Human pelvis injury risk curves from underbody blast impact.

INTRODUCTION: Underbody blast loading can result in injuries to the pelvis and the lumbosacral spine. The purpose of this study was to determine human tolerance in this region based on survival analysis. METHODS: Twenty-six unembalmed postmortem human surrogate lumbopelvic complexes were procured and pretest medical images were obtained. They were fixed in polymethylmethacrylate at the cranial end and a six-axis load cell was attached. The specimens were aligned in a seated soldier posture. Impacts were applied to the pelvis using a custom vertical accelerator. The experimental design consisted of non-injury and injury tests. Pretest and post-test X-rays and palpation were done following non-injury test, and after injury test medical imaging and gross dissections were done. Injuries were scored using the Abbreviated Injury Scale (AIS). Axial and resultant forces were used to develop human injury probability curves (HIPCs) at AIS 3+ and AIS 4 severities using survival analysis. Then ±95% CI was computed using the delta method, normalised CI size was obtained, and the quality of the injury risk curves was assigned adjectival ratings. RESULTS: At the 50% probability level, the resultant and axial forces at the AIS 3+ level were 6.6 kN and 5.9 kN, and at the AIS 4 level these were 8.4 kN and 7.5 kN, respectively. Individual injury risk curves along with ±95% CIs are presented in the paper. Increased injury severity increased the HIPC metrics. Curve qualities were in the good and fair ranges for axial and shear forces at all probability levels and for both injury severities. CONCLUSIONS: This is the first study to develop axial and resultant force-based HIPCs defining human tolerance to injuries to the pelvis from vertical impacts using parametric survival analysis. Data can be used to advance military safety under vertical loading to the seated pelvis.

Verification of High-Rate Vertical Loading Laboratory Skeletal Fractures by Comparison with Theater Injury Patterns.

For the current study, an existing theater injury data set was compared to component and whole body experiments meant to replicate the theater high rate vertical loading environment. The theater injury data set was derived from real world events that were within the design range of the Warrior Injury Assessment Manikin. A qualitative and quantitative assessment of the whole body fracture patterns was developed to determine whether the laboratory loading was correctly representing the resulting injuries seen in theater Underbody Blast (UBB) events. Results indicated that most of the experimental test fracture patterns were similar to the theater injuries for Abbreviated Injury Scale body regions of interest (lower extremities, pelvis, and spine); however, some of the body regions had higher similarity scores compared to others. Whole body fracture distribution was less similar than the component tests because of differences in injury distributions. The lower extremity whole body similarity was lower than spine and pelvis similarity. This analysis was able to identify some experimental tests that might not represent theater loading. In conclusion, this analysis confirmed that some laboratory testing produced skeletal injury patterns that are seen in comparable theater UBB events.

Estimating single nucleotide polymorphism associations using pedigree data: applications to breast cancer.

BACKGROUND: Pedigrees with multiple genotyped family members have been underutilised in breast cancer (BC) genetic-association studies. We developed a pedigree-based analytical framework to characterise single-nucleotide polymorphism (SNP) associations with BC risk using data from 736 BC families ascertained through multiple affected individuals. On average, eight family members had been genotyped for 24 SNPs previously associated with BC. METHODS: Breast cancer incidence was modelled on the basis of SNP effects and residual polygenic effects. Relative risk (RR) estimates were obtained by maximising the retrospective likelihood (RL) of observing the family genotypes conditional on all disease phenotypes. Models were extended to assess parent-of-origin effects (POEs). RESULTS: Thirteen SNPs were significantly associated with BC under the pedigree RL approach. This approach yielded estimates consistent with those from large population-based studies. Logistic regression models ignoring pedigree structure generally gave larger RRs and association P-values. SNP rs3817198 in LSP1, previously shown to exhibit POE, yielded maternal and paternal RR estimates that were similar to those previously reported (paternal RR=1.12 (95% confidence interval (CI): 0.99-1.27), P=0.081, one-sided P=0.04; maternal RR=0.94 (95% CI: 0.84-1.06), P=0.33). No other SNP exhibited POE. CONCLUSION: Our pedigree-based methods provide a valuable and efficient tool for characterising genetic associations with BC risk or other diseases and can complement population-based studies.

Unravelling modifiers of breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: update on genetic modifiers.

Pathogenic mutations in the tumour suppressor genes BRCA1 and BRCA2 confer increased risks for breast and ovarian cancer and account for approximately 15% of the excess familial risk of breast cancer amongst first-degree relatives of patients with breast cancer. There is considerable evidence indicating that these risks vary by other genetic and environmental factors clustering in families. In the past few years, based on the availability of genome-wide association data and samples from large collaborative studies, several common alleles have been found to modify breast or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. These common alleles explain a small proportion of the genetic variability in breast or ovarian cancer risk for mutation carriers, suggesting more modifiers remain to be identified. We review the so far identified genetic modifiers of breast and ovarian cancer risk and consider the implications for risk prediction. BRCA1 and BRCA2 mutation carriers could be some of the first to benefit from clinical applications of common variants identified through genome-wide association studies. However, to be able to provide more individualized risk estimates, it will be important to understand how the associations vary with different tumour characteristics and their interactions with other genetic and environmental modifiers.

Detecting estrus in synchronized heifers-using tailpaint and an aerosol raddle.

A synchronization treatment was initiated when each of 1227 heifers (four trials) was tailpainted. The tailpaint was sprayed with an aerosol raddle at the end of the treatment period. The heifers were in herds of 20 to 279 animals. Each herd was observed for estrus at selected post treatment intervals. A heifer was considered to be (or to have been) in estrus when the raddle was rubbed off. In three of the trials, animals which had the raddle removed were inseminated at 48 h following the end of the synchronization treatment. The tailpaint of an inseminated animal was scored from 0 (less than 10% of the paint remained) to 5 (more than 90% of the paint remained) and was then reraddled with a second color. The detection-insemination sequence was always repeated at 72 and 96 h, and sometimes at 120 h. Animals which had been previously inseminated, but then had paint scores reduced by at least 2 units were reinseminated 24 h later. Over the four trials, 94.5% of the heifers were detected in estrus through the use of the tailpaint and raddle system. The remaining 67 animals included only 10 (0.8%) which had ovulated without being detected in estrus. The reinsemination rate on consecutive days was 11.3% and was highest among animals that had a tailpaint score of 4 or 5 at 48 h. The proportion of animals detected in estrus at selected posttreatment intervals varied with the different synchronization treatments used within one herd, or with the same treatment used in different herds. The combination of tailpaint, raddling, tailpaint scoring and reraddling is a simple sequence which can be effectively used to detect estrus among heifers synchronized in research or commercial herds.

Radical radiation and oral and intra-vesical misonidazole for bladder cancer.

Patients with T2 grade 3 and T3 bladder cancer were entered into studies to evaluate the efficacy of 40 Gy in 2 Gy fractions (5/week) to the whole pelvis followed by 12 Gy in 6 Gy fractions (1/week) to a coned down volume plus oral and intravesical misonidazole (MISO). In a pilot study of 22 patients the complete response rate at cystoscopy at 6 months was 73% and the 5-year survival rate (life-table) with and without bladder preservation was 48% and 54% respectively. The 5-year bowel major complication rate (life-table method) was 8%. These results are statistically significantly improved over that seen in a series of historical controls. A prospective randomized trial has been completed comparing the above regimen with 40 Gy to the whole pelvis followed by 20 Gy to the coned down volume in 2 Gy fractions (5/week). Fifty-eight patients were entered and 53 are evaluable. The complete response rate at cystoscopy at 6 months is 69% (18/26) in the patients treated with MISO and 63% (17/27) in those treated without MISO. As this is an important prognostic indicator, it is unlikely that there will be an advantage in either group and this is supported by the initial follow-up data. The complete response rate at cystoscopy at 6 months is higher in both arms of this study than in the historical series.

Radical irradiation and misonidazole for T2 grade III and T3 bladder cancer: 2 year follow-up.

Patients with T2 grade III and T3 bladder cancer were treated in a Phase II trial of radical irradiation plus Misonidazole (MISO). Forty Gy in 2 Gy fractions (5 per week) to the whole pelvis were followed by 12 Gy in 6 Gy fractions (1 per week) plus oral and intravesical MISO to a coned down volume. Twenty-two patients were treated and the results compared with historical controls. The cystoscopic complete tumor response between 6 and 12 months post therapy were 73 and 43%, respectively. The patient two year survival was 81 and 51%, respectively, and the patient 2 year survival with bladder preservation was 61 and 48%, respectively--4 patients in the MISO study having undergone salvage cystectomy. Complications that may be radiation related in the MISO study are wound sepsis after salvage cystectomy in 2 patients, rectal stenosis requiring colostomy 16 months after salvage cystectomy in 1 patient and the development of a contracted bladder in 1 patient with a history of prior extensive endoscopic therapy. No misonidazole neurotoxicity seen. These findings are being further evaluated in a prospective randomized trial.

Radical irradiation of T2 grade III and T3 bladder cancer--tumor response and prognosis.

A retrospective review was undertaken of the records of 69 patients treated by radical irradiation between 1972 and 1977 for T2 Grade III and T3 bladder cancer. Twenty-six of the patients were treated to a tumor dose of 54 Gy in 2 Gy fractions using five daily fractions per week and 24 of the patients were treated to a tumor dose of 48.6 Gy in 3.47 Gy fractions given tri-weekly. The tumor response and its relationship to patient five year survival with bladder conservation was determined. Tumor response was assessed on the basis of the documented gross cystoscopic findings between 6 and 12 months after radiotherapy. This could be done in 63 of the 69 patients. The complete response rate was 43%. The five year survival rate with bladder conservation for all the patients in the study was 24%; for those with a complete response at cystoscopy, 54%; and for those failing to achieve a complete response, 5.8%. A statistically significant improvement in survival with bladder conservation for patients with complete response was found in both subgroups of uniformly treated patients. A 17% incidence of severe late gastrointestinal tract complications was noted in the subgroup of patients treated with large radiation fractions. These results confirm the prognostic value of the tumor response at cystoscopy after radical radiotherapy, expand the total dose or TDF range over which it has been observed and document its occurrence with an unconventional radiation fractionation schedule.

Radical irradiation and misonidazole in the treatment of T2 grade III and T3 bladder cancer.

The results of 2 pilot studies using a new radiation fractionation schedule plus misonidazole (MISO) in the radical radiotherapy of T2 Grade III and T3 carcinoma of the bladder are presented. Forty Gy in 20 daily fractions of 2 Gy was administered to the whole pelvis over 4 weeks followed by 12 Gy in 2 weekly fractions of 6 Gy. These last 2 doses were given after MISO administration. In an initial pilot study (Pilot Study I) MISO was administered orally only. The first two patients received MISO at a dose of 4.5g/m2 orally with each radiation fraction, after which the dose was reduced to 3.0g/m2 because of drug toxicity. In the second pilot study (Pilot Study II) MISO was administered orally at a dose of 3.0g/m2 and intravesically at a dose of 1.0g to 22 patients. The complete response rate at cystoscopy at 6 months in the latter group of patients is 73%, which is significantly better than that of 43% obtained in a retrospective study of historical controls. There have been no late radiation complications in any of the patients nor any MISO toxicity apart from nausea in the patients receiving 3.0g/m2 orally with or without the intravesical MISO.

Immediate reconstruction of mandibular defects with a composite sternocleidomastoid musculoclavicular graft.

The problem of mandibular reconstruction has been approached using many surgical techniques. This article studies one such approach--reconstruction using full-thickness clavicle pedicled on the sternocleidomastoid muscle. Five patients with stage II and stage III carcinoma of the anterior part of the floor of the mouth were treated with mandibular resection and neck dissection. The resulting defects were immediately reconstructed with the clavicle-sternocleidomastoid muscle technique. The patients were observed from one to three years and were examined postoperatively with technetium Tc 99m medronate scans, which demonstrated the grafts to be viable. The technique proved reliable in a limited clinical trial.

Priapism - a surgical emergency.

Priapism is a surgical emergency, and a glandular cavernous shunt is good emergency treatment. The technique is simple, easy and quick, can be performed under local anaesthesia if necessary, and has a good chance of success; should it fail or the priapism recur, a more formidable shunt may be performed.

Prolapse of the laryngeal ventricle.

Many varied lesions may protrude into the laryngeal lumen from between the true and false vocal cords. These protrusions can be precisely diagnosed only by biopsy. Prolapse of the laryngeal ventricle is one of these lesions; it is a distinct clinicopathologic entity, a primary lesion unrelated to other laryngeal or systemic disease. Eversion of the ventricle (or saccule) is a similar protrusion that is secondary to pulsion or traction by an associated laryngeal lesion. Other lesions that may produce similar clinical findings and gross appearance include benign tumors, cysts, and, rarely, squamous cell carcinoma. Biopsy is therefore mandatory to plan rational treatment. A review of 26 patients who had been diagnosed as having prolapse resulted in the reclassification of 20 cases of prolapse and six cases of eversion. Prolapse is possibly unrelated etiologically to cough, or chronic laryngeal or respiratory tract infection. The histopathologic data suggest further that prolapse is a result of fatty infiltration, edema, and inflammation of the periventricular tissue above the ventricle, which cause the tissue to enlarge and protrude into the laryngeal lumen from between the true and false vocal cords.