Treatment of Periprosthetic Femoral Fractures Vancouver Type B2: Revision Arthroplasty Versus Open Reduction and Internal Fixation With Locking Compression Plate.

INTRODUCTION: The Vancouver algorithm recommends revision arthroplasty (RA) for Vancouver type B2 (VTB2) fractures. However, open reduction and internal fixation (ORIF) using locking compression plates (LCP) may be a valid and less invasive alternative treatment. MATERIALS AND METHODS: Between January 2007 and March 2017, we retrospectively recruited all patients treated with either ORIF with LCP or RA for VTB2 fractures in our clinic. All of the following were reviewed: the length of hospital stay, the operating time, the need for blood transfusions during and/or after surgery, implant-related and patient-related complications, need for revision surgery, and the radiological outcome. Additionally, the functional outcome was investigated. RESULTS: Fifty-nine patients were recruited. Thirty-five (59.3%) patients underwent RA, while 24 (40.7%) patients received ORIF with LCP. The median surgical time was 137.50 minutes in the LCP group compared to 160.00 minutes in the RA group (P = .051). Three (12.5%) patients in the LCP group and 10 (28.6%) patients in the RA group experienced an implant-associated complication (P = .131). Patient-related complications occurred in 3 (12.5%) patients in the LCP group versus 6 (17.1%) patients in the RA group (P = .628). The mean preoperative Parker mobility score was 9 points in both groups and decreased in both groups to a mean of 5 points in the LCP and 7 points in the RA group. DISCUSSION: Open reduction and internal fixation with LCP seems to be a less invasive procedure for VTB2 fractures in comparison to RA. It is a bone-sparing procedure that can be advantageous for further revision operations. Moreover, some fractures can only be anatomically reduced by ORIF with LCP, whereas for proximal fractures with a radiologically unambiguously loosened stem RA might be advantageous. CONCLUSION: In line with previously published studies, our data suggest that ORIF using LCP is a valid treatment option for VTB2 fractures.

Evaluation of radiographic fracture position 1 year after variable angle locking volar distal radius plating: a prospective multicentre case series.

Treatment with a variable angle locking plate can, in theory, maintain near anatomic reduction of intra-articular distal radius fractures, but it is unknown to what extent reduction is maintained as measured by computed tomography. We assessed changes in radiographic fracture position 1 year post-operatively. We included 73 patients of whom 66 patients (90%) had radiographs available for review at 1 year post-operatively. We found a small (less than 2 mm or 2°) but statistically significant change in several measures. Accounting for inter-observer variability, this is probably within measurement error. We found no difference in change in fracture position or range of motion, grip strength or patient-reported outcome between the use of one or two distal rows of screws. Our results show that minimal changes in reduction can be expected after volar plate fixation in most patients. We recommend using only one screw row routinely, limiting costs, surgical time and the risk of misplacement of screws. LEVEL OF EVIDENCE: IV.

[Osteosynthesis of metacarpal fractures with 2.0 mm LCP system and functional postoperative treatment]. / Osteosynthese von Metakarpalefrakturen mit 2,0-mm-LCP und funktionelle postoperative Nachbehandlung.

BACKGROUND: Locking head systems are an additional option in the surgical treatment of metacarpal fractures. In this clinic 2.0 mm locking compression plates (LCP) are used, which provide the possibility of functional postoperative treatment even for complex and osteoporotic metacarpal fractures. For simple fractures and good bone quality the LCP system is used as a compression or neutralization plate. Depending on the type and localization of the fracture, different osteosynthesis techniques are used in order to achieve a functional postoperative treatment in as many patients as possible. MATERIAL AND METHODS: Between July 2009 and December 2010 a total of 49 patients were enrolled in a prospective trial. All patients underwent surgical treatment with a 2.0 mm LCP system. Postoperative functionality of the hand was restored without immobilization. Clinical and radiological examinations were performed after 6 and 12 weeks and after 6 and 12 months with documentation of the range of motion (ROM), grip strength, fingertip to palm distance and the disabilities of the arm, shoulder and hand (DASH) score. RESULTS: After 6 months a good functional result was achieved in all patients with no cases of malrotation. Radiographs showed a completely consolidated bone healing. CONCLUSION: After osteosynthesis with 2.0 mm LCPs all types of metacarpal fractures can be treated without immobilization.

Gender-specific hip fracture risk in community-dwelling and institutionalized seniors age 65 years and older.

UNLABELLED: In this study of acute hip fracture patients, we show that hip fracture rates differ by gender between community-dwelling seniors and seniors residing in nursing homes. While women have a significantly higher rate of hip fracture among the community-dwelling seniors, men have a significantly higher rate among nursing home residents. INTRODUCTION: Differences in gender-specific hip fracture risk between community-dwelling and institutionalized seniors have not been well established, and seasonality of hip fracture risk has been controversial. METHODS: We analyzed detailed data from 1,084 hip fracture patients age 65 years and older admitted to one large hospital center in Zurich, Switzerland. In a sensitivity analysis, we extend to de-personalized data from 1,265 hip fracture patients from the other two large hospital centers in Zurich within the same time frame (total n = 2,349). The denominators were person-times accumulated by the Zurich population in the corresponding age/gender/type of dwelling stratum in each calendar season for the period of the study. RESULTS: In the primary analysis of 1,084 hip fracture patients (mean age 85.1 years; 78% women): Among community-dwelling seniors, the risk of hip fracture was twofold higher among women compared with men (RR = 2.16; 95% CI, 1.74-2.69) independent of age, season, number of comorbidities, and cognitive function; among institutionalized seniors, the risk of hip fracture was 26% lower among women compared with men (RR = 0.77; 95% CI: 0.63-0.95) adjusting for the same confounders. In the sensitivity analysis of 2,349 hip fracture patients (mean age 85.0 years, 76% women), this pattern remained largely unchanged. There is no seasonal swing in hip fracture incidence. CONCLUSION: We confirm for seniors living in the community that women have a higher risk of hip fracture than men. However, among institutionalized seniors, men are at higher risk for hip fracture.

Before and after hip fracture, vitamin D deficiency may not be treated sufficiently.

UNLABELLED: Our findings show that only about 20% of seniors receive vitamin D supplementation prior to their index hip fracture or after the event. We further confirm the high prevalence of severe vitamin D deficiency in this population and show that those who receive supplementation have significantly higher 25-hydroxyvitamin D (25(OH)D) status. INTRODUCTION: The aim of this study is to assess current practice in pre- and post-hip fracture care practice with respect to vitamin D supplementation. METHODS: We surveyed 1,090 acute hip fracture patients age 65 and older admitted to acute care for hip fracture repair; 844 had serum 25-hydroxyvitamin D levels measured upon admission to acute care, and 362 agreed to be followed at 12 month after their hip fracture. Prevalence of vitamin D supplementation was assessed upon admission to acute care (at the time of hip fracture), upon discharge from acute care, and at 6 and 12 months follow-up. RESULTS: Of 1,090 acute hip fracture patients (mean age 85 years, 78% women, 59 % community-dwelling), 19% had received any dose of vitamin D prior to the index hip fracture, 27% (of 854 assessed) at discharge from acute care, 22 % (of 321 assessed) at 6 month, and 21% (of 285 assessed) at 12 month after their hip fracture. At the time of fracture, 45% had 25(OH)D levels below 10 ng/ml, 81% had levels below 20 ng/ml, and 96% had levels below 30 ng/ml. Notably, 25(OH)D levels did not differ by season or gender but were significantly higher among 164 hip fracture patients, with any vitamin D supplementation compared with 680 without supplementation (19.9 versus 10.8 ng/ml; p < 0.0001). CONCLUSION: Only about 20% of seniors receive vitamin D at the time of their fracture and after the event. This is despite the documented 81% prevalence of vitamin D deficiency. Interdisciplinary efforts may be warranted to improve vitamin D supplementation in seniors both before a hip fracture occurs and after.

Mild to moderate cognitive impairment is a major risk factor for mortality and nursing home admission in the first year after hip fracture.

BACKGROUND: It is not well established if and to what extent mild to moderate cognitive impairment predicts mortality and risk of nursing home admission after hip fracture. OBJECTIVE: To investigate prospectively whether and to what extent mild to moderate cognitive impairment, contributes to mortality and admission to nursing home in the first year after acute hip fracture. METHODS: We enrolled 173 patients with acute hip fracture age 65 and older who reached a Mini-Mental State Examination (MMSE) score of at least 15 during acute care after hip fracture repair. An MMSE score of 15 to 24 (median) was classified as mild to moderate cognitive impairment. Primary outcomes were mortality in all and admission to nursing home among seniors who lived at home prior to their hip fracture. Follow-up was 12 months with clinical visits at baseline, 6, and 12 months, plus monthly phone calls. We used Cox proportional hazards models controlling for age, sex, body mass index, baseline number of comorbidities and 25-hydroxyvitamin D status, and severe incident infections to assess the risk of mortality and nursing home admission. Because the study population was enrolled in a factorial design clinical trial testing high dose vitamin D and/or an exercise home program, all analyses also controlled for these treatment strategies. RESULTS: Of 173 acute hip fracture patients enrolled, 79% were women, 77% were admitted from home, and 80% were vitamin D deficient (<20ng/ml). Mean age was 84 years. 54% had mild to moderate cognitive impairment. Over the 12-month follow-up, 20 patients died (27% of 173) and 47 (35% of 134) were newly admitted to a nursing home. Mild to moderate cognitive impairment was associated with a more than 5-fold increased risk of mortality (HR=5.77; 95% CI: 1.55-21.55) and a more than 7-fold increased risk of nursing home admission (HR=7.37; 95% CI: 1.75-30.95). Additional independent risk factors of mortality were male gender (HR=3.55; 95% CI: 1.26-9.97), low BMI (HR=7.25; 95% CI: 1.61-33.74), and baseline 25-hydroxyvitamin D level (per 1ng/ml: HR=0.93; 95% CI: 0.87-0.998; p=0.04). CONCLUSIONS: Mild to moderate cognitive impairment in patients with acute hip fracture is associated with a high risk of mortality and nursing home admission during the first year after hip fracture. Female gender, a greater BMI and a higher 25-hydroxyvitamin D status may protect against mortality after hip fracture independent of cognitive function.

[Clinical and radiological results after operative treatment of mallet fracture using Kirschner wire technique]. / Klinische und radiologische Ergebnisse nach operativ versorgten Frakturen dorsal an der Fingerendgliedbasismit Kirschnerdrähten.

BACKGROUND: In our clinic dorsal distal phalanx fractures involving more than 30% of the articulare line in the lateral view are treated operatively using the Kirschner wire technique. Recently conservative treatment of these fractures is more and more recommended. Therefore we investigated in a retrospective study our patients with special regards to complications. PURPOSE: The aim of this study was to evaluate the complications, as well as the clinical and radiological results of patients after operative treatment of dorsal distal phalanx fractures using the Kirschner wire technique. PATIENTS AND METHODS: 43 patients with dorsal intraarticular fractures of the distal phalanx involving at least one third of the articular surface of the distal interphalangeal (DIP) joint were treated between 02/05 and 08/09 using Kirschner wire technique. At a mean follow-up of 28 (8-60, median 24,5) months, 32 patients were evaluated clinically and radiologically as well as with ultrasound. RESULTS: 5 patients developed superficial wound infections and were treated with antibiotics. 2 of these patients needed an early removal of the Kirschner wires. 2 patients showed nail deformity and 2 had an ulnar deviation of the DIP joint. The mean extension lag was 10° (0-30°, median 10°), the mean flexion lag was 19° (0-60°, median 15°). 11 patients had a flexion lag of more than 20°. 4 patients had an extension lag of more than 20°. All of these patients showed tendon tears or large lesions by ultrasound. Degenerative changes were noted in radiographs of 15 patients. CONCLUSIONS: Because of unsatisfactory results in 63% (n=20), conservative treatment will be our treatment of choice in the future. Operative treatment will only be done in patients with subluxation of the distal phalanx.

Evaluation of critical incidents in general surgery.

BACKGROUND: The analysis of adverse events is a central step in critical incident reporting, but has not been described in a surgical setting. The aim of this study was to develop an evaluation protocol and assess its feasibility. METHODS: All incidents were analysed by a multidisciplinary team. A coding system based on three published theories was used to assess all incidents and their underlying causes. A risk analysis was also conducted. RESULTS: Between July 2004 and December 2005, 9785 inpatients were treated and 139 critical incidents reported. Classification of active errors revealed 47.7 per cent to be execution failures and 45.9 per cent knowledge-based errors. The distribution of medical errors was 12.9 per cent diagnostic, 46.0 per cent treatment, 17.3 per cent preventive and 23.7 per cent other. Some 282 latent failures were identified among the 139 incidents. Risk analysis revealed a severe incident rate of 21.6 per cent. CONCLUSION: This study has shown the feasibility of an evaluation protocol based on a combination of three classification systems and a risk analysis. It allows a thorough assessment of critical incidents, identification of priorities and tailored countermeasures.

Treatment of the open abdomen with the commercially available vacuum-assisted closure system in patients with abdominal sepsis: low primary closure rate.

BACKGROUND: Abdominal Vacuum-Assisted Closure (V.A.C.) systems for treatment of open abdomens have been predominantly used for trauma patients with a high primary fascial closure rate. Use of the V.A.C. technique in abdominal sepsis is less well established. METHODS: All patients with abdominal sepsis and treatment with the abdominal V.A.C. system between 2004 and 2007 were prospectively assessed. End points were fascial closure, V.A.C.-related morbidity, and quality of life score (SF-36) at follow-up. RESULTS: Thirty patients with abdominal sepsis were included in the study. Primary fascial closure was feasible in 10, partial closure in 4, and no closure in 16 patients. Median number of V.A.C. changes was 3 (range, 1-10). Nine patients died. V.A.C.-related morbidity was as follows: two fistulas, three fascial edge necroses, one skin blister, and four prolapses of small bowel between the fascia and foam. Univariate analysis showed no variables influencing primary closure rate or V.A.C.-related morbidity. Mortality was significantly influenced by age (P < 0.001), respiratory failure (P = 0.01), and pneumonia (P = 0.03). At follow-up, V.A.C. patients scored lower in the physical health scores and similar in the mental health scores compared with the normal population. CONCLUSIONS: Treatment of the open abdomen in patients with abdominal sepsis with the abdominal V.A.C. system is safe with good long-term quality of life. Primary closure rate in these patients is substantially lower than in trauma patients. Stepwise closure of the fascia during V.A.C. changes should be attempted to avoid additional lateral retraction of fascial edges. V.A.C.-related complications may be avoided with careful surgical technique.

[Combined dorsal and palmar plate osteosynthesis for intraarticular distal radius fractures]. / Kombinierte dorsale und palmare Plattenosteosynthese bei distalen intraartikulären Radiusfrakturen.

BACKGROUND: Complex comminuted intraarticular fractures of the distal radius require anatomic restoration. In rare cases, this aim can only be achieved by a combined dorsal and volar plate fixation despite increasing experience with volar locking compression implants. This retrospective quality control study investigated functional, radiological and subjective outcomes of patients treated with this technique. METHODS: Between March 1999 and January 2003, 30 out of 360 patients who were operated on for an unstable distal radius fracture with complex C2/C3 type distal radius fractures at the Division of Trauma Surgery of the University Hospital Zurich, had been treated with a combined dorso-palmar plate fixation (dorsal two 1/4 tubular plates, volar 3.5 mm T-plate) and were included in this study (9 female, 21 male, mean age 52 years). Of the 30 patients 25 could be evaluated at an average of 29 months after injury. RESULTS: Anatomic reconstruction could not be achieved in all cases, 56% showed mild and 28% explicit signs of arthrosis. Flexion reached 66% and extension 75% of the contralateral wrist, whereas pronation reached 98% and supination 91%, respectively. Grip strength achieved 75% of that of the contralateral side and 10 patients (40%) developed a complex regional pain syndrome (CRPS). Return to work was possible 120 days after the injury. CONCLUSION: With the dorso-palmar plate fixation joint reconstruction in complex intraarticular distal radius fractures can be achieved with a satisfactory subjective, functional, and radiologic result, although additional soft tissue injury was caused by the bilateral approach. The patient has to be informed of the high rate of CRPS and the long period of disability.

Severe vitamin D deficiency in Swiss hip fracture patients.

BACKGROUND: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l. AIM: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture. METHODS: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women. RESULTS: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels. CONCLUSION: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.

[Complex fracture of the proximal humerus in the elderly. Locking plate osteosynthesis vs hemiarthroplasty]. / Komplexe proximale Humerusfraktur beim alten Menschen. Winkelstabile Plattenosteosynthese vs. Hemiarthroplastik.

BACKGROUND: The purpose of the present study was a direct comparison of fixed-angle plate fixation (FAPF) and shoulder hemiarthroplasty (SHA) for complex fractures of the proximal humerus in the elderly. PATIENTS AND METHODS: A single-institution case series of 52 consecutive geriatric patients (age > or =70 years) treated with FAPF for three- and four-part fractures of the proximal humerus between 2003 and 2005 was analysed 1 year after surgery. The analysis included Constant Score (CS), Oxford Shoulder Score (OSS), and radiological evaluation. Outcome was compared with a similar historic group of patients (n=59) who received SHA in an earlier period (1995--1997). RESULTS: The patient groups showed no differences in age, gender, or fracture type. Median CS was significantly better for FAPF (71 vs 41). Evaluation of pain demonstrated no differences between the two treatment modalities in the OSS. Revision surgery was performed more often in the FAPF group (25% vs 2%). CONCLUSION: Compared to SHA, functional outcome was superior with FAPF. However, this was associated with a higher rate of revision surgery. Most patients were still able to live independently in their original environment, regardless of the type of surgery.

[Long-term prognosis of former very and extremely preterm babies in adulthood in Germany]. / Langzeitprognose sehr kleiner Frühgeborener in Deutschland.

Previous studies about the prognosis of former very and extremely small preterm babies (birthweight <1500 g, gestational age <32 weeks) in Germany only reached till puberty. Well known are significant increases of cognitive deficits, cerebral palsy and sensory impairments in correlation with gestational age and compared with term newborns. After a pilot project at the Children's University Hospital in Wuerzburg we collected the data of 291 people from 10 different children's Hospitals in Germany who were born between Jan 1st 1979 and Dec 31st 1986. We could recognize a clear increase of surviving babies after 1982. 50 (17%) of them had a birth weight under 1000 g. 27% finished school with the highest grade ("Abitur"), 37% with a high school degree and 22% with a normal degree. Most of them are still in an occupational training. 22% referred about chronic bronchitis, 54% need spectacles, 19% have regular physiotherapy. By a questionnaire about the quality of life (KIDDO KINDL) we recorded criteria in the fields of physical and psychological wellness and the all day functioning which were without significant differences to a normal cohort. In addition there was no difference in the quality of life criteria between former preterm babies born in West-Germany and those born in East-German hospitals. Further analyses of these results are necessary. In conclusion we could find that quality of life in those former very preterm babies in Germany who are now in adulthood and took part in our study is not significantly worse in comparison with people without any risk factors in the perinatal period. For more exact analysis of many influencing factors on the long term prognosis of former very preterm babies a national multicenter study is absolutely necessary, especially for preterms under 1000 g birthweight.

[The osteosynthesis of fractures of distal radius with the AO/ASIF Titanium Pi Plate]. / Osteosynthese distaler Radiusfrakturen mit der AO/ASIF Titan-Pi-Platte.

The AO/ASIF Titanium Pi Plate has been developed for dorsal plating of fractures of the distal radius. It is designed by reflection of the anatomy, to ensure stability of the angle using a juxtaarticular band and to minimize tissue reaction by low profile design. The aim of this study was to evaluate the subjective and objective outcome of 61 consecutively operated patients after a minimum of 12 months (12-29 months) postoperatively. There were 3 A2, 23 A3, 1 B1, 12 C1 and 22 C2 fractures (AO-Classification). The subjective results were good to very good. The range of motion showed over 80% compared to the uninjured side. Overall, there were no ruptures of tendons and 18% irritations. Extension, ulnar abduction and force were significantly better in patients in which the plate has been removed. In this collective the tendon irritations were only 3.8%. With the AO/ASIF Pi Plate good subjective and objective results can be achieved. The indication for removal of the plate should be given generously.

[The role of transarterial embolisation in the treatment of patients with abdominal injuries]. / Transarterielle Embolisation. Stellenwert in der Behandlung von Patienten mit Abdominaltrauma.

INTRODUCTION: The role of transarterial embolisation in patients with abdominal injuries is controversial. Some trauma centres advocate routine angiography, whereas others believe in restricted indications such as increasing haematomas or persistent/recurrent haematuria. METHOD: We prospectively studied 167 patients with blunt and penetrating abdominal trauma. We used restricted indications for angiography and embolisation. RESULTS: Eleven of 167 patients with abdominal trauma (7%) were treated with angiography and embolisation., Overall, three of 11 patients (27%) with angiography and embolisation were treated emergently and eight of them (73%) at an average of 7.3 days. There were no complications due to the embolisation procedure, and all bleeding could be stopped. CONCLUSION: Transarterial angiography and embolisation is an important and safe tool in the treatment of acute abdominal injury when used for restricted indications. We believe this should not be performed as a routine procedure, especially in unstable patients.

[Reconstruction of posttraumatic bony defects of the lower extremity: callotaxis or free vascularized fibula graft?]. / Rekonstruktion posttraumatischer Knochendefekte an den unteren Extremitäten: Kallusdistraktion oder freie mikrovaskularisierte Knochentransplantation?

PURPOSE/BACKGROUND: Several methods have been established for the treatment of bony defects of the lower extremity. The purpose of this paper is to evaluate the use of a free vascularized fibula graft for these defects in comparison to callotaxis and segmental transport. METHOD AND CLINICAL MATERIAL: Retrospective analysis of data from 32 patients treated between 1981 and 1999 at the University Hospital in Zurich, Switzerland with bony defects of the lower extremity. RESULTS: The reconstruction of the bony defect was successful in 80 % with fibula graft, in 94 % with callotaxis and in 83 % with segmental transport. In the group with the fibula transplantation 2.6 re-interventions due to complications had to be performed, in the callotaxis group there were 3.6 and in the segmental transport group 5.2 surgical re-interventions. The time between primary intervention and full weight bearing was 16 months in the fibula transplantation group, 7.6 months in the callotaxis group and 10.7 months in the segmental transport group. CONCLUSION: The results show that these three options can be used for different indications. Reconstruction can be planned according to the following rules: Segmental bony defects of the entire circumference of up to 5 cm are best treated by initial shortening followed by callus distraction. Bony defects from 5 to 12 cm are best treated by segmental transport while maintaining limb length. Defects > 12 cm are best treated by reconstruction with a vascularized free fibula graft.

Analyses of phagocytosis, evoked oxidative burst, and killing of black yeasts by human neutrophils: a tool for estimating their pathogenicity?

The pathogenicity of several dematiaceous yeasts that have, to date, rarely been isolated in humans remains unclear. Because professional phagocytes are prominent in lesions caused by dematiaceous fungi, we address this issue by comparing phagocytosis, evoked oxidative burst and killing by human neutrophils of different black yeasts in vitro. Whereas phagocytosis of all black yeasts tested and evoked oxidative burst yielded comparable results, in contrast, the degree of killing differed significantly after 5 h. Thereby, two groups could be identified; one in which strains are killed at high rates, for example, Hortaea werneckii (81 +/- 11.6%), Exophiala castellanii (96 +/- 8.6%), Phaeoannellomyces elegans (93 +/- 9.7%), Phaeococcomyces exophialae (87 +/- 8.7%), and the other in which strains are killed to a lesser degree, for example, Exophiala dermatitidis (ATCC 34100) (61 +/- 9.5%), E. dermatitidis (CBS 207.35) (66 +/- 7.5%), E. jeanselmei (50 +/- 10.5%), E. mesophila (63 +/- 11.6%), E. bergeri (63 +/- 9.1%), and E. spinifera (57 +/- 9.6%). Non-pigmented yeasts were killed at levels comparable with those at which the white mutant strain of E. dermatitidis (ATCC 44504) was killed (95 +/- 7.5%); the yeast strains tested were Candida albicans (DSM 11943) (95 +/- 4.0% killing) and Saccharomyces cerevisiae (DSM 1333) (95 +/- 10.3%). Comparison of killing rates with the observed pathogenicity of the melanized species suggests that low killing rates might indicate or even predict a high degree of invasiveness. Although previous experiments revealed that melanization conferred killing resistance on E. dermatitidis, the differences in killing rates of other dematious fungi suggest that melanization of the cell wall is in itself insufficient to confer virulence.

Novel O6-methylguanine-DNA methyltransferase SNPs: a frequency comparison of patients with familial melanoma and healthy individuals in Sweden.

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is involved in the cellular defense against alkylating agents. Genetic alterations in the MGMT gene may impair the protein's ability to remove alkyl groups from the O6-position of guanine, thereby raising the mutation rate and increasing the risk of cancer. We assessed polymorphisms in the promoter region and the 5 exons of the MGMT gene by PCR/SSCP and nucleotide sequence analysis of DNA extracted from blood samples. The population studied consisted of 89 melanoma patients, each belonging to a different family with a hereditary predisposition for melanoma, and 76 healthy individuals (blood donors). A total of 11 single nucleotide polymorphisms (SNPs) were detected, five in the promoter region, one in exon 1, two in exon 3 and three in exon 5. Six of the alterations were novel polymorphisms, of which five were located in the promoter region and one in exon 5. When the distribution of specific SNPs in cases and controls with only one variant was calculated; C575A was present only in melanoma patients (p=0.072). Moreover, while 20% of the healthy individuals had no SNPs this was the case in only 12.4% of the melanoma patients. However, no statistically significant differences were seen between cases and controls for any of the 11 SNPs.

Mutations in the TP53 gene in human malignant melanomas derived from sun-exposed skin and unexposed mucosal membranes.

Mutations in the p53 tumour suppressor gene ( ) have been linked to several types of cancer. We therefore investigated whether such mutations occur in malignant melanomas and, if so, whether they are linked to ultraviolet (sun) light exposure. For the first time, mutations in mucosal membranes and adjacent tissues shielded from sunlight were compared with those in cutaneous melanomas from sun-exposed skin. Archival tissues were obtained from 35 patients with a primary melanoma taken from unexposed mucosal areas and from 34 patients with a primary melanoma located in chronically sun-exposed head and neck skin. was characterized by means of polymerase chain reaction amplification and single-strand conformation polymorphism assay followed by nucleotide sequencing. The results showed that 17.6% of the primary cutaneous and 28.6% of the primary mucosal melanomas had point mutations in. Among the cutaneous melanomas, one showed three mutations in exon 7, and one had two mutations in exon 5; the mutation was in the same allele in both cases. One mucosal melanoma had two mutations in exon 7, both in the same allele, and another had two mutations, one in exon 7 and one in intron 6, both in the same allele. C<--T mutations at dipyrimidine sites, considered fingerprints for ultraviolet light-induced mutations, were about equally distributed among patients with melanomas from chronically sun-exposed areas (six out of nine; 67%) and those with melanomas from unexposed mucosal areas and adjacent skin (eight out of 14; 57%). Our data, demonstrating the presence of such mutations even in melanomas from mucosal membranes, clearly suggest that factors other than, or additional to, ultraviolet radiation are operational in the induction of mutations in melanomas.