Adaptation to blockade of human immunodeficiency virus type 1 entry imposed by the anti-CCR5 monoclonal antibody 2D7.

The second extracellular loop (ECL2) domain of CC-chemokine receptor 5 (CCR5) has been proposed as a specific target site for therapeutic agents aimed at blocking CCR5-dependent entry by human immunodeficiency virus type I (HIV-1). We have adapted two CCR5-using HIV-1 isolates, prototypic JR-CSF, and a primary isolate, 11-121, to replicate in vitro in the presence of high concentrations of a monoclonal antibody (MAb 2D7) specific for the CCR5 ECL2 domain. The 75% inhibitory concentrations (IC(75)) for the two 2D7-adapted isolates were approximately 100-fold higher than those for corresponding control isolates passaged without the MAb. Adapted isolates did not acquire the ability to use CXCR4, CCR3, or CCR1. Env clones derived from MAb 2D7-adapted JR-CSF showed several gp120 mutations that were not found in any of the control JR-CSF clones. The in vitro observations suggest that CCR5-using HIV-1 strains might also be able to adapt in vivo to evade an ECL2-blocking therapeutic agent.

Encephalitozoon cuniculi isolated from the urine of an AIDS patient, which differs from canine and murine isolates.

A species of Encephalitozoon has been isolated from the urine of a patient with the acquired immunodeficiency syndrome and maintained in vitro in Madin Darby Canine Kidney cells. When examined by random amplified polymorphic DNA polymerase chain reaction the new isolate was found to differ from E. hellem and to have amplified products in common with murine and canine E. cuniculi. However, it more closely resembled the canine than the murine isolate. Sodium dodecylsulphate polyacrylamide gel electrophoresis differentiated between all three isolates of E. cuniculi, with a band at 42-45 kDa present in the murine isolate only, bands at 52 kDa present in the canine and human isolates but not the murine, and a single band at 60 kDa (murine) and 65 kDa (canine) replaced by two bands at 55 and 70 kDa in the human isolate. The 55 kDa and 70 kDa antigens were also revealed as characteristic bands of the human isolate by Western blotting. The study has thus revealed that the species Encephalitozoon cuniculi is not a homogeneous entity.

Reversible renal failure caused by a microsporidian infection.

OBJECTIVE: To report a case of renal failure associated with microsporidian infection in an HIV-seropositive patient. DESIGN: Case report. SETTING: Chelsea and Westminster Hospital, London, England, UK. PATIENT: An HIV-seropositive patient presented febrile with abdominal pain who developed renal failure. Renal biopsy and urinalysis showed infection with a microsporidian of the genus Encephalitozoon. INTERVENTION: Treatment with albendazole (400 mg) twice daily was associated with disappearance of infection from the urine, clinical improvement and return of renal function virtually to normal. CONCLUSION: HIV-seropositive individuals with renal failure should have urine screened for microsporidia. The administration of albendazole in such cases may reverse renal failure.

Preregistration house officers in the Thames regions: changes in quality of training after four years.

OBJECTIVE: To measure changes in the training and workload of preregistration house officers over four years. DESIGN: Postal questionnaire. SETTING: The Thames health regions. PARTICIPANTS: 1049 preregistration house officers. RESULTS: Response rate was 69% (725 replies). The proportion of house officers officially on duty > 83 hours a week fell from at least 42% to 21%, and the proportion officially on duty < or = 72 hours rose from no more than 9% to 40%. Adequate guidance in breaking bad news increased from 25% to 46% (p < 0.0001; 95% confidence interval for difference, 16.2% to 25.8%) and guidance in pain control increased from 36% to 46% (p < 0.01; 5.0% to 15.0%). The number of house officers attending an induction course increased from 61% to 94% (p < 0.001; 28.9% to 37.1%). There was no change in the proportion unable to attend formal educational sessions because of clinical commitments or in levels of satisfaction with consultants' educational supervision. The median number of inpatients under house officers' care fell from 20 to 17, but the numbers of patients clerked in an average week showed little change. House officers were less satisfied with the clinical experience their post provided (proportion dissatisfied rose from 30% to 39%; p < 0.01; 4.2% to 13.8%) and less enthusiastic about recommending their post to a friend (proportion neutral or not recommending rose from 30% to 42%, p < 0.0001; 7.9% to 16.9%). CONCLUSION: Despite progress in reducing hours of duty and providing induction courses, the training that hospitals and consultants provide for house officers is still unsatisfactory and inconsistent with the General Medical Council's recommendations.

Preregistration house officers in eight English regions: survey of quality of training.

OBJECTIVE: To assess the quality of preregistration house officer training in eight English regions. DESIGN: Postal questionnaire. SETTING: Thames, East Anglian, Mersey, Northern, and Wessex regions. PARTICIPANTS: 1670 preregistration house officers. MAIN OUTCOME MEASURES: Education, hours of work, workload, conditions of work, and attitudes to job and medicine as a career. RESULTS: Response rate was 69% (1146 replies). Most house officers had attended induction courses (1036/1129 (92%)); 74% (757/1024) found them satisfactory. The proportions who had never received adequate guidance on how to break bad news and how to control pain were 59% (670/1135) and 56% (634/1136) respectively. There was much variation between regions. Overall, 65% (736/1138) reported confidence in performing cardiopulmonary resuscitation. Most respondents (95% (1089/1142)) worked an on call rota, 3% (36) a partial shift, and 0.6% (seven) a full shift; 19% (202) were on duty for average weekly hours that exceeded the targets for 1 April 1993. House officers had a median of 20 patients under their care and clerked a median of 10 emergency cases, six routine cases, and two day cases a week. Over half (690/1128 (61%)) could not obtain hot food after 8 pm, 20% (223/1095) did not always have clean sheets available in their on call room, and 45% (462/1036) did not consider the protection of staff against violence to be adequate at their hospital. The most important problems with the preregistration year were inappropriate or non-medical tasks (ranked first by 360 respondents), hours of work (359), and pay for out of hours work (167). Overall 57% (646/1125) would encourage a friend to apply for their post, but only 24% (266/1112) would encourage a friend to take up medicine and 44% (494/1112) would discourage the idea. CONCLUSIONS: House officers' training is deficient in important respects, with inappropriate tasks and heavy clinical workloads impeding the provision of proper education.

Aseptic arthritis associated with herpes zoster.

Arthritis associated with herpes zoster is rarely reported. We describe the clinical features of an immunocompromised 54-year-old woman who developed sterile arthritis of a knee in association with acute ipsilateral zoster of the L1/L2 dermatomes.

Survey of "do not resuscitate" orders in a district general hospital.

OBJECTIVE: To evaluate the local use of written "Do not resuscitate" orders to designate inpatients unsuitable for cardiopulmonary resuscitation in the event of cardiac arrest. DESIGN: Point prevalence questionnaire survey of inpatients' medical and nursing records. SETTING: 10 acute medical and six acute surgical wards of a district general hospital. PARTICIPANTS: Questionnaires were filled in anonymously by nurses and doctors working on the wards surveyed. MAIN OUTCOME MEASURES: Responses to questionnaire items concerning details about each patient, written orders not to resuscitate in the medical case notes and nursing records, whether prognosis had been discussed with patients' relatives, whether a "crash call" was perceived as appropriate for each patient, and whether the "crash team" would be called in the event of arrest. RESULTS: Information was obtained on 297 (93.7%) of 317 eligible patients. Prognosis had been discussed with the relatives of 32 of 88 patients perceived by doctors as unsuitable for resuscitation. Of these 88 patients, 24 had orders not to resuscitate in their medical notes, and only eight of these had similar orders in their nursing notes. CONCLUSIONS: In the absence of guidelines on decisions about resuscitation, orders not to resuscitate are rarely included in the notes of patients for whom cardiopulmonary resuscitation is thought to be inappropriate. Elective decisions not to resuscitate are not effectively communicated to nurses. There should be more discussion of patients' suitability for resuscitation between doctors, nurses, patients, and patients' relatives. Suitability for resuscitation should be reviewed on every consultant ward round.

Preregistration house officers in the four Thames regions: I. Survey of education and workload.

OBJECTIVE: To assess the education and workload of preregistration house officers in the four Thames regions. DESIGN: Postal questionnaire. SETTING: Teaching and non-teaching hospitals in the four Thames regions. PARTICIPANTS: 1064 Preregistration house officers. RESULTS: Response rate was 70% (740 replies). Nine per cent of house officers (66/729) worked a rota of one in two. The average house officer had 20.4 inpatients under his or her care and admitted 23.2 patients per week. Sixty two per cent of house officers (459/740) felt that they spent an excessive amount of time on non-medical tasks of no educational merit; 75% (546/725) had never received adequate guidance on breaking bad news and 64% (467/729) had never received adequate guidance on pain control; 34% (249/731) did not feel confident that they could perform cardiopulmonary resuscitation unsupervised. House officers would tend to recommend their post to a friend. CONCLUSIONS: There are deficiencies in preregistration training in the four Thames regions. The General Medical Council's requirements are not being heeded.

Preregistration house officers in the four Thames regions: II. Comparison of education and workload in teaching and non-teaching hospitals.

OBJECTIVE: To detect differences in the education and workload of preregistration house officers working in teaching and non-teaching hospitals. DESIGN: A postal questionnaire. SETTING: Teaching and non-teaching hospitals in the four Thames regions. PARTICIPANTS: 1064 Preregistration house officers. RESULTS: Response rate was 61% for teaching hospitals and 73% for non-teaching hospitals. House officers in teaching hospitals had significantly fewer inpatients under their care (house physicians 16.9 v 22.9, house surgeons 17.9 v 20.3) and admitted fewer emergency patients per week (house physicians 7.7 v 12.7, house surgeons 6.5 v 9.8). More house officers in teaching hospitals reported that they had too few patients to provide adequate clinical experience. More of their time was consumed by administrative activities devoid of educational value. CONCLUSION: Preregistration house officer posts at teaching hospitals provide less clinical activity and are perceived as less educationally satisfactory by their holders than those elsewhere.