 50%. In the groups of OSA patients, the mean peak intensity of the snoring sound decreased from 71.6 dB to 62.0 dB (p < 0.001) and in the group of snorers, from 63.5 dB to 57.5 dB (p < 0.05). Eighteen of the 22 OSA patients decreased their ODI values by > or = 50% (responders). The mean ODI decreased from 15.4 to 3.5 (p < 0.001) and the blood oxygen saturation, SaO(2) nadir, increased from mean 81.9 to 85.7 (n.s.). Most patients with tongue base hyperplasia were classified as responders to the MPD treatment. In conclusion, a 6-month perspective shows that the MPD could be an effective treatment in reducing signs and symptoms of OSA and/or snoring, the compliance was acceptable and only minor adverse events occurred.

Case-control study on radiology work, medical x-ray investigations, and use of cellular telephones as risk factors for brain tumors.

CONTEXT: Ionizing radiation is a well-established risk factor for brain tumors. During recent years, microwave exposure from the use of cellular telephones has been discussed as a potential risk factor. OBJECTIVE: To determine risk factors for brain tumors. DESIGN: A case-control study, with exposure assessed by questionnaires. PARTICIPANTS: A total of 233 currently living men and women, aged 20 to 80 years, were included. The case patients had histopathologically verified brain tumors and lived in the Uppsala-Orebro region (1994-1996) or the Stockholm region (1995-1996). Two matched controls to each case were selected from the Swedish Population Register. MAIN OUTCOME MEASURES: Ionizing radiation and use of cellular telephones as risk factors for brain tumors. RESULTS: A total of 209 cases (90%) and 425 controls (91%) answered the questionnaire. Work as a physician yielded an odds ratio (OR) of 6.00, with a 95% confidence interval (CI) of 0.62 to 57.7. All three case patients had worked with fluoroscopy. Radiotherapy of the head and neck region yielded an OR of 3.61 (95% CI, 0.65-19.9). Medical diagnostic x-ray examination of the same area yielded an OR of 2.10 (95% CI, 1.25-3.53), with a tumor induction period of 5 years or more. Chemical industry work yielded an OR of 4.10 (95% CI, 1.25-13.4), and laboratory work yielded an OR of 3.21 (95% CI, 1.16-8.85). Ipsilateral use of cellular telephones increased the risk for tumors in the temporal, temporoparietal, and occipital lobes (OR, 2.42; 95% CI, 0.97-6.05), ie, the anatomic areas with highest exposure to microwaves from a mobile telephone. The result was further strengthened (OR, 2.62; 95% CI, 1.02-6.71) in a multivariate analysis that included laboratory work and medical diagnostic x-ray investigations of the head and neck. CONCLUSION: Exposure to ionizing radiation, work in laboratories, and work in the chemical industry increased the risk of brain tumors. Use of a cellular telephone was associated with an increased risk in the anatomic area with highest exposure.

Use of cellular telephones and the risk for brain tumours: A case-control study.

The use of cellular telephones has increased dramatically during the 1990's in the world. In the 1980's the analogue NMT system was used whereas the digital GSM system was introduced in early 1990's and is now the preferred system. Case reports of brain tumours in users initiated this case-control study on brain tumours and use of cellular telephones. Also other exposures were assessed. All cases, both males and females, with histopathologically verified brain tumour living in Uppsala-Orebro region (1994-96) and Stockholm region (1995-96) aged 20-80 at the time of diagnosis and alive at start of the study were included, 233 in total. Two controls to each case were selected from the Swedish Population Register matched for sex, age and study region. Exposure was assessed by questionnaires supplemented over the phone. The analyses were based on answers from 209 (90%) cases and 425 (91%) controls. Use of cellular telephone gave odds ratio (OR) = 0.98 with 95% confidence interval (CI) = 0. 69-1.41. For the digital GSM system OR = 0.97, CI = 0.61-1.56 and for the analogue NMT system OR = 0.94, CI = 0.62-1.44 were calculated. Dose-response analysis and using different tumour induction periods gave similar results. Non-significantly increased risk was found for tumour in the temporal or occipital lobe on the same side as a cellular phone had been used, right side OR = 2.45, CI = 0.78-7.76, left side OR = 2.40, CI = 0.52-10.9 Increased risk was found only for use of the NMT system. For GSM use the observation time is still too short for definite conclusions. An increased risk for brain tumour in the anatomical area close to the use of a cellular telephone should be especially studied in the future.

Air sampling of fungal spores on filters. An investigation on passive sampling and viability.

In this study, glycerol was tested as a collection substrate for passive bioaerosol sampling. Filters (mixed cellulose acetate and nitrate) were soaked in glycerol and exposed for an aerosol from three different fungal species: Penicillum commune, Aspergillus versicolor and Paecilomyces variotii. The passive sampling method was compared with a closed-face polycarbonate filter sampling method. Exposure was performed in an exposure chamber. The total number of spores was determined by microscopic techniques, and the cultivable number was determined by cultivation on Malt Extract Agar dishes. The glycerol soaked filter demonstrated a good correlation with the closed-face sampler with regard to the total count. Spores stored in a pumped filter cassette were not affected by storage for up to 7 days. On the other hand, the culturability of the spores was markedly decreased after 1 day when stored on glycerol soaked filters.

Elevated antibody levels to Epstein-Bbarr virus antigens in patients with hairy cell leukemia compared to controls in relation to exposure to pesticides, organic solvents, animals, and exhausts.

Epstein-Barr virus (EBV) is a B-lymphotropic human herpes virus infecting B-cells, which has been associated with lymphoid malignancies, above all non-Hodgkin lymphomas (NHL). Severe immunosuppression is the best recognized risk factor for NHL. Many factors in the environment that have been described as risk factors for NHL cause measurable changes in immune functions. Hairy cell leukemia (HCL) is a rare, indolent non-Hodgkin lymphoma, originating from B-lymphocytes. This was a case-control study including 111 male cases with HCL and 400 controls. In a subgroup of 57 cases and 65 controls analysis of antibodies to EBV early antigen, viral capsid antigen, and EBNA-1, measured as P107, was performed. In this study, we confirm other studies describing elevated levels of antibodies to the EBV early antigen (EA) in patients with HCL compared to controls. We found only minor differences in the levels of antibodies to the viral capsid antigen (VCA) and EBNA-1. measured as P107. We found a positive association of a titer to EA IgG > or =40 (OR 4.1; CI 1.9-9.5). The ORs were further elevated when subjects with high levels of EA IgG and exposed to environmental agents such as organic solvents, certain pesticides, impregnating agents, animals, and exhausts were compared to those subjects with low levels that were not exposed. Antibody reactivity against the EBV EBNA 1-alanine-glycine repeat (P107 IgG) above the median gave an increased OR for HCL, which further increased in subjects exposed to organic solvents, certain pesticides. impregnating agents, animals, and exhausts. However, the numbers of exposed cases and controls were small in some of the calculations.

Case-control study on risk factors for testicular cancer.

Occupational exposures were assessed in a case-control study on testicular cancer using self administered questionnaires. Answers were obtained for 148 (91%) cases and 314 (87%) controls. Of the cases 101 had seminoma and 47 had embryonal testicular cancer. Occupational plastics work yielded odds ratio (OR) 2.9 with 95% confidence interval (CI) 1.3-6.5. Increased risk was found for embryonal cancer regarding farming (OR 3.1; CI 1.03-9.1) and contact with farm animals (OR 3.3; CI 1.00-10.9), but not for seminoma. For all testicular cancer exposure to insects repellents, mostly containing N,N-diethyl-m-toluamide (DEET) gave OR 1.7; CI 1.03-2.8, with a dose-response effect. Somewhat increased risks were found for amateur radio operators (OR 2.2; CI 0.7-6.6), work with radar equipment (OR 2.0; CI 0.3-14.2) and engineers in electronics and telecommunication industry (OR 2.3; CI 0.8-6.7) based on few exposed subjects, however. Video display unit work gave OR 1.5; CI 0.98-2.3 and for exposure 480 working days (median number) the risk increased further to OR 1.8; CI 1.1-3.2. Because of low numbers of exposed subjects in some calculations some of these results might be spurious and need to be further studied.

The secretion of soluble amyloid beta precursor protein (A beta PPs) by chick neurons in serum-free primary culture is not regulated by protein kinase C.

The metabolism of amyloid precursor protein (A beta PP) in chick neurons cultured in serum-free medium is described. A beta PP immunoreactivity, detected with the 22C11 antibody, was seen at approximately 135 and approximately 120 kDa. A beta PPs (approximately 120 kDa) was released from the cells and could be detected in the culture medium without the need of a purification step. The content of A beta PPs increased with time after medium change, but was not affected by either carbachol (100 microM), glutamate (50 microM), veratrine (20 microM), oleic acid (200 microM), A23187 (5 microM), phorbol 12, 13-dibutyrate (PDBu, 1 microM), staurosporine (1 microM), Gö 6976 (1 microM) or okadaic acid (50 nM) although the combination of PDBu and okadaic acid reduced the secretion. Addition of the muscarinic receptor agonist carbachol to the neurons increased the rate of phosphoinositide breakdown. In Western blot experiments using antibodies to the alpha, beta II and epsilon isoforms of protein kinase C and conditions whereby robust signals could be seen with rat brain lysates, no immunoreactive bands that could be inhibited by appropriate positive control peptides were seen. It is concluded A beta PPs production by chick neurons in culture is mainly constitutive in nature.