Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus.

Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMF-prednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 +/- 19 mL/min vs. 63 +/- 18 mL/min, p = 0.57) or 2 years (61 +/- 17 mL/min vs. 61 +/- 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone.

Kidney transplantation without calcineurin inhibitors using sirolimus.

INTRODUCTION: With the introduction of new immunosuppressive medicines, it has become possible to determine the extent to which nephrotoxic medicines contribute to CAN. The aim of this study is to compare the safety and efficacy of calcineurin inhibitor (CI) free immunosuppression in a prospective, randomized trial comparing sirolimus-mycophenolate mofetil (MMF)-prednisone to tacrolimus- MMF-prednisone. METHODS: Patients are randomized at the time of transplant to receive either tacrolimus (target level 12 to 15 ng/mL in the first month) or sirolimus (target level 12 to 18 ng/mL in the first month). All patients also receive MMF (750 mg bid) and prednisone tapered to 10 mg/d by 3 months and thymoglobulin induction (1.5 mg/kg/d on days 0, 1, 2, 4 and 6). RESULTS: At this point we have 4-month follow-up in 85 patients. The acute rejection rate is 7.5% (3/40) in the tacrolimus group and 6.7% (3/45) in the sirolimus group. We have discontinued sirolimus in eight patients so far, with wound complications being the most common indication. Renal function appears to be better in the sirolimus group at 1 month after transplantation, but the difference is not statistically significant. CONCLUSIONS: While longer follow-up is needed, these results demonstrate that total avoidance of CI can be achieved with extremely low acute cellular rejection rates using sirolimus-based immunosuppression in combination with thymoglobulin, MMF, and prednisone.

Capillary electrophoresis-inductively coupled plasma mass spectrometry interface with minimised dead volume for high separation efficiency.

A modified microconcentric nebulizer (MCN-100) has been used to construct an improved interface with minimised liquid and gas phase dead volumes for the coupling of capillary electrophoresis (CE) and inductively coupled plasma mass spectrometry (ICP-MS). A plate number of 3.6 x 10(6) plates m(-1) has been achieved. This is an order of magnitude better than the results previously reported for CE-ICP-MS. The separation efficiency of the system is demonstrated by the baseline separation of eight rare earth metals within a time span of 14.6 s. The system was used to control the purity of vitamin B12 and glutaredoxin 2 from Escherichia coli.

Determination of arsenic by inductively coupled plasma mass spectrometry--comparison of sample introduction techniques.

A comparison is made of four sample introduction techniques for the determination of As by inductively coupled plasma mass spectrometry. The techniques studied were 1) flow injection with pneumatic nebulization (FIA-PN), 2) direct electrothermal vaporization (ETV), 3) continuous hydride generation (HG) and 4) hydride generation with in situ trapping followed by electrothermal vaporization (HG-ETV). It was found that FIA-PN and ETV gave similar detection limits in concentration units (about 20 pg mL(-1)), although ETV had a much lower absolute detection limit (0.2 pg). Sample introduction by hydride generation gave an inferior detection limit (100-200 pg mL(-1)), also in combination with in situ trapping and ETV, owing to the blank signal from traces of As in NaBH4 which is difficult to eliminate. The results indicate that the more elaborate sample introduction techniques based on ETV and HG may not offer significant advantages compared to normal solution nebulization for the determination of As in simple sample matrices such as natural fresh waters, where matrix removal is not required.

Speciation of aluminium in tea infusions studied by size exclusion chromatography with detection by post-column reaction.

Aluminium-organic species in tea infusions were studied by size exclusion chromatography, using a Superose 12 HR column, a mobile phase of 0.12 mol l-1 tris(hydroxymethyl)aminomethane adjusted to pH 5.5 and detection by UV-visible spectrophotometry. Aluminium was detected after post-column reaction with pyrocatechol violet at 585 nm and the organic material was detected at 280 nm. Teas of different origin were analyzed; the results indicate that aluminium is bound to the same relatively narrow size-range of large organic molecules in the tea infusions, irrespective of the origin of the tea.

Determination of aluminium in liver from reindeer, moose and sheep by electrothermal atomic absorption spectrometry.

Aluminium in liver from reindeer, moose and sheep from the northeast part of Norway was determined by graphite furnace atomic absorption spectrometry following digestion of the samples with nitric acid. The concentration of aluminium in the liver was markedly higher for reindeer than for moose and sheep; the median values obtained were 0.56 microgram g-1 Al (wet wt.) for 101 reindeer, 0.06 microgram g-1 Al for 72 moose and 0.09 microgram g-1 Al for 40 sheep. The detection limit of the method was 0.01 microgram g-1 Al. The NIST SRM 1577a Bovine Liver was also analyzed.

Swallowing in motor neurone disease.

Ninety-two patients with motor neurone disease have been assessed clinically and radiologically for evidence of swallowing problems. At the time of examination, moderate or severe swallowing difficulty was present in 89% of those whose disease had presented as bulbar palsy, in 45% of those in whom the disease began many months before as progressive muscular atrophy and in 29% of those with amyotrophic lateral sclerosis. Patients with more severe swallowing symptoms appeared more likely to have abnormal findings on videofluoroscopy overall. However, not all patients with an abnormal radiological picture had swallowing difficulties. It is suggested that radiological signs should only be used within the context of clinical symptoms and signs in the selection of patients for palliative surgery. Thirteen patients with pseudobulbar symptoms and signs had a cricopharyngeal myotomy performed: two suffered major post-operative complications. However, the satisfaction rate was 89% and we recommend cricopharyngeal myotomy for such patients. Pharyngostomy was performed for seven patients unable to initiate swallowing, six had post-operative complications.

Elemental analysis of bovine liver by inductively coupled plasma atomic emission spectrometry by using a simple dissolution procedure.

A simple digestion with nitric acid followed by filtration of the undigested lipids was found to be suitable for the decomposition of bovine liver, prior to multielement determination by inductively coupled plasma atomic emission spectrometry. Using reference materials, accurate results were obtained for cadmium, copper, iron, manganese, molybdenum and zinc.

Long-term results of submandibular duct transposition for drooling.

This study examines the long-term results and morbidity of submandibular duct transposition in drooling children. Twenty-two patients, aged 3 to 18 years, with neurological dysfunction and excessive drooling underwent submandibular duct transposition between 1984 and 1987. In January 1990, 20 patients were reviewed. Their degree of drooling pre-operatively, immediately post-operatively and currently was assessed. The rate of improvement and the occurrence of complications were noted. Drooling was 'much better' in the early post-operative period in 17 of the 20 patients, and this improvement was invariably noted within three weeks. In the three other patients drooling was 'better'. Deterioration occurred in only three patients over the entire follow-up period. Complications all occurred in the first 18 months following surgery; they consisted of salivary retention cysts in four and transient submandibular gland swelling in a fifth patient.

Pharyngeal pouch carcinoma: two unusual cases.

Two patients with carcinomata arising in pharyngeal pouches are reported. In one, the tumour was detected preoperatively by a contrast radiographic study. In the second the lesion was a carcinoma in situ. The English literature is reviewed with reference to these two unusual features.

Factors influencing the preservation of the facial nerve during acoustic surgery.

We reviewed the last 30 acoustic neuromas excised in our department and attempted to find out the factors associated with preservation of the facial and cochlear nerves. While the size of the tumour was the most important factor, vascularity and consistency were both important. Facial and cochlear nerves were preserved in 63% and 10% of the patients respectively. The importance of early diagnosis cannot be overemphasized.

Determination of iodine in seaweed and table salt by an indirect atomic-absorption method.

Decomposition methods based on fusion with alkali are discussed, with respect to the determination of iodine in biological material. It is shown that sodium hydroxide can be used for the decomposition of seaweed without loss of iodine. In spite of the oxidizing conditions, the iodine will be present as iodide in the final ash. The iodide can be determined by an indirect atomic-absorption method, based on the reaction between iodide and mercury(II), with determination of mercury by cold vapour atomic-absorption spectrometry. The basis of the method is discussed, and it is shown that the use of tin(II) as reductant is essential. The effect of the oxidation state of the iodine on the sensitivity of the method is pointed out. High concentrations of chloride interfere, but it is still possible to determine iodide in iodinated table salt.

The determination of nitrate and sulphate in 50% sodium hydroxide solution by ion-chromatography.

Electrolysis in combination with a cation-selective membrane is used to reduce the concentration of sodium hydroxide in the sample, prior to the ion-chromatographic determination of nitrate and sulphate. The advantage and disadvantage of this type of sample pretreatment are discussed.

The surgery of congenital deafness. The Oxford, England series of 235 ears.

This paper outlines the indications for surgery of congenital ears in complete meatal aplasia and an operative technique used in 35 ears. It is felt that otologic surgery should be done before the pinna reconstruction as it is very important to try and introduce sound into these children at an early age. Most of the patients in this series were 2 to 3 years' old. In addition, the position of the new auricle can be made more satisfactorily around an already established meatus. The value of radiology of the internal as well as the middle ear is stressed and the necessity for providing a stable and uninfected meatus emphasised with regard to the possible fitting of a hearing aid. Failure to achieve a permanent unaided hearing improvement is due to fibrosis at the bottom of the meatus, a problem which is yet to be solved.

Electrolytic preconcentration in instrumental analysis.

The use of electrolytic deposition as a separation and preconcentration step in trace metal analysis is reviewed. Both the principles and applications of the technique are dealt with in some detail. Electrolytic preconcentration can be combined with a variety of instrumental techniques. Special attention is given to stripping voltammetry, potentiometric stripping analysis, different combinations with atomic-absorption spectrometry, and the use of flow-through porous electrodes. It is pointed out that the electrolytic preconcentration technique deserves more extensive use as well as fundamental investigation.

Trace metal analysis by anodic-stripping voltammetry Effect of surface-active substances.

The presence of cationic, anionic, and neutral surfactants and humic substances is shown to affect the peak heights of copper, lead and cadmium in synthetic sea-water analysed by differential pulse anodic-stripping voltammetry. At surfactant concentrations below 0.1 mg/l. the effect is insignificant, but at higher concentrations the peak heights usually decrease, although for copper an increase in the peak height was also observed. The peak heights do not depend to any great extent on the pH of the solution, except in alkaline solution and in the presence of humic substances. Adsorption and complex formation may account for the observed dependences.