Combining clinical judgement and statistical data in expert systems: Over-the-telephone management decisions for critical congenital heart disease in the first month of life

When a new-born baby with congenital heart disease is referred to a regional specialist centre, the transportation management is crucial but must be decided on the basis of clinical information obtained over the telephone. We consider algorithmic and naive statistical approaches to helping in this decision, and on the basis of preliminary results the relative strengths and weaknesses are discussed. A synthesised logical and probabilistic approach appears to have the best potential and could be implemented on hand-held computers.Paper presented at symposium on Computer-assisted Decision Support and Database Management in Anaesthesia, Intensive Care and Cardio-pulmonary Medicine, Rotterdam, 1988.     

Sexual harassment at work: issues and answers for health care administrators

Sexual harassment is not new to the health care industry. What is new is that recent media attention has heightened awareness that sexual harassment is illegal. This fact, coupled with the substantial liability that employers may incur if they fail to control sexual harassment, mandates the need for outlining the major issues relative to sexual harassment in today's health care setting. This article gives particular emphasis to the fact that sexual harassment can be prevented by taking a proactive stance.     

Effect of Restricted Conformational Flexibility on the Permeation of Model Hexapeptides Across Caco-2 Cell Monolayers

Purpose. To determine how restricted conformational flexibility of hexapeptides influences their cellular permeation characteristics. Methods. Linear (Ac-Trp-Ala-Gly-Gly-X-Ala-NH₂; X = Asp, Asn, Lys) and cyclic (cyclo[Trp-Ala-Gly-Gly-X-Ala]; X = Asp, Asn, Lys) hexapeptides were synthesized, and their transport characteristics were assessed using the Caco-2 cell culture model. The lipophilicities of the hexapeptides were determined using an immobilized artificial membrane. Diffusion coefficients used to calculate molecular radii were determined by NMR. Two-dimensional NMR spectroscopy, circular dichroism, and molecular dynamic simulations were used to elucidate the most favorable solution structure of the cyclic Asp-containing peptide. Results. The cyclic hexapeptides used in this study were 2–3 times more able to permeate (e.g., P_app = 9.3 ± 0.3 × 10^–8 cm/sec, X = Asp) the Caco-2 cell monolayer than were their linear analogs (e.g., P_app = 3.2 ± 0.3 × 10_–8 cm/sec, X = Asp). In contrast to the linear hexapeptides, the flux of the cyclic hexapeptides was independent of charge. The cyclic hexapeptides were shown to be more lipophilic than the linear hexapeptides as determined by their retention times on an immobilized phospholipid column. Determination of molecular radii by two different techniques suggests little or no difference in size between the linear and cyclic hexapeptides. Spectroscopic data indicate that the Asp-containing linear hexapeptide exists in a dynamic equilibrium between random coil and -turn structures while the cyclic Asp-containing hexapeptide exists in a well-defined compact amphophilic structure containing two -turns. Conclusions. Cyclization of the linear hexapeptides increased their lipophilicities. The increased permeation characteristics of the cyclic hexapeptides as compared to their linear analogs appears to be due to an increase in their flux via the transcellular route because of these increased lipophilicities. Structural analyses of the cyclic Asp-containing hexapeptide suggest that its well-defined solution structure and, specifically the existence of two -turns, explain its greater lipophilicity.     

Use of Sequentially Administered Stable Lead Isotopes to Investigate Changes in Blood Lead during Pregnancy in a Nonhuman Primate (Macaca fascicularis)

The effects of pregnancy on the flux of lead from maternal bonewere investigated in five females from a unique colony of cynomolgusmonkeys (Macaca fascicularis) which had been dosed orally withlead (approximately 1100–1300 µg Pb/kg body wt)throughout their lives (about 14 years). Through the use ofstable lead isotopes ²⁰⁴Pb, ²⁰⁶Pb, and ²⁰⁷Pb, it was possibleto differentiate between the lead contributed to blood leadfrom the skeleton and the lead contributed from the currentoral dose. Blood samples and bone biopsy samples taken before,during, and after pregnancy were analyzed for lead (total andstable isotope ratios) by thermal ionization mass spectrometry.Through the use of end-member unmixing equations, the contributionto blood of lead from maternal bone during pregnancy was estimatedand compared to the contribution of lead from maternal bonebefore pregnancy. A 29 to 56% decrease in bone lead mobilizationin the first trimester was followed by an increase in the secondand third trimesters, up to 44% over baseline levels. In onemonkey, the third-trimester increase did not reach baselinelevels. In a single low-lead monkey, a similar decrease in thefirst trimester was followed by a 60% increase in the thirdtrimester, indicating that a similar pattern of flux is seenover a wide range of lead concentrations. Analysis of maternalbone and fetal bone, brain, liver, and kidneys confirmed a substantialtransplacental transfer of endogenous lead. Lead concentrationsin fetal bone often exceeded maternal bone lead concentrations.From 7 to 39% of the lead in the fetal skeleton originated fromthe maternal skeleton.     

Phase II studies of Elsamitrucin in breast cancer, colorectal cancer, non-small cell lung cancer and ovarian cancer

PURPOSE:: To test the antitumor activity of Elsamitrucin in metastaticcancer of the breast, colon and rectum, non-small cell lungand ovary. PATIENTS AND METHODS:: Eligibility required histologically proven cancer. Patientswith colorectal or non-small cell lung cancer could not havereceived prior chemotherapy. Patients were entered if WHO PSwas 2 and organ functions were normal. Treatment consisted ofElsamitrucin 25 mg/m²/week given as a 5–10 min infusionfor at least 3–6 weekly doses. RESULTS:: One hundred and five patients entered the studies, 97 were eligible,94 are evaluable for toxicity and 75 for response. Toxicitymainly consisted of mild nausea/vomiting, and less frequentlyreversible hepatotoxicity and malaise. No objective responseswere seen. CONCLUSION:: Elsamitrucin at this dose and schedule is not an active drugin metastatic breast cancer, colorectal cancer, non-small celllung cancer or ovarian cancer. Elsamitrucin, phase II, breast, colorectum, nonsmall cell lung, ovary     

Long-lasting increase in anxiety after electrolytic lesions of the pedunculopontine tegmental nucleus.

This study examined the effect of electrolytic lesions of the pedunculopontine tegmental nucleus (PPTg) on emotionality in rats. Rats with PPTg or sham lesions were tested in the elevated plus-maze, the social interaction test, the open-field test, and the conditioned fear paradigm. Histology showed that lesions were concentrated on the caudal half of the PPTg. In the plus-maze, behavioral scores were biased toward increased "anxiety" on the 1st testing day. Five consecutive exposures to the apparatus led to marked habituation in sham-lesioned but not in PPTg-lesioned rats. On the 5th day, most indexes of emotionality indicated elevated anxiety in PPTg-lesioned rats. Increased anxiety was also found in PPTg-lesioned rats in the social interaction test. In the conditioned fear paradigm, movement suppression during the postconditioned stimulus period was found in both groups on the 1st day of extinction but only in PPTg-lesioned rats on the 2nd extinction day, indicating extinction was slower in PPTg-lesioned rats. Lesions of the caudal PPTg appear to produce long-lasting anxiety in rats.     

Use of limited color-flow duplex for a carotid screening project.

BACKGROUND: Although the efficacy of carotid endarterectomy for asymptomatic carotid stenosis has been established, no cost-effective approach for identification of these patients has yet been devised. The purpose of this study was to develop a limited carotid duplex screening examination to be utilized for the detection of asymptomatic carotid stenoses. METHODS: Carotid screening examinations employed rapid identification of the carotid bifurcation using color-flow duplex imaging and an immediate Doppler-derived velocity of the segment of the internal carotid artery with the most turbulent flow. Complete examinations were then finished using well-established protocols in our accredited vascular laboratory. A total of 512 patients were referred for complete studies based upon standard indications. Criteria for at least a 50% internal carotid artery stenosis on the complete examination was defined as a peak systolic velocity (PSV) of at least 125 cm/sec. Receiver operator characteristic (ROC) curves were then constructed to identify the optimal screening velocity criteria as compared with the final results on the complete examination. RESULTS: Five screening examinations were technically limited yielding a total of 507 patients with 1,014 carotid arteries available for analysis. Comparison of screening examinations versus complete examinations for a PSV of 125 cm/sec yielded sensitivity 86%, specificity 98%, positive predictive value (PPV) 95%, and a negative predictive value (NPV) 93%. ROC analysis identified a "cut point" of 115 cm/sec on the screening examinations to achieve sensitivity 91%, specificity 95%, PPV 89%, and NPV 96%. Time to perform screening examinations averaged 3.2 minutes per patient. Three patients had common carotid lesions not identified on the limited internal carotid screening examinations. CONCLUSIONS: Screening carotid examinations are a rapid, reliable, and relatively inexpensive method for detection of patients with asymptomatic internal carotid artery stenosis. Limited screening examinations should be developed in each vascular laboratory and utilized in high-risk patients.     

Understanding CNS remyelination: clues from developmental and regeneration biology.

A guiding principle in remyelination research has been to seek clues to its nature in developmental studies on myelination. This "recapitulation hypothesis" argues that the regenerative response involves rerunning much the same programme as occurs during the developmental process. Here we examine the extent to which current evidence supports this hypothesis and whether this is a useful conceptual framework within which to study remyelination and suggest that an equally fruitful approach is to look to regenerative processes in other tissues.     

Systematic review of antistaphylococcal antibiotic therapy in cystic fibrosis

BACKGROUND: The respiratory tract in patients with cystic fibrosis is frequently colonised with Staphylococcus aureus. There is great diversity of clinical practice in this area of cystic fibrosis. A systematic review was conducted to study the evidence relating antistaphylococcal therapy to clinical outcome in patients with cystic fibrosis. METHODS: A search strategy already evaluated for the study of the epidemiology of cystic fibrosis clinical trials was used. This yielded 3188 references from which 13 clinical trials of antistaphylococcal therapy were identified. RESULTS: Substantial heterogeneity was observed between trials. In the 13 clinical trials a total of 19 antibiotics were used to assess a wide variety of outcome measures (11 clinical, six laboratory). Both intermittent and continuous treatment strategies were used. Sputum clearance of S aureus was more frequently achieved than any other beneficial outcome. A beneficial effect on pulmonary function was rarely measured or observed. Although five randomised clinical trials were identified, the extent of heterogeneity precluded the use of meta-analysis for further synthesis of information. CONCLUSIONS: Antistaphylococcal treatment achieves sputum clearance of S aureus in patients with cystic fibrosis. Prophylactic antistaphylococcal treatment in young children with cystic fibrosis is likely to be of clinical benefit. It remains to be determined whether the use of "prophylactic" versus "intermittent" antistaphylococcal therapy in cystic fibrosis is associated with improved lung function and/or chest radiographic scores, an increase in bacterial resistance, or earlier acquisition of Pseudomonas aeruginosa. A large randomised clinical trial lasting approximately two years is urgently required to address this problem.