Ten-year results of the Press Fit Condylar Sigma total knee replacement.

We report ten-year clinical and radiological follow-up data for the Sigma Press Fit Condylar total knee replacement system (Sigma PFC TKR). Between October 1998 and October 1999 a total of 235 consecutive PFC Sigma TKRs were carried out in 203 patients. Patients were seen at a specialist nurse-led clinic seven to ten days before admission and at six and 18 months, three, five and eight to ten years after surgery. Data were recorded prospectively at each clinic visit. Radiographs were obtained at the five- and eight- to ten-year follow-up appointments. Of the 203 patients, 147 (171 knees) were alive at ten years and 12 were lost to follow-up. A total of eight knees (3.4%) were revised, five for infection and three to change the polyethylene insert. The survival at ten years with an endpoint of revision for any reason was 95.9%, and with an endpoint of revision for aseptic failure was 98.7%. The mean American Knee Society Score (AKSS) was 79 (10 to 99) at eight to ten years, compared with 31 (2 to 62) pre-operatively. Of 109 knee with radiographs reviewed, 47 knees had radiolucent lines but none showed evidence of loosening.

Does obesity influence clinical outcome at nine years following total knee replacement?

A total of 445 consecutive primary total knee replacements (TKRs) were followed up prospectively at six and 18 months and three, six and nine years. Patients were divided into two groups: non-obese (body mass index (BMI) < 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). The obese group was subdivided into mildly obese (BMI 30 to 35 kg/m(2)) and highly obese (BMI ≥ 35 kg/m(2)) in order to determine the effects of increasing obesity on outcome. The clinical data analysed included the Knee Society score, peri-operative complications and implant survival. There was no difference in the overall complication rates or implant survival between the two groups. Obesity appears to have a small but significant adverse effect on clinical outcome, with highly obese patients showing lower function scores than non-obese patients. However, significant improvements in outcome are sustained in all groups nine years after TKR. Given the substantial, sustainable relief of symptoms after TKR and the low peri-operative complication and revision rates in these two groups, we have found no reason to limit access to TKR in obese patients.

Acute Q-fever and history taking--a lesson learned.

A 50-year-old patient underwent a routine primary total hip replacement. Soon after surgery, he developed acute respiratory failure from post-operative sepsis. His condition deteriorated rapidly despite supportive management and he required admission into intensive care unit for assisted ventilation. It took almost one week before the underlying cause of the deterioration was determined to be unrelated to complications of surgery. A diagnosis of Q-fever was made following detailed attention to the clinical history. Appropriate treatment was started and the patient made a full recovery. The diagnosis was confirmed later following discharge from hospital.

Does a history of cardiac disease or hypertension increase mortality following primary elective total hip arthroplasty?

Preoperative co-morbidities such as known coronary artery disease have commonly deemed a patient at 'high risk' for primary elective Total Hip Arthroplasty (THA). We prospectively collected data on 1744 patients who underwent primary elective THA between 1998 and 2004; 273 had a history of cardiac disease defined as a previous hospital admission with a diagnosis of angina pectoris or myocardial infarction; 594 patients had hypertension defined as that requiring treatment with antihypertensives. We also had data on preoperative age, sex and body mass index (BMI). There was no statistically significant increase in early mortality at three months with a history of cardiac disease or hypertension and this remained so when adjusting for the other factors in a multivariate analysis. Sex or BMI also did not have a statistically significant effect on the risk of death within three months. Increasing age was the only significant risk factor for early mortality (p<0.001). Longer-term mortality at two and five years in relation to these factors was also examined. Statistical analysis revealed that coronary history now showed a highly significant association (p<0.001) with long-term mortality in patients who survived more than three months. This remained significant (p=0.002) when adjusted for the other factors. Hypertension continued to have no effect, as did BMI. Age remained a significant risk factor and ASA was also a predictor of death, as has been previously shown. The overall long-term mortality following THAwas less than expected from the normal population, even in the subgroup with a coronary history. This study will assist clinicians when advising patients who have one of these common risk factors when seeking primary elective THA.

Total knee replacement in morbidly obese patients. Results of a prospective, matched study.

The results of 41 consecutive total knee replacements performed on morbidly obese patients with a body mass index > 40 kg/m(2), were compared with a matched group of 41 similar procedures carried out in non-obese patients (body mass index < 30 kg/m(2)). The groups were matched for age, gender, diagnosis, type of prosthesis, laterality and pre-operative Knee Society Score. We prospectively followed up the patients for a mean of 38.5 months (6 to 66). No patients were lost to follow-up. At less than four years after operation, the results were worse in the morbidly obese group compared with the non-obese, as demonstrated by inferior Knee Society Scores (mean knee score 85.7 and 90.5 respectively, p = 0.08; mean function score 75.6 and 83.4, p = 0.01), a higher incidence of radiolucent lines on post-operative radiographs (29% and 7%, respectively, p = 0.02), a higher rate of complications (32% and 0%, respectively, p = 0.001) and inferior survivorship using revision and pain as end-points (72.3% and 97.6%, respectively, p = 0.02). Patients with a body mass index > 40 kg/m(2) should be advised to lose weight prior to total knee replacement and to maintain weight reduction. They should also be counselled regarding the inferior results which may occur if they do not lose weight before surgery.

Practical experience and confidence in managing emergencies among preregistration house officers.

OBJECTIVES: To assess the experience gained by pre-registration house officers (PRHOs) at the end of their first post. To assess confidence in managing common emergencies and experience gained in practical procedures. To compare traditional six month posts with four month posts and to compare the experiences of PRHOs posted in teaching hospitals (THs) with those based in district general hospitals (DGHs). DESIGN: Interview questionnaire. PARTICIPANTS: 152 graduates from Edinburgh University Medical School in 2000 who had completed their first PRHO post by February 2001. RESULTS: There were few significant differences in confidence in managing emergencies and in numbers of practical procedures attempted between respondents from four and six month posts or between those holding TH and DGH posts. PRHOs had gained little experience in practical procedures: fewer than 15% had performed five or more of a number of procedures including lumbar puncture, pleural aspiration, chest drainage, and insertion of nasogastric tube. A high proportion of PRHOs indicated that they felt confident initiating management of conditions in specialties of which they had little or no experience. CONCLUSIONS: Rotations of three four month posts do not seem to reduce overall experience in the PRHO year. There is little difference in experience gained between TH and DGH posts. PRHOs perform few practical procedures and some may be overconfident in their own abilities.

Incidence of benign pathology in patients undergoing hepatic resection for suspected malignancy.

BACKGROUND: Confirming the presence of hepatic or proximal bile duct malignancy pre-operatively remains difficult and some patients may undergo surgical resection for suspected malignant lesions which subsequently turn out to be benign. The aim of this study was to establish whether improvements in pre-operative staging might better identify this patient population. METHODS: Analysis of a prospectively collected database, which has been maintained in our unit since 1988. RESULTS: Of 250 consecutive patients undergoing hepatic resection for presumed malignancy, 18 (7.2%) were shown to have benign pathology. These "false positive" rates were 4 out of 160 (2.5%) resections for colorectal metastases, 4 out of 49 (8.2%) resections for other solid hepatobiliary tumours and 10 out of 41 (24.4%) resections for hilar cholangiocarcinoma. Four of the 18 patients (22%) developed post-operative complications but there was no postoperative mortality. CONCLUSION: Although hepatic resection remains a potentially curative procedure for patients with tumours involving the liver parenchyma or proximal bile ducts, pre-operative confirmation of malignancy remains difficult. Despite appropriate investigation a subset of patients with benign disease will still be subjected to major hepatic resection which should be undertaken in a specialist unit.

Hepatocellular carcinoma secondary to cholecystectomy: a one in a million chance.

BACKGROUND: Cholecystectomy is a common procedure and its complications are well documented. CASE OUTLINE: A 63-year-old female sustained a bile duct injury during cholecystectomy requiring choledochoduodenostomy. She subsequently developed secondary biliary cirrhosis and ultimately required orthotopic liver transplantation. A focus of hepatocellular carcinoma was discovered within her liver. DISCUSSION: This case represents the first documented case of hepatocellular carcinoma as a late complication of cholecystectomy. The risk of this occurring can be estimated at 1:1,140,000 (range 1:11,000 to 1:120,000,000).

The effect of acute alteration in oxygen tension on the bronchodilator response to salbutamol in vitro and in vivo in man.

These studies examine the effect of acute hypoxia on airway smooth muscle relaxation in response to salbutamol in vitro in human isolated bronchi from non-asthmatics and in vivo in-patients with asthma. Isometric responses were measured from rings of human bronchi pre-constricted with methacholine under oxygen tensions of 95% (hyperoxia), 20% (normoxia) and 4% (hypoxia). Once contractions had plateaued, concentration - response curves were conducted to salbutamol (10(-9)-10(-4)m). Twelve stable asthmatic patients were studied in a randomised double blind fashion. On two study days following baseline measurements, patients were randomised to receive either oxygen (FiO(2)1.0) or a hypoxic gas mixture (FiO(2)0.15) followed by three incremental doses of nebulised salbutamol at 15 min intervals. On two further study days nebulised saline was administered instead of salbutamol. In isolated bronchi, salbutamol-induced relaxations were significantly (P< 0.001) greater in hyperoxia and normoxia (P< 0.01) when compared to hypoxia. Among patients with asthma no significant differences were found in the mean maximum % change in forced expiratory volume (FEV(1)) from baseline between the hypoxic and hyperoxic study days on which nebulised salbutamol was administered. We conclude that acute hypoxia attenuates airway smooth muscle relaxation in response to salbutamol in vitro but has no effect on salbutamol-induced bronchodilation in in-patients with asthma.

Screening for herpesvirus genomes in common acute lymphoblastic leukemia.

There is epidemiological evidence that infection may play a role in the etiology of childhood leukemia in particular common B cell precursor acute lymphoblastic leukemia. A panel of 20 leukemic samples (panel 1) was examined for the presence of four lymphotropic herpesviruses using conventional molecular techniques. A second independent panel of 27 leukemic samples (panel 2), along with 28 control peripheral blood samples from children with other forms of cancer, was tested for the presence of the same four viruses using sensitive real-time quantitative PCR. While herpesvirus genomes were detected, they were present at very low levels; detection rates and levels were similar in the leukemic and control panels. In addition we surveyed 18 leukemic samples (five from panel 1, six from panel 2 and a further seven samples not previously analyzed) using a degenerate PCR assay capable of detecting the genomes of known herpesviruses plus putative new members of the family. No novel herpesvirus genomes were detected suggesting that a herpesvirus is unlikely to be etiologically involved as a transforming agent in common acute lymphoblastic leukemia.

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Chronic exposure to hypoxia attenuates contractile responses in rat airways in vitro: a possible role for nitric oxide.

We investigated the effect of chronic hypoxia (10% O(2) for 14 days) on airway responsiveness in rats. Chronic hypoxia significantly (P<0. 05, P<0.01, P<0.01, respectively) attenuated contractions evoked by methacholine (10(-9)-3x10(-4) M), endothelin-1 (10(-10)-3x10(-7) M) and potassium chloride (10(-3)-7x10(-2) M) in rat isolated trachea. To investigate this attenuation, we studied the effect of epithelial removal, indomethacin (3x10(-6) M), and L-nitro arginine methyl ester (L-NAME, 10(-4) M), on contractile responses in control and chronically hypoxic rat trachea. Indomethacin did not alter contractions evoked by methacholine or endothelin-1 in control or hypoxic rats. In contrast, epithelial removal and L-NAME both significantly potentiated responses to methacholine and endothelin-1 in trachea from control and chronically hypoxic rats. In separate experiments, tracheal rings were first contracted with methacholine (10(-6) M) and then relaxed, either by the nitric oxide donor sodium nitroprusside or by the beta(2)-adrenoceptor agonist, salbutamol. Sodium nitroprusside was significantly (P<0.001) more effective at reversing induced tone in tracheal rings from chronically hypoxic than control rats. Salbutamol, however, was equally effective in chronically hypoxic and control rats. These results suggest that, in trachea from both control and chronically hypoxic rats, contractile responses to methacholine and endothelin-1 are inhibited by nitric oxide, probably released from the epithelium. The attenuation of contractile responses in airways from chronically hypoxic rats may be due to an enhanced guanylyl cyclase activity and hence, an increased response to nitric oxide.

The effect of chronic hypoxia on endothelin receptor subtype-mediated responses in rat isolated airways.

Contractile responses to endothelin-1 (ET-1) were investigated in isolated trachea from rats previously exposed to chronic hypoxia (10% O(2)) or room air for 14 days. Concentration-response curves were constructed to ET-1 (10(-11)-3x10(-7)m ) in the presence and absence of the ET(A)receptor antagonist FR 139317 (10(-8), 10(-7)and 10(-6)m ), the ET(B)receptor antagonist BQ 788 (10(-6)and 3x10(-6)m ), the non-selective ET receptor antagonist SB 209670 (10(-7)and 10(-6)m ) and a combination of FR 139317 (10(-6)m ) and BQ 788 (10(-6)m ). Concentration-response curves were also conducted to the ET(B)receptor agonist sarafotoxin S6c (10(-11)-3x10(-7)m ). In addition, responses to ET-1 (10(-11)-3x10(-7)m ) were examined in the presence and absence of the nitric oxide synthase inhibitor, L-NAME. In control rat trachea, both FR 139317 and BQ 788 failed to inhibit ET-1-induced contractions and, indeed, FR 139317 (10(-8)m ) and BQ 788 actually potentiated responses. In trachea from chronic hypoxic rats, FR 139317 did not alter ET-1 responses whereas BQ 788 again potentiated ET-1-induced contractions. The non-selective ET receptor antagonist SB 209670 attenuated ET-1-evoked contractions in trachea from control and chronically hypoxic rats. A combination of FR 139317 (10(-6)m ) and BQ 788 (10(-6)m ) also attenuated ET-1 responses in control rat trachea, but not trachea from chronically hypoxic rats. In trachea from both control and chronically hypoxic rats, L-NAME significantly potentiated responses to ET-1. To investigate ET receptor-mediated relaxation, tissues were preconstricted with methacholine and concentration-response curves were conducted to ET-1 (10(-13)-10(-8)m ) in the presence and absence of BQ 788 (10(-6)m ) and to the ET(B)receptor agonist sarafotoxin S6c (10(-13)-10(-8)m ). In trachea from control and chronic hypoxic rats, ET-1 and sarafotoxin S6c evoked only very small, non-reproducible relaxatory responses.

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Findings emerging from complete microbial genome sequences.

Sixteen microorganisms, including one eukaryote, four archaeons, and 11 eubacteria, have been completely sequenced and published. More than 50 genomes are scheduled to be completed by the year 2000. This explosive growth of information is forcing change in many scientific disciplines (e.g. bioinformatics and molecular genetics), spawning new fields, and even changing the way scientific information is used and shared. Novel, global genome sequence comparisons seem slow to appear but the infrastructure for these projects is being built, and we expect exciting developments in the near future.