Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Estimating the cost of expanding an apheresis program

To determine the cost of expanding blood product operations, the concept of marginal cost must be used. This article reports the development and implementation of a method of costing increases in collecting plasma using apheresis operations. The model takes into account the fact that certain resource inputs--notably, direct labor and machines--increase in discrete steps rather than in a continuous manner. To address this fact, a stepwise cost analysis function was developed, which related operating costs to the volume of apheresis collections. This function was used to predict the marginal costs of potential increases in the supply of plasma at a blood center in Canada. Differences were noted in the cost of plasma in Canada and the United States, much of which could be attributed to different standards regarding the volume of plasma per collection and to differences in pricing materials.     

Funktionelle und subjektive Ergebnisse nach subtalaren Luxationen

Background

The objective of our study is to evaluate the functional and subjective results following subtalar dislocations without any associated bone injuries and to examine whether the direction of dislocation has any effect on the post-traumatic results.

Methods

Over the period from February 1998 to May 2006, 56 patients with a subtalar dislocation were enrolled in the study. A subtalar dislocation without any associated bone injuries was only present in 13 patients. Follow-up examination after an average of 39.8 months was performed using the AOFAS Ankle-Hindfoot scale. The adapted classification developed by Altman was used to assess the post-traumatic degree of arthrosis radiologically.

Results

The average AOFAS score was 81, with good results in 11 patients and satisfactory results in 2 patients. The range of motion (ROM) for the ankle-hindfoot joint was 39.2°.

Conclusion

Despite the severity of the injury, the functional and subjective results of subtalar dislocations without any bone injuries are good. Generally, no early post-traumatic arthrosis occurs if there are no associated bone injuries. No differences were established between medial and lateral subtalar dislocations.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

IDEAL PAIN RELIEF FOLLOWING LAPAROSCOPIC CHOLECYSTECTOMY

In a previous report the effectiveness of intraperitoneal bupivacaine in reducing pain following laparoscopic cholecystectomy was demonstrated. Other methods of pain relief are commonly used but none has been compared following laparoscopic cholecystectomy. In two further studies we have compared the analgesic effect of intraperitoneal bupivacaine against wound infiltration with bupivacaine, and against intraperitoneal bupivacaine with the addition of a non-steroidal anti-inflammatory drug (NSAID) in patients undergoing laparoscopic cholecystectomy. Two consecutive studies were performed. In the first, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine injected into the trocar wounds. In the second study, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity and a diclofenac suppository (100 mg) one hour before surgery. Postoperative pain was assessed with a visual analogue pain scale. There was no difference in pain scores in the two groups in either study. Intraperitoneal bupivacaine is as effective as wound infiltration. The addition of an NSAID makes no difference in the reduction of postoperative pain following laparoscopic cholecystectomy.     

Ecstasy cannot be assumed to be 3,4-methylenedioxyamphetamine (MDMA)

LINKED ARTICLES

This is a rebuttal by the authors (Green et al., pp. 1523–1536 of this issue) to a commentary by Parrott, pp. 1518–1520 of this issue. To view the article by Green et al. visit http://dx.doi.org/10.1111/j.1476-5381.2011.01819.x. To view the commentary by Parrott visit http://dx.doi.org/10.1111/j.1476-5381.2012.01941.xWe thank Prof Parrott (Parrott 2012) for his interest in our review (Green et al., 2012). Our main aim was to discuss the problems that arise in interpreting data obtained when administering 3,4-methylenedioxymethamphetamine (MDMA) to experimental animals in terms of possible clinical consequences and vice versa, not to disparage the evidence that Ecstasy is neurotoxic in humans. We presented evidence that the pharmacokinetics of MDMA in rats and primates are fundamentally different from the pharmacokinetics of the drug in humans. Because the plasma half-life of the drug in rats is 10 times shorter than in humans, the acute adverse events in rats may be minimal compared with those in humans, and this includes body temperature and endocrine changes. Conversely, the rapid metabolism of the drug in rats to form neurotoxic metabolites may result in more severe long-term effects in that species than those that may occur in humans.We had no intention of suggesting that there was no evidence for some recreational Ecstasy users presenting with evidence of 5-HT neurotoxicity, albeit it is clear from the literature that some of this evidence remains open to several interpretations. What we did claim was that pure 3,4-methylenedioxymethamphetamine (MDMA) taken alone was unlikely to cause 5-HT neurotoxicity in man. Here we must emphasize the term MDMA, as it is crucial to our discussion. Parrott, in contrast, uses the term ‘Ecstasy/MDMA’ several times when discussing neurotoxicity (Parrott, 2012). This association of Ecstasy with MDMA is one of the major problems of translation that we addressed. The Ecstasy tablet that most recreational users buy and ingest is not necessarily MDMA. Indeed, in many cases, it clearly is not. The tablet is often adulterated with other compounds, and one investigation identified no less than 14 substances other than MDMA in Ecstasy tablets, which users nevertheless presumably believed contained only MDMA (Vogels et al., 2009). Many of the adulterants identified were also psychoactive and included compounds structurally related to MDMA such as 3,4-methylenedioxyethylamphetamine and 2-methylamino-1-(3,4-methylenedioxyphenyl)butane, which have poorly researched pharmacology and toxicology. In addition, most recreational users of Ecstasy also knowingly ingest other psychoactive compounds such as alcohol and cannabis. Alcohol, for example, alters the pharmacokinetics of MDMA (Hamida et al., 2009). While, as Parrott states, clinical studies have attempted to allow for these confounding factors in any examination of the physical and psychological effects of MDMA in humans, such analysis is always limited not only by the other compounds the evaluators are unaware of, but also drugs perhaps not even considered to be relevant by the user and therefore not disclosed. It is unlikely that coffee and ‘energy drinks’ such as Red Bull are always disclosed, but there is now good preclinical evidence that caffeine, which incidentally has also been found as an adulterant in Ecstasy tablets, enhances both the hyperthermia and neurotoxicity induced in rats by MDMA (Camarasa et al., 2006; Vanattou-Saïfoudine et al., 2010). And this brings us to the crux of the problem and weakness of all the clinical data cited by Parrott (2012). A basic tenet of all good clinical pharmacology is accurate knowledge of the doses administered, frequency of administration and any confounding factors such as other drugs being consumed. None of these data are available with any precision in the clinical studies quoted. Of course one has some indication as to dose (although as Vogels et al., (2009) reported, the dose contained in illicitly obtained tablets is highly variable) and frequency of drug ingestion, but this information is generally obtained from the user whose recall is likely to be limited or who decides to obfuscate. Crucially, the information can never take into account the problem of drug tablet adulteration. The fact that hair or urine samples detect MDMA merely shows the user has consumed the drug, not how much or when or what other drugs were taken concurrently.We never suggested that MDMA exposure was not going to be associated with physical or psychological change. However such changes are not necessarily associated with long-term neurotoxic damage. We have shown that long-term behavioural effects can occur in rats both with and without 5-HT neurotoxicity (Fone et al., 2002; Bull et al., 2003; Rodsiri et al., 2011). It is interesting that Parrott approvingly quotes the Verheyden et al. (2003) study in support of his contention that neurotoxic damage has occurred. Because this study noted that the majority of persons reporting chronic psychiatric problems reported ‘improved mental health’ after quitting the drug, this surely allows us to conclude that the drug had produced subacute changes rather than any that could be associated with long-term neurotoxic damage.A further limitation to any clinical study is that one cannot perform prospective studies with the aim of investigating whether long-term neurotoxic events occur, so weaknesses arise with regard to any psychological abnormalities observed. Are persons with high risk of psychiatric problems more likely to misuse the drug, or does the drug induce changes in high-risk individuals? If high risk also happened to be associated with 5-HT abnormalities in the brains, then any conclusion that MDMA has induced neurotoxicity is spurious.We most certainly did not suggest that MDMA acted as a neurotoxin only under conditions of severe hyperthermia as is stated by Parrot in his sixth paragraph (Parrott, 2012). We have been involved in many studies on the effects of MDMA on body temperature in rats (see Docherty and Green, 2010) including one that demonstrated that neurotoxicity can occur in the absence of hyperthermia (O''Shea et al., 1998) and another that showed that hyperthermia worsens neurotoxic damage (Green et al., 2004). In our review, what we did propose was that because of the very different pharmacokinetics of MDMA in rats and humans, it is probable that humans would suffer serious or fatal adverse events at plasma levels below those likely to be required to induce 5-HT neurotoxicity.We emphasize again that we are not denying the clinical observations reviewed by Parrott, but conclude that the effects seen cannot be ascribed solely to the effects of MDMA, as he seems to be proposing. We also repeat our contention that MDMA in combination with other drugs may induce neurotoxicity and this could be said to be supported by the clinical studies quoted by Parrott.Finally, we can but assume that Parrott concurs with our principal conclusion that ‘the doses currently being used to investigate the possible therapeutic benefits of MDMA are unlikely to produce any severe acute or importantly any long-term neurotoxic damage in the human brain’ as he used such a dose (100 mg or approximately 1.4 mg·kg ⁻¹) in one of his recent studies in human volunteers (Parrott et al., 2011).