The leptin to adiponectin ratio (LAR) is reduced by sleeve gastrectomy in adults with severe obesity: a prospective cohort study.

Bariatric surgery is known to reduce leptin and increase adiponectin levels, but the influence of sleeve gastrectomy on the leptin: adiponectin ratio (LAR), a measure of insulin sensitivity and cardiovascular risk, has not previously been described. We sought to determine the influence of sleeve gastrectomy on LAR in adults with severe obesity.In a single centre prospective cohort study of adults undergoing laparoscopic sleeve gastrectomy over a four-month period in our unit, we measured LAR preoperatively and 12 months after surgery. Of 22 patients undergoing sleeve gastrectomy, 17 (12 females, 12 with type 2 diabetes) had follow-up LAR measured at 12.1 ± 1 months. Mean body weight decreased from 130.6 ± 30.8 kg to 97.6 ± 21.6 kg, body mass index (BMI) from 46.9 ± 7.8 to 35.3 ± 7.2 kg m-2 and excess body weight from 87.5 ± 31.3 to 41.3 ± 28.8% (all p < 0.001). The reduction in leptin from 40.7 ± 24.9 to 30.9 ± 30.5 ng/ml was not significant (p = 0.11), but adiponectin increased from 4.49 ± 1.6 to 8.93 ± 6.36 µg/ml (p = 0.005) and LAR decreased from 8.89 ± 4.8 to 5.26 ± 6.52 ng/µg (p = 0.001), equivalent to a 70.9% increase in insulin sensitivity. The correlation with the amount of weight lost was stronger for LAR than it was for leptin or adiponectin alone. In this single-centre, interventional prospective cohort, patients undergoing laparoscopic sleeve gastrectomy had a substantial reduction in their LAR after 12 months which was proportional to the amount of weight lost. This may indicate an improvement in insulin sensitivity and a reduction in cardiovascular risk.

'Rapid transit' constipation in children: a possible genesis for irritable bowel syndrome.

Children with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called 'Rapid transit constipation (RTC)' first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment. Unexpectedly, we found that RTC occured in 29% of 1000 transit studies in a retrospective audit. Irritable bowel syndrome (IBS) occurs in 7-21% of the population, with a higher prevalence in young children and with constipation type dominating in the young. While 60% improve with time, 40% continue with symptoms. First-line therapy for IBS in adults is a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols which reduces symptoms in > 70% of patients. In children with functional gastrointestinal disorders, fructose intolerance occurs in 35-55%. Reducing fructose produced significant improvement in 77-82% of intolerant patients. In children with RTC and a positive breath test upon fructose challenge, we found that exclusion of fructose significantly improved constipation, abdominal pain, stool consistency and decreased laxative use. We hypothesise that positive breath tests and improvement of pain and bowel frequency with sugar exclusion diets in RTC suggest these children have IBS-C. These observations raise the possibility that many children with CIC could be treated by reducing fructose early in their diet and this might prevent the development of IBS in later life.

Influence of socioeconomic factors on litigation in surgery: Addressing the gap in malpractice literature.

The practice of medicine is occasionally volatile and increasingly litigious. Within the specialities, plastic surgery has a high risk, with negative outcomes seen as dissatisfaction, as compared to actual physical harm. To date, most research has focused on potential triggers for litigation, such as poor communication and perceived behavioural deficiencies among physicians. Few studies have addressed patient characteristics or socioeconomic factors. The 'Influence of Socio-Economic Factors on Attitudes Towards Surgery' questionnaire was designed to reflect these goals. It was distributed for a 12-month period to patients in an Emergency Department waiting room. Three hundred twelve completed questionnaires were submitted for analysis. Within the study population, we identified certain socioeconomic trends among those with a low threshold to pursue litigation. Patients with a low threshold to sue were more likely to be male, aged 25-55 years, currently unemployed, without dependents and divorced. However, these parameters did not reach statistical significance. Although these characteristics are interesting, they cannot reliably identify or predict those with a low threshold for litigation. For now, the clinical focus should remain on careful adherence to best practice in an effort to reduce the risk of potential litigation.

Use of plasma "reconstitution" during cardio pulmonary bypass for a heart transplant after previous left ventricular assist device implant surgery.

The case report describes a novel technique of pre-emptive plasma "reconstitution" prior to disengagement from cardiopulmonary bypass (CPB) to minimize RV volume overload. The concomitant use of hemoconcentration facilitates volume and blood product management in cardiac transplant after previous left ventricular assist device implant surgery.

Analytical determination of apparent stability constants using a copper ion selective electrode.

Copper(II) complexes of di-, tri- and tetra peptides with previously published protonation constants were re-investigated using pH and copper ion selective electrode (ISE) potentiometry in conjunction with a modified version of HYPERQUAD computer program. The purpose was to demonstrate the suitability of the ISE approach for the determination of apparent stability constants for copper(II) complexes with ligands for which proton stability constants were not available. The interactions of Cu(2+) with oligopeptides were also analysed using surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-ToF-MS). The results provide an insight into the metal complex species formed, their apparent stabilities under selected conditions and the effect of the relative positions of certain amino acids within the peptide sequence.

Review paper: Implications of the "cancer stem cell" hypothesis on murine models of colon cancer and colitis-associated cancer.

The use of murine models to investigate human diseases has been an invaluable tool. In the areas of inflammation and oncogenesis, such models have provided unique insights into pathogenesis and mechanisms to evaluate potential therapy. As such, one facet of these disease processes links inflammation and cancer. Inflammation is associated with at least 15% of the world's malignancies. One example of this relationship is documented in the association between colitis and colorectal cancer. To date, the precise molecular events linking inflammation and cancer remain unclear. A new paradigm that may bridge these processes includes the cancer stem cell hypothesis. In this review, murine models of colitis, colon cancer, and colitis-associated cancer are discussed in reference to the potential of this paradigm to clarify the relationship of these devastating diseases.

Influence of Nitinol wire surface treatment on oxide thickness and composition and its subsequent effect on corrosion resistance and nickel ion release.

Medical implants and devices are now used successfully in surgical procedures on a daily basis. Alloys of nickel and titanium, and in particular Nitinol are of special interest in the medical device industry, because of their shape memory and superelastic properties. The corrosion behavior of nitinol in the body is also of critical importance because of the known toxicological effects of nickel. The stability of a NiTi alloy in the physiological environment is dependant primarily on the properties of the mostly TiO(2) oxide layer that is present on the surface. For the present study, a range of nitinol wires have been prepared using different drawing processes and a range of surface preparation procedures. It is clear from the results obtained that the wire samples with very thick oxides also contain a high nickel content in the oxide layer. The untreated samples with the thicker oxides show the lowest pitting potential values and greater nickel release in both long and short-term experiments. It was also found that after long-term immersion tests breakdown potentials increased for samples that exhibited lower values initially. From these results it would appear that surface treatment is essential for the optimum bioperformance of nitinol.

The use of tranexamic acid to reduce blood loss during total hip arthroplasty: an observational study.

INTRODUCTION: To test the hypothesis that the fall in haemoglobin following total hip arthroplasty is reduced by tranexamic acid administration. PATIENTS AND METHODS: A cohort of 64 patients were studied, 32 received tranexamic acid 20 mg/kg on induction. Surgery was performed by the senior author in a standardised fashion. Haemoglobin levels were measured 2 weeks pre- and 3 days postoperatively. Any complications were noted. The study group was matched using the bone and joint research database for age, sex, procedure, disease and pre-operative haemoglobin level. RESULTS: In the group receiving no tranexamic acid, the mean fall in haemoglobin was 3.8 g/dl (CI of mean 3.4-4.3) and in the group treated with tranexamic acid 2.8 g/dl (CI of mean 2.5-3.2) P < 0.05. Complications included one non-fatal pulmonary embolus in the tranexamic acid group. CONCLUSIONS: The administration of 20 mg/kg of tranexamic acid on induction of surgery is an effective method of reducing the haemoglobin fall following hip arthroplasty.

TamA interacts with LeuB, the homologue of Saccharomyces cerevisiae Leu3p, to regulate gdhA expression in Aspergillus nidulans.

Previous studies have shown that expression of the gdhA gene, encoding NADP-linked glutamate dehydrogenase (NADP-GDH), in Aspergillus nidulans is regulated by the major nitrogen regulatory protein AreA and its co-activator TamA. We show here that loss of TamA function has a more severe effect on the levels of gdhA expression than loss of AreA function. Using TamA as the bait in a yeast two-hybrid screen, we have identified a second protein that interacts with TamA. Sequencing analysis and functional studies have shown that this protein, designated LeuB, is a transcriptional activator with similar function to the homologous Leu3p of Saccharomyces cerevisiae. Inactivation of leuB revealed that this gene is involved in the regulation of gdhA, and an areA; leuB double mutant was shown to have similar NADP-GDH levels to a tamA single mutant. The requirement for TamA function to promote gdhA expression is likely to be due to its dual interaction with AreA and LeuB.

Traumatic patella tendon rupture: early mobilisation following surgical repair.

This study aims to demonstrate that postoperative immobilisation in a cast is unnecessary following suture repair of the patella tendon and retinacula protected by a cerlage wire. We present 11 patients mean age 42 years evaluated at a mean of 26 months (range 14-38 months). The mean Lysholm knee score at review was 97 (range 92-100). The mean Insall Salvati measurement (length patella/length tendon (LP/LT)) was 1 (range 0.95-1.1). No patients had fixed flexion deformities or demonstrated an extensor lag and the average range of motion was 0-137 degrees. The difference between the operated and control knee at the time of assessment was: a mean loss of power of 6% (range 2-11) when measuring concentric extension and a mean loss of 7% power (range 13 to an increase of 12) in concentric flexion. We conclude that primary repair protected with a cerlage wire and early mobilisation gives excellent results in the treatment of isolated traumatic patella tendon ruptures and cast immobilisation postoperatively is not required.

Short-term results of hemi-resurfacing for osteonecrosis of the femoral head.

Published evidence has supported the use of femoral head resurfacing for patients with osteonecrosis of the femoral head. Between June 1999 and April 2001 we prospectively studied 15 femoral heads resurfaced in 12 patients with the Conserve Resurfacing Hemiarthroplasty. The male to female ratio was 8:4 and the mean age 38.7 years (range 26-60). The mean follow-up was 22.8 months (range 4-36). The senior author performed all procedures. There was one case of Ficat stage II, 9 cases of stage III and 5 cases of early stage IV. The mean time from onset of symptoms to surgery was 33.5 months (range 9-60). There were no intra or post-operative complications associated with any of the hemiarthroplasty procedures. RESULTS: Nine of the fifteen patients had a poor result that warranted revision surgery within two years of prosthesis implantation. We conclude that in our hands the results of femoral resurfacing hemiarthroplasty are unpredictable and advise caution when recommending the procedure to patients with osteonecrosis of the femoral head. (Hip International 2004; 14: 174-81).

The use of tranexamic acid to reduce blood loss during total knee arthroplasty.

HYPOTHESIS: The fall in haemoglobin following unilateral total knee arthroplasty is reduced by tranexamic acid administration. METHODS: 60 patients were studied in total, 30 received tranexamic acid 10 mg/kg on induction and a further dose shortly before the release of the tourniquet. Surgery was performed by the senior author in a standardised fashion using the Freeman Samuelson cemented total knee replacement. Haemoglobin levels were measured 2 weeks pre and 3 days post operatively. Any complications were noted. A control group was matched using the Bone and Joint Research Unit database for age, sex, disease and pre-operative haemoglobin level. This group had been monitored in the same way as the group treated with tranexamic acid. RESULTS: In the group receiving no tranexamic acid the mean fall in haemoglobin was 2.8 g/dl (95% CI of mean 2.5-3.2) and in the group treated with tranexamic acid 1.7 g/dl (95% CI of mean 1.3-2) P<0.01. There were no complications in either group. CONCLUSIONS: The administration of tranexamic acid is an effective method of reducing the haemoglobin fall following knee arthroplasty.

The provision of secondary cardiac prevention measures in a hospital cardiac clinic population and the relationship to psychological variables.

BACKGROUND: Implementing preventive measures in patients with established heart disease is one of the most effective health promotion activities, but there is little research on the relationship between cognition and secondary preventive behaviour. AIM: To determine the provision of secondary cardiac prevention measures among patients with established heart disease attending a cardiac outpatient clinic. METHODS: The study was conducted in an outpatient department over a 14-week period in 1999. Management of risk markers was noted from the medical records and lifestyle and psychological variables were self-reported. RESULTS: Of 294 patients with heart disease, 41% were available for study. Fourteen per cent were current smokers, one-quarter of males and one-third of females had a body mass index (BMI) greater that 30. Almost 90% attend their GP bimonthly, 67% had a normal systolic and 88.3% a normal diastolic pressure, 34% had normal cholesterol levels and 75% were on aspirin. Lifestyle variables were significantly affected by patient cardiac knowledge, sense of control over their heart disease and perceptions of their illness. CONCLUSIONS: These results highlight the potential health gain available to patients with established heart disease. The results also suggest that psychological factors may play a role in patients' health behaviours.

Role of glutamine synthetase in nitrogen metabolite repression in Aspergillus nidulans.

Glutamine synthetase (GS), EC 6.3.1.2, is a central enzyme in the assimilation of nitrogen and the biosynthesis of glutamine. We have isolated the Aspergillus nidulans glnA gene encoding GS and have shown that glnA encodes a highly expressed but not highly regulated mRNA. Inactivation of glnA results in an absolute glutamine requirement, indicating that GS is responsible for the synthesis of this essential amino acid. Even when supplemented with high levels of glutamine, strains lacking a functional glnA gene have an inhibited morphology, and a wide range of compounds have been shown to interfere with repair of the glutamine auxotrophy. Heterologous expression of the prokaryotic Anabaena glnA gene from the A. nidulans alcA promoter allowed full complementation of the A. nidulans glnADelta mutation. However, the A. nidulans fluG gene, which encodes a protein with similarity to prokaryotic GS, did not replace A. nidulans glnA function when similarly expressed. Our studies with the glnADelta mutant confirm that glutamine, and not GS, is the key effector of nitrogen metabolite repression. Additionally, ammonium and its immediate product glutamate may also act directly to signal nitrogen sufficiency.

Toxicological assessment of gadoversetamide injection (OptiMARK), a new contrast-enhancement agent for use in magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A series of preclinical tests were undertaken during the developmental process to determine the safety profile of gadoversetamide injection (OptiMARK). METHODS: Acute intravenous, acute intracisternal, and repeated-dose toxicities; cardiovascular effects; and genetic and reproductive toxicology characteristics were assessed in several animal species. RESULTS: Gadoversetamide injection demonstrated an acute intravenous median lethal dose of 25 to 28 mmol/kg and a maximum nonlethal dose of 14 mmol/kg in mice. In the dog, acute administration of gadoversetamide injection showed a no observable effect level at 3 mmol/kg. Dosed daily for 4 weeks, gadoversetamide injection (0.1 mmol x kg(-1) x d(-1)) caused no serious irreversible changes in any organs in rats and dogs. At a dose of 0.1 mmol/kg, gadoversetamide injection caused no significant (P < 0.05) changes in cardiovascular function in anesthetized dogs. Gadoversetamide injection showed no mutagenic activity. Fertility, reproductive performance, and postnatal fetal development were not affected at doses up to 0.5 mmol x kg(-1) x d(-1) in the rat. No teratogenicity was observed at doses up to 4.2 mmol x kg(-1) x d(-1) in the rat and up to 1.6 mmol x kg(-1) x d(-1) in the rabbit. CONCLUSIONS: Data from our toxicological assessment demonstrate the safety of gadoversetamide injection in a number of animal species at doses exceeding the intended human clinical dose.

A single gene produces mitochondrial, cytoplasmic, and peroxisomal NADP-dependent isocitrate dehydrogenase in Aspergillus nidulans.

NADP-dependent isocitrate dehydrogenase enzymes catalyze the decarboxylation of isocitrate to 2-oxoglutarate accompanied by the production of NADPH. In mammals two different genes encode mitochondrial and cytoplasmic/peroxisomal located enzymes, whereas in Saccharomyces cerevisiae three separate genes specify compartment specific enzymes. We have identified a single gene, idpA, in the filamentous fungus Aspergillus nidulans that specifies a protein with a high degree of identity to mammalian and S. cerevisiae enzymes. Northern blot analysis and reverse transcription-polymerase chain reaction revealed the presence of two idpA transcripts and two transcription start points were identified by sequencing cDNA clones and by 5'-rapid amplification of cDNA ends. The shorter transcript was found to be inducible by acetate and by fatty acids while the longer transcript was present in higher amounts during growth in glucose containing media. The longer transcript is predicted to encode a polypeptide containing an N-terminal mitochondrial targeting sequence as well as a C-terminal tripeptide (ARL) as a potential peroxisomal targeting signal. The shorter transcript is predicted to encode a polypeptide lacking the mitochondrial targeting signal but retaining the C-terminal sequence. Immunoblotting using antibody raised against S. cerevisiae Idp1p detected two polypeptides consistent with these predictions. The functions of the predicted targeting sequences were confirmed by microscopic analysis of transformants containing fluorescent protein fusion constructs. Using anti-Idp1p antibodies, protein localization to mitochondria and peroxisomes was observed during growth on glucose whereas cytoplasmic and peroxisomal localization was found upon acetate or fatty acid induction. Therefore, we have established that by the use of two transcription start points a single gene is sufficient to specify localization of NADP-dependent isocitrate dehydrogenase to three different cellular compartments in A. nidulans.

Analysis of the genetic region encoding a novel rhizobiocin from Rhizobium leguminosarum bv. viciae strain 306.

Cross-testing of a number of strains of Rhizobium leguminosarum for bacteriocin production revealed that strain 306 produced at least two distinct bacteriocins. Further analysis involving plasmid transfer to Agrobacterium and other hosts demonstrated that there were bacteriocin determinants on plasmids pRle306b and pRle306c, as well as a third bacteriocin. The bacteriocin encoded by pRle306b was indistinguishable from the bacteriocin encoded by strain 248, whereas the bacteriocin encoded by plasmid pRle306c had a distinctive spectrum of activity against susceptible strains, as well as different physical properties from other bacteriocins that we have studied in our lab. Two mutants altered in production of the pRle306c bacteriocin were generated by transposon Tn5 mutagenesis, and the DNA flanking the transposon inserts in these mutants was cloned and characterized. DNA sequence analysis suggested that the pRle306c bacteriocin was a large protein belonging to the RTX family, and that a type I secretion system involving an ABC type transporter was required for export of the bacteriocin. A mutant unable to produce this bacteriocin was unaltered in its competitive properties, both in broth and in nodulation assays, suggesting that the bacteriocin may not play a major role in determining the ecological success of this strain.

Functional analysis of TamA, a coactivator of nitrogen-regulated gene expression in Aspergillus nidulans.

The tam A gene of Aspergillus nidulans encodes a 739-amino acid protein with similarity to Uga35p/Dal81p/DurLp of Saccharomyces cerevisiae. It has been proposed that TamA functions as a co-activator of AreA, the major nitrogen regulatory protein in A. nidulans. Because AreA functions as a transcriptional activator under nitrogen-limiting conditions, we investigated whether TamA was also present in the nucleus. We found that a GFP-TamA fusion protein was predominantly localised to the nucleus in the presence and absence of ammonium, and that AreA was not required for this distribution. As the predicted DNA-binding domain of TamA is not essential for function, we have used a number of approaches to further define functionally important regions. We have cloned the tamA gene of A. oryzae and compared its functional and sequence characteristics with those of A. nidulans tamA and S. cerevisiae UGA35/DAL81/DURL. The Aspergillus homologues are highly conserved and functionally interchangeable, whereas the S. cerevisiae gene does not complement a tamA mutant when expressed in A. nidulans. Uga35p/Dal81p/DurLp was also found to be unable to recruit AreA. The sequence changes in a number of tamA mutant alleles were determined, and altered versions of TamA were tested for tamA complementation and interaction with AreA. Changes in most regions of TamA appeared to destroy its function, suggesting that the overall conformation of the protein may be critical for its activity.