Assessment and management of pain in haemophilia patients.

Haemophilia patients experience acute pain during joint bleeds and chronic pain from haemophilic arthropathy. More than 50% of haemophilia patients have painful joints that cause disability and impair quality of life. Unfortunately, only a few clinical studies have investigated the non-pharmacological or pharmacological treatments for pain or the adverse effects of pain on the health and quality of life of children and adults with haemophilia. There are no detailed algorithms or guidelines for pain management in haemophilia patients, and treatment is largely empirical. Therefore, a standardized approach to the management of pain in haemophilia patients is needed. This approach should include a close relationship between pain specialists and the staffs at haemophilia treatment centres; validated instruments specific to haemophilia for assessing pain, quality of life and disability; and stepwise algorithms/protocols for treatment of chronic vs. acute pain and prophylactic vs early treatment. A pain treatment protocol should include a definition of the problem of pain and best practices for physicians. A call to action is needed to standardize treatment approaches to pain and to develop algorithms/protocols for the management of pain in haemophilia patients. This review will highlight the prevalence and devastating impact of pain in haemophilia patients, currently available treatment options and identify the unmet needs for pain management.

Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis.

Regions where one type of epithelium replaces another (metaplasia) have a predilection for cancer formation. Environmental factors are closely linked to metaplastic carcinogenesis. In particular, cervical cancers associated with human papillomavirus (HPV) infection develop primarily at the transformation zone, a region where metaplastic squamous cells are detected in otherwise columnar epithelial-lined endocervical glands. Previously, we reported estrogen-induced multistage vaginal and cervical carcinogenesis in transgenic mice expressing HPV16 oncogenes in basal squamous epithelial cells. In the present study to investigate the threshold neoplastic response to exogenous estrogen, we treated groups of transgenic mice with lower hormone doses. A 5-fold reduction in estrogen dose induced squamous carcinogenesis solely at the cervical transformation zone compared with other reproductive tract sites. Further study delineated stages of transformation zone carcinogenesis, including formation of hyperplastic lower uterine glands and emergence of multiple foci of squamous metaplasia from individual stem-like glandular reserve cells, followed by neoplastic progression of metaplasia to dysplasia and squamous cancer. We propose that a combination of low-dose estrogen and low-level HPV oncogene expression biases transformation zone glandular reserve cells toward squamous rather than columnar epithelial fate decisions. Synergistic activation of proliferation by viral oncoprotein cell cycle dysregulation and estrogen receptor signaling, together with altered paracrine stromal-epithelial interactions, may conspire to support and promote neoplastic progression and cancer formation.

Difluoromethylornithine chemoprevention of epidermal carcinogenesis in K14-HPV16 transgenic mice.

To be informative for chemoprevention, animal models must both closely emulate human disease and possess surrogate endpoint biomarkers that facilitate rapid drug screening. This study elucidated site-specific histopathological and biochemical surrogate endpoint biomarkers of spontaneous epidermal carcinogenesis in K14-HPV16 transgenic mice and demonstrated that the incidence and severity of these markers were decreased by the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). The cumulative incidence of visible epidermal cancers in 127 untreated transgenic mice was 42% by 52 weeks of age, most frequently affecting the chest as flat lesions in association with chronic ulcers, or in the ear as protuberant masses. Microscopic malignancies were detected in 39% of 32-week-old transgenic mice and were found to emerge from precursor lesions that were of two distinct types: dysplastic sessile ear papillomas and hyperproliferative follicular/interfollicular chest dysplasias. ODC activity and tissue polyamine contents were differentially elevated in ear and chest skin during carcinogenesis, such that there was a marked elevation of both parameters of polyamine metabolism as early as 4 weeks of age in the ear, whereas in the chest, polyamine metabolism was increased significantly only in the late stages of neoplastic progression and in epidermal cancers. Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age prevented both visible and microscopic malignancies and significantly decreased the incidence of chest and ear precursor lesions. ODC activity and tissue putrescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a more modest decline of these parameters in chest skin. DFMO treatment of transgenic mice from 28 to 32 weeks of age was associated with an absence of ear cancer and a marked regression of dysplastic papillomas. In contrast, the results in chest skin were complex in that the severity of chest precursors diminished, but their incidence was unchanged, and microscopic cancers were still detectable within these lesions. Collectively, this study highlights the utility of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice both for the study of the biology of, and as a screening tool for, novel drugs and chemopreventive regimens.

Growth and carcass characteristics of Angus and American Wagyu steers.

Ten purebred Angus and ten crossbred (3/4-7/8) American Wagyu steers were fed a corn and barley-based diet for 552 days and slaughtered. All USDA and Japanese yield and quality grade factors were evaluated and the amount of extractable lipid and moisture in totally trimmed muscle was determined. Angus steers gained 0·9 kg/head/day and American Wagyus gained 0·7 kg/head/day. This difference in growth rate resulted in Angus steers having a heavier final weight (P < 0·05). Angus steers required less feed per unit of gain than did American Wagyu steers. Adjusted fat thickness over M. longissimus dorsi opposite the 12th rib was approximately 3·5 cm and was not statistically different between the two breeds (P > 0·05). Average ribeye area and kidney, pelvic and heart fat were similar for the two breeds. The calculated USDA yield grade for both breeds exceeded 6. Average USDA marbling score was nearly a degree of marbling higher for American Wagyu than for Angus, but variation within breed groups was high. Average USDA quality grade was well into USDA Prime for all carcasses and did not differ by breed (P > 0·05). Japanese yield grade factors were similar for both breeds except for cold left side weight and the yield estimation which includes an adjustment factor that favors American Wagyu. American Wagyu steers merited a higher Japanese marbling score than did Angus (P < 0·05). Beef color score, firmness, texture and firmness and texture grade were also different between the breeds (P < 0·05). Fat colour, luster and quality were not different (P > 0·05). These data clearly show that some American Wagyu steers have the genetic ability to deposit as much marbling as Japanese Black cattle raised in Japan.

Chronological age and breed-type effects on carcass characteristics and palatability of bull beef.

Bulls (n = 115) of four slaughter ages (9, 12, 15 or 18 months) and of 15 genotypes were studied. In this analysis, each bullock was assigned to one of four breed groups-British and British crosses, Brahman and Brahman crosses. Jersey and Jersey crosses or Holstein and Holstein crosses. Slaughter age had an (P < 0·01) effect on marbling score, longissimus muscle area, fat thickness and yield grade while breed group had an (P < 0·01) effect on marbling score and quality grade. In general, British and British cross bullocks produced carcasses with the thickest subcutaneous fat, the highest marbling score and the highest USDA quality grade while Jersey and Jersey cross bullocks yielded carcasses with the lowest weight, smallest longissimus muscle area and the lowest USDA quality grade of the four breed-type groups. Increases in chronological age (from 9 to 18 months) were generally associated with a decrease in USDA maturity score, and increases in marbling score, USDA quality grade, longissimus muscle area, subcutaneous fat thickness and USDA yield grade. Shear force values decreased as bulls matured from 9 to 18 months of age. The meat from Brahman-type bulls had higher shear force values (P < 0·01) than that from bulls of the other breed groups. Steaks from British-type carcasses received the highest numerical ratings for sustained juiciness and flavor while steaks from the Brahman-type carcasses were assigned the lowest numerical ratings for juiciness. Breed-type had a greater effect on tenderness of bull beef than did chronological age.

Follow-up assessment of St. Jude Medical prosthetic valve in the tricuspid position: clinical and hemodynamic results.

Seven patients underwent postoperative right heart catheterization implantation of the St. Jude Medical prosthetic valve in the tricuspid position. Six patients were in atrial fibrillation at catheterization, and 1 was in normal sinus rhythm. At postoperative catheterization, the mean right atrial pressure ranged between 4 and 16 mm Hg (mean, 9.7 mm Hg); right ventricular systolic pressure was normal in 1 patient, mildly elevated (less than 50 mm Hg) in 4 patients, and moderately elevated (65 and 70 mm Hg) in 2. The cardiac output ranged between 3.0 and 7.0 L/min (mean, 4.2 L/min). There was no end-diastolic gradient across the St. Jude Medical prosthesis in 6 patients. The other patient had a gradient of 2 mm Hg across the valve when cardiac output was 7.0 L/min. On fluoroscopy, both discs demonstrated full excursion in all patients. These data demonstrate that a normally functioning St. Jude Medical valve in the tricuspid position does not create obstruction to forward flow, and they support use of this prosthesis in patients with tricuspid valve disease.

Evaluation of Retail and Palatability Characteristics of Electrically Stimulated U.S. Choice Beef After Commercial Transport-Distribution.

The left sides of U.S. Choice carcasses were electrically stimulated (ES) and the right sides were not (Not-ES); sides were transported to a retail distribution center, cut and packaged. Vacuum-packaged subprimal cuts (top round; outside round; full loin, trimmed; ribeye roll; chuck--blade portion; shoulder clod roast) were shipped to a retail store and cut into retail cuts. Weight loss of vacuum-packaged primals during storage did not differ (P>0.05) between ES and Not-ES treatments for any of the six subprimal cuts. Muscle color of 7-bone roasts at the beginning of retail display was the only appearance characteristic improved (P<0.05) for any steak or roast as a result of ES. No differences (P>0.05) were observed between ES and Not-ES beef for muscle color, surface discoloration or overall appearance of top round or porterhouse steaks. ES did not (P>0.05) affect the shrink loss of retail cuts at 2 or 3 days of display. Microbiological evaluations of ES and Not-ES retail cuts did not produce consistent results. Muscle fiber tenderness for sirloin steaks ( gluteus medius ) increased (P<0.05) as a result of ES; however, ES resulted in higher (P<0.02) shear force values for ribeye steaks ( longissimus ). Neither sensory panel ratings nor shear force values differed (P>0.05) between treatments for bottom round roasts; however, shoulder pot roasts from ES sides had more detectable connective tissue (P<0.03), less overall tenderness (P<0.008) and less overall palatability (P<0.04) than did shoulder pot roasts from Not-ES sides.

Post-traumatic abnormalities of the pubic bone simulating malignancy.

Three cases are presented in which unusual healing patterns of pubic features simulated malignant processes. Consideration of trauma as an etiologic factor in such cases may obviate the need for extensive clinical and histologic evaluation.