Bringing together the orthodox and alternative in health care.

This paper charts the developing historical relationship between orthodox and alternative medicine in Britain, focusing on the work of health practitioners. It begins by defining the concepts of orthodox and alternative medicine, noting that this was not really a meaningful distinction until the mid-nineteenth century with the rise of the medical profession. Before this time there was a relatively undifferentiated playing field. Thereafter doctors gained state-underwritten professional standing, with alternative therapists becoming increasingly marginalised by the mid-twentieth century. However, in the wake of the medical counterculture of the 1960s and 1970s there has been growing public interest in alternative medicine coupled with an associated increase in the numbers of its practitioners, particularly in the private sector. Despite initial resistance, alternative medicine has now gained greater acceptance by medical orthodoxy. The paper concludes by considering how orthodox and alternative health care can be brought together in more integrated fashion in the future-for the benefit of the wider public.

Context effects in forensic science: a review and application of the science of science to crime laboratory practice in the United States.

This article discusses the phenomenon of "context effects" by reviewing the findings and practices of a range of scientific fields, including astronomy, physics, biology, medicine, and especially the relevant research and theory from psychology. Context information, such as expectations about what one is supposed to see or conclude, has been found to have a small but relentless impact on human perception, judgment, and decision-making. The article then considers the vulnerability of forensic science practice to context effects, and concludes by suggesting that forensic science adopt practices familiar in other fields of scientific work, in particular blind or double-blind testing and also the use of evidence line-ups.

Comparison of transvaginal ultrasound, hysteroscopy, and dilatation and curettage in the diagnosis of abnormal vaginal bleeding and intrauterine pathology in perimenopausal and postmenopausal women.

STUDY OBJECTIVE: To compare transvaginal ultrasound, hysteroscopy, and dilation and curettage (D&C) in the evaluation of women with perimenopausal and postmenopausal bleeding. DESIGN: Descriptive study (Canadian Task Force classification II-1). SETTING: Seven outpatient clinics. PATIENTS: One thousand two hundred eighty-six women. INTERVENTION: Transvaginal ultrasound, hysteroscopy, and D&C. MEASUREMENTS AND MAIN RESULTS: Of our patient population, 29 (2.26%) had a histologic diagnosis of endometrial carcinoma; in 2 of them (7.14%) endometrial thickness was 5 mm or less. In 10 women (34.5%), endometrial carcinoma was missed by hysteroscopy (sensitivity 65.52%, specificity 99.92%). Complication rate of D&C was 1.4%. CONCLUSION: In women with perimenopausal and postmenopausal bleeding neither transvaginal ultrasound nor hysteroscopy as a single diagnostic tool is suitable to rule out endometrial cancer.

The impact of jury instructions on the fusion of liability and compensatory damages.

This study examined whether special jury instructions or the bifurcation of liability and compensation decisions would counter the tendency for evidence concerning the defendant's liability to affect damages awards. Mock jurors made liability and award decisions in response to a case description in which the level of defendant responsibility for the plaintiff's injuries and the type or timing of damages instructions were systematically varied. Instructions not to discount awards for uncertainty about the defendant's fault and instructions not to increase awards to punish the defendant's carelessness reduced the impact of the defendant's conduct on awards, while bifurcation did not. Additional findings suggest, at least in the context of the present study, that discounting may be a somewhat more potent process than surcharging. Possible explanations for these effects are discussed.

The application of signal detection theory to decision-making in forensic science.

Signal Detection Theory (SDT) has come to be used in a wide variety of fields where noise and imperfect signals present challenges to the task of separating hits and correct rejections from misses and false alarms. The application of SDT helps illuminate and improve the quality of decision-making in those fields in a number of ways. The present article is designed to make SDT more accessible to forensic scientists by: (a) explaining what SDT is and how it works, (b) explicating the potential usefulness of SDT to forensic science, (c) illustrating SDT analysis using forensic science data, and (d) suggesting ways to gain the benefits of SDT analyses in the course of carrying out existing programs of quality assessment and other research on forensic science examinations.

tRNA leucine identity and recognition sets.

Transfer RNAs (tRNAs) are grouped into two classes based on the structure of their variable loop. In Escherichia coli, tRNAs from three isoaccepting groups are classified as type II. Leucine tRNAs comprise one such group. We used both in vivo and in vitro approaches to determine the nucleotides that are required for tRNA(Leu) function. In addition, to investigate the role of the tRNA fold, we compared the in vivo and in vitro characteristics of type I tRNA(Leu) variants with their type II counterparts.A minimum of six conserved tRNA(Leu) nucleotides were required to change the amino acid identity and recognition of a type II tRNA(Ser) amber suppressor from a serine to a leucine residue. Five of these nucleotides affect tRNA tertiary structure; the G15-C48 tertiary "Levitt base-pair" in tRNA(Ser) was changed to A15-U48; the number of nucleotides in the alpha and beta regions of the D-loop was changed to achieve the positioning of G18 and G19 that is found in all tRNA(Leu); a base was inserted at position 47n between the base-paired extra stem and the T-stem; in addition the G73 "discriminator" base of tRNA(Ser) was changed to A73. This minimally altered tRNA(Ser) exclusively inserted leucine residues and was an excellent in vitro substrate for LeuRS. In a parallel experiment, nucleotide substitutions were made in a glutamine-inserting type I tRNA (RNA(SerDelta); an amber suppressor in which the tRNA(Ser) type II extra-stem-loop is replaced by a consensus type I loop). This "type I" swap experiment was successful both in vivo and in vitro but required more nucleotide substitutions than did the type II swap. The type I and II swaps revealed differences in the contributions of the tRNA(Leu) acceptor stem base-pairs to tRNA(Leu) function: in the type I, but not the type II fold, leucine specificity was contingent on the presence of the tRNA(Leu) acceptor stem sequence. The type I and II tRNAs used in this study differed only in the sequence and structure of the variable loop. By altering this loop, and thereby possibly introducing subtle changes into the overall tRNA fold, it became possible to detect otherwise cryptic contributions of the acceptor stem sequence to recognition by LeuRS. Possible reasons for this effect are discussed.

Evolution of a transfer RNA gene through a point mutation in the anticodon.

The transfer RNA (tRNA) multigene family comprises 20 amino acid-accepting groups, many of which contain isoacceptors. The addition of isoacceptors to the tRNA repertoire was critical to establishing the genetic code, yet the origin of isoacceptors remains largely unexplored. A model of tRNA evolution, termed "tRNA gene recruitment," was formulated. It proposes that a tRNA gene can be recruited from one isoaccepting group to another by a point mutation that concurrently changes tRNA amino acid identity and messenger RNA coupling capacity. A test of the model showed that an Escherichia coli strain, in which the essential tRNAUGUThr gene was inactivated, was rendered viable when a tRNAArg with a point mutation that changed its anticodon from UCU to UGU (threonine) was expressed. Insertion of threonine at threonine codons by the "recruited" tRNAArg was corroborated by in vitro aminoacylation assays showing that its specificity had been changed from arginine to threonine. Therefore, the recruitment model may account for the evolution of some tRNA genes.

Explaining "pain and suffering" awards: the role of injury characteristics and fault attributions.

The present research explored factors thought to affect compensatory awards for non-economic harm ("pain and suffering") in personal injury cases. Experiment 1 showed that the nature and severity of the plaintiff's injury had a strong effect on perceptions of the extent of harm suffered and on award amounts. The parties' relatively active or passive roles in causing the injury affected assessments of their degree of fault, but perceived fault had little influence on awards. Experiment 2 replicated with more varied cases the strong impact of injury severity on harm perception and on awards for pain and suffering. In both studies, the disability and the mental suffering associated with injuries were stronger predictors of awards than were pain and disfigurement.

Alternative therapies: are they holistic?

This paper discusses the extent to which alternative therapies are distinctively holistic. It begins by defining what is meant by 'alternative therapies' and 'holism'. In this process, alternative medicine is contrasted with the biomedical basis of orthodox medicine; the critique of which has led to the development of contemporary notions of holistic practice. The historical background to the holistic health movement is then charted with reference to the rise of the medical profession, which has become increasingly unified around biomedicine. The largely holistic nature of alternative health care today is illustrated by case studies of specific alternative therapies and their practice contexts. However, it is argued that not every aspect of alternative medicine can be seen as holistic, nor should it be assumed that all elements of orthodox practice are non-holistic. The paper concludes by emphasizing the opportunities that exist for nurses and other allied professionals to become more involved with alternative therapies in order to extend their holistic approach to health care.

An engineered Tetrahymena tRNAGln for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression.

A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique. The construct is a modification of tRNAGln(CUA) from Tetrahymena thermophila, which naturally recognizes the stop codon UAG. Using electrophysiological studies of mutations at several sites of the nicotinic acetylcholine receptor, it is established that THG73 represents a major improvement over previous nonsense suppressors both in terms of efficiency and fidelity of unnatural amino acid incorporation. Compared with a previous tRNA used for in vivo suppression, THG73 is as much as 100-fold less likely to be acylated by endogenous synthetases of the Xenopus oocyte. This effectively eliminates a major concern of the in vivo suppression methodology, the undesirable incorporation of natural amino acids at the suppression site. In addition, THG73 is 4-10-fold more efficient at incorporating unnatural amino acids in the oocyte system. Taken together, these two advances should greatly expand the range of applicability of the in vivo nonsense suppression methodology.

Ambulatory Gynecologic Surgery

A retrospective study evaluated the feasibility and safety of operative gynecologic procedures performed in an ambulatory surgical center. Between July 1993 and December 1995, 5766 women (mean age 36.9 yrs, range 13-95 yrs) who were referred to our center underwent surgery. The most common preoperative diagnoses were dysfunctional bleeding, missed abortion, postmenopausal bleeding, cervical dysplasia, mullerian duct malformation, infertility, endometriosis, adhesions, desire for sterilization, adnexal mass, lower abdominal pain, ectopic pregnancy, and fibroids. A total of 2351 laparoscopies, 2 laparotomies, and 3415 vaginal procedures were performed. The most common procedures were dilatation and curettage, 1455; hysteroscopy, 1051; adnexal surgery, 810; tubal ligation, 679; abdominal myomectomy, 186; operative hysteroscopy, 145; and cone biopsy, 118. The duration of surgery was 10 to 210 minutes. Most patients (99.51%) were discharged between 2 and 8 hours after surgery. Only 28 (0.49%) had to be admitted to the hospital; 18 women had preoperatively planned admissions and 10 were unexpectedly admitted postoperatively. The intraoperative and postoperative complication rate was 0.50% (29). We believe that ambulatory surgery is safe and efficient with proper patient selection and when the surgeon and the anesthetist have significant expertise.

Variant minihelix RNAs reveal sequence-specific recognition of the helical tRNA(Ser) acceptor stem by E.coli seryl-tRNA synthetase.

Aminoacylation rate determinations for a series of variant RNA minihelix substrates revealed that Escherichia coli seryl-tRNA synthetase (SerRS) recognizes the 1--72 through 5--68 base pairs of the E.coli tRNA(Ser) acceptor stem with the major recognition elements clustered between positions 2--71 and 4--69. The rank order of effects of canonical base pair substitutions at each position on kcat/Km was used to assess the involvement of major groove functional groups in recognition. Conclusions based on the biochemical data are largely consistent with the interactions revealed by the refined structure of the homologous Thermus thermophilus tRNA(Ser)-SerRS complex that Cusack and colleagues report in the accompanying paper. Disruption of an end-on hydrophobic interaction between the major groove C5(H) of pyrimidine 69 and an aromatic side chain of SerRS is shown to significantly decrease kcat/Km of a minihelix substrate. This type of interaction provides a means by which proteins can recognize the binary information of 'degenerate' sequences, such as the purine-pyrimidine base pairs of tRNA(Ser). The 3--70 base pair is shown to contribute to recognition by SerRS even though it is not contacted specifically by the protein. The latter effect derives from the organization of the specific contacts that SerRS makes with the neighboring 2--71 and 4--69 acceptor stem base pairs.

Evolution of tRNA recognition systems and tRNA gene sequences.

The aminoacylation of tRNAs by the aminoacyl-tRNA synthetases recapitulates the genetic code by dictating the association between amino acids and tRNA anticodons. The sequences of tRNAs were analyzed to investigate the nature of primordial recognition systems and to make inferences about the evolution of tRNA gene sequences and the evolution of the genetic code. Evidence is presented that primordial synthetases recognized acceptor stem nucleotides prior to the establishment of the three major phylogenetic lineages. However, acceptor stem sequences probably did not achieve a level of sequence diversity sufficient to faithfully specify the anticodon assignments of all 20 amino acids. This putative bottleneck in the evolution of the genetic code may have been alleviated by the advent of anticodon recognition. A phylogenetic analysis of tRNA gene sequences from the deep Archaea revealed groups that are united by sequence motifs which are located within a region of the tRNA that is involved in determining its tertiary structure. An association between the third anticodon nucleotide (N36) and these sequence motifs suggests that a tRNA-like structure existed close to the time that amino acid-anticodon assignments were being established. The sequence analysis also revealed that tRNA genes may evolve by anticodon mutations that recruit tRNAs from one isoaccepting group to another. Thus tRNA gene evolution may not always be monophyletic with respect to each isoaccepting group.

Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells.

The nonsense codon suppression method for unnatural amino acid incorporation has been applied to intact cells and combined with electrophysiological analysis to probe structure-function relations in the nicotinic acetylcholine receptor. Functional receptors were expressed in Xenopus oocytes when tyrosine and phenylalanine derivatives were incorporated at positions 93, 190, and 198 in the binding site of the alpha subunit. Subtle changes in the structure of an individual side chain produced readily detectable changes in the function of this large channel protein. At each position, distinct features of side chain structure dominated the dose-response relation, probably by governing the agonist-receptor binding.

Laparoscopic Treatment of Benign Ovarian Dermoid Cysts

Forty-four women underwent laparoscopic surgery for treatment of 49 benign dermoid cysts in 1992 and 1993. Four patients presented with bilateral ovarian masses and one patient had two teratomas within one ovary. In the majority of cases (78.9%) the correct diagnosis was made preoperatively by pelvic examination and vaginal ultrasound. The average tumor size was 5.5 cm, ranging from 1 to 11 cm. Preservation of the ovary was achieved in most cases (40/81.6%). Uni- or bilateral adnexectomy was the treatment of choice in all postmenopausal women (5); in the remaining four patients salpingo-oophorectomy was performed due to torsion of a cyst (1), extensive adhesions (1) and large tumor size (2). CA 19-9 levels were elevated in 11 out of 20 patients, reaching a maximum value of 3,400 U/ml. No severe complications were encountered: two patients developed fever postoperatively, one of whom was suspected of having a chemical granulomatous peritonitis. We conclude that laparoscopic management of benign dermoid cysts is safe and effective and can therefore be highly recommended.

Comparison of minimally invasive surgery and laparotomy in the treatment of adnexal masses.

STUDY OBJECTIVE: To compare the outcome of laparoscopic treatment of adnexal masses with treatment by laparotomy. The procedures, their duration, and associated complications also were evaluated. DESIGN: Women were randomized to undergo either procedure based on the ward to which they were admitted. SETTING: A university teaching hospital. PATIENTS: The 192 patients were admitted with a preoperative diagnosis of adnexal mass. INTERVENTIONS: Surgical procedures were cystectomy, salpingectomy, oophorectomy, and unilateral or bilateral salpingo-oophorectomy. Organ-preserving techniques were used wherever possible. All tissue specimens were examined histologically. MEASUREMENTS AND MAIN RESULTS: The mean duration of surgery was statistically not significantly different between the groups, 96.8 minutes for minimally invasive surgery, and 116 minutes for laparotomy. Organ preservation did reach statistical significance at 65.7% and 17.2% respectively (p <0.001). Postoperative morbidity was statistically lower in patients undergoing minimally invasive procedures. Preoperative tumor marker levels did not correlate well with postoperative histology. One woman in the laparotomy group had histologically proved ovarian cancer. Minimally invasive surgery was converted to laparotomy in three patients in whom malignancy was suspected at the start of operation. CONCLUSIONS: Laparoscopic management of adnexal masses has definite advantages over laparotomy, for example, lower postoperative morbidity. In addition, intraoperative endoscopic diagnosis is highly accurate, and the frequency of unnecessary procedures is lower.

The transfer RNA identity problem: a search for rules.

Correct recognition of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases is central to the maintenance of translational fidelity. The hypothesis that synthetases recognize anticodon nucleotides was proposed in 1964 and had considerable experimental support by the mid-1970s. Nevertheless, the idea was not widely accepted until relatively recently in part because the methodologies initially available for examining tRNA recognition proved hampering for adequately testing alternative hypotheses. Implementation of new technologies has led to a reasonably complete picture of how tRNAs are recognized. The anticodon is indeed important for 17 of the 20 Escherichia coli isoaccepting groups. For many of the isoaccepting groups, the acceptor stem or position 73 (or both) is important as well.