Acral lentiginous melanoma: a skin cancer with unfavourable prognostic features. A study of the German central malignant melanoma registry (CMMR) in 2050 patients.

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. OBJECTIVES: To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. METHODS: The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. RESULTS: In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. CONCLUSIONS: ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.

Complex phenotypes blur conventional borders between Say-Barber-Biesecker-Young-Simpson syndrome and genitopatellar syndrome.

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as 'KAT6B spectrum disorders' or 'KAT6B related disorders', rather than their current SBBYSS and GTPTS classification.

Algorithm for detection of small-bowel metastasis in malignant melanoma of the skin.

BACKGROUND AND STUDY AIM: The aim of this study was to develop an algorithm to detect small-bowel metastasis (SBM) of melanoma by sequential laboratory parameters and pan-intestinal endoscopy (PIE) including video capsule endoscopy (VCE). PATIENTS AND METHODS: A total of 390 melanoma patients (AJCC stage I/II/III/IV, 140/80/121/49) were screened for signs of intestinal blood loss (fecal occult blood test [FOBT] or overt bleeding) in an open, multicenter, prospective study, and those who were positive underwent PIE. Independent of the presence of intestinal bleeding, all stage IV patients were offered PIE. Follow-up was obtained in 357 patients (91.5 %) for a median of 16 months. We undertook to identify possible associations between SBM and clinical and laboratory data. Survival data were analyzed with regard to clinical and laboratory data and small-bowel findings. RESULTS: Intestinal blood loss was suspected in 49 of 390 patients (12.6 %), 38 of whom (77.6 %) agreed to undergo endoscopy. In 10 patients, SBM was detected by VCE (intention-to-diagnose, 20.4 %; AJCC III, n = 2; AJCC IV, n = 8). The SBM was resected in five patients. Total detection rates of SBM were 14 of 49 patients in stage IV (28.6 %, intention-to-diagnose), 2 of 121 in stage III (1.7 %), and 0 in stage I/II. In FOBT-positive patients, SBM detection rates were 72.7 %, 14.3 %, and 0 % in tumor stages IV, III, and I/II, respectively. Positive FOBT proved to be an independent negative prognostic factor for total survival in stage III and IV melanoma. CONCLUSIONS: SBMs are frequent in advanced melanoma. In stage III patients, screening for intestinal blood loss by PIE may help to identify SBMs. In stage IV, indication for PIE should depend on the individual consequences of detecting SBM, but not on bleeding symptoms alone.

Impact of native, heat-processed and encapsulated hazelnuts on the allergic response in hazelnut-allergic patients.

BACKGROUND: Pollen-associated food allergy is common. However, systemic reactions or even life-threatening anaphylaxis are rare. OBJECTIVE: The aim of this study was to investigate the clinical impact of native, heat-processed and encapsulated hazelnuts (HN) in patients with proven HN allergy. METHODS: One hundred and thirty-two patients with a positive history of HN allergy were recruited. Sensitization was confirmed by a skin prick test (SPT) and sIgE against HN. After an HN-free diet, double-blind placebo-controlled challenges were performed with increasing amounts of native and roasted HN. A subset of patients were given HN capsules to circumvent the oral mucosa. Basophil activation was measured by flow cytometry before and after provocation but also ex vivo using native and roasted HN extracts. RESULTS: Three groups of HN-allergic patients were identified depending on their clinical reaction pattern. The dosages by which allergic reactions were elicitated varied for native HN from 0.01 to 2.0 g, with a median of 0.1 g, for roasted HN from 0.01 to 10.0 g, with a median of 0.23 g, and for encapsulated HN from 0.1 to 3.0 g, with a median of 0.3 g. Accordingly, the SPT was more frequently positive and resulted in greater weal reactions if native HN was used. This finding was confirmed by ex vivo basophil activation showing that significantly higher allergen extract concentrations (roasted>native) were necessary to induce 50% basophil activation. CONCLUSION: Our data show that heat processing of HN reduces its allergenicity. SPT but also the basophil activation test can be used to determine the reactivity of an allergen extract.

[Symptomatic cardiac metastasis. Isolated visceral manifestation of a cutaneous malignant melanoma]. / Symptomatische Herzmetastase. Solitäre viszerale Manifestation eines kutanen malignen Melanoms.

Symptomatic cardiac melanoma metastases are very rare. A 76-year-old woman was admitted because of dyspnea and intrathoracic pain 8 years after surgery of a superficial spreading melanoma and 4 years after resection of in-transit metastases. MRI and echocardiography disclosed an intracavitary right atrial mass. Histologically a cardiac melanoma metastasis was found. Unspecific cardiac symptoms in a patient with elevated risk for distant metastases of melanoma should be further investigated to discover cardiac metastasis early.

Genomic organization and expression pattern of scapinin (PHACTR3) in mouse and human.

Scapinin has been found to bind to cytoplasmic actin and is also a putative regulatory subunit of protein phosphatase-1 (PP1). It is found attached to the nuclear matrix-intermediate filament (NM-IF) and is down-regulated by differentiation of tumor cells. We have analyzed the genomic structure and tissue-specific expression pattern of both the human scapinin gene (PHACTR3) and the orthologous mouse gene. Both genes showed a highly conserved complex genomic organization with four different leader exons. Alternative splicing of exon 5 was found to be limited to human and variable polyadenylation in mouse transcripts only. In both species expression seems to occur predominantly in the brain. By Northern blot analysis two major transcripts in human and three transcripts in mouse were detected. Expression analysis in the mouse revealed a tissue-specific complex transcription pattern in the brain and a specific pattern was observed during prenatal development. Based on the transcriptional data we therefore assume scapinin to have a distinct biological function in the mammalian brain.

Retrospective interactive rigid fusion of (18)F-FDG-PET and CT. Additional diagnostic information in melanoma patients.

AIM: This study investigates whether interactive rigid fusion of routine PET and CT data improves localization, detection and characterization of lesions compared to separate reading. For this purpose, routine PET and CT scans of patients with metastases from malignant melanoma were used. PATIENTS, METHODS: In 34 patients with histologically confirmed malignant melanoma, FDG-PET and spiral CT were performed using clinical standard protocols. For all of these patients, gold standard was available. Clinical and radiological follow-up identified 82 lesions as definitely pathological. Two board-certified nuclear medicine physicians and two board-certified radiologists analyzed PET and CT images independently from each other. For each patient up to 32 anatomical regions (24 lymph node regions, 8 extranodular regions) were systematically classified. Discordant areas were interactively analyzed in manually and rigidly registered images using a commercially available fusion tool. No side-by-side reading was performed. RESULTS: Image fusion disclosed that the evaluation of the PET images alone led to a mislocalization in 26 of 91 focally FDG enhancing lesions. The overall sensitivities of PET, CT, and image fusion were 85, 88, and 94%, respectively; the overall specificities of PET, CT and image fusion were 98, 95 and 100%, respectively. Image fusion exhibited statistically significant higher specificity values as compared with CT. Ten definitely malignant sites were false-negative in CT, but could be detected by PET. On the other hand, twelve metastases were false-negative in PET, but could be detected by CT. These included two lesions, which had a clear correlate on the PET image when the fused images were evaluated. On the whole, registration of the PET and CT images yielded additional diagnostic information in 44% of the definitely malignant lesions. CONCLUSION: Retrospective image fusion of independently obtained PET and CT data is particularly valuable in exactly localizing foci of abnormal FDG uptake and improves the detection of metastases of malignant melanoma.

Attenuation correction of SPECT images based on separately performed CT: Effect on the measurement of regional uptake values.

AIM: A new software approach uses separately acquired CT images for attenuation correction after retrospective fusion with the SPECT data. This study evaluates the effect of this CT-based attenuation correction on indium-111-pentetreotide-SPECT images. METHODS: Indium-111-pentetreotide-SPECT imaging using a dual-head gamma camera e.cam (Siemens Medical Solutions, Erlangen, Germany) as well as separate spiral computed tomography (CT) was performed in 13 patients. After fusion of SPECT and CT data, the bilinear attenuation coefficients were calculated for each pixel in the CT image volume using their Hounsfield unit values and attenuation-corrected images were reconstructed iteratively (OSEM 2D). Regions of interest (ROIs) were drawn on 24 suspicious foci and background, and target to background ratios were calculated for corrected (TBAC) and uncorrected (TBNAC) images. The shortest distance from the centre of the lesion to the surface of the body (DS) was measured on the corresponding CT slice. Furthermore, ROIs were drawn over the rim and the centre of the liver. Ratios of hepatic count rates for corrected (LRAC) and uncorrected (LRNAC) images were also compared. RESULTS: In lesions located more centrally, TBAC was up to 52% higher, whereas in peripherally located lesions, TBAC was up to 63% lower than TBNAC. The TBAC/TBNAC quotient was linearly correlated with DS. In the liver, attenuation correction resulted in a 35% increase of LRAC compared with LRNAC. CONCLUSIONS: Attenuation correction of SPECT images performed by separately acquired CT data is quick and simple. It improves the contrast between target and background for lesions located more centrally in the body and improves homogeneity of the visualisation of tracer uptake in the liver.

Postnatal development of two nicotinic cholinergic receptors in seven mouse brain regions.

The developmental profiles for binding of alpha-[125I]bungarotoxin and L-[3H]nicotine to putative nicotinic cholinergic receptors were determined in seven mouse brain regions. The overall pattern of development of alpha-bungarotoxin binding was similar in all of the regions. Neonatal binding values tended to be greater than those observed in adult brain regions. Maximal binding occurred within 10 days of birth and adult binding values were reached by 20 days of age. The patterns of development of nicotine binding in each of the seven brain regions differed according to region. Gross similarities in developmental profiles for nicotine binding were found among the more caudal and among the more rostral regions. In hindbrain and cerebellum, maximal nicotine binding was found at birth (5 days of age in cerebellum); binding declined approximately 4-fold by 20 days and remained relatively constant thereafter. In midbrain and hypothalamus, a less extensive decrease in nicotine binding occurred from birth to adulthood (midbrain, 25%; hypothalamus, 50%). Nicotine binding in hippocampus and cortex remained unchanged between birth and adulthood. The developmental pattern for nicotine binding in striatum differed from that found in the other brain regions. At 5 days of age, binding was about 65% of adult binding, which was reached at 30 days of age. In most of the brain regions the developmental profile for alpha-bungarotoxin binding was different from that of nicotine. This difference was especially notable in striatum, where adult nicotine binding was higher than neonatal nicotine binding, whereas adult alpha-bungarotoxin binding was lower than neonatal alpha-bungarotoxin binding.

Etonitazine-induced rigidity and its antagonism by centrally acting muscle relaxants.

Some narcotic drugs have been reported to produce increases in muscle tone in rats. In our laboratory we have found that etonitazine produces a 'lead-pipe' rigidity of the trunk and limb musculature. The reported studies were conducted to characterize etonitazine-induced rigidity more fully, to compare the degree of rigidity with that produced by morphine, codeine and methadone, and to assess the sensitivity of this rigidity to centrally acting muscle relaxants. Of the 4 narcotics tested, etonitazine was far more potent than methadone or morphine for producing rigidity; codeine did not produce peak rigidity comparable to the other 3 narcotics. Etonitazine-induced rigidity occurs at a supraspinal level since the effect was prevented by spinal transsection. Etonitazine-induced rigidity was prevented by the narcotic antagonists cyclazocine, pentazocine and naloxone but not by the serotonin depletor, p-chlorophenylalanine. Etonitazine-induced rigidity was antagonized by centrally acting muscle relaxants, including diazepam, methocarbamol, carisoprodol and zoxazolamine; in agreement with their relative clinical muscle relaxant potencies, diazepam is the most potent antagonist of etonitazine-induced rigidity.

Pelvic adhesion formation after intraperitoneal installation of gallstones in a rabbit model.

OBJECTIVE: To investigate whether intraperitoneal gallstones increase the risk of pelvic adhesions in a rabbit model. DESIGN: Prospective, randomized, blinded, sham and human antigen controlled trial. SETTING: An academic research environment. SUBJECT(S): Twelve New Zealand white rabbits. INTERVENTION(S): Twelve rabbits were divided into three groups of four each; a sham operation group, a gallstone and bile group (study group), and a human serum albumin and bile group (antigenic control). Three weeks after the operation individual subjects were randomized, with groups concealed to observers, and a necropsy was performed on each rabbit. MAIN OUTCOME MEASUREMENT(S): Necropsy was performed on each rabbit, and the adhesions were scored for extent, type, tenacity, inflammation, and gallstone involvement. RESULT(S): There was a statistically and biologically significant increase in gallstone involvement in adhesions, especially pelvic adhesions, in the study group. CONCLUSION(S): This study, along with an increasing number of case reports, suggests that gallstones inadvertently left in the peritoneal cavity may increase the morbidity of laparoscopic cholecystectomy. In females of reproductive age these gallstones may induce pelvic adhesions that may interfere with fertility or be associated with pelvic pain.

Is weight gain after smoking cessation inevitable?

Weight gain after smoking cessation was studied in a naturalistic setting where (1) all smokers quit and (b) risk factors for postcessation weight gain were modified. Participants were 332 military recruits (227 men, 105 women), 86 of whom were smokers who quit during 6 weeks of basic training. Results showed no significant weight changes for smokers who quit. Pretest smoking rates and feat of weight gain were unrelated to changes in weight. Results suggest that an intensive program that limits access to alcohol and foods that are high in fat and that increases physical activity can attenuate weight gain after smoking cessation.

Recollections of conflict with parents and family support in the personality disorders.

This study examined the relationships between personality disorders and retrospective reports of family support and conflict with parents. Participants were 798 United States Air Force recruits who were participating in a larger program of research on the peer assessment of personality disorders. Correlational analyses revealed consistent but modest associations between personality disorder features and both measures of family adversity. Borderline, antisocial, and paranoid features maintained small, unique associations after controlling for the general component of personality disorder. Further analyses, however, showed that differences among the correlations between personality disorder traits and family adversity measures account for little explained variance. In general, it does not appear that individual personality disorders have unique relations with retrospective reports of family adversity. Instead, the relation between personality disorders and family adversity seems to depend on a component common to all personality disorders.

[Image quality and radiation exposure in digital mammography with storage phosphor screens in a magnification technic]. / Bildgüte und Strahlenexposition bei der digitalen Mammographie mit Speicherfolien in Vergrösserungstechnik.

PURPOSE: Comparison of image quality between digital phosphor storage plate mammography in magnification technique and a conventional film screen system regarding the special aspect of radiation exposure. MATERIALS AND METHODS: Radiograms of a RMI-mammography phantom were acquired using a conventional film screen system and two digital storage plate systems. Additionally, the radiograms of one digital system were post-processed emphasizing contrast and included in the comparison. RESULTS: The detectability of details in storage plate mammographies with magnification technique is almost equal to that of film screen mammographies. Thereby, lower radiation exposures were necessary using the digital systems. CONCLUSIONS: Based on these results, storage plate mammography in magnification technique is used in clinical routine at our institution. The correct parameters in image postprocessing are of elementary importance for detail detectability. Future studies must show, whether the lower radiation exposure in digital radiograms of the breast, revealing much higher background noise, will allow the same detail detectability as film screen mammographies.

[Time consumption and quality of an automated fusion tool for SPECT and MRI images of the brain]. / Automatisierte Fusion von SPECT- und MRT-Bildern des Gehirns: Zeitbedarf und Ergebnisqualität.

AIM: Although the fusion of images from different modalities may improve diagnostic accuracy, it is rarely used in clinical routine work due to logistic problems. Therefore we evaluated performance and time needed for fusing MRI and SPECT images using a semiautomated dedicated software. PATIENTS, MATERIAL AND METHOD: In 32 patients regional cerebral blood flow was measured using (99m)Tc ethylcystein dimer (ECD) and the three-headed SPECT camera MultiSPECT 3. MRI scans of the brain were performed using either a 0,2 T Open or a 1,5 T Sonata. Twelve of the MRI data sets were acquired using a 3D-T1w MPRAGE sequence, 20 with a 2D acquisition technique and different echo sequences. Image fusion was performed on a Syngo workstation using an entropy minimizing algorithm by an experienced user of the software. The fusion results were classified. We measured the time needed for the automated fusion procedure and in case of need that for manual realignment after automated, but insufficient fusion. RESULTS: The mean time of the automated fusion procedure was 123 s. It was for the 2D significantly shorter than for the 3D MRI datasets. For four of the 2D data sets and two of the 3D data sets an optimal fit was reached using the automated approach. The remaining 26 data sets required manual correction. The sum of the time required for automated fusion and that needed for manual correction averaged 320 s (50-886 s). CONCLUSION: The fusion of 3D MRI data sets lasted significantly longer than that of the 2D MRI data. The automated fusion tool delivered in 20% an optimal fit, in 80% manual correction was necessary. Nevertheless, each of the 32 SPECT data sets could be merged in less than 15 min with the corresponding MRI data, which seems acceptable for clinical routine use.

Development and current status of USAF mental health screening.

Early detection and appropriate disposition of non-adaptable military recruits has been a concern of the military for many years. In the 1950s and 1960s, various branches of the military conducted large studies searching for accurate, cost-effective ways to predict which recruits could and could not adapt to military training. In the 1970s, research in this area spawned the development of the Air Force Medical Evaluation Test (AFMET), the three-phase mental health screening process used by the Air Force today. This article briefly reviews the development of AFMET, and presents current data supporting its utility and effectiveness.

Childhood physical and sexual abuse and failure to complete military basic training.

Forty percent of a group of 25 military basic trainees discharged from training for mental health reasons admitted histories of childhood physical and/or sexual abuse. In a control group of 25 successful trainees, only 1 gave a history of abuse. Consistent with published studies of childhood abuse in psychiatric patient samples, women in our discharge group were more likely to report abuse histories than men. Perpetrators were usually reported as non-biological male family members of the respective victims. The authors conclude that adult survivors of childhood abuse appear to be less able to tolerate the stresses of military basic training, and discuss the need for identifying and therapeutically assisting these individuals during their training.

Susceptibility to maladaptive responses to stress in basic military training based on variants of temperament and character.

The purpose of this study was to compare the relationship of Temperament and Character Inventory (TCI) scores of three groups of U.S. Air Force basic trainees. The following groups were used: those who were psychiatrically hospitalized, a control group, and a group identified as being at risk for early separation from basic training because of psychological reasons. The instrument used was the TCI. The data were analyzed with analysis of variance, Tukey post hoc comparisons, and stepwise backward discriminant analysis. The controls were found to have healthier temperament and character profiles than both the at-risk (p < 0.01) and hospitalized (p < 0.01) groups. No difference was found between the at-risk and hospitalized groups on TCI scores. The TCI was found to successfully predict 82% of controls, 25% of at-risk, and 64% of hospitalized recruits. Risk factors for maladaptive responses to stress and possible ways of primary prevention are presented.