The brain‐derived neutrophic factor val66met polymorphism and sudden unexpected infant death

Aim: Findings of hypoxia prior to death and involvement of a dysregulation of the serotonergic network in sudden infant death syndrome (SIDS) may indicate that brain‐derived neutrophic factor (BDNF) also is of importance with regard to sudden unexpected infant death. Based on this, the purpose of this study was to investigate the BDNF val66met polymorphism in SIDS cases, cases of infectious death and controls. Methods: The polymorphism was investigated in 163 SIDS cases, 34 cases of infectious death and 121 controls, using real‐time PCR and fluorescence melting curve analysis. Results: There were no differences in val66met genotype distribution between neither the SIDS cases nor the cases of infectious death and controls (p = 0.95 and p = 0.52, respectively). Conclusion: The study indicates that the val66met polymorphism is not important for sudden unexpected infant death. However, several other SNPs in the BDNF gene, as well as in other genes involved in this pathway, including G‐protein, have to be investigated to fully exclude any involvement of BDNF in SIDS.     

Current Clinical Practice DIC 2002: A Review of Disseminated Intravascular Coagulation

The turn of the millennium has seen clear advances in the understanding and management of Disseminated Intravascular Coagulation (DIC). The recognition that its pathogenesis stems from sustained thrombin generation in fuelling the cycle between inflammation and coagulation has seen the first successful treatment in severe sepsis through targeting this activity. An advance in treatment brings heightened relevance to laboratory testing, which now emphasises earlier detection and better monitoring to facilitate improved risk-identification and assessment of therapeutic efficacy. This review article also provides insights into future strategies that might build on the foundation of improving prognosis for the patient with DIC.     

Modulation of metallothionein isoforms is associated with collagen deposition in proliferating keloid fibroblasts in vitro

Please cite this paper as: Modulation of metallothionein isoforms is associated with collagen deposition in proliferating keloid fibroblasts in vitro. Experimental Dermatology 2010; 19 : 987–993. Abstract: The keloid fibroblast (KF) is known to have higher proliferative capacity than normal dermal fibroblast (NF). Metallothionein (MT), a metal‐binding protein, has been reported to promote cell proliferation. In this study, we evaluated the expression of MT isoforms at the mRNA level in fetal bovine serum (FBS)‐stimulated proliferating KF. Although the morphological appearance of NF and KF was similar when viewed under light, confocal and transmission electron microscopy, there was surprisingly a generally lower expression of MT isoforms in KF when compared with NF and also reduced MT staining in dermal fibroblasts of keloids as opposed to normal skin. Primary cultures of KF grown in 5% FBS or 10% FBS compared to without FBS demonstrated significantly higher proliferative activity and more abundant deposition of collagen. Contrary to expectation, MT‐1A, ‐1F, ‐1G, ‐1X and ‐2A isoforms were significantly down‐regulated in proliferating KF. Moreover, stimulating KF with TGF β1, which is known to promote collagen synthesis and keloid formation, increased expression of Collagen 1A and 3A genes accompanied by reduction in MT‐2A gene expression. Furthermore, down‐regulation of the MT‐2A gene in proliferating KF by siRNA‐mediated silencing enhanced cell proliferation with concomitant up‐regulation of the NF‐κB gene and 10 of 13 other NF‐κB pathway–related genes analysed but no alteration of the Collagen 1 and Collagen 3 gene expression. It would appear that down‐regulation of MT isoforms in proliferating KF, in particular MT‐2A, enhances keloidogenesis with the possible involvement of the NF‐κB signalling pathway.     

Peri-implant soft tissue integration of immediately loaded implants in the posterior macaque mandible: a histomorphometric study

BACKGROUND: Today, one critical goal in implant placement is the achievement of optimal soft tissue integration. Reports thus far have demonstrated successful soft tissue preservation in delayed loaded implants placed in anterior jaws. The aim of this study was to histomorphometrically examine the soft tissues around immediately loaded implants placed in the macaque posterior mandible. METHODS: Splinted crowns on screw-shaped titanium implants (8 mm length, 3.5 mm diameter) were utilized. Three implants each were placed in the premolar-molar edentulous mandibular segments of 6 adult monkeys (Macaca fascicularis); one side served as the control (delayed loading) and the other as the test sites (immediate loading). The animals were sacrificed after 3 months of loading. Histomorphometry of 6 soft tissue indices including the sulcus depth (SD), junctional epithelium (JE), connective tissue contact (CTC), biologic width (BW = SD + JE + CTC), DIM (distance between the implant top and coronal gingiva), and DIB (distance between the implant top and first implant-to-bone contact) was performed on non-decalcified sections. RESULTS: No significant differences in the mean soft tissue scores (mm) between the test (SD = 0.68 +/- 0.63; JE = 1.71 +/- 1.04; CTC = 1.51 +/- 1.14; DIM = 2.27 +/- 1.18; DIB = 1.32 +/- 1.21; BW = 3.9) and control (SD = 0.88 + 0.57; JE = 1.66 + 0.77; CTC = 1.24 +/- 0.92; DIM = 2.38 +/- 0.81; DIB = 1.19 +/- 0.91; BW = 3.78) groups were observed (P > 0.01). CONCLUSION: These findings suggest that the dimensions of the peri-implant soft tissues were within the biologic range and were not influenced by immediate functional loading or posterior location of the implants in the macaque mandible.     

Transcorporal artificial urinary sphincter cuff placement in cases requiring revision for erosion and urethral atrophy

PURPOSE: A distal cuff location is often required in patients undergoing artificial urinary sphincter reimplantation after previous erosion or in those requiring revision because of urethral atrophy at the original cuff site. Dissecting the urethra at a more distal site increases the risk of urethral injury and erosion, and often the urethral circumference is so small that a 4 cm. cuff is too large. We present a novel technique for distal cuff placement using transcorporal dissection that leaves corporal tunica albuginea on the dorsal surface of the urethra, allowing for its safer mobilization and adding to its bulk. MATERIALS AND METHODS: We reviewed the charts of 31 men who underwent this technique and contacted 26 by telephone. The indications for distal transcorporal cuff placement varied. In 7 men with inadequate urethral coaptation with a 4 cm. proximal cuff at initial implantation a primary transcorporal tandem cuff was implanted distal. In 8 men persistent or recurrent incontinence despite a 4 cm. proximal cuff led to secondary distal reimplantation. Previous artificial urinary sphincter erosion and/or infection in 10 cases, previous urethral surgery at the optimal cuff site in 5 and radiation changes at the optimal cuff site in 1 led to selection of the more distal site and technique. Of the transcorporally placed cuffs 18 were 4 cm. and 13 were 4.5 cm. Preoperatively 5.2 pads were used daily. Of the 31 patients 27 were impotent preoperatively, 1 had normal erections, 1 had partial erections with the MUSE drug delivery system (Vivus, Inc., Menlo Park, California) and 2 had a previously placed penile prosthesis. RESULTS: At a mean followup of 17 months 26 of the 31 patients (84%) had occasional or no stress incontinence requiring 0 to 1 pad daily, 2 with pure urge incontinence used 1 to 2 pads daily and 3 had mixed incontinence requiring 0 to 3 pads daily. Of the 26 men surveyed 25 were very satisfied with the postoperative level of incontinence. Postoperatively erectile function deteriorated in 1 patient and was unchanged in the remainder. There was no erosion or infection of the transcorporally placed cuffs, although 3 were replaced for malfunction. CONCLUSIONS: This technique offers significant advantages in cases of revision. The technique protects the urethra from intraoperative dissection injury and decreases the risk of erosion because the urethra is buttressed at its vulnerable location. In addition, bulk is added to the urethra, allowing for better cuff sizing, which is usually a problem at this location where the urethra is small, thereby, improving continence in revised cases. Our success has recently led us to abandon tandem cuff placement altogether. There is a potential for deteriorating erectile function in potent men who undergo implantation in this fashion.     

Locoregional adoptive immunotherapy resulted in regression in distant metastases of a recurrent esophageal cancer

 Esophageal cancer is one of the most common malignant diseases. However, postoperative recurrences are still resistant to currently available radiochemotherapy. We recently reported a study on the initial clinical efficacy of locoregional adoptive immunotherapy for advanced esophageal cancer. We report here our clinical experience of remarked responses in distant metastatic lesions in a patient with recurrent cancer after receiving this immunotherapy. A male patient underwent curative surgery, and presented with multiple recurrent metastases in the supraclavicular lymph nodes (LNs), liver, and abdominal aortic LNs. Autologous tumor-activated lymphocytes (AuTLs) generated ex vivo were regionally injected into supraclavicular LNs every 2 weeks 13 times. Mean numbers of the administrated cells were 0.8 × 10⁹ cells/injection. AuTLs established from peripheral blood lymphocytes stimulated by autologous tumor cells with interleukin-2 were tested for their cytotoxicity before every treatment. During immunotherapy, Grade 2 diarrhea and fever were observed. The clinical partial responses were obtained in all lesions and were sustained for 11 months. Because clinical toxicity was tolerable, this immunotherapy might be useful for patients with far-advanced esophageal cancers. Received: June 19, 2002 / Accepted: September 26, 2002 Correspondence to:U. Toh     

Intraarterial cellular immunotherapy for patients with inoperable liver metastases of esophageal cancer

PURPOSE: We report 2 patients with refractory liver metastatic tumor after esophagectomy for advanced esophageal cancer, who responded markedly to locoregional cellular immunotherapy by repeated intraarterial infusions of autologous tumor cell-activated T lymphocytes (AuTL), even after they failed the standard chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU). METHODS: AuTL administrations were made through the hepatic artery via a subcutaneous reservoir located at the right upper leg. Six injections were administered to both patients, repeated at 2-week intervals. The total number of administered T cells reached 2.4 x 10(9) and 3.1 x 10(9), respectively. RESULTS: A 39% and 51% regression in each infused field, compared with the size of liver tumor before treatment, was observed by computed tomography (CT) scan in patient 1 and 2, respectively. The responses continued up to the 10th and 11th month after the intraarterial infusion, confirmed by follow-up CT scan. The adverse effects of intraarterial immunotherapy were tolerable, with grade 1-2 fever and nausea in each patient. CONCLUSIONS: Clinical regression of liver metastases of esophageal cancer was observed in both patients who received this intraarterial cellular immunotherapy. Liver metastases of esophageal cancer may be controlled effectively and safely by repeating the intraarterial AuTL infusion as a locoregional immunotherapy over a long period.     

A case of advanced gastric cancer responding to combination chemotherapy with low-dose 5-FU plus CDDP

A 56-year-old man presented with dysphagia, and was found to have a type 3 advanced gastric cancer with bilateral multiple lung metastases. This patient was treated with low-dose 5-FU plus CDDP chemotherapy. In the first course, CDDP (6 mg/m2/day) plus 5-FU (300 mg/m2/day) were infused for 5 successive days a week, but a tumor response was not achieved. Therefore, in the second course, CDDP (6 mg/m2/day) plus 5-FU (600 mg/m2/day) were infused every other day (3 days a week). In response to the treatment, both the gastric tumor and the lung metastases almost completely disappeared (reduction rate 95%), and PR was achieved. The CEA level markedly decreased, from 260.3 to 1.4 ng/ml and the patient's symptoms disappeared. Following this treatment, low-dose CDDP plus UFT therapy was performed and the PR was maintained for 12 months. This report shows a case of advanced gastric cancer that responded to low-dose 5-FU plus CDDP.