How genomic selection has increased rates of genetic gain and inbreeding in the Australian national herd, genomic information nucleus, and bulls.

Genomic selection has been commonly used for selection for over a decade. In this time, the rate of genetic gain has more than doubled in some countries, while inbreeding per year has also increased. Inbreeding can result in a loss of genetic diversity, decreased long-term response to selection, reduced animal performance and ultimately, decreased farm profitability. We quantified and compared changes in genetic gain and diversity resulting from genomic selection in Australian Holstein and Jersey cattle populations. To increase the accuracy of genomic selection, Australia has had a female genomic reference population since 2013, specifically designed to be representative of commercial populations and thus including both Holstein and Jersey cows. Herds that kept excellent health and fertility data were invited to join this population and most their animals were genotyped. In both breeds, the rate of genetic gain and inbreeding was greatest in bulls, and then the female genomic reference population, and finally the wider national herd. When comparing pre- and postgenomic selection, the rates of genetic gain for the national economic index has increased by ~160% in Holstein females and ~100% in Jersey females. This has been accompanied by doubling of the rates of inbreeding in female populations, and the rate of inbreeding has increased several fold in Holstein bulls since the widespread use of genomic selection. Where cow genotype data were available to perform a more accurate genomic analysis, greater rates of pedigree and genomic inbreeding were observed, indicating actual inbreeding levels could be underestimated in the national population due to gaps in pedigrees. Based on current rates of genetic gain, the female reference population is progressing ahead of the national herd and could be used to infer and track the future inbreeding and genetic trends of the national herds.

Effect of basic fibroblast growth factor on the cellular repopulation of decellularized anterior cruciate ligament allografts.

The use of decellularized anterior cruciate ligament (ACL) allografts in ACL replacement surgery may allow for the native structure of the ligament to be retained, thereby recapturing the function of the ligament post-injury. Our previous work has focused on repopulating decellularized allograft ACL tissue with ACL fibroblasts in order to prevent destructive remodelling of the implanted tissue by extrinsic host cells. In this study, the use of basic fibroblast growth factor (bFGF) to improve the cellular repopulation of decellularized ACL tissue was assessed. A concentration of 6 ng/ml bFGF was demonstrated to be effective in increasing cellular growth in the absence of tissue; however, this concentration, as well as reduced and increased levels of bFGF (0.1 and 60 ng/ml, respectively), failed to increase cellular repopulation of ACL fibroblast-seeded decellularized tissue after 28 days of culture. Mean repopulation levels of 11-19% of fresh tissue [3200-5300 cells/mg dry weight (dwt) tissue] were achieved after 28 days in culture. Qualitative observation of histological samples suggested that different repopulation characteristics exist at various concentrations of bFGF and, in particular, that bFGF may be stimulating a catabolic pathway resulting in matrix destruction. Significant differences in the effects of bFGF observed between cell-only and cell-and-tissue studies serve to reinforce the concept that cells respond to stimuli in a different manner, depending on the surrounding environment. As a result, caution should be used when information obtained from studies utilizing cells alone is applied to the development of tissue-engineered constructs.

Cross-presentation of tumour antigens: evaluation of threshold, duration, distribution and regulation.

The development of technology to measure antigen presentation in the secondary lymphoid system has provided the opportunity of analysing components of the host antitumour immune response that have, until now, been unavailable for study. In particular, this technology has enabled us to evaluate threshold levels of tumour antigen required for cross-presentation in draining lymph nodes, the duration of this antigen presentation and processes that regulate tumour antigen presentation. Thus, we have been able to dissect out the relationship between antigen presentation and the resultant development of effector function in class I-restricted T cells, as well as the role of regulatory CD4 cells. We have also used this technology to evaluate the effects of antitumour therapy on local antigen cross-presentation.

The tongue-in-groove technique in septorhinoplasty. A 10-year experience.

BACKGROUND: Correction of the lower third of the nose is perhaps the most challenging component of performing a rhinoplasty. The tongue-in-groove (TIG) technique provides a method for correcting excess columellar show and maintaining correction of caudal deviation. It is also indicated for controlling nasal tip rotation and projection while preserving the integrity of the lobular cartilaginous complex and may be combined with either the external or endonasal rhinoplasty. It is typically used in combination with other septorhinoplasty maneuvers. The TIG technique consists of a method by which the medial crura are advanced cephaloposteriorly onto the caudal septum into a surgically created space between them. OBJECTIVE: To determine the effectiveness of the TIG technique to aid in correction of columellar show, a deviated caudal septum, and various tip rotation and projection problems. SETTING: Private practices of 2 authors (R.W.H.K., Houston, Tex, and H.M.T.F., Alexandria, Egypt). PATIENTS: The records of 287 patients who underwent TIG rhinoplasties in one private practice from 1989 through early 1999 (n = 203) and in another practice from 1994 through early 1999 (n = 84) were reviewed. MAIN OUTCOME MEASURES: Physician judgment of outcome was based on reduction of columellar show, change in tip rotation or projection, narrowing of the columella, and straightening of a deviated caudal septum as indicated in preoperative and postoperative photographs taken of all but 4 of the 287 patients. Patient judgment of outcome was measured by patient requests for revision and patient comments made during follow-up visits. RESULTS: Of 287 patients, 278 (97%) had satisfactory to excellent results. Only 9 (3%) required revisions related to the TIG technique. Eight of these 9 did not achieve enough reduction of columellar show or adequate rotation or projection. A repeated TIG technique was used in these 8 patients with satisfactory revision results. One of the 9 was overprojected and required revision. Of the 108 patients who had preoperative caudal septal deviation, none needed further surgery. CONCLUSIONS: The TIG technique provides a direct, effective solution to columellar show and is a reliable, reproducible method for achieving predictable tip rotation and projection. Furthermore, when used in conjunction with septoplasty techniques, it helps maintain the correction of a deviated caudal septum.

Imaging advances in the diagnosis of endocrine neoplasia.

Endocrine neoplasms are rare tumors that have traditionally been imaged with ultrasound, CT, magnetic resonance imaging, and angiography. Additional imaging modalities are now available. Endoscopic ultrasound is a new imaging approach to islet cell tumors of the pancreas, in which they typically appear round, homogeneous, and slightly hypoechoic compared with the pancreatic parenchyma. Carcinoid tumors can now be localized with 111In octreotide scintigraphy, which binds to the somatostatin receptors in the tumor. Pheochromocytomas have a distinctive appearance on magnetic resonance imaging, but important advances have occurred using 131I metaiodobenzylguanidine (MIBG). 131I MIBG scanning has a high diagnostic accuracy in detecting pheochromocytoma, with sensitivity greater than 90%. The various tumors and recent advances in their imaging are discussed.

Comparing prospective and retrospective evaluations of temporomandibular disorders after orthognathic surgery.

The authors conducted a study to document agreement between prospective examinations performed by trained clinical trial examiners and retrospective surgical chart reviews in identifying signs and symptoms of temporomandibular disorders, or TMD. Only a small fraction of the signs and symptoms identified by clinical trial examiners were documented in the surgical charts. Studies relying on retrospective chart reviews may seriously underestimate signs and symptoms of TMD.

Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome.

BACKGROUND: To the authors' knowledge, the natural history of myelosuppression and infectious complications associated with the use of standard cytarabine (ARA-C) plus daunorubicin ("7 + 3") remission-induction therapy for adult acute myeloid leukemia (AML) and high dose ARA-C (HDARA-C) consolidation has not been described completely. METHODS: A retrospective study of untreated adult AML patients receiving standard 7 + 3 induction followed by "5 + 2" and HDARA-C consolidation was undertaken to describe the relationship of the myelosuppression profiles, blood product use, and infectious morbidity, and to correlate this finding with the outcome of antileukemic therapy. Multivariate techniques were used to evaluate variables of prognostic importance. RESULTS: Fifty-nine percent of the patients achieved remission after a median of 35 days; almost half (48%) of these patients required more than one 7 + 3 induction course. For one, two, and three induction courses, the mean number of days the patients experienced severe neutropenia (< 0.5 x 10(9)/l) were 22.5 +/- 10.9, 39.3 +/- 14.3, and 47.4 +/- 9.7 days (P < 0.001), respectively, and the infection rates were 1.45, 2.45, and 3 infections per course (P < 0.0001), respectively. The pattern of blood product use was similar. HDARA-C consolidation was the most significant factor related to prolonged disease free survival, however the myelosuppression profiles and infection rates were surprisingly similar to those for the single 7 + 3 induction courses. CONCLUSIONS: The 7 + 3 induction regimen used in this center provided only limited antileukemic activity, while requiring multiple induction courses in a high proportion of patients. The use of multiple induction courses had consequences of prolonged myelosuppression, increased blood product use, and incremental risks of infectious complications. HDARA-C consolidation for those who experienced complete remission appeared to improve disease free survival with myelosuppression comparable with that of patients who received primary induction therapy. The infection risk was acceptable, with only a marginal increase in bacteremic and fungal infections.

Posttympanostomy otorrhea: the efficacy of canal preparation.

Otorrhea is the most common posttympanostomy complication. This study is designed to determine the efficacy of canal preparation prior to tympanostomy tube placement. One hundred thirty ears were prospectively randomized into prepared (Betadine and alcohol) and nonprepared (control) groups. Cultures obtained before, during, and after preparation were analyzed to determine the external canal flora and effectiveness of sterilization. Prepared ears and nonprepared control ears were examined for relation to otorrhea. Forty percent of the canals were sterile before preparation, and only 8% harbored suspected pathogenic organisms. Canal preparation successfully sterilized only 33% of the ears that contained bacteria. There was no difference in the otorrhea incidence among treatment groups (9.8%). Based on these bacteriologic and clinical findings, it is concluded that canal preparation with Betadine and alcohol does not reduce posttympanostomy otorrhea.

Massive epistaxis due to pseudoaneurysm. Treated with detachable balloons.

A case of massive epistaxis refractory to nasal packing and bilateral surgical ligation of the internal maxillary and ethmoidal arteries is presented. Angiography revealed a pseudoaneurysm of the cervical portion of the internal carotid artery, and intravascular detachable balloons were used for epistaxis control. The appropriate use of intravascular diagnostic and therapeutic techniques is described.

Post-tympanostomy otorrhea: a randomized clinical trial of topical prophylaxis.

Myringotomy with the insertion of tympanostomy tubes has become the most frequently performed otolaryngologic procedure, and otorrhea is the most common post-tympanostomy complication. Many otolaryngologists routinely use prophylactic topical antibiotic solutions when performing tympanostomy tube placement. Relatively little has been written regarding early post-tympanostomy otorrhea and scarcely any examining the efficacy of such prophylaxis. The current study is a randomized clinical trial to critically evaluate the efficacy of prophylactic otic drops after tympanostomy tube placement. The ototoxic potential of these solutions, combined with constant pressures to decrease medication expenses and eliminate unnecessary use of antibiotics, makes determination of the shortest effective course of application paramount. Subjects were randomized at the time of surgery into one of three groups: one group received no prophylaxis, a second group received gentamicin otic drops immediately after tympanostomy tube placement in the operating room only, and the third group received an additional 48 hours of drops (4 drops in each ear, three times a day). All patients were seen within 2 weeks postoperatively. An overall early post-tympanostomy otorrhea incidence of 8.7% is documented with 12%, 8.8%, and 5.6% for each study group, respectively. While these findings may suggest possible efficacy of topical prophylaxis, a statistically significant difference between the treatment groups was not proved (p = 0.62). Further analysis by subdivision of the patients, on the basis of middle ear cavity finding at the time of surgery, reveals a highly significant statistical association of the occurrence of post-tympanostomy otorrhea in ears having mucoid effusions (p less than 0.001) as compared to ears without effusion or with serous effusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Resident work hours and working environment in otolaryngology. Analysis of daily activity and resident perception.

OBJECTIVE: --To analyze the working environment and work hours of a cohort of otolaryngology--head and neck surgery residents. DESIGN: --Environmental analysis questionnaire and a log of daily activities. SETTING: --Residents were on a clinical rotation system. PARTICIPANTS: --Fifty-nine residents from six programs, including three public and three private institutions, from geographically diverse regions of the country were involved in the study. Residents were equally distributed from their second year through their fifth year of postgraduate work. All eligible residents participated in and completed the study. INTERVENTION: --The environmental analysis survey was designed to elicit resident perception of different aspects of their working environment. The daily activity log required the resident to report on activities for each half-hour period for 7 consecutive days. RESULTS: --Residents were on call an average of 52.8 hours (2.2 days) and worked 79.4 hours per week. Seventy-five percent believed that the level of faculty supervision and the degree of resident responsibility was about right. Two major inefficiencies were the time involved in completion of paperwork and the lack of nonmedical support services. Thirty-one percent of the residents responded that fatigue resulted in substandard patient care 10% of the time. Forty-seven percent responded that their educational experience was substandard 25% of the time secondary to fatigue. Two thirds responded that the demands of residency training had a negative impact on their family and personal life. CONCLUSIONS: --Seventy percent of the otolaryngology--head and neck surgery residents surveyed at six institutions believe that an 80-hour workweek, including being on call every third night with no more than 24 hours of continuous work without sleep, approximates a reasonable, maximum work schedule. Residents working the longest hours expressed concern about rendering substandard care and developing negative attitudes toward patients. Noneducational inefficiencies were identified and solutions were proposed. Demands of residency training, even within guidelines established as reasonable, can have detrimental effects on residents' educational activities and personal life.

Computed tomographic diagnosis of ruptured giant posterior cerebral artery aneurysms.

Ruptured giant posterior cerebral artery (PCA) aneurysms are encountered rarely. Although computed tomographic (CT) scan features of giant intracranial aneurysms have been described. CT scan features of acutely ruptured giant saccular PCA aneurysms have not been reported. A case of an acutely ruptured giant saccular PCA aneurysm with diagnostic CT scan features and autopsy confirmation is presented. Two additional cases of apoplexy with identical clinical courses and CT scan appearances, both attributed to giant saccular PCA aneurysms, are described. Diagnostic CT scan features included evidence of intraparenchymal temporal lobe and intraventricular hemorrhage, the presence of a filling defect in the temporal lobe hematoma that enhanced after intravenous contrast administration, and evidence of proximal PCA entrance into the contrast-enhanced filling defect in the intracerebral hematoma. The incidence of PCA aneurysms and the anatomy of the PCA as it relates to these giant aneurysms, their clinical presentation, and diagnostic features of the CT scan are discussed.

Aldosterone and dexamethasone binding in human arterial smooth muscle cells.

Regulation of blood pressure by direct action of corticosteroids on blood vessel walls was first hypothesized in 1952 [1]. The presence of receptors specific for these hormones within the peripheral vessel walls is a pre-requisite of this hypothesis. This report documents specific binding of both aldosterone (AL) and dexamethasone (DM) in cultured human arterial smooth muscle cells. After the arterial smooth muscle cultures were incubated with tritiated AL or DM at 37 degrees C for 30-60 min, the cells were sonicated and the protein bound steroid fraction isolated on a Sephadex G25 column. Using ion exchange chromatography of this fraction, each corticosteroid receptor complex displayed a distinct, reproducible elution pattern. Aldosterone showed a single peak at 0.096 +/- 0.005 mol/l sodium phosphate and DM had two peaks at 0.029 +/- 0.003 and 0.050 +/- 0.004 mol/l sodium phosphate. The Scatchard plots of specific binding from AL saturation curves are linear and revealed mean +/- s.d. steady state binding parameters of dissociation constant (Kd) = 0.35 +/- 0.15 nmol/l and maximum binding capacity (Bmax) = 98 +/- 53 X 10(-18) mol/micrograms DNA. Similarly, the mean +/- s.d. steady state binding parameters for DM are Kd = 4.4 +/- 2.0 nmol and Bmax = 3031 +/- 1385 X 10(-18) mol/micrograms DNA. Therefore, there are approximately 1150 AL binding sites and 30000 DM binding sites per cell. The Kd and Bmax values are similar to those previously described for corticoid receptors in rat aortic smooth muscle cells and are consistent with physiological steroid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective gut decontamination with nalidixic acid or trimethoprim-sulfamethoxazole for infection prophylaxis in neutropenic cancer patients: relationship of efficacy to antimicrobial spectrum and timing of administration.

Eighty-four cancer patients at risk of infection because of neutropenia were randomized to receive nalidixic acid as an alternative to trimethoprim-sulfamethoxazole (TMP-SMX) for infection prophylaxis. Infections were documented significantly earlier and more often among patients who entered the trial with neutrophil counts of less than 0.1 X 10(9)/liter. TMP-SMX recipients experienced fewer microbiologically documented infections and bacteremias and were free of infection for a higher proportion of days with severe neutropenia (less than 0.1 X 10(9)/liter) than nalidixic acid recipients. Gram-negative bacillary and Staphylococcus aureus infections accounted for the major differences. Although the majority of aerobic gram-negative bacilli were eliminated from the feces after 1 week of prophylaxis with either agent, TMP-SMX was proved superior to nalidixic acid in this regard and was associated with acquired drug resistance by gram-negative bacilli less frequently. Both agents selected for colonization and subsequent infection by gram-positive cocci. Our data suggest that prophylaxis is most likely to be effective if administered to patients for at least 1 week before they become severely neutropenic. Nalidixic acid used as a single agent in doses of 4 g daily, however, cannot be recommended as an alternative to TMP-SMX for infection prophylaxis in neutropenic cancer patients.

The Beirut terrorist bombing.

The Beirut terrorist bombing on October 23, 1983, caused 234 immediate deaths and injured at least 112 survivors. Military medical records were available for each casualty; postmortem examination reports were available for each immediate fatality. This represented a unique opportunity to assess type, incidence, treatment, and outcome of neurological injuries suffered in a mass casualty terrorist bombing situation. Three categories of neurological injuries are described: head injuries, spine and spinal cord injuries, and peripheral nerve injuries. The following types and numbers of injuries occurred among the 112 immediate survivors of the explosion: 37 head injuries--28 concussions, 20 scalp lacerations, 13 skull fractures, 6 facial bone fractures, 4 cerebral contusions, 5 dural lacerations, 2 cerebrospinal fluid fistulas, and 2 intracerebral hematomas; 2 spine or spinal cord injuries--1 cervical and 1 thoracolumbar spine fracture associated with neurological deficit; and 9 peripheral nerve injuries--1 facial nerve palsy, 2 brachial plexus palsies, 1 median and 1 radial nerve palsy, and 4 peroneal nerve palsies. Among 234 immediate fatalities, the types and numbers of neurological injuries were: 167 head injuries--93 scalp lacerations, 85 skull fractures, and 24 facial bone fractures; and 22 spine and spinal cord injuries--15 cervical and 7 thoracolumbar fractures. Seven of the 112 immediate survivors died; 4 of these deaths were related to severe head injuries. The treatment and outcome of survivors with neurological injuries is briefly described. One-third of the immediate survivors who suffered either a scalp laceration or a concussion had a concomitant skull fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrathecal phenol and glycerin in metrizamide for treatment of intractable spasms in paraplegia. Case report.

Intractable lower extremity spasms after spinal cord injury is a significant source of morbidity. A case of refractory spasticity in paraplegia was successfully converted to flaccid paraplegia by intrathecal injection of phenol and glycerin in metrizamide. This chemical rhizolysis is simple and effective, and the presence of metrizamide allows both fluoroscopic guidance for accurate intrathecal phenol placement and good miscibility with cerebrospinal fluid. A brief comparative review of alternative therapeutic modalities is presented.