Resistance testing debate: does it make the grade?

An overview of genotypic and phenotypic drug-resistance assays, or tests, are described. Genotypic assays identify changes in the sequence of nucleotide bases in HIV by detecting amino acid substitutions. Genotypic tests can only discern mutations already identified by researchers, and must be conducted on individuals whose viral load is a minimum of 500 copies. More sensitive tests should be available by the end of 1999. Phenotypic tests assess the ability of HIV to replicate when exposed to particular drugs, and may help researchers identify the necessary quantity of a drug to halt reproduction. Also discussed are HIV subpopulations which are often not detected by the assays, and may be resistant to certain drugs. Two clinical trials are cited, GART (Genotypic Antiretroviral Resistance Testing) and VIRADAPT, which observed benefits from conducting genotypic testing. A glossary of terms used in the article is provided.     

Riedel's lobe of the liver: Fact or fiction?

Riedel's lobe should be considered in all patients undergoing cross-sectional imaging. It may harbor a lesion that might not be demonstrated unless the most inferior aspect of the liver is imaged. We have tried to identify the prevalence of Riedel's lobe in a series of patients with normal abdominopelvic computed tomographic (CT) findings. We reviewed the digital CT data of 105 patients, ages 20–89 years, to define the position of the liver in relation to the costal margin and the iliac crest. There were no significant differences in the prevalence of Riedel's lobe between sexes. The proportion of individuals in whom the most caudal margin of the liver was inferior to the most caudal costal margin was age-dependent and increased to 65% in the 50–59 age group. The craniocaudal dimension of the liver decreased with age (P < 0.02). Riedel's lobe appears to be a common variant of normal anatomy, its prevalence being dependent on age-related changes in liver size and skeletal shape. Clin. Anat. 11:47–49, 1998. © 1998 Wiley-Liss, Inc.     

Ambulatory paediatrics: does it work?

To determine whether a paediatric ambulatory assessment service is an effective and acceptable replacement for an inpatient unit. Analysis of hospital paediatric medical admissions. Postal questionnaire survey of local general practitioners. Telephone survey of parents of children who had attended the ambulatory service. Rural General Hospital in Northern Ireland. General practitioners. Parents of children referred to assessment service. Number of paediatric medical hospital admissions from the local area before and after the introduction of an ambulatory assessment service. General practitioner satisfaction levels. Parental satisfaction levels. Since the introduction of the new service in April 1996 there has been a marked progressive reduction in paediatric medical hospital admissions from the local area. By the third year of operation of the ambulatory service (1998/99), a 47% reduction in admissions was recorded, compared to the 1995/96 baseline year. The response rate to the general practitioner questionnaire was 65% (37 of 57) of whom most (31, 84%) found the service beneficial. Of the 37 respondents, 31 had referred patients to the service. The majority of these general practitioners (30, 97%) reported that the service was easy to access, and the same proportion felt that requests for consultation were met promptly. Most felt that feedback was appropriate (29, 94%). A telephone survey of 50 parents showed that most were either very satisfied (38, 76%), or satisfied (11, 22%) with the service. Most parents (41, 82%) felt their child had benefited by not being admitted to hospital. Most (46, 92%) felt they had received adequate information regarding their child's illness. A paediatric ambulatory assessment unit can reduce the number of children admitted to hospital and meet the needs of children, their families and general practitioners.     

Patient-practitioner agreement: does it matter?

BACKGROUND: Good communication is a crucial clinical skill. Previous research demonstrated better clinical outcomes when practitioners and patients agree about the nature of patients' core presenting complaints. We investigated the nature of this agreement and its impact on outcome among depressed primary care patients. METHOD: We compared presenting problem formulations completed by patients, GPs and therapists in a primary care randomized controlled trial of cognitive-behavioural therapy and non-directive counselling for depression. Participants compiled formulations from a list of 13 potential problems of self-completed questionnaires. Subjects scored at least 14 on the Beck Depression Inventory (BDI) at baseline. Outcome measure for this study included BDI at 4 and 12 months, failure to attend for therapy when referred, dropout from therapy and patient satisfaction. RESULTS: Among 464 trial patients, 395 received therapy. Patient baseline problem formulations included significantly more items than GPs, who identified significantly more items than therapists. Agreement levels varied according to a range of patient and professional variables. While patients in complete agreement with their therapists about their main problem after assessment had lower average BDI scores at 12 months (9.7 v. 12.8, P=0.03); we found no other significant associations between the extent of agreement and clinical outcome. There were significant (but relatively weak) associations between agreement and aspects of patient satisfaction. CONCLUSION: Our results suggest that detailed mutual understanding of the presenting complaints may be less important than agreement that the core problem is psychological, and that referral for psychological therapy is appropriate.     

Toll‐like receptor signalling on Tregs: to suppress or not to suppress?

To balance self-tolerance and immunity against pathogens or tumours, the immune system depends on both activation mechanisms and down-regulatory mechanisms. Immunologists have long been focusing on activation mechanisms, and a major breakthrough was the identification of the Toll-like receptor (TLR) family of proteins. TLRs recognize conserved molecular patterns present on pathogens, including bacteria, viruses, fungi and protozoa. Pathogen recognition via TLRs activates the innate as well as the adaptive immune response. The discovery of a suppressive T-cell subset that constitutively expresses the interleukin (IL)-2 receptor alpha-chain (CD25) has boosted efforts to investigate the negative regulation of immune responses. It is now well appreciated that these regulatory T cells (Tregs) play a pivotal role in controlling immune function. Interestingly, recent studies revealed that TLR2 signalling affects Treg expansion and function. This review will focus on the presence and influence of different TLRs on T lymphocytes, including Tregs, and their role in cancer.     

Attenuation of shock-induced inflammation in the rat liver depends on the time of TNF-α inhibition

The relevance of tumor necrosis factor- (TNF-) inducing early inflammatory reactions in the liver after hemorrhagic shock, for example, leukocyte adhesion, has been well described. This study evaluated the anti-inflammatory effects of a monoclonal antibody against TNF- (TN3.19.12) in terms of the time of application, namely, prior to shock induction, at the time of resuscitation, and after resuscitation. The hepatic micro-circulation was investigated by intravital fluorescence microscopy in female Sprague-Dawley rats undergoing severe hemorrhagic shock for 60 min and subsequent resuscitation. TN3.19.12 or placebo was given in a randomized and blinded manner either 60 min prior to shock induction, l min prior to resuscitation, or 15 min after the onset of resuscitation. The number of firmly adherent leukocytes in the livers of treated animals depended on the time of application of TN3.19.12. Leukocyte adhesion was significantly reduced when TN3.19.12 was given prior to shock induction or at the time of resuscitation and was less effective when administered after the onset of resuscitation. The results further confirm that TNF- initiates very early pathological leukocyte adhesion in the liver 5 h following shock. Inhibition of leukocyte adhesion after shock, however, depends strongly on the time of TNF- blocking. While TN3.19.12 prior to shock induction resulted in most effective attenuation, only very early treatment allowed limitation of posttraumatically increased leukocyte adhesion.Abbreviations CO Cardiac output - HR Heart rate - IL Interleukin - MAP Mean arterial pressure - WBC White blood cells     

Unexplained infertility: does it really exist? Does it matter?

Unexplained infertility (UI) refers to a diagnosis made in couples in whom standard investigations including semen analysis, tests of ovulation and tubal patency are normal. It has been suggested that the term UI is unsustainable, as conditions such as endometriosis, tubal infertility, premature ovarian ageing and immunological infertility tend to be misdiagnosed as UI. In this debate, we present the view that, although scientifically unsatisfying, the diagnosis of UI is sustainable from a clinical and practical perspective. Given our present treatment options, further investigations leading to a more 'accurate' diagnosis is unlikely to change our management in these cases. Scientific curiosity must take second place to a more pragmatic approach, which takes into account the clinical and financial costs of making a more 'accurate' diagnosis.     

Pediatrician-parent-child communication: problem-related or not?

Pediatricians are generally confronted with a variety of health problems. Each of these problems may benefit from another pattern of healthcare communication. It is unknown whether the communication process during pediatric visits actually differs by the nature of the child's problem. This study first examined whether three formerly identified communication patterns could be distinguished within real-life pediatric outpatient encounters (N=846). Then, communication patterns during encounters with children with respiratory (n=269) or behavioral problems (n=77) were compared. Videotaped visits were observed using the Roter Interaction Analysis System. Two-level multivariate logistic regression analysis examined what factors contributed to the communication patterns. A biopsychosocial communication pattern was observed in 45%, a psychosocial in 15% and a biomedical pattern in 40% of the visits. Child's age and pediatrician's experience were related to the communication pattern. Different patterns did indeed prevail in respiratory and behavioral problems. As less experienced pediatricians attend to psychosocial issues less, they may have to be specifically encouraged to do so.