Non-muscle myosin II as a predictive factor in head and neck squamous cell carcinoma.

BACKGROUND: The present study attempted to provide information regarding non-muscle myosin II (MII) isoforms immunoreactivity in patients with head and neck squamous cell carcinoma (HNSCC) and analysis of the patients' clinical status after 5 years of monitoring. MATERIAL AND METHODS: A semiquantitative analysis of the immunoreactivity of the MII isoforms was performed in 54 surgical specimens and its correlation with clinical and pathological variables and prognosis was verified. Data were analyzed using chi-square, Mann-Whitney and Kruskal-Wallis tests. To evaluate the survival over the total monitoring time and any connection with the proteins studied, the Kaplan-Meier analysis was used. P values ≤0.05 were considered statistically significant. RESULTS: In the advanced stages of pathological tumor-node-metastasis, the expression of MIIB in adjacent non-neoplastic epithelial tissues tended to increase (p = 0.057). In tumoral zones there was an association of high expression among the three isoforms (MIIA/MIIB p=0,001, MIIB/MIIC p=0,006 and MIIA/MIIC p=0,012). Negative clinical evolution in patients was directly correlated to increased MIIC expression in the tumoral zone of invasion in HNSCC (p = 0.017). Based on clinical evolution after the monitoring period, patients with tumors expressing MIIC had poorer prognoses (p = 0.048). CONCLUSIONS: The present study suggests that MIIB expression in non-neoplastic adjacent epithelial tissues may indicate a potential for regional metastasis and that MIIC expression in the tumoral zone of invasion is predictive of negative evolution of the disease.

Epithelial oral mucosal cells: Do they behave differently when exposed to oral carcinogens?

OBJECTIVE: To assess the level of maturation and proliferation of epithelial cells and the correlation with immunocytochemical expression of adhesion (E-cadherin) and cell differentiation (involucrin) markers. METHODS: Cytopathological samples were obtained from four groups of patients: control (CG, n=30); alcohol/tobacco (ATG, n=31), leucoplakia (LG, n=31), and squamous cell carcinoma (SCCG, n=22). Cytopathological smears were collected from all groups for AgNOR, Papanicolaou and immunocytochemical staining. RESULTS: There was an increase in anucleated cells in ATG compared to CG and in LG compared to lesion-free groups (P<.05). In addition, there was a higher rate of intermediate cells in lesion-free groups than in LG (P=.001). When these findings were correlated with positive E-cadherin expression, there was a smaller number of anucleated and intermediate cells (P<.05). The proliferation rate was higher in the SCCG than in the CG (P<.05) and in the ATG compared to LG (P<.05). Moreover, cell proliferation increased in the presence of positive E-cadherin expression in the ATG and LG. No statistically significant results were obtained for involucrin analysis. CONCLUSION: Cytopathology combined with quantitative techniques such as Papanicolaou, AgNOR, and immunocytochemical expression of E-cadherin detects changes associated with oral carcinogenesis. The innovative approach used in this study allows assessing the expression of cell adhesion (E-cadherin) and differentiation (involucrin) markers by means of oral mucosal cytopathology. The E-cadherin imunocytochemical expression indicated changes associated with the oral carcinogenesis process. An increase in cell proliferation rate in oral squamous cell carcinoma group was associated with the lower immunoexpression of E-cadherin. Cytopathology combined with quantitative techniques and immunocytochemical expression of E-cadherin may detect early alterations associated with oral carcinogenesis.

The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial.

Study question: Does the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5-12 oocytes after IVF? Summary answer: The addition of AMH did not alter the rate of targeted ovarian response, 5-12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response. What is known already: Controlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes. Study design, size and duration: Between January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians. Participants/materials, setting, methods: Women aged >18 and <40 years, with a BMI above 18.0 and below 35.0 kg/m2 starting their first IVF cycle where standard IVF was planned, were eligible. All patients were treated with a GnRH agonist protocol and recombinant FSH was used for stimulation. The study was performed as a single-centre study at a large IVF unit at a university hospital. Main results and the role of chance: The rate of patients having the targeted number of oocytes retrieved was 81/152 (53.3%) in the intervention group versus 96/155 (61.9%) in the control group (P = 0.16, difference: -8.6, 95% CI: -20.3; 3.0). Cycles with poor response (<5 oocytes) were more frequent in the AMH group, 39/152 (25.7%) versus the non-AMH group, 17/155 (11.0%) (P < 0.01), while the number of cancelled cycles due to poor ovarian response did not differ 7/152 (4.6%) and 4/155 (2.6%) (P = 0.52). An excessive response (>12 oocytes) was seen in 32/152 (21.1%) and 42/155 (27.1%) patients, respectively (P = 0.27). Moderate or severe OHSS was observed among 5/152 (3.3%) and 6/155 (3.9%) patients, respectively (P = 1.0). Live birth rates were 48/152 (31.6%) and 42/155 (27.1%) per started cycle. Limitations, reasons for caution: The categorization of AMH values in predicted low, normal and high responders was originally established using the Diagnostic Systems Laboratories assay and was translated to more recently released assays, lacking international standards and well-established reference intervals. The interpretation of AMH values between different assays should therefore be made with some caution. Wider implications of the findings: An individualised dosage regimen including AMH compared with a non-AMH dosage regimen in an unselected patient population did not alter the number of women achieving the targeted number of oocytes, or the cancellation rate due to poor response or the occurrence of moderate/severe OHSS. However, this study cannot answer the question if using an algorithm for dose decision of FSH is superior to a standard dose and neither which ovarian reserve test is the most effective. Study funding/competing interest: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and unrestricted grants from Ferring Pharmaceuticals and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest. Trial registration: The study was registered at www.clinicaltrials.gov NCT02013973. Trial registration date: 6 December 2013. DATE OF FIRST PATIENT RANDOMIZED: 14 January 2013.

Selective intra-arterial dual-energy CT angiography (s-CTA) in lower extremity arterial occlusive disease.

OBJECTIVE: In patients with peripheral arterial occlusive disease, renal impairment is a common contraindication to iodine and gadolinium contrast media, which limits the utility of conventional computed tomography angiography (CTA) and magnetic resonance angiography (MRA). It is proposed that selective intra-arterial dual-energy CT-angiography (s-CTA), that is CTA with intra-arterial injection of an ultra-low dose iodine contrast media, is a feasible, safe and accurate alternative imaging method to conventional non-invasive contrast enhanced vascular imaging in this patient group. The aim of this study was to report a preliminary experience of s-CTA in patients with critical limb ischemia and renal insufficiency with respect to safety, feasibility, and diagnostic accuracy. MATERIALS AND METHODS: Ten non-consecutive patients with ischemic foot ulcers underwent s-CTA of one leg. Procedure related complications were recorded and imaging results were compared with conventional digital subtraction angiography (DSA). RESULTS: A median 17 mL (range 10-19 mL) contrast media (400 mg I/mL) was used. The median baseline plasma creatinine was 163 µmol/L (range 105-569) pre s-CTA versus 153 µmol/L (range 105-562) post s-CTA (p = .24). There was no puncture site complication. Among the patients selected for intervention (n = 6 with 30 arterial segments) the s-CTA findings correlated well with the DSA findings; the diagnostic sensitivity was 100%, the specificity 89%, and the accuracy 93%. CONCLUSION: In this pilot study, a novel imaging method (s-CTA) is presented that provides high-quality arterial phase images with ultra-low dose iodine contrast media useful also for patients unsuitable for conventional contrast enhanced imaging methods because of renal insufficiency.

Young adults looking back at their experiences of treatment and care for nonsuicidal self-injury during adolescence: a qualitative study.

BACKGROUND: Nonsuicidal self-injury (NSSI) is associated with stigma, and negative attitudes among healthcare professionals toward NSSI have been reported. A person-centered approach that focuses on how individuals with lived experience of NSSI perceive the treatment and care they receive is invaluable in reducing barriers to help-seeking and improving treatment and mental healthcare services. The aim of the current qualitative study was to explore the perceptions of young adults when they look back upon their experiences of psychiatric treatment for NSSI during adolescence. METHODS: Twenty-six individuals with lived experience of NSSI who were in contact with child and adolescent psychiatry during adolescence were interviewed. The interviews were analyzed using thematic analysis. RESULTS: Three main themes were developed: Changed perceptions in retrospect, The importance of a collaborative conceptualization and Lasting impression of the relationship. Participants' perception of themselves as well as the treatment changed over time. The importance of a joint understanding of NSSI and an agreed-upon treatment focus was emphasized. The relationship to the mental health professionals, and experiences of how NSSI was communicated, were salient several years later. CONCLUSIONS: Healthcare professionals need to communicate about NSSI in a respectful manner and include the perspective of the adolescent with lived experience of NSSI in a joint conceptualization of NSSI and treatment focus.

Familial influence and childhood trauma in female alcoholism.

BACKGROUND: To assess the role of genetic and environmental factors in female alcoholism using a large population-based twin sample, taking into account possible differences between early and late onset disease subtype. METHOD: Twins aged 20-47 years from the Swedish Twin Registry (n=24 119) answered questions to establish lifetime alcohol use disorders. Subjects with alcoholism were classified for subtype. Structural equation modeling was used to quantify the proportion of phenotypic variance due to genetic and environmental factors and test whether heritability in women differed from that in men. The association between childhood trauma and alcoholism was then examined in females, controlling for background familial factors. RESULTS: Lifetime prevalence of alcohol dependence was 4.9% in women and 8.6% in men. Overall, heritability for alcohol dependence was 55%, and did not differ significantly between men and women, although women had a significantly greater heritability for late onset (type I). Childhood physical trauma and sexual abuse had a stronger association with early onset compared to late onset alcoholism [odds ratio (OR) 2.54, 95% confidence interval (CI) 1.53-3.88 and OR 2.29, 95% CI 1.38-3.79 respectively]. Co-twin analysis indicated that familial factors largely accounted for the influence of physical trauma whereas the association with childhood sexual abuse reflected both familial and specific effects. CONCLUSIONS: Heritability of alcoholism in women is similar to that in men. Early onset alcoholism is strongly association with childhood trauma, which seems to be both a marker of familial background factors and a specific individual risk factor per se.

Obstetric and perinatal risks after the use of donor sperm: A systematic review and meta-analysis.

Donor sperm is widely used in infertility treatments. The purpose of the study was to investigate, whether use of donor sperm in intrauterine insemination (IUI) or in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments affect maternal and perinatal risks compared with spontaneously conceived pregnancies or use of partner sperm in IUI, IVF or ICSI. We provide a systematic review and meta-analyses on the most clinically relevant obstetric and perinatal outcomes after use of donor sperm compared with partner sperm: hypertensive disorders of pregnancy, preeclampsia, low birth weight, and preterm birth. Our meta-analyses showed an increased risk for preeclampsia (pooled adjusted odds ratio (aOR) 1.77, 95% CI 1.26-2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95%, CI 1.20-2.00) in pregnancies resulting from IUI with donor sperm compared with IUI with partner sperm. No increased risk was seen for low birth weight or preterm birth after the use of donor sperm in IUI compared with the use of partner sperm in IUI. Subgroup analysis for singletons only did not change these results. The meta-analysis on low birth weight showed a lower risk after in IVF with donor sperm compared with IVF with partner sperm (pooled aOR 0.89, 95% CI 0.83-0.94). For hypertensive disorders of pregnancy, preeclampsia and preterm birth, no difference was found between IVF with donor sperm vs. partner sperm. Patients need to be informed about the moderately increased risk of hypertensive disorders of pregnancy and preeclampsia in pregnancies after IUI with donor sperm.

Comparison of quality of urinary bladder filling in CT urography with different doses of furosemide in the work-up of patients with macroscopic hematuria.

INTRODUCTION: The protocol for preparation of computed tomography urography (CTU) examinations at our hospital was changed in 2013 to improve the quality of urinary bladder filling in the excretory phase. The aim of this study was to evaluate the quality of urinary bladder filling on CTU after different doses of furosemide were administered to patients with macroscopic hematuria. METHODS: The cohort was 215 patients who underwent elective CTU due to macroscopic hematuria between 2014 and 2018. 5 mg furosemide were administrated to 100 patients, 2.5 mg to 100 patients and 0 mg to 15 patients. Contrast medium layered bladders were excluded, leaving 193 patients: 92, 89 and 12 in each group. Urinary bladder volume was calculated in corticomedullary (CMP) and excretory phase (EP). Bladder distension was classified as satisfactory or not. Attenuation of bladder content in EP was noted. RESULTS: Average volume in EP was 370 ± 224 ml (28-1052) after 5 mg furosemide, 274 ± 120 ml (43-628) after 2.5 mg and 180 ± 104 ml (53-351) after 0 mg. 85% of the bladders were satisfactory distended after 5 mg, 80% after 2.5 mg and 58% after 0 mg. Average attenuation was 266 ± 89 HU (103-524) after 5 mg, 362 ± 156 HU (118-948) after 2.5 mg and 761 ± 331 HU (347-1206) after 0 mg. The differences in volume and attenuation were significant. CONCLUSION: 5 mg furosemide is preferred rather than 2.5 mg in preparation for CTU examinations of patients with macroscopic hematuria. There was no difference between the doses concerning rate of satisfactory bladder distension, but the higher dose resulted in larger bladder volume and more suitable attenuation of bladder content. IMPLICATIONS FOR PRACTICE: Development of CTU-image quality could improve bladder cancer diagnostics.

Optimization of computed tomography urography protocol, 1997 to 2008: effects on radiation dose.

BACKGROUND: Since computed tomography (CT) urography began to replace excretory urography as the primary imaging technique in uroradiology, the collective radiation dose to the patients has increased. PURPOSE: To examine the changes in the CT urography protocol for investigating suspected urinary tract malignancy between the years 1997 and 2008, and how these changes have influenced the mean effective dose. MATERIAL AND METHODS: The study was based on 102 patients (mean age 66.1+/-14.8 years, range 31-89 years; 30 female, 72 male) divided into five groups (groups A-E) corresponding to the time points at which changes were made to the CT urography protocol. The mean effective doses were estimated using the ImPACT CT Patient Dosimetry Calculator. RESULTS: The number of scan phases at CT urography was reduced from four to three in 1999, resulting in a reduction of the mean effective dose from 29.9/22.5 (female [F]/male [M]) mSv (group A) to 26.1/18.9 (F/M) mSv (group B). In 2001, mAs settings were adapted to patient size, and the mean effective dose was reduced to 16.8/12.0 (F/M) mSv (group C). In 2005, scans were performed with a multidetector-row CT equipped with automatic tube current modulation in the x- and y-axis (CARE Dose). The effective mAs was also lowered in the unenhanced and excretory phase, yet the mean effective dose increased to 18.2/13.1 (F/M) mSv (group D), since the effective mAs had to be increased in the corticomedullary phase to maintain image quality. In 2008, as tube current modulation in the x-, y-, and z-axis was introduced (CARE Dose4D), the mean effective dose was reduced to 11.7/8.8 (F/M) mSv (group E). CONCLUSION: This study shows that the individual mean effective dose to patients undergoing CT urography has decreased by 60%, from 29.9/22.5 (F/M) mSv in 1997 to 11.7/8.8 (F/M) mSv in 2008.

Outcome after percutaneous transluminal angioplasty of arterial stenosis in renal transplant patients.

BACKGROUND: Ensuring graft survival in renal transplant patients is of paramount importance. Early detection and treatment of complications such as transplant renal artery stenosis (TRAS) are essential. PURPOSE: To evaluate the technical and clinical success rate of renal transplant patients with stenosis in the transplant renal artery or in the iliac artery after percutaneous transluminal angioplasty (PTA). MATERIAL AND METHODS: PTA was carried out on 24 patients with TRAS or iliac artery stenosis. Altogether, 28 stenoses were treated with PTA. The immediate technical result and the clinical outcomes after 1 and 3 months were assessed as well as clinical adverse events. A reduction in serum creatinine and/or a reduction in the number of antihypertensive drugs were criteria for clinical success. RESULTS: The immediate technical success rate after PTA was 93%. The clinical success rate after 1 month was 58%, increasing to 75% after 3 months. CONCLUSION: The technical success rate is not equivalent to the clinical success rate when treating TRAS with PTA. Furthermore, there is a delay in clinical response, sometimes of 3 months, after a technically successful PTA.

The correlation between AMH assays differs depending on actual AMH levels.

STUDY QUESTION: What is the correlation of serum anti-Müllerian hormone (AMH) levels between two frequently used laboratory assays? SUMMARY ANSWER: A considerable difference was found in serum AMH levels measured with the two different assays, particularly for low AMH values. WHAT IS KNOWN ALREADY: AMH is regarded as being a robust, highly sensitive and specific biomarker for ovarian response and has become widely used as the basis for fertility treatment decisions. However, several available assays with different reference values, in addition to inter-laboratory variations and issues of sample stability, make interpretation of the AMH values and their clinical implications complicated. STUDY DESIGN SIZE DURATION: An observational study was performed including 269 serum samples from infertile women, originating from a RCT conducted in 2013-2016 (www.clinicaltrials.gov NCT02013973). PARTICIPANTS/MATERIALS SETTING METHOD: Serum AMH levels analysed with the Modified Beckman Coulter Gen II ELISA assay (Premix method) were compared to AMH levels analysed with the Beckman Coulter Gen II ELISA original assay (Gen II original). All samples were handled identically and analysed with the two assays in a parallel setting. MAIN RESULTS AND THE ROLE OF CHANCE: The slope of the regression line showed a mean of 18% higher values with the Premix method compared to the Gen II original assay, and more than 40% higher values for AMH levels in the lower range. LIMITATIONS REASONS FOR CAUTION: The Gen II original assay is no longer in clinical use as it has been replaced by the Premix method, which, in turn, recently has been further developed into an automated method. WIDER IMPLICATIONS OF THE FINDINGS: The finding of differences in AMH levels between assays is clinically important and may imply an incorrect classification in the assessment of ovarian reserve. The robustness of serum AMH as a marker for ovarian reserve and as a tool for fertility counselling has to be investigated further. There is an urgent need for international standards on interpretation of AMH values for different assays. STUDY FUNDING/COMPETING INTERESTS: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70940) and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

Latent classes in diagnoses among psychiatric inpatients predicting mortality and imprisonment - a nationwide cohort study.

PURPOSE: Identify risk factors of death or imprisonment within classes defined by demographic factors and diagnoses within one year of first psychiatric admission. METHODS: Nationwide data was obtained from hospital registers from psychiatric hospitals in Iceland 1983-2007. Mortality and cause of death as well as information about imprisonments during the study period, and discharge diagnoses for the first year after initial admission were obtained for each individual. Individuals aged 18 during the study period with at least one year of follow-up were included. Latent Class Analysis was used to identify groups with distinguishable risk of either being alive, dead or having been imprisoned at the end of follow-up. RESULTS: Among psychiatric patients, 4677 were included, average age was 27 years (range 18-43). Four latent classes were identified with different risks of adverse outcomes. Class B (16%), predominantly males with substance use disorder (SUD) diagnoses, had highly increased risk of imprisonment and death accounting for 85 and 34% of these outcomes, respectively. Class A (12%), all with alcohol use disorder, had similar mortality rate as the general population and no imprisonments. Class C (23%) were younger at first admission with some SUD and increased risk of mortality. Class D (46%) had increased mortality rate, SUDs were rare but depression common. CONCLUSIONS: Risk of mortality and criminal trends among psychiatric inpatients can be described as distinct clusters of risk factors present at first admission to a psychiatric hospital. Treatment and interventions to reduce mortality and criminality should take these risk differences into account.

Methylphenidate disintegration from oral formulations for intravenous use by experienced substance users.

BACKGROUND AND AIMS: Methylphenidate (MPH) is a prescription stimulant used to treat attention-deficit hyperactivity disorder. MPH is currently the preferred substance among most intravenous (i.v.) substance users in Iceland. Four types of MPH preparations were available in Iceland at the time of study: Immediate-release (IR), sustained-release (SR), osmotic controlled-release oral delivery (OROS) tablet and osmotic-controlled release (OCR). MPH OROS has previously been rated the least desirable by i.v. users and we hypothesized that this was associated with difficulty of disintegrating MPH from OROS formulation. The aim of the study was to measure the amount of MPH and the viscosity of the disintegrated solutions that were made from the four MPH formulations by four i.v.-users and non-users. METHODS: A convenience sample of four i.v. substance users and 12 non-users. Non-users imitated the methods applied by experienced i.v. substance users for disintegrated MPH formulations. RESULTS: Both groups managed to disintegrate over 50% of MPH from IR and SR formulations but only 20% from OROS (p<0.0001). The viscosity of the disintegrated MPH was significantly higher for MPH OROS and MPH OCR and the preparation was significantly more time-consuming than for the other MPH samples. No differences were observed between users and non-users. CONCLUSIONS: To our knowledge, this is the first investigation of viscosity and the amount of disintegrated MPH from prescription drugs for i.v. use. The results indicate that the ease of disintegration, amount of MPH and viscosity may explain the difference in popularity for i.v. use between different MPH formulations.

Insight, symptoms and neurocognition in bipolar I patients.

BACKGROUND: Level of insight and its relationship to clinical variables and neurocognitive functions was assessed in bipolar I patients. METHODS: Verbal memory, executive functioning, sustained attention, general intelligence and other neurocognitive functions were compared between 37 chronic in- and outpatients and 31 matched normal controls. Detailed psychiatric interviews were completed to define the level of symptomatology and psychosocial functioning. Insight was assessed by the Scale to Assess Unawareness of Mental Disorder (SUMD). RESULTS: Seventy percent of the patients were classified as having impaired insight. Prevalence of impaired insight was 47% and 94% in remitted and symptomatic patients, respectively. Symptomatic patients scored significantly below remitted patients on insight and neurocognition. Illness and symptom unawareness were related to overall level of symptoms, measures of memory, conceptual ability and right hand psychomotor speed and accuracy. Misattribution of symptoms and signs was correlated to visuomotor speed and visuospatial performance in addition to affective symptoms and thought disturbance. CONCLUSIONS: Our findings support the hypothesis that impaired insight and other neurocognitive dysfunctions were present in a large percentage of cases among symptomatic as well as remitted bipolar patients. This may be of clinical relevance and raises important questions about the course and outcome of the illness.

Pelvicaliceal biomodeling as an aid to achieving optimal access in percutaneous nephrolithotripsy.

PURPOSE: To investigate prospectively the benefits of three-dimensional stereolithographic biomodeling produced from CT data as an aid to achieving optimal access for percutaneous nephrolithotripsy (PCNL). PATIENTS AND METHODS: Eight patients with complex urinary calculi were selected. Multislice CT scans of the kidney in native and excretory phases were acquired with the patient in the prone position to simulate the position during surgery. Contiguous reconstructed slices were produced from the data volume. The data of interest were processed to transform them into a format acceptable for production of a biomodel. Exact plastic replicas of the pelvicaliceal system and the calculi were created and used for morphologic assessment, preoperative planning, patient education, and surgical navigation. RESULTS: The survey results were based on subjective opinions rather than objective data. The biomodels enhanced the ability to visualize a patient's unique anatomy before surgery. This aided the planning and rehearsal of endourologic procedures. CONCLUSION: Although this study is only a preliminary investigation, we postulate that biomodeling has the advantage of allowing imaging data to be displayed in a physical form. In difficult cases, this technique may improve treatment, operative planning, and communication with colleagues and patients. The limitations of the technology include the manufacturing time and cost, but more accurate puncture-site selection may reduce costs by saving operating time.

Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity.

Twenty patients with malignant carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers and size. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%) had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these patients.

Living by themselves? Psychiatric nurses' views on supported housing for persons with severe and persistent mental illness.

The main principle directing the development of supported dwellings for persons with long-term mental illness is that to live in the community would improve their quality of life. The aim of this study was to describe psychiatric nurses' experiences of different types of supported dwelling for persons with long-term mental illness, and their views on what they consider to be important principles to provide for in order to facilitate their social integration into the community. Nine psychiatric nurses were interviewed. A qualitative content analysis revealed 'attempting to uphold the principle, respect for the patient's right to self-determination' as the main theme, which was linked to three sub-themes: the nurses' view on their moral responsibility; the nurses' views on social norms that patients must follow in order to be accepted by their neighbours; and the nurses' views on supported dwelling of good quality. The nurses perceived that personal contact between the neighbour and the mentally ill person was one essential way to reduce fear of the mentally ill person. They viewed themselves as a link between the mentally ill person and other neighbours. Without the personal contact between the mentally ill person and the neighbours, there may be a risk that the integration will fail no matter how excellent the supported dwelling is framed.

Nuclear changes in oral mucosa of alcoholics and crack cocaine users.

The effects of drugs of abuse on oral mucosa are only partly understood. The aims of the present study were to: (1) evaluate the frequency of nuclear changes in normal-appearing oral mucosa of alcoholics and crack cocaine users and (2) assess their association with cell proliferation rate. Oral smears were obtained from the border of the tongue and floor of the mouth of 26 crack cocaine users (24 males and 2 females), 29 alcoholics (17 males and 12 females), and 35 controls (17 males and 18 females). Histological slides were submitted to Feulgen staining to assess the frequency of micronuclei (MN), binucleated cells (BN), broken eggs (BE), and karyorrhexis (KR). A significant increase in the frequency of MN was observed in cells exfoliated from the tongue of crack cocaine users (p = 0.01), and alcoholics showed a higher frequency of KR in cells obtained from the floor of the mouth (p = 0.01). Our findings suggest that the use of crack cocaine induces clastogenic effects, whereas alcoholism is associated with higher degrees of keratinization in the floor of the mouth.

The prevalence of seasonal affective disorder is low among descendants of Icelandic emigrants in Canada.

OBJECTIVE: To examine whether a genetic selection within the Icelandic population helps it to adapt to the long arctic winter. PARTICIPANTS AND SETTING: The target population was a group of adults in the Interlake district of Manitoba, Canada, wholly descended from Icelandic emigrants. The ancestry of every individual in this group can be traced back to 1840. DESIGN: The Seasonal Pattern Assessment Questionnaire was mailed to a random sample of the study population. The data were compared with results obtained with similar methods in populations in Iceland and on the eastern seaboard of the United States. MAIN OUTCOME MEASURES: Prevalence rates of seasonal affective disorder and subsyndromal seasonal affective disorder. RESULTS: The prevalence rates of seasonal affective disorder and subsyndromal seasonal affective disorder were found to be 1.2% and 3.3%, respectively, in this group of Canadians of wholly Icelandic descent. These are significantly lower than those measured with similar methods among people living along the east coast of the United States (chi 2 = 12.6 and 14.4, respectively, P < .001). Standardized rate ratio for this group compared with the American group was 0.18 for seasonal affective disorder and 0.38 for subsyndromal seasonal affective disorder. CONCLUSIONS: This is the second study to find the prevalence of seasonal affective disorder and subsyndromal seasonal affective disorder to be lower among Icelanders or their descendants than among populations along the east coast of the United States. The results indicate that the relationship between prevalence of these disorders and geographic latitude is more complex than has previously been suggested; genetic adaptation in Icelandic populations may play an important role.

Prevalence of seasonal affective disorder in Iceland.

OBJECTIVE: To investigate seasonal patterns in mood and behavior and estimate the prevalence of seasonal affective disorder (SAD) and subsyndromal seasonal affective disorder (S-SAD) in the Icelandic population. PARTICIPANTS AND SETTING: A random sample generated from the Icelandic National Register, consisting of 1000 men and women aged 17 to 67 years from all parts of Iceland. It represents 6.4 per million of the Icelandic population in this age group. DESIGN: The Seasonal Pattern Assessment Questionnaire, an instrument for investigating mood and behavioral changes with the seasons, was mailed to a random sample of the Icelandic population. The data were compared with results obtained with similar methods in populations in the United States. MAIN OUTCOME MEASURES: Seasonality score and prevalence rates of seasonal affective disorder and subsyndromal seasonal affective disorder. RESULTS: The prevalence of SAD and S-SAD were estimated at 3.8% and 7.5%, respectively, which is significantly lower than prevalence rates obtained with the same method on the east coast of the United States (chi 2 = 9.29 and 7.3; P < .01). The standardized rate ratios for Iceland compared with the United States were 0.49 and 0.63 for SAD and S-SAD, respectively. No case of summer SAD was found. CONCLUSIONS: Seasonal affective disorder and S-SAD are more common in younger individuals and among women. The weight gained by patients during the winter does not seem to result in chronic obesity. The prevalence of SAD and S-SAD was lower in Iceland than on the East Coast of the United States, in spite of Iceland's more northern latitude. These results are unexpected since the prevalence of these disorders has been found to increase in more northern latitudes. The Icelandic population has remained remarkably isolated during the past 1000 years. It is conceivable that persons with a predisposition to SAD have been at a disadvantage and that there may have been a population selection toward increased tolerance of winter darkness.