Unusual osseous metastases from rectal adenocarcinoma: a case report and review of the literature.

INTRODUCTION: Rectal adenocarcinoma typically metastasizes to the liver. When osseous spread occurs, it is most commonly detected in the vertebrae and pelvis. Distal osseous spread is unusual and may be the first presentation of the carcinoma. We present a review of the current literature on unusual osseous rectal adenocarcinoma metastases and highlight a case of a scapular lesion as the first presentation of rectal carcinoma from our institution. MATERIALS AND METHODS: A Pubmed search using keywords 'rectal carcinoma metastases,' 'colorectal cancer metastases' and 'skeletal metastases' was performed. RESULTS: Twenty-four cases were identified (54 % male, mean age at diagnosis 61 ± 16 years). The most common site was the mandible, followed by the foot. In four cases, the metastasis was the first presentation of the carcinoma. Mean time from resection of the primary tumour to osseous metastases diagnosis of skeletal metastases was 26 ± 17 (SD) months. Mean time from diagnosis of skeletal metastases to death was 3.2 (±2.8) months. CONCLUSION: Rectal adenocarcinoma osseous metastases located distal to the pelvis and/or vertebrae are rare and associated with a poor prognosis. Unusual bony lesions should raise an index of suspicion for distal carcinoma, including rectal carcinoma.

Delayed presentation of carotid artery dissection following major orthopaedic trauma resulting in dense hemiparesis.

We report a 30-year-old patient who was involved in a high-velocity road traffic accident and developed a left-sided hemiparesis, which was noted in the post-operative period following bilateral femoral intramedullary nailing. CT scanning of the brain revealed infarcts in the right frontal and parietal lobes in the distribution of the right middle cerebral artery. CT angiography showed occlusion of the right internal carotid artery consistent with internal carotid artery dissection. He was anticoagulated and nine months later was able to walk independently. An awareness of this injury is needed to diagnose blunt trauma to the internal carotid artery. Even in the absence of obvious neck trauma, carotid artery dissection should be suspected in patients with a neurological deficit in the peri-operative period.

The influence of preclinical anaemia on outcome following total hip replacement.

INTRODUCTION: Preoperative anaemia confers a higher intraoperative and postoperative risk of complications on a patient. Preclinical anaemia is defined as a patient with laboratory indices of anaemia but without any of the symptoms. The patient population who undergo total hip replacement (THR) are elderly and are more likely to fall into this category. Our aim was to assess the effect of preclinical anaemia on a patient's postoperative course. MATERIALS AND METHODS: A prospective analysis of elective THRs performed over a 10-month period was carried out. Preoperative haematological indices were recorded and correlated with postoperative complication rates. RESULTS: A total of 225 elective THRs were included in the study. Patients with preclinical anaemia on admission had a higher incidence of postoperative infection and transfusion (p<0.001) and a longer postoperative inpatient stay. Preoperative iron supplementation in patients with preclinical iron deficiency anaemia resulted in a reduction in transfusion requirements (p=0.00125). CONCLUSIONS: Identification and treatment of patients with preclinical anaemia preoperatively may reduce postoperative infection and transfusion needs and result in a shorter inpatient stay.

Hurling-related hand injuries.

Hurling is a contact sport, associated with significant morbidity. We have identified specific hand injuries sustained by participants and quantified the functional and financial implications of these injuries. Over a 3-month period, all hand injuries seen in the fracture clinic of our regional trauma unit were studied prospectively. Of the 123 consecutive injuries, 41 (33%) were sustained during hurling matches. Metacarpal (47%) and proximal phalangeal (37%) fractures were the most frequent. Eight hurlers (20%) required surgical intervention. Only four (10%) of the injured players were wearing hand protection. The mean cost of injury to the player was pound 615. We suggest the introduction of the mandatory use of hand protection for hurling.

The evolution of HOM-C homeoboxes in the Dipteran family Drosophilidae.

Forty-five new Homeotic Complex (HOM-C) homeobox sequences from six species of Drosophilidae (Drosophila heteroneura, D. adiastola, Zaprionus vittiger, Chymomyza amoena, Scaptodrosophila pattersoni and Hirtodrosophila pictiventris) were obtained using a PCR-cloning method. These new homeoboxes are from the labial, proboscipedia, Deformed, Sex combs reduced, fushi tarazu, Antennapedia, Ultrabithorax, abdominal-A and Abdominal-B genes. Phylogenetic signal in the homeobox sequences was assessed and several aspects of sequence evolution were examined. In particular, codon bias was examined and found to exist between the drosophilid species examined here and Anopheles gambiae outgroup sequences. In addition, different patterns of codon bias were detected in homeoboxes interrupted with introns when compared to homeoboxes that are uninterrupted.

Hierarchical structure in the Drosophila mojavensis cluster (Diptera: Drosophilidae).

Sequences from three gene regions from the nuclear and mitochondrial genomes were used to examine the extent and nature of hierarchical structure in the Drosophilamojavensis cluster (Drosophila arizonae, D. mojavensis and D. navojoa) of the D. repleta species group. To determine the genetic divergence of these three species, sequence data were analyzed using maximum parsimony and population aggregation analysis. Individual and combined gene genealogies indicate that D. arizonae and D. mojavensis are neither diagnosable nor monophyletic with respect to one another. Although D. navojoa has differentiated from D. arizonae and D. mojavensis, as diagnosed by nuclear gene sequences, it may have undergone a reticulation event with D. arizonae. Our results suggest that either these taxa are still undergoing differentiation at the molecular level or have experienced gene flow in the recent past.

Genetic divergence within the Drosophila mayaguana subcluster, a closely related triad of Caribbean species in the repleta species group.

The mayaguana triad of the Drosophila repleta species group includes D. mayaguana, D. straubae, and D. parisiena, the latter two of which are very similar when examined morphologically. Many morphological characters used to define these taxa are quantitative and overlap substantially among some forms--it is only through suites of such characters that species can be identified. We apply Population Aggregation Analysis and tree building methods to five rapidly evolving gene regions--the mitochondrial AT rich region and the nuclear acetylcholinesterase, hunchback, mastermind, and vestigial loci to test the morphological species delineations within the morphocryptic mayaguana triad. We find that D. mayaguana is diagnosable using DNA sequences, but the other two species form a non-diagnosable paraphyletic assemblage. A single ecological factor, oviposition substrate, is an important diagnostic character distinguishing D. straubae from D. parisiena, highlighting the importance of examining a diverse array of data (morphological, molecular, ecological, and behavioral) when defining species limits.

Shallow genomics, phylogenetics, and evolution in the family Drosophilidae.

The effects of the genomic revolution are beginning to be felt in all disciplines of the biological sciences. Evolutionary biology in general, and phylogenetic systematics in particular, are being revolutionized by these advances. The advent of rapid nucleotide sequencing techniques have provided phylogenetic biologists with the tools required to quickly and efficiently generate large amounts of character information. We use family Drosophilidae as a model system to study phylogenetics and genome evolution by combining high throughput sequencing methods from the field genomics and standard phylogenetic methodology. This paper presents preliminary results from this work. Separate data partitions, based on either gene function or linkage group, are compared to a combined analysis of all the data to assess support on phylogenetic trees.

Phylogeny of the subgenus sophophora (Diptera: drosophilidae) based on combined analysis of nuclear and mitochondrial sequences.

Sequences from the nuclear (nu) alcohol dehydrogenase gene, the nu 28S ribosomal RNA locus, and the mitochondrial cytochrome oxidase II gene were used both individually and in combined analyses to infer the phylogeny of the subgenus Sophophora (Diptera: Drosophilidae). We used several optimality criteria, including maximum likelihood, maximum parsimony, and minimum evolution, to analyze these partitions to test the monophyly of the subgenus Sophophora and its four largest species groups, melanogaster, obscura, saltans, and willistoni. Our results suggest that the melanogaster and obscura species groups are each monophyletic and form a closely related clade. The Neotropical clade, containing the saltans and willistoni species groups, is also recovered, as previous studies have suggested. While the saltans species group is strongly supported as monophyletic, the results of several analyses indicate that the willistoni species group may be paraphyletic with respect to the saltans species group.

Polytene chromosomes as indicators of phylogeny in several species groups of Drosophila.

BACKGROUND: Polytene chromosome banding patterns have long been used by Drosophila evolutionists to infer degree of relatedness among taxa. Recently, nucleotide sequences have preempted this traditional method. We place the classical Drosophila evolutionary biology tools of polytene chromosome inversion analysis in a phylogenetic context and assess their utility in comparison to nucleotide sequences. RESULTS: A simultaneous analysis framework was used to examine the congruence of the chromosomal inversion data with more recent DNA sequence data in four Drosophila species groups - the melanogaster, virilis, repleta, and picture wing. Inversions and nucleotides were highly congruent with one another based on incongruence length difference and partitioned Bremer support values. Inversion phylogenies were less resolved because of fewer numbers of characters. Partitioned Bremer supports, corrected for the number of characters in each matrix, were higher for inversion matrices. CONCLUSIONS: Polytene chromosome data are highly congruent with DNA sequence data and, when placed in a simultaneous analysis framework, are shown to be more information rich than nucleotide data.

Omapatrilat in patients with hepatic cirrhosis. Pharmacodynamics and pharmacokinetics.

OBJECTIVE: The pharmacodynamics and pharmacokinetics of omapatrilat, a member of a new class of cardiovascular compounds, the vasopeptidase inhibitors, were evaluated in subjects with hepatic cirrhosis (n = 10) and in healthy subjects (n = 10) matched for age, weight, gender and smoking history. METHODS: All subjects received omapatrilat 25 mg orally once daily for 14 days. Plasma renin and urinary atrial natriuretic peptide (ANP) levels were measured to assess the effect of omapatrilat on cirrhotic subjects. The effect of omapatrilat on blood pressure as well as changes in ANP and plasma renin levels were not altered by hepatic impairment. Pharmacokinetic parameters were determined from plasma omapatrilat concentrations. RESULTS: There were no significant differences between the two subject groups with regard to log-transformed area under the curve or maximum observed plasma concentration. Systemic accumulation was similar in the two groups. CONCLUSION: These results suggest, based on findings in otherwise healthy cirrhotic subjects, that no adjustment of standard dosing regimens is indicated for hypertensive patients with mild to moderate cirrhosis.

A critical appraisal of the out-patient fracture clinic: is communication really the key?

The most common factor in an adversarial doctor-patient relationship is failed communication. We audited our communication skills, patient satisfaction and assessed patients' capacity for retaining information. 120 consecutive first time patients with one of 5 fracture types were assessed. Patients scored (a) the doctor's communication skills and (b) their overall fracture clinic experience. Patient satisfaction was high, mean 8.2 (range 2-10, SD 1.76) points. There was a statistically significant difference in a patient's knowledge pre and post consultation. Forty-three patients (36%) could recall a specific consequence of the fracture (p<0.005). Forty (31%) and twenty six (22%) patients could recall the name of the Registrar and Consultant respectively. Doctors scored 9.2 (range 7-10, SD 1.23) points for communication skills. Patients are concerned with a fracture's impact on daily activities, often failing to register who treats them and any serious consequences. With doctors being scored so highly, the dilemma remains of how better to deliver the message.

Feasibility of assessing quality in medical oncology practices.

PURPOSE: This study was designed to test the feasibility of conducting routine quality assessment within community medical oncology practices. DESCRIPTION OF STUDY: Eleven medical oncologists practicing within the Fox Chase Network were surveyed over an 8-month period, using a standardized 10-item checklist. Eight of the items (ie, board certification, continuing education, office procedure manual for chemotherapy, chemotherapy flow sheets, body surface area calculations, adherence to guidelines for follow-up of breast cancer, adjuvant hormones in women with estrogen receptor-positive breast cancer, and patient satisfaction survey) were chosen because they measure structural and process variables particularly relevant to the high-volume clinical services seen in private practice oncology. The authors also calculated two rates (protocol accrual and neutropenic complications of chemotherapy) to test as putative indicators of quality. RESULTS: The authors found a high level of both physician interest in developing the audit measures and compliance with the survey process. Overall quality of care, as measured by structure and process variables, was excellent with negligible internal variability. Derived rates of protocol accrual (0.003-0.373; mean 0.11, SD 0.11) and neutropenic sepsis (0.004-0.014; mean 0.007, SD 0.004) show considerable variability, however, and are only minimally correlated (r= -.36). These are both potential indicators of quality that should be further evaluated. CLINICAL IMPLICATIONS: The authors have demonstrated the feasibility of conducting quality assessment within private medical oncology practices and have identified two easily calculated rates that merit further study as potential indicators of quality.

Evaluation of titanium brackets for orthodontic treatment: Part II--The active configuration.

After each archwire was ligated into a bracket with a 0.010-in stainless steel wire, both stainless steel and beta-titanium archwires (0.017- x 0.025-in) were slid through commercially pure titanium brackets (0.018-in slot size) at 34 degrees C in both the dry and wet conditions. As controls, stainless steel archwire versus stainless steel bracket couples were used with comparable dimensions. The drawing forces were measured at 5 angulations (0 degrees, 3 degrees, 7 degrees, 9 degrees, and 11 degrees ) for 5 normal forces (nominally 0.2, 0.4, 0.6, 0.8, and 1.0 kg). Regression lines were determined for each frictional couple (P <.05). In the passive configuration, the kinetic frictional coefficients of control and test couples in the dry condition were comparable to previously reported values at 0.11 +/- 0.01 for stainless steel versus stainless steel, 0.12 +/- 0.00 for stainless steel versus titanium, and 0.26 +/- 0.02 for beta-titanium versus titanium. As the angulation was increased from 0 degrees to 11 degrees and the normal force was maintained at 0.2 kg, the resistance to sliding values increased by 208 g for stainless steel versus stainless steel, by 222 g for stainless steel versus titanium, and by 185 g for beta-titanium versus titanium. When the normal force was increased to 1.0 kg, the resistance to sliding values increased to 277 g, 246 g, and 245 g, respectively. Although resistance to sliding increased with angulation and normal force, the passive layer did not breakdown. Titanium brackets remained comparable to stainless steel brackets in the active configuration.

Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis.

Two open-label studies assessed the pharmacokinetics of single orally administered doses of 40 mg of stavudine in subjects with renal impairment. In one study (study I), 15 subjects with selected degrees of renal impairment, but not requiring hemodialysis, were stratified into three groups of five subjects each according to creatinine clearance (CL(CR)) normalized by body surface area (ml/min/1.73 m(2)): mild (CL(CR), 60 to 80), moderate (30 to 50), and severe (/= 90) were also enrolled. The stavudine area under the curve from 0 h to infinity (AUC(0-infinity)) increased nonlinearly with declining renal function: 1,864, 2,215, 3,609, and 5,928 ng. h/ml for normal renal function and for mild, moderate, and severe renal impairment, respectively (P = 0.0001 between renal impairment groups). The following stavudine dosage recommendations for renal impairment were proposed for subjects weighing >/=60 kg: CL(CR) of >50 ml/min/1.73 m(2), 40 mg every 12 h; CL(CR) of 21 to 50 ml/min/1. 73 m(2), 20 mg every 12 h; and CL(CR) of 10 to 20 ml/min/1.73 m(2), 20 mg every 24 h. For subjects weighing <60 kg, the proposed doses were 30, 15, and 15 mg, respectively, with the same dosing intervals specified above. In a second study (study II), 12 subjects with end-stage renal disease requiring hemodialysis three times a week were enrolled in a randomized, open-label crossover study (dialysis 2 h after dosing and lasting 4 h or dosing without dialysis). There were no statistically significant differences for AUC(0-infinity), AUC(2-6), time to maximum concentration of drug in serum, half-life, or apparent oral clearance when the two treatment dosage regimens were compared. As a result of study II, the recommended dosing rate for subjects requiring hemodialysis was the same as that proposed for those with severe renal impairment not requiring hemodialysis; however, dosing was recommended to follow hemodialysis and to occur at the same time each day.

An investigation into the role of oxygen free radical scavengers in preventing polymethylmethacrylate-induced necrosis in an osteoblast cell culture.

This study examined the effect of polymethylmethacrylate (PMMA) on osteocytic necrosis and the role of free radical scavengers in minimizing this damage. Bovine osteoblast cells with a characteristic phenotype were seeded at a density of 4x10(4) cells/cm2 and cultured in a DMEM supplemented with 10% fetal calf serum. A transwell insert with 2 cc of PMMA was suspended above the culture, and a time log response curve was established following elusion of free radicals around the osteoblast media. Chemiluminescence was used to determine quantitative free radical release. Using a Student's two-tailed t test there was a significant difference in the amount of hydroxyl radical released at 1-6 hours compared with controls (P=.028). Using histologic markers, there was a significant correlation between the use of PMMA and osteoblast cell necrosis. Transwell plates were coated with varying concentrations of mannitol, a known hydroxyl radical scavenger. A log dose response curve was established. There was a clear statistical association between a 10% mannitol solution and a reduction in the free radical release from PMMA (P=.03). Similarly, using Trypan blue histologic staining, there was a significant reduction in PMMA-induced cell necrosis when 10% mannitol was used as a scavenger (P=.01). A Rockwell superficial hardness test was used to determine whether mannitol had any effect on the surface hardness of the polymer. No statistical difference could be found between those treated with mannitol and controls at a depth of up to 1 mm. These results demonstrate hydroxyl radical is released from the polymerization reaction of PMMA. These radicals cause cell death in an osteoblast culture medium. This has been addressed using a 10% mannitol solution, which reduced cell necrosis.

Intrinsic polymerase activities of UmuD'(2)C and MucA'(2)B are responsible for their different mutagenic properties during bypass of a T-T cis-syn cyclobutane dimer.

In wild-type Escherichia coli, translesion replication is largely dependent upon the UmuD'(2)C complex (DNA polymerase V [polV]) or its plasmid-encoded homologs, such as MucA'(2)B. Interestingly, both the efficiency of translesion replication of a T-T cis-syn dimer and the spectra of mutations observed are different in Umu- and Muc-expressing strains. We have investigated whether the polIII core is responsible for these differences by measuring the frequency of dimer bypass, the error rate of bypass, and the resulting mutation spectrum in mutants carrying a deletion of dnaQ (epsilon subunit) or holE (theta subunit) or carrying the dnaQ allele mutD5, which is deficient in proofreading but is competent in the structural function of epsilon, or the dnaE antimutator allele spq-2. The chromosomal copy of the umuDC operon was deleted in each strain, and the UmuDC, UmuD'C, MucAB, or MucA'B proteins were expressed from a low-copy-number plasmid. With only few exceptions, we found that the characteristically different mutation spectra resulting from Umu- and Muc-mediated bypass are maintained in all of the strains investigated, indicating that differences in the activity or structure of the polIII core are not responsible for the observed phenotype. We also demonstrate that the MucA'(2)B complex is more efficient in promoting translesion replication than the UmuD'(2)C proteins and show that, contrary to expectation, the T-T dimer is bypassed more accurately by MucA'(2)B than by UmuD'(2)C. These results are consistent with the view that in a wild-type cell, the polV-like enzymes are responsible for the spectra of mutations generated during translesion replication and that polIII may simply be required to fix the misincorporations as mutations by completing chromosomal replication. Our observations also show that the mutagenic properties of a lesion can depend strongly on the particular enzyme employed in bypass.