Anabolic-androgenic steroids: medical assessment of present, past and potential users

OBJECTIVE: To document adverse effects of anabolic-androgenic steroid (AAS) use in community-based users attending a medical clinic. DESIGN AND SETTING: Prospective recruitment, questionnaire-based interview, physical examination and investigations, with follow-up, of people who attended, anonymously, an inner-city hospital clinic established specifically to examine AAS use. PARTICIPANTS: 58 men, comprising 27 past AAS users, 14 present users and 17 potential users (who formed the control group). MAIN OUTCOME MEASURE: Clinical adverse effects and abnormal laboratory findings. RESULTS: Cyclical use of oral and intramuscular, human and veterinary AASs were reported. The most commonly reported source of AASs was friends (59%), gymnasiums (25%) and doctors (14%). The most common reported adverse effects were alterations in libido (61%), changes in mood (48%), reduced testis volume (46%) and acne (43%). Although mean systolic and diastolic blood pressure was not significantly different between groups, five present (29%), 10 past (37%) and one potential user (8%) were hypertensive. Gynaecomastia was found in 10 past users (37%; P<0.01 v. potential users), two present users (12%) and no potential users. Mean testis volume was significantly smaller in present users (18 mL; P<0.02) than in the other groups. Twenty past users (83%), eight present users (62%) and five potential users (71%) had abnormal liver function test results (P=0.5). After discussion of test results, only 11 participants (19%) reported they would not use AASs in the future. CONCLUSIONS: Adverse effects were reported by or detected in most of the AAS users who attended the clinic. Despite awareness of adverse consequences, most participants planned future use of AASs.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

In-situ emergency paediatric surgery in the intensive care unit

The role of surgery in the intensive care unit (ICU) remains unclear. Although previously shown not to increase morbidity for patent ductus arteriosus ligation, Broviac catheter insertion, and recently, general neonatal and paediatric surgery, there remains a reluctance to operate on sick patients in the ICU (in-situ surgery, ISS). A retrospective study of 25 critically ill children and neonates who underwent ISS was performed. Surgery was aided by operating loupes and a high-intensity headlight. ISS was not associated with any morbidity, and although a 36% mortality occurred in this small series, in no case was this due to ISS. ISS avoids the risks of transfer to the operating theatre and the potential delays in theatre access. Our results suggest that ISS in a tertiary-level paediatric surgical hospital is safe and does not impact adversely on clinical outcome. Accepted: 7 January 1998     

Clearance of yttrium-90-labelled anti-tumour antibodies with antibodies raised against the 12N4 DOTA macrocycle.

Radioimmunotherapy (RIT) is currently limited by toxicity to normal tissues as a result of prolonged circulating radioantibody in the blood. In this study, the use of a clearing antibody was investigated (second antibody) in an attempt to reduce blood background levels of [90Y]A5B7 immunoglobulin G (IgG) activity, and, therefore, improve the therapeutic tumour-blood ratio in nude mice bearing human colorectal tumour xenografts. The second antibody was raised against the 12N4 macrocycle group used for chelation of 90Y, and is, thus, applicable to any anti-tumour antibody labelled with this methodology. Second antibody was administered 18, 24 or 48 h after radiolabelled antibody injection and produced up to a tenfold reduction in blood levels and a tenfold improvement in tumour-blood ratios. This has the advantage of reducing the risk of myelotoxicity caused by prolonged retention of activity in the blood. For all normal tissues, there was a similar or slightly lower uptake of [90Y]IgG with second antibody clearance, apart from a transient rise in liver activity due to complexes of primary and secondary antibody clearing via the liver. As a result of clearance of [90Y]IgG from the blood pool, there was an associated fall in the amount of antibody at the tumour site (up to 3.3-fold) at later time points for mice injected with second antibody. However, despite this, tumour-blood ratios remained superior to the control group at these later time points. Estimated dosimetry evaluation revealed that total dose to normal tissues, blood and tumour was lower than for the non-clearance group. Surprisingly, however, there was little improvement in total estimated tumour-blood dose ratio over the time period studied. This was probably because the majority of the dose was delivered to both the blood and tumour within the first 24 h after administration of [90Y]IgG, so that giving the clearing agent after this time did not produce a large difference in total estimated dose. The anti-macrocycle second antibody proved to be a successful clearing agent and could potentially be applied to any anti-tumour antibody coupled with the 12N4 macrocycle. In the light of the estimated dosimetry results described here, it would probably be most useful given at earlier time points (i.e. before 18 h after injection of primary antibody) to produce an improved tumour-blood ratio of total dose. Development of this strategy may allow higher levels of activity to be administered for RIT, and repeated dosing regimens.     

Exploring the decision-making preferences of people with colorectal cancer

OBJECTIVES: To explore patient views on participation in treatment, physical care and psychological care decisions and factors that facilitate and hinder patients from making decisions. DESIGN: Qualitative study using semi-structured interviews with patients. SETTING AND PARTICIPANTS: Three NHS Trusts in the north-west of England. Theoretical sampling including 41 patients who had been treated for colorectal cancer. RESULTS: For patients, participation in the decision-making process was about being informed and feeling involved in the consultation process, whether patients actually made decisions or not. The perceived availability of treatment choices (surgery, radiotherapy, chemotherapy) was related to type of treatment. Factors that impacted on whether patients wanted to make decisions included a lack of information, a lack of medical knowledge and trust in medical expertise. Patients perceived that they could have a more participatory role in decisions related to physical and psychological care. CONCLUSION: This study has implications for health professionals aiming to implement policy guidelines that promote patient participation and shared partnerships. Patients in this study wanted to be well informed and involved in the consultation process but did not necessarily want to use the information they received to make decisions. The presentation of choices and preferences for participation may be context specific and it cannot be assumed that patients who do not want to make decisions about one aspect of their care and treatment do not want to make decisions about other aspects of their care and treatment.     

Heterogeneity in the ultrastructure of the mucous (goblet) cells of the rabbit palpebral conjunctiva

Aim: The purpose of this study was to assess objectively the ultrastructure of the secretory granules in rabbit conjunctival mucin‐producing ‘goblet’ cells. Method: The upper eyelids from five young adult dioestrous female rabbits were dissected out, stretched onto a cardboard support and prepared for transmission electron microscopy by repeated application of an isotonic two per cent glutaraldehyde fixative at room temperature. Post‐fixation treatment included osmium tetroxide and staining with uranyl acetate and lead citrate. Low magnification micrographs were taken of the goblet cells of the conjunctiva, printed at a magnification of approximately 6,000 and the number, size and features of the secretory granules assessed. Results: Across the entire palpebral conjunctiva of ail five rabbits, the majority of mucous cells displayed a goblet shape and the secretory granules were uniformly pale in staining. The average width of the goblet cells was 10.8 ± 1.1 μm and the diameter of the secretory granules was 0.82 ± 0.16 μm. However, in localised regions across the palpebral conjunctiva of two of the rabbits, some goblet cells were different in that the secretory granules had either a denser‐staining core, in which some of the granules were densely staining (while others were pale) or most of the granules were densely staining. These mucous cells had an average diameter of 10.3 ± 1.7 μm and the granule diameters averaged 0.88 ± 0.01 μm. For these abnormal goblet cells, inflammatory cells were found in their immediate vicinity. Occasionally, goblet cells were seen to be in the process of degranulation with associated apparent cell necrosis and the mucin granule diameter was close to 1 μm. Conclusions: The ultrastructure of the mucin‐containing secretory granules of the conjunctival mucous cells is not necessarily homogeneous in character and further attention needs to be given to the effects of localised inflammation in the tissue and to possible hormonal influences.     

Development and initial validation of a new preference-based disease-specific health-related quality of life instrument for erectile function

Health-related quality of life instruments may be generic or specific. In general, only generic instruments use preference-based scoring. We report on a novel approach to combine in one instrument the strengths of the specific approach, greater disease relevance and responsiveness, with those of preference-based scoring, generalizability through utilities. OBJECTIVES: The primary objective was to develop a self-administered, preference-based instrument capable of measuring utilities in the disease-specific context of erectile dysfunction (ED). METHODS: Content derivation/validation began with a literature review. Eight attributes (domains) were selected to provide clinical experts structure for focus group discussion. Four levels describing a continuum of dysfunction-function were defined for each domain. Each domain, including functional levels, was reviewed and modified until consensus was achieved regarding content. This content was then integrated into a preference based scoring instrument using two visual analogue scales (VAS) with which patients rated three 'marker' health states (representing mild, moderate and severe ED), their self-state and a previously validated external marker state. The instrument was pilot tested, and implemented in a clinical trial. Initial validation analyses have been performed. RESULTS: A self-administered, preference-based, VAS instrument was developed for use in the ED population, and the instrument was feasible to complete, was reliable beyond the threshold of acceptability established a priori and demonstrated good validity. Evidence of these properties accumulates over time and this study begins that process with this instrument. Responsiveness is being assessed in the context of a clinical trial.     

Thrombosed giant coronary artery aneurysm presenting as an intracardiac mass

Giant coronary artery aneurysms are rare in adults and are usually found in association with Kawasaki's disease arising in childhood. We report a case of a thrombosed giant right coronary artery aneurysm presenting as an intracardiac mass detected after inferior wall myocardial infarction. Histologic analysis indicated that fibromuscular dysplasia was the underlying cause of the aneurysm.