Immunomonitoring of renal transplant recipients in the early posttransplant period by sequential analysis of chemokine and chemokine receptor gene expression in peripheral blood mononuclear cells.

INTRODUCTION: We sought to determine whether sequential changes in chemokine ligand/receptor gene expression in the early posttransplant period of human renal allografts can be detected in peripheral blood mononuclear cells (PBMCs) and whether any such changes are predictive of clinical events. METHODS: Blood samples from 106 renal transplant recipients and 29 donor nephrectomy patients were taken preoperatively and daily for 14 days. Within the study period 22 patients had biopsy-proven acute rejection. From each blood sample PBMCs were separated and gene expression levels for chemokines CCL3, CCL4, CCL5, CXCL10, and their receptors CCR1, CCR5, and CXCR3, were determined using real-time quantitative PCR. RESULTS: Different gene expression patterns were seen between the rejector and nonrejector groups with decreases in CCL4 and CCR5 expression on days 6 to 8 and increases in CCR1 expression on days 9 and 10 posttransplant. With CXCL10, decreases in expression were seen in the nonrejector group but increases were seen in the rejector group posttransplant. With data aligned to time of rejection diagnosis, statistically significant increases, that preceded the clinical detection of acute rejection were seen in CCR1 and CXCL10 expression. Both their expression levels returned to pretransplant baseline values after successful antirejection therapy. CONCLUSION: We have demonstrated that changes in chemokine receptor/ligand gene expression by sequential monitoring in PBMCs can be detected in the early posttransplant period. In particular, CCR1 and CXCL10, which showed increased expression prior to rejection and returned to baseline levels with antirejection therapy, may have potential use in immunomonitoring and as predictive factors of rejection prior to its clinical manifestation.

Timing of urgent laparoscopic cholecystectomy does not influence conversion rate.

BACKGROUND: The optimal treatment of acute gallstone disease is urgent laparoscopic cholecystectomy, but there is confusion about the effect of delay in operation on conversion rates. Most reports suggest that delay beyond 3 or 4 days leads to a higher conversion rate. This study assessed the conversion rate in relation to the timing of laparoscopic surgery. METHODS: This institution operates a specialist-led protocol for the urgent management of all admissions with acute gallstone disease. Data were collected prospectively over 6 months. RESULTS: Between March and August 2002, 84 patients with acute gallstone disease underwent urgent laparoscopic cholecystectomy at the index admission with an overall conversion rate of 12 per cent. Four of 40 procedures carried out within 3 days of admission were converted, compared with six of 44 after 3 days. Five of 46 carried out within 4 days of admission were converted, compared with five of 38 after 4 days. There were no deaths and one common bile duct injury. CONCLUSION: As long as the procedure is carried out by experienced upper gastrointestinal surgeons working within a specialist-led protocol, the conversion rate for laparoscopic cholecystectomy can be as low as 12 per cent. The timing of urgent laparoscopic cholecystectomy has no impact on the conversion rate.

Implementation of a specialist-led service for the management of acute gallstone disease.

BACKGROUND: The 'gold standard' treatment for acute cholecystitis and biliary colic requiring hospital admission is urgent laparoscopic cholecystectomy. This is not routinely available in all hospitals. METHODS: A retrospective audit of emergency admissions with acute cholecystitis or biliary colic from January to December 2000 led to the development and implementation of a specialist-led protocol for the urgent management of acute gallstone disease. A second audit was carried out covering the 6 months after implementation. RESULTS: One hundred and fifty-eight patients were admitted with acute cholecystitis or biliary colic in the first audit period and 110 in the second interval. The rate of cholecystectomy at index admission increased from 37.3 to 67.3 per cent, at a median of 3 days after admission, and the conversion rate to open surgery fell from 32 to 12 per cent. Median hospital stay fell from 9 to 5.5 days, and the unplanned readmission rate decreased from 19.0 to 3.6 per cent. CONCLUSION: Urgent cholecystectomy for the management of acute gallstone disease is feasible and achievable in an acute services hospital with a specialist upper gastrointestinal team. It can lead to a reduced conversion rate, shorter hospital stay, fewer unplanned readmissions, an acceptable operating time and a low complication rate. The protocol is recommended for implementation in other hospitals.

Developmental morphological and histological studies on structures of the human fetal shoulder joint.

In the present work, morphological changes in the interior structures of the developing human shoulder joint were studied at different prenatal ages (9, 12, 16, 23 and 40 weeks) and were compared with the same structures in the adult joint. It was found that the shoulder joint had gone through important developmental changes during the 12th week of the prenatal life and it is assumed that genetic factors operative during this stage of development were more important than mechanical factors. A subsequent development of the intracapsular glenohumeral ligaments was present at the 16th week. The glenoid labrum, the biceps tendon and the three glenohumeral ligaments formed a complete ring around the glenoid fossa which constituted a functional unit, which seemed to have a role in stabilizing the joint. In the present work, histological prenatal studies were done on sagittal and radial sections from the glenoid fossa and its associated structures and the results were compared with the same structures in adults. At a crown-rump length of 30 mm (9 weeks), intermingling of the collagen fibres of the superior labrum and the biceps tendon was observed and the superior labrum could be considered as an extension of the biceps tendon. While the superior and inferior parts of the labrum appeared fibrous, the posterior labrum appeared as a primitive cellular condensation. At the 12th week, it became a fibrocellular structure and changed to a fibrocartilaginous structure at the 16th week. But until full term, no definitive fibrocartilage was found due to its hypercellularity compared to the adult. It was found that at all ages, the capsule was formed of cellular and fibrous elements, its collagenous content was progressively increased with age and at full term, it became generally fibrous but was still different compared to adults. In all stages of development, the synovial tissue of different regions of the same joint exhibited marked variations in thickness, vascularity, cellular density and collagenous content. It lined the capsule, surrounded the biceps tendon and reflected on the labrum. Its cell density as well as their vascular and collagenous contents were progressively increased with age. At full term, the synovial tissue was thickest at its inferior reflection and forming large folds. The synovial tissue lining the capsule was thinner than the synovial tissue at its reflection from the labrum, many villi and processes arising from it and projecting into the joint cavity.

An unusual abdominal mass in a renal transplant recipient.

Renal transplant recipients are at increased risk of malignancy and infection. We present the case of a 72-year-old-man with recurrent bladder carcinoma, abdominal aortic aneurysm repair, and end-stage renal failure due to renovascular disease. He received a cadaveric renal allograft into his left iliac fossa, was given cyclosporin A, azathioprine, and prednisolone triple therapy immunosuppression, and had no rejection episodes. He presented four years post-transplantation with a two-year history of intermittent sweats and fevers. Previous episodes had been investigated with no firm diagnosis made. This time he had right iliac fossa pain of three weeks' duration. Examination revealed a tender mass. Investigations showed unchanged graft function, but elevated inflammatory indices. Ultrasonography and computed tomography detailed an infiltrating mass associated with the sigmoid colon, which colonoscopy failed to visualise. At laparotomy a 6-cm tumor was removed, with adherent sigmoid colon and bladder dome. Macroscopically the mass was an abscess, and microscopy found acute and chronic inflammatory giant cells and fibrillary masses suggestive of actinomycosis, with no malignancy. The patient recovered uneventfully on antibiotics. At six months' follow-up, examination, inflammatory markers, and radiographic imaging showed no evidence of recurrence. Twelve months later the patient died of rupture of his proximal abdominal aorta. There was no evidence of recurrence at postmortem examination. We conclude with a brief review of actinomycosis in transplant recipients.

Temporal bone dissection: a possible route for prion transmission?

The aim of this study was to determine whether neural tissue is present in the bone 'dust' given off during temporal bone drilling. Bone 'dust' from three temporal bone dissections was collected and examined. Evidence of neural tissue was present in two out of the three specimens. Neural tissue is present in the bone dust given off during temporal bone drilling. This poses the question as to the risk of prion transmission during such dissection.

Sequential monitoring of peripheral T-lymphocyte cytokine gene expression in the early post renal allograft period.

BACKGROUND: Despite numerous studies, the precise role of cytokines in acute renal allograft rejection remains unclear. In this study we have monitored sequential changes in peripheral T cell cytokine gene expression, correlating the changes with clinical events after adult renal transplantation, to provide a deeper insight of the role of cytokines in allograft rejection. METHODS: Sequential changes in peripheral Th-1 [interleukin- (IL) 2 and interferon-gamma] and Th-2 (IL-4, IL-5, IL-10, and IL-13) cytokine gene expression in 43 patients with (n=15) and without (n=28) episodes of biopsy-proven rejection was monitored in the first 6 weeks after renal transplantation using a sensitive, semi-quantitative reverse-transcriptase polymerase chain reaction ELISA approach. RESULTS: Th-2 cytokines: IL-5 and IL13 expression increased before and during acute rejection, and decreased after successful antirejection therapy. A significant fall in IL-4 expression after transplantation and subsequent return to its baseline level of expression was observed in both nonrejectors and rejectors. IL-10 showed persistently high expression in nonrejectors, but in rejectors the expression fell during acute rejection, with a subsequent rise after antirejection therapy. Th-1 cytokines: IL-2 and IFN-gamma decreased in expression in the first week posttransplant in the rejectors, at the time of acute rejection (IL-2 only) and immediately after completion of antirejection therapy. CONCLUSIONS: Sequential monitoring of peripheral T cell cytokine gene expression after renal transplantation detected changes in expression that correlated with episodes of acute rejection and response to antirejection therapy. This approach may be applicable in the clinical laboratory for monitoring posttransplant changes in T cell alloreactivity and immunosuppression.

Influence of patient and donor cytokine genotypes on renal allograft rejection: evidence from a single centre study.

Cytokines are key immune mediators and it has been suggested that cytokine gene polymorphisms affecting expression influence rejection or tolerance. This study sought to examine this hypothesis with the aim of identifying predictive genotype markers for rejection. The study group consisted of 120 consecutive first cadaveric recipient-donor pairs transplanted at a single centre, between 1994 and 1997. PCR utilising sequence-specific primers (SSP) methodology was optimised for genotyping recipient and donor DNA for the following polymorphisms: tumour necrosis factor (TNF) -alpha (-308, G/A), interleukin (IL)-10 (-1082, G/A), IL-4 (-590, C/T), transforming growth factor (TGF) -beta1 (+915, G/C). Recipient-donor pairs were divided into rejectors (n = 28) and non-rejectors (n = 92). Each group was further stratified according to number of rejection episodes and HLA-DR mismatching. Recipient-donor pairs both lacking the IL-4*T allele (recipient low producer/donor low producer) were significantly increased in the rejector group (P = 0.02). Also, the combination of recipient IL-10*A negative/donor IL-10*A positive (recipient high producer/donor low producer), was significantly decreased in multiple rejectors (P = 0.04). No significant associations were detected between TNF-alpha and TGF-beta1, and rejection. This study suggests that the combination of recipient-donor IL-4 and IL-10 genotypes may be important in renal transplantation outcome. The results appear to corroborate the protective role of both of these cytokines, possibly due to their ability to suppress inflammation. However, due to conflicting results from this and other studies, a multi-centre collaborative study may be required to determine whether cytokine genotypes are significant, independent predictors of renal allograft rejection.

The efficacy of topical anaesthesia in flexible nasendoscopy: a double-blind randomised controlled trial.

The routine use of topical anaesthesia during flexible nasendoscopy has been questioned, and the degree to which topical vasoconstrictors can affect patient discomfort has yet to be elucidated. Patients' experiences with Lignocaineand phenylephrine, Lignocaine alone, xylometazoline and no preparation were compared. One hundred patients were recruited in this double-blind, randomised control trial and put into these four groups. Each patient completed a visual analogue scoring chart to determine the severity of unpleasantness and other undesirable effects (pain, bad taste, burning, choking, numbness and difficulty in swallowing). The results confirmed that vasoconstriction is a major contributing factor towards reducing overall unpleasantness (P = 0.022), topical anaesthesia can produce a bad taste (P = 0.022), and that none of the preparations have any effect on the pain during nasendoscopy. In conclusion, xylometazoline is recommended for nasendoscopy as it is effective and is significantly cheaper than the other preparations. Not using any preparations leads to the experience of severe symptoms.

The inferior vena caval conduit--a neglected technique in transplantation of the right cadaveric kidney?

A short right renal vein may reduce access or compromise optimal positioning during transplantation of the right cadaveric kidney. This difficulty could be overcome by using the inferior vena cava (IVC) as a venous conduit to lengthen the short right renal vein. This manoeuvre would also facilitate training by ensuring safe tension-free vascular anastomoses since the kidney can be lifted up a comfortable distance, thus improving exposure of the operative field. In a postal survey, only a third of UK renal transplant units utilised the IVC conduit. Despite 81.5% of units claiming that they harvest the IVC during organ retrieval, a 2-year retrospective audit revealed that only 4.3% of imported right kidneys had the IVC. The IVC remains a much under-utilised resource in the UK despite its potential benefit as a venous conduit in transplanting the right cadaveric kidney. We urge all retrieving surgeons to routinely harvest the IVC with right cadaveric kidneys during organ procurement.

Antrochoanal polyp presenting with obstructive sleep apnoea and cachexia.

A rare presentation of an antrochoanal polyp is reported. A 14-year-old boy presented with obstructive sleep apnoea and subnormal growth velocity for height and weight over a 1-year period. Examination revealed a post-nasal mass which following removal was confirmed histopathologically as an antrochoanal polyp. Relief of the airway obstruction was promptly followed by catch-up growth and subsequent normal growth velocities. The possible mechanisms underlying the cachexia are explored including the possible association with the obstructive sleep apnoea.

Developmental morphological and histological studies on structures of the human fetal elbow joint.

In the present work, morphological changes in the developing human elbow joint were studied at different prenatal ages (8, 12, 16, 20, 29 and 40 weeks) and were compared with the same structures in the adult joint. The elbow joint had gone through its most important developmental changes during the 20th week of prenatal life, probably due to the direct dynamic effect of the newly developed fetal movement. During later prenatal development, the articular surfaces of the lower end of humerus and the upper ends of radius and ulna developed their characteristic congruencies, so that the highly curved convexities always articulate with the highly curved concavities. That process progressed postnatally and even till adult age. In full-term infants it was found that the lower end of humerus had acquired its adult shape, while the shape of the upper ends of radius and ulna were still not fully developed. They continued development in postnatal life even till adult age. In the present work, histological prenatal studies were done on longitudinal sections from the back of the capsule and synovial tissue, early (8 weeks) and late in full term, and the results were also compared with the same structures in adults. It was found that at all ages, the capsules were formed of cellular and fibrous elements, but at early prenatal age (8 weeks), this cellular condensation was more massive and prominent while in full-term infants, it became generally more fibrous, but was still different compared to adults. Basic cellular structures of the synovial tissue changed very little during the late prenatal developmental stage, as it did not become more fibrous than cellular during these periods, but differences in vascularity became more obvious. The cartilaginous content of the articular surface at 8 weeks was highly cellular with very little intercellular matrix. In contrast to that of full term, this cartilage became fully chondrogenous with a notable decrease in cellular density and massive increase in matrix content.

Congenital bilateral choanal atresia: a novel stenting technique in neonates.

A new stenting technique is described which may reduce the incidence of restenosis in choanal atresia after decannulation. Eight neonatal cases with bilateral congenital bony choanal atresia were treated by endonasal perforation. A modified stenting technique utilising endotracheal tubes provided good fixation and stability. This aided epithelialisation of the newly formed tract. Furthermore the stents projected beyond the atretic plate preventing granulation tissue growth over the choanae, thus preventing restenosis. The stents were left in situ for six to eight weeks. The patients were followed up for periods ranging from eighteen months to eleven years. Seven did not require further treatment, and one required unilateral dilatation. Meticulous care in fixing and securing a well designed stent for an appropriate time may be a factor in reducing the incidence of restenosis.

Paediatric neurobrucellosis: case report and literature review.

Neurological complications are rare in childhood brucellosis: there are only 33 reported cases. In children, neurobrucellosis is usually of acute presentation involving the central nervous system. We report our experience with an 8-year-old boy with brucella meningitis who demonstrated a Jarisch-Herxheimer-like reaction, i.e. initial clinical deterioration following the commencement of antibrucella treatment, associated with increased pleocytosis and shift from lymphocytic to polymorphic predominance and an already increased CSF lactate. These CSF findings have not been previously described. The patient recovered completely after 3 months' therapy consisting of rifampicin, doxycycline and gentamicin. Paediatric neurobrucellosis therapy should be a combination of three antibrucella antibiotic that include an aminoglycoside; for a period of 8-12 weeks, steroids may be added to treat complications. The prognosis of neurobrucellosis in children is usually good.

Congenital bilateral choanal atresia.

Eight neonatal patients with bilateral congenital choanal atresia were treated by endonasal perforation with a curved trocar. In two of these the atresia plate was perforated under direct vision using a 0 degree Hopkins rod endoscope. A stenting technique is described, the aim of which is to provide good fixation and easy postoperative nursing care. Of the cases, seven did not require further treatment. A single case required further dilatation on one side. The trans-nasal endoscopic technique and the described method of stenting is a safe, quick and efficient procedure for the correction of choanal atresia in neonates. A familial tendency is described in seven of the eight cases.

Paradoxical clinical deterioration despite near-complete pathological response to neoadjuvant chemotherapy for locally advanced gastro-oesophageal adenocarcinoma.

Neoadjuvant chemotherapy for proximal gastric cancer has shown promise in early clinical trials. We report on a clinical deterioration, yet near-complete pathological and radiological response to a combination of cisplatin and fluorouracil in a patient with locally-advanced gastric adenocarcinoma.