Carcinoma of the maxillary antrum — A 10 year experience

A retrospective analysis was performed of 250 cases of carcinoma of the maxillary antrum seen over a 10 years period (1975–1984). 98.24% patients were seen in T3 and T4 stages (UICC 1985). 40.7% patients presented with clinically palpable nodes. 42.9% patients were treated by radical radiation and 18.6% by a combination of preoperative radiation followed by surgery. Rest 38.5% patients were treated with palliative intention. Three year disease free survival was 39.58% with radiation alone and 51.91% with combined modality treatment which includes patients salvaged by surgery. Failures were mainly at the local site, 75.86% with radiation alone and 60% with combined modality treatment. Combined modality treatment, preferably preoperative radiation followed by radical surgery, gives the best results in the management of carcinoma of the maxillary antrum.     

The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report

STUDY DESIGN: A prospective randomized controlled human clinical pilot trial. OBJECTIVES: To determine the feasibility of using rhBMP-2/collagen as a substitute for autogenous bone graft inside interbody fusion cages to achieve arthrodesis in humans. SUMMARY OF BACKGROUND DATA: Preclinical studies have shown rhBMP-2 to be an effective substitute for autogenous bone graft, but there are no studies to date documenting such efficacy for human spine fusion. METHODS: Fourteen patients with single-level lumbar degenerative disc disease refractory to nonoperative management were randomized to receive lumbar interbody arthrodesis with a tapered cylindrical threaded fusion cage filled with rhBMP-2/collagen sponge or autogenous iliac crest bone. Patients were evaluated with radiographs, sagittally reformatted computed tomography scans, and Short Form-36 and Oswestry outcome questionnaires. RESULTS: All 11 patients who received rhBMP-2 were judged by three independent radiologists to have solid fusions (at 6, 12, and 24 months postimplantation), whereas only 2 of the 3 control patients, who received the standard treatment of autogenous iliac crest bone, were deemed to be fused. The Oswestry Disability Questionnaire scores of the rhBMP-2 group improved sooner (after 3 months) than those of the autograft group, with both groups demonstrating similar improvement at 6 months. Short Form 36 scores continued to improve up to 24 months. CONCLUSION: The arthrodesis was found to occur more reliably in patients treated with rhBMP-2-filled fusion cages than in controls treated with autogenous bone graft, although the sample size was limited. There were no adverse events related to the rhBMP-2 treatment. This study is one of the first to show consistent and unequivocal osteoinduction by a recombinant growth factor in-humans.     

Human serum induces apoptosis of xenogenic cardiomyocytes in vivo and in vitro

Abstract: Discordant xenotransplantation is complicated by delayed xenograft rejection (DXR). Previous studies have demonstrated that anti‐apoptotic genes are protective against DXR. This study examines the hypothesis that apoptosis plays a role in human anti‐xenograft responses. C57BL/6 mice and NOD SCID mice were given a single intravenous injection of either a lethal dose (LD, survival < 30 min) or a sublethal dose (SLD) of human serum, and isolated pig and mouse rod‐shaped cardiomyocytes were exposed to human serum in vitro. In situ detection of apoptotic cells in mouse hearts was assessed using a terminal deoxynucleotidyl transferase‐mediated dUTP nicked‐end labeling assay. Mice transfused with human serum had approximately a 10‐fold increased percentage of apoptotic cells after SLD 18 h post‐injection compared with animals given saline, and a fourfold increase over LD. Administration of cobra venom factor (CVF) decomplemented SLD 18 h did not significantly ( P  > 0.05) alter the percentage apoptosis. The addition of 20 mM Gal‐α‐1,3‐Gal to SLD 18 h significantly ( P  < 0.05) reduced percentage apoptosis to levels comparable to saline treated control animals. In vitro using mouse and pig cardiomyocytes demonstrated parallel results as in vivo experiments.
Human serum induces apoptosis of cardiomyocytes in immunocompetent and immunoincompetent mice in vivo, as well as mouse and pig cardiomyocytes in vitro. Further, this apoptotic response can be inhibited by the addition of Gal‐α‐1,3‐Gal without affecting the capacity of the serum to cause HAR. These results demonstrate that a putative human serum factor induces a delayed apoptotic injury of xenograft tissues, and supports the hypothesis that apoptosis may be an important mediator of DXR.     

An unusually severe phenotype for familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is a dominantly inherited predisposition to the development of many hundreds to thousands of adenomatous polyps of the colon. The mean age of onset is around 15 years, symptoms may arise in the third decade, and the median age for the development of colonic cancer is 35-40 years. Prophylactic colectomy reduces the risk of death from colorectal cancer to such an extent that late sequelae such as upper gastrointestinal tumours have become the main cause of mortality in appropriately managed patients. The age at which colonic surveillance begins reflects the natural history of the disease. Onset of polyp formation and cancer in childhood is very unusual, but has recently been associated with a specific mutation at codon 1309 in exon 15 where a more severe phenotype is sometimes observed. The case histories of two families are reported in which there is childhood onset of polyps in the youngest generation and in one case a carcinoma, in whom mutations have been identified in exon 11 of the APC gene. Several other affected relatives were diagnosed at ages ranging from 5-48 years, some already with a cancer at the time of first screening. Since the aim of screening for colonic polyps is prevention of colonic cancer, family members at risk should be offered genetic assessment and direct mutation testing where this is possible, usually in the early teens. In the absence of a genetic test (the situation in about one third of families) or in a known gene carrier, annual colonoscopy examination is advised from the same age. Clinicians should take note of the family history and be prepared to consider much earlier intervention if symptoms occur in a child with a family history of FAP. Where childhood onset of polyps has occurred, other children at risk in the family must be offered earlier genetic testing and endoscopic surveillance.

     

Tracheoesophageal fistula: New option in management

Tracheoesophageal fistula is a life threatening condition. Patients not managed surgically ultimately die of their disease. Surgical management is the treatment of choice. We present a case of a patient that developed a tracheoesophageal fistula after tracheostomy. Surgical repair was done which failed due to infection. The patient was managed with the help of an esophageal stent and Trichloroacetic Acid cautery. This approach can be used in selected patients, depending upon the size and site of TEE Larger fistulae and those situated lower down e.g. supra carinal cannot be managed by this technique.     

Anterior lumbar interbody fusion with osteoinductive growth factors

Anterior intervertebral fusion increasingly is used as a treatment for discogenic or intersegmental pathologic diseases of the lumbar spine. This is in part attributable to the evolution and refinement of laparoscopic and minimally invasive surgical techniques that now can be used to access the anterior spinal column. It also is attributable to the availability of newer generation intervertebral fixation devices such as the threaded titanium cages or threaded allograft bone dowels, both of which are technically simpler to implant. Recently, limited clinical studies of intervertebral lumbar fusion have examined the use of these devices combined with osteoinductive growth factors as substitutes for autogenous bone graft. Early clinical results of lumbar fusion using threaded intervertebral implants filled with recombinant human bone morphogenetic protein-2 have been favorable. Higher fusion rates, shorter operative times, and shorter hospital stays have been reported in the initial series. Clinical trials involving larger cohorts with various spinal applications for osteoinductive molecules currently are in progress.     

Pharmacological similarities between native brain and heterologously expressed alpha4beta2 nicotinic receptors

1 We studied the pharmacological properties of native rat brain and heterologously expressed rat alpha4beta2 nicotinic receptors immunoprecipitated onto a fixed substrate with the anti-alpha4 antibody mAb 299. 2 Immunodepletion with the anti-beta2 antibody mAb 270 showed that 89% of the mAb-299-precipitated rat brain receptors contained beta2. 3 The association and dissociation rate constants for 30 pM +/-[3H]-epibatidine binding to alpha4beta2 receptors expressed in oocytes were 0.02+/-0.01 and 0.03+/-0.01 min-1 (+/-standard error, degrees of freedom=7 - 8) at 20 - 23 degrees C. 4 The Hill coefficients for +/-[3H]epibatidine binding to the native brain, alpha4beta2 receptors expressed in oocytes, and alpha4beta2 receptors expressed in CV-1 cells (using recombinant adenovirus) were 0.69 - 0.70 suggesting a heterogeneous receptor population. Fits of the +/-[3H]-epibatidine concentration-binding data to a two-site model gave KD s of 8 - 30 and 560 - 1,200 pM. The high-affinity sites comprised 73 - 74% of the native brain and oocyte alpha4beta2 receptor population, 85% of the CV-1 alpha4beta2 receptor population. 5 The expression of rat alpha4beta2 receptors in CV-1 cells using vaccinia viral infection-transfection resulted in a more homogeneous receptor population (Hill coefficient of 1. 0+/-0.2). Fits of the +/-[3H]-epibatidine binding data to a single-site model gave a KD of 40+/-3 pM. 6 DHbetaE (IC50=260-470 nM) and the novel nicotine analogue NDNI (IC50=7-10 microM) inhibited 30 pM+/-[3H]-epibatidine binding to the native brain and heterologously expressed alpha4beta2 receptors equally well. 7 The results show that alpha4beta2-containing nicotinic receptors in the rat brain and heterologously expressed rat alpha4beta2 receptors have similar affinities for +/-[3H]-epibatidine, DHbetaE, and NDNI.