Epistaxis: diagnosis and treatment.

Oral and maxillofacial surgeons are called on to evaluate and treat various emergencies, including acute epistaxis. Epistaxis is relatively benign in nature, but it can produce a serious, life-threatening situation. It has been estimated that up to 60% of the population has had at least 1 episode of epistaxis throughout their lifetime. Of this group, 6% seek medical care to treat epistaxis, with 1.6 in 10,000 requiring hospitalization. With fewer and fewer otorhinolaryngologists participating on hospital call schedules, it is critical for the oral and maxillofacial surgeon to be familiar with the anatomy, diagnosis, and treatment of acute epistaxis and associated medical concerns. Considerations concerning mechanism of injury, coagulopathies, and potential treatment options need to be assessed quickly and accurately to ensure the most appropriate treatment and positive outcome for the patient. The need to treat epistaxis in an emergent setting will often require the involvement of an oral and maxillofacial surgeon. By reviewing the anatomy, potential complications arising from associated medical conditions, and treatment options, patients can be accurately assessed and treated appropriately.

Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer.

BACKGROUND: Disruption of normal mechanisms for cell cycle regulation is important in carcinogenesis. SAK and PLK are members of the polo family of serine threonine kinases, which in lower organisms have been shown to be required for the precise regulation of mitosis. Studies of human polo family members have focused on PLK, which has been found to be overexpressed in several tumor types, with the degree of overexpression correlating with adverse clinical outcome. However, PLK expression had not previously been analyzed in colorectal cancer. SAK, a polo family member with unique properties, had not been systematically studied in any tumor type. METHODS: In this study, SAK expression was evaluated in a series of sporadic human colorectal cancer specimens (n = 74) and compared with that of PLK. Expression was assessed by reverse transcription-polymerase chain reaction. RESULTS: In the majority of cases, both SAK and PLK were more highly expressed in tumor tissue than in adjacent normal intestinal mucosa. Levels of SAK and PLK expression in tumor relative to paired normal mucosa correlated directly with patient age and with each other but did not correlate with tumor stage. These results suggest a mechanism for augmented disruption of mitotic regulation in older patients. CONCLUSIONS: The polo family mitotic regulators SAK and PLK are both aberrantly expressed in colorectal cancer. The potential prognostic significance of SAK and PLK expression in colorectal cancer will be evaluated in the future.

Late mitotic failure in mice lacking Sak, a polo-like kinase.

Polo-like kinases in yeast, flies, and mammals regulate key events in mitosis. Such events include spindle formation at G2/M, the anaphase-promoting complex (APC) at the exit from mitosis, the cleavage structure at cytokinesis, and DNA damage checkpoints in G2/M. Polo-like kinases are distinguished by two C-terminal polo box (pb) motifs, which localize the enzymes to mitotic structures. We previously identified Sak, a novel polo-like kinase found in Drosophila and mammals. Here, we demonstrate that the Sak kinase has a functional pb domain that localizes the enzyme to the nucleolus during G2, to the centrosomes in G2/M, and to the cleavage furrow during cytokinesis. To study the role of Sak in embryo development, we generated a Sak null allele, the first polo-like kinase to be mutated in mice. Sak(-/-) embryos arrested after gastrulation at E7.5, with a marked increase in mitotic and apoptotic cells. Sak(-/-) embryos displayed cells in late anaphase or telophase that continued to express cyclin B1 and phosphorylated histone H3. Our results suggest that Sak is required for the APC-dependent destruction of cyclin B1 and for exit from mitosis in the postgastrulation embryo.

Sak kinase gene structure and transcriptional regulation.

The Sak gene encodes a serine/threonine kinase, which is a member of the Polo family of mitotic regulators. Sak transcripts are present in S/G2/M phase cells, and in proliferating cell layers of the mouse embryo and adult tissues. In this report, we have characterized the murine Sak gene structure, the Sak chromosomal location, and identified the promoter. The murine Sak gene is located on the proximal arm of mouse chromosome 13, as determined by RFLP analysis. The murine gene comprises 15 coding exons spanning 16kb of genomic sequence, and encodes two alternately spliced transcripts. Sak-a, the predominant transcript, is encoded by 15 exons, while early termination of transcription and alternative splicing at exons 5 and 6 results in Sak-b. This truncated transcript encodes the complete kinase domain and a carboxyl end translated from 147bp of sequence contiguous with exon 5. Human Sak-a (Stk18) cDNA is reported to contain an insertion of sequence corresponding to the mouse Sak-b tail. Primer extension analysis of murine Sak revealed one major transcription start site at position -303bp relative to the start of translation. A genomic fragment of 3.5kb located 5' of the Sak transcriptional start drives expression of a luciferase-reporter gene in CHO and GC1-SPG cells in an orientation-dependent fashion. Using various Sak promoter/luciferase constructs, the core promoter region required for expression was located within 400bp of the message Cap site, and sequence further 5' strongly suppressed transcription.

Experimentally induced upper facial third fractures in unembalmed human cadaver heads.

Considerable need exists in the transportation industry to develop safety guidelines to protect the head and neck. One of the goals of this study was to produce facial fractures similar to those induced in motor vehicle crashes. Unembalmed cadaver heads were fixed to a supporting device and impacted with a steel pipe. The most common fracture was of the frontal sinus; multiple orbital wall, naso-orbitoethmoid, Le Fort I, II, and III fractures were also produced. Average impact speeds of 7.2 meters per second striking at the supraorbital rims created severe injury to both skull and contents. Energy absorption values accounted for the actual total contact time between head and pipe with tolerance level values measuring the force at specific intervals. The method described may be used to reproduce reliably those forces resulting in the facial fractures seen in the emergency room setting after motor vehicle crashes.

Bilateral cervicofacial arteriovenous malformations: a case report with unusual complications.

Arteriovenous malformations (AVM) of the craniofacial region are complex problems that require a multidisciplinary approach. Early recognition and proper treatment are essential for an acceptable longterm outcome. This article describes the case of an improperly handled AVM. During the course of retreatment, the left external carotid artery was reanastomosed to gain access for embolization in an attempt to treat the patient definitively. There is also a discussion of classification theories of formation, contemporary treatment, and complications.

Identification of new localized RNAs in the Xenopus oocyte by differential display PCR.

We have identified localized transcripts in full-grown Xenopus oocytes by differential display PCR. One clone, An4a, has two transcripts, which localize to the animal half of the stage VI oocyte. The transcripts are expressed throughout early development, with embryonic expression primarily in anterior neural tissues. An4a has a high degree of sequence identity to a human cDNA clone of unknown function. Another clone, the previously identified beta-transducin repeat containing protein (beta-TrCP), has three transcripts with a unique pattern of localization, one localized to the animal half and two localized primarily to the vegetal cortex. This cDNA has previously been shown to rescue a yeast cell division cycle mutant, raising the possibility that the different Xenopus transcripts are involved in animal and vegetal cell cycles. Embryonic expression is primarily in the cement gland. These new localized transcripts contribute to the general observation that the vegetal cortex, but not the animal cortex, is a specific site for RNA localization.

The Christensen prosthesis. A retrospective clinical study.

The objective of this study was to determine if the Christensen temporomandibular joint prosthesis system in an effective alternative in treating patients with severe temporomandibular joint disorders. A total of 69 patients who were not responsive to either nonsurgical or prior surgical treatments were placed into one of three treatment groups depending on the following diagnoses: (1) placement of a glenoid fossa-eminence prosthesis with meniscus retention (22 patients, 40 joints); (2) placement of a glenoid fossa-eminence prosthesis without retention of the meniscus (26 patients, 49 joints); (3) total joint replacement (21 patients, 34 joints). Patients were evaluated immediately before surgery and at regular intervals after surgery for an average of 3.1 years. Success was measured as a significant improvement of function and decrease in pain as measured on a visual analogue scale, as well as improved incisor opening as measured with a Therabite Scale (Lorenz Surgical, Jacksonville, Fla.). Comparison of mean and average pre- and postsurgical values for all groups and criteria showed significant improvement. Results of this study indicate that the Christensen temporomandibular joint prosthesis system may offer a viable method for the treatment of severe temporomandibular joint disease with a high degree of success.

Use of pedicled fat pad graft as an adjunct in the reconstruction of palatal cleft defects.

The purpose of this article is to provide the rationale for the use of pedicled buccal fat pad grafts as an adjunct to the reconstruction of palatal or dentoalveolar clefts in cases when healing by secondary intention may need to be considered and integrated into the initial treatment plan because of the size of the defect or qualitative or quantitative tissue constraints. Four representative cases are presented in which a pedicled buccal fat graft was adjunctively used in conjunction with pedicled mucosal flaps to gain closure of large oroantral or oronasal cleft deformity.

Contributions within dental science to cleft lip/palate management: a literature review.

Dentistry has consistently provided cleft lip/palate care with new advancements in management and technology. However, there is a significant disparity in the general knowledge base of the general dental and medical practitioner regarding this relatively common orofacial deformity. Fortunately, contributions from the dental arts continue to provide momentum and major influence in the cleft-care arena. Modifications in pharyngeal flap procedures for management of velopharyngeal incompetence have been advanced by oral and maxillofacial surgery. Application of contemporary integrated prosthesis technologies to cleft dental habilitation are now being used. Recently, significant contributions to cleft lip/palate science from the realm of fetal surgery and fetal wound healing may eventually have broader applications and benefit all facets of health care.

Osteomyelitis of the jaws: a 50-year perspective.

The incidence of osteomyelitis of the jaws has decreased dramatically, except for a few subsets of individuals. This has been due, in no small part, to the availability of bacteriocidal antimicrobial therapy. The pathogenesis of osteomyelitis of the jaws is predominately due to odontogenic microorganisms rather than the classic skin contaminant, Staphylococcus. This causative relationship relegates the classification of osteomyelitis of the bimaxillary skeleton to predominately that of contiguous foci. These may be regionally progressive, secondary to microvascular compromise brought about by inherent flaws in regional anatomic calcified tissue vascular perfusion as well as by inflammatory metaplastic processes. Diagnosis is based on the presence of painful sequestra and suppurative areas of tooth-bearing jaw bone unresponsive to debridement and conservative therapy. This is usually accompanied by regional or systemic compromise of the immune response, microvascular decompensation, or both. Treatment of both acute and chronic forms of the disease, as outlined in Table 5, is successful if surgically supported. Sustained bacteriocidal antibiotic therapy is pertinent, especially in the face of potentially refractory virulent microorganisms and compromised regional vascular penetrance. The use of adjunctive hyperbaric oxygen therapy also may be included in the more refractory forms of osteomyelitis of the jaws to enhance the local and regional immune response of the jaws as well as to produce microvascular neoangiogenesis for reperfusion support. With resolution of infection, hard and soft tissue reconstruction may be necessary to augment the reparative process.

Evolution of allosteric control in glycogen phosphorylase.

In relation to the primary sequence and three-dimensional structure of rabbit muscle glycogen phosphorylase, we have carried out a comparative sequence analysis of phosphorylases from human, rat, Dictyostelium, yeast, potato and Escherichia coli. Based on sequence similarity, a large region of the protein is shared by these enzymes extending from alpha-helix-1 to the last alpha-helix-33. Conserved residues are equally distributed between the N and C-terminal domains and occur primarily in buried residues. Phylogenetic analysis indicates that the two isozymes within either E. coli, potato or Dictyostelium are more closely related to each other than they are to other phosphorylases. Yeast phosphorylase is most closely related to the Dictyostelium isozymes. Mammalian muscle and brain isozymes are more closely related to each other than to the liver isozyme and the muscle isozyme is evolving at the slowest rate. All phosphorylases exhibit high conservation of active site and pyridoxal phosphate binding residues. Most phosphorylases also exhibit high conservation of sugar binding residues in the glycogen storage site. Phosphorylation and AMP binding site residues are poorly conserved in non-mammalian phosphorylases. In contrast, glucose-6-P binding residues are highly conserved in four of the seven non-mammalian enzymes. Analysis of interacting pairs of dimer contact residues indicates that they can be grouped into three relatively independent networks. One network contains phosphorylation and AMP binding residues and is poorly conserved in non-mammalian enzymes. A second network contains glucose-6-P binding residues and is highly conserved in enzymes containing a conserved glucose-6-P binding site. A third, conserved network contains residues within the tower helix and gate loop. A model for the evolution of allostery in phosphorylase is proposed, suggesting that glucose-6-P inhibition was an early control mechanism. The later creation of primarily distinct ligand binding sites for AMP/phosphorylation control may have allowed the establishment of a separate dimer contact network for propagating conformational changes leading to activation rather than inhibition of enzyme activity.

Comparative analysis of species-independent, isozyme-specific amino-acid substitutions in mammalian muscle, brain and liver glycogen phosphorylases.

Mammalian glycogen phosphorylases exist as three isozymes, muscle, brain and liver, that exhibit different responses to activation by phosphorylation and AMP, regardless of species. To identify species-independent, amino-acid substitutions that may be important determinants in differential isozyme control, we have sequenced cDNAs containing the entire protein coding regions of rat muscle and brain phosphorylases. Nucleotide sequence comparisons with rat liver, rabbit muscle, and human muscle, brain and liver phosphorylase genes, indicate that muscle and brain isozymes are more related to each other than to the liver isozyme. Unlike the human isozymes, there is little difference in GC content of codons in the rat isozymes. In relation to the rabbit muscle isozyme three-dimensional structure, amino-acid sequence comparisons indicate that very few nonconservative isozyme-specific substitutions occur in buried and dimer contact residues. There is strict conservation of active site, pyridoxal-phosphate-binding site and nucleoside inhibitor site residues, as well as CAP loop and helix-2 residues that comprise the phosphorylation activation and part of the AMP binding sites. In contrast, five liver isozyme-specific substitutions occur between residues 313-325 and another at residue 78 which may be important determinants in the poor activation of this isozyme by AMP. Substitutions in the brain isozyme at residues 21-23, 405 and 435 may play a role in its poor response to activation by phosphorylation.

Cholesterol measurement and treatment in community practices.

A study was designed to examine the cholesterol measurement and treatment activities of primary care physicians in community practices. Three family practices of comparable size (one faculty practice and two community small-group practices) participated in the study. A random sample of 450 adult patients (150 from each site) was drawn from patient logs using a time series sampling method. Charts were reviewed for serum lipid evaluations, documentation of coronary heart disease risk factors, lipid-lowering activities, and other coronary heart disease risk-factor interventions. Sixty-seven percent of the sample had cholesterol measures recorded. No differences were found in the rates of measurement for men and women. Multiple, detailed serum lipid evaluations were common, and recognition of high cholesterol as a problem even before 1980 was apparent. Almost one half (47%) of individuals with cholesterol greater than 5.2 mmol/L (200 mg/dL) had a charted intervention, 64% if cholesterol greater than 6.2 mmol/L (240 mg/dL). Diet was the most common intervention (73%), and medication was used in only eight cases. Nonpharmaceutical interventions appeared to be undercharted. An analysis of interpractice variations revealed strikingly consistent results, although some interesting differences were noted. These rates are at least double previously reported rates and suggest that primary care physicians play a major role in this national priority.

Localization of the muscle, liver, and brain glycogen phosphorylase genes on linkage maps of mouse chromosomes 19, 12, and 2, respectively.

Mammalian glycogen phosphorylases comprise a family of three isozymes, muscle, liver, and brain, which are expressed selectively and to varying extents in a wide variety of cell types. To better understand the regulation of phosphorylase gene expression, we isolated partial cDNAs for all three isozymes from the rat and used these to map the corresponding genes in the mouse. Chromosome mapping was accomplished by comparing the segregation of phosphorylase restriction fragment length polymorphisms (RFLPs) with 16 reference loci in a multipoint interspecies backcross between Mus musculus domesticus and Mus spretus. The genes encoding muscle, liver, and brain phosphorylases (Pygm, Pygl, and Pygb) are assigned to mouse chromosomes 19, 12, and 2, respectively. Their location on separate chromosomes indicates that distinct cis-acting elements govern the differential expression of phosphorylase isozymes in various tissues. Our findings significantly extend the genetic maps of mouse chromosomes 2, 12, and 19 and can be used to define the location of phosphorylase genes in man more precisely. Finally, this analysis suggests that the previously mapped "muscle-deficient" mutation in mouse, mdf, is closely linked to the muscle phosphorylase gene. However, muscle phosphorylase gene structure and expression appear to be unaltered in mdf/mdf mice, indicating that this mutation is not an animal model for the human genetic disorder McArdle's disease.