Erkki Tukiainen

Decreased uptake of 5-hydroxytryptamine in blood platelets from patients with endogenous depression

Abstract5-Hydroxytryptamine (5-HT) uptake was studied by using blood platelets from 13 patients with endogenous depression (Hamilton rating scale 33±7) and 13 healthy volunteers. An improved method with a short incubation time and low substrate concentration was used, and the incubation was performed in Krebs-Henscleit buffer (pH 7.4) at 37° C. A clear difference in 5-HT uptake by blood platelets was noted: The Vmax of the reaction in patients was 39, and in controls 71 pmol per 2×107 platelets in 5 min. There was no significant difference in the Km. After a 4-week treatment with imipramine, a competitive inhibition of 5-HT uptake with an increased Km was seen; after a similar treatment with amoxapine there was little change in 5-HT uptake. Amoxapine was inferior to imipramine as an inhibitor of 5-HT uptake, also in vitro. There was no difference in clinical recovery in these treatment groups. These results may be of importance so as to understand the potential biological differences between depressed patients and normal persons.

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.

Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma.

Background:Immunosuppression and Merkel-cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin.Methods:We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR.Results:We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2–64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2–46.0, P<0.01). Merkel-cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis.Conclusions:We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.

Vascular endothelial growth factor-C gene therapy restores lymphatic flow across incision wounds

Edema and insufficient blood perfusion are common problems in reconstructive surgery. The blood vasculature is reconstructed in microvascular flaps, whereas lymphatic vessel function is lost after surgical incision. Here, we demonstrate that vascular endothelial growth factor C (VEGF‐C) gene transfer can be used to reconstruct a lymphatic vessel network severed by incision of skin flaps. We used adenoviral VEGF‐C gene transfer at the edges of epigastric skin flaps in mice. Our results show that VEGF‐C gene expression results in the formation of anastomoses between the lymphatic vessels of the skin flap and the surrounding lymphatic vasculature. Some spontaneous lymphangiogenesis also took place in the control mice, but the lymphatic vessels generated remained nonfunctional even 2 months postoperatively. In contrast, the VEGF‐C treated mice demonstrated persistent lymphatic vessel function during the 2 month follow‐up despite the transient nature of the adenoviral VEGF‐C gene expression. The restoration of lymphatic function by VEGF‐C in skin flaps provides new tools to promote vascular perfusion and to reduce tissue edema in skin and muscle flaps. These results have important implications for the prevention and treatment of surgically induced secondary lymphedema.

Merkel cell carcinoma: a clinicopathological study of 34 patients

BACKGROUND Merkel cell carcinoma (MCC) is a rare cutaneous malignant tumour. Its natural course is fast progression of the primary tumour and rapid regional metastasis. METHODS The pathological archives of Helsinki University Hospital and Vaasa Central Hospital were reviewed from 1987 to 2001. Specimens were re-evaluated by two pathologists and size was measured from primary tumours. Multivariate analysis was performed for age, sex, primary tumour size, and method of initial surgery, development of metastatic disease and development of local recurrence. Overall survival (OS) was calculated by the Kaplan-Meier method. RESULTS Of 34 patients, 12 male and 22 female patients, are reported. Their median age was 76.4 years. Half of the primaries were located in the head and neck region. All patients were treated surgically. The mean OS was 2.7 years by the Kaplan-Meier method. The 2-year survival rate was 65% and 5-year rate was 50%. The mean OS for tumour size >2 cm was 1.7 years and for tumour size <or=2 cm 4.48. Poor prognostic factors for OS were: male sex, size of the primary tumour (>2 cm) and metastatic dissemination. A favourable prognosis seemed to correlate to more aggressive surgical management as use of primary excision with split skin graft or reconstruction with a local flap. CONCLUSION MCC affects the elderly patients. In this study, female patients predominated. Primary tumour size >2 cm predicts poorer outcome of the disease. A wide surgical excision is recommended for the primary treatment of MCC.

Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group.

Leiomyosarcoma of nonvisceral soft tissues is an uncommon malignant tumor; thus, only small numbers of cases have been reported. This study was based on a large series of patients from the Scandinavian Sarcoma Group Register acquired during a 15‐year period (from 1986 to 2001). Follow‐up information was available for all patients.

Postoperative wound complications after internal fixation of closed calcaneal fractures : A retrospective analysis of 126 consecutive patients with 148 fractures

Aim: The aim of the study was to analyse the number of soft-tissue complications after internal fixation of calcaneal fractures and to evaluate risk factors leading to these complications. Material: A retrospective analysis of 126 consecutive patients with 148 operatively treated calcaneal fractures was performed. Only primarily closed fractures were included in the study. Results: Wound healing was problematic in 35 cases (24 per cent). The wound was infected in 23 cases (16 per cent) and a wound edge necrosis was observed in 12 cases (8 per cent). The soft tissue complication needed operative treatment in 20 cases (14 per cent). The complications did not lead to amputations in any case. In the end of the follow up all wounds had healed. Conclusions: The statistical analysis identified a longer delay in surgery and longer operation time to be positive risk factors for wound complications.

Incidence of Merkel cell carcinoma in renal transplant recipients

BACKGROUND The risk factors for Merkel cell carcinoma (MCC), a rare type of skin cancer, are poorly understood. Some evidence suggests that MCC is more common in individuals with abnormal immune function resulting from viral infection, autoimmune disease or organ trans- plantation. METHODS The national Renal Transplant Registry and the Finnish Cancer Registry data were searched for recipients of a renal transplant who were diagnosed with MCC. The MCC diagnoses were confirmed using immunohistochemistry. RESULTS Three cases of MCC were detected among 4200 individuals who underwent renal transplantation from 1967 to 2005 [expected number 0.05, standardized incidence ratio (SIR) 66, 95% CI 14-194, P <0.001]. The latency period between the transplant and detection of MCC ranged from 6 to 19 years. In all three cases, the cause of transplantation was an autoimmune disease. All three died from aggressive MCC with a survival time ranging from 0.5 to 2.1 years. CONCLUSIONS The results indicate that the risk of MCC is greatly increased among subjects who have undergone renal transplantation. The course of the disease appears aggressive in this patient population. The physicians who treat recipients of a kidney transplant should be aware of the substantially increased risk of MCC.

Never amputate without consultation of a vascular surgeon

Lower limb ischaemia is one of the determinants in the development of diabetic foot ulcers and the most important factor preventing their healing. There are a number of misleading factors masking the presence of atherosclerotic disease and tissue damage; these are reduced inflammatory response to infection, autosympathectomy and mediasclerosis, which all diminish the clinical suspicion of ischaemia. Therefore, adequate assessment of the lower limb circulation should be routinely performed in complicated diabetic foot. This evaluation can often be made with simple methods. In addition to clinical examination ankle/brachial pressure index, systolic toe pressure, plethysmographic pulse volume recordings and simple hand‐held Doppler auscultation are most often sufficient to make a decision as to whether angiography is needed or not. Duplex examination can give more profound information on the severity and extent of arterial occlusive disease, but the method is strongly user‐dependent. Early vascular consultation is mandatory in diabetic foot work‐up and should be undertaken within 2 weeks if a new skin lesion shows no tendency to heal. Long bypass grafting procedures and microvascular free flap techniques have been shown to achieve excellent results in relieving critical leg ischaemia, even in the presence of large foot lesions, and should be used to prevent major amputation. The timing of various procedures is a controversial issue. Feet with small ulcers or restricted dry gangrena can be revascularised first, with minor amputations and local surgery of the ulcer being done thereafter. In the septic neuroischaemic foot, major amputation may be unavailable but if the infection is not immediately life‐threatening the infected part of the foot should be drained and debrided properly and left wide open, sometimes with a guillotine amputation in order not to risk the bypass graft, which can be done a couple of days later. Copyright

Overrepresentation of 1q21–23 and 12q13–21 in lipoma-like liposarcomas but not in benign lipomas: A comparative genomic hybridization study

Twenty lipomatous tumors, including eight lipoma-like liposarcomas and 12 benign lipomas, were analyzed using comparative genomic hybridization (CGH). DNA sequence copy number changes detected in five lipoma-like liposarcomas (mean, 1.1 aberrations/tumor; range, 0-2) consisted of gains of 12q13-21 (five tumors) and 1q21-23 (four tumors). Two of the tumors showed high-level amplification at 12q14-21 and one tumor at 1q21-22. No copy number changes were found in lipomas. Overrepresentation of 1q and 12q sequences was a recurrent finding in lipoma-like liposarcomas but not in lipomas. Thus, CGH may help in the differential diagnosis of low-grade or borderline adipose neoplasms.