Experience with a Hospital Laboratory Admission Screen

A comprehensive laboratory admission screen can be instituted in any large laboratory but only in one in command of conventional technology and with the co-operation of the laboratory, medical, nursing and admitting staff.The capital equipment required is costly and subject to early obsolescence. The operating costs are initially high, but the influence of the screen on the general work load indicates that the total overall procedures ordered by the physician will be reduced in number and that over a three-year period, in an economy subject to continuous inflationary pressure, the total cost will approach what might have been expected had the screen not been instituted.By presenting, shortly after admission, a truly comprehensive laboratory profile, the total number of procedures ordered will be reduced and this reduction bears no relationship to whether or not the data supplied are medically useful.The equipment more recently available for a large admission screen is far superior, from the point of view of speed of assay and cost of maintenance and production, to the equipment that has been available to us in this study.It is believed that the unit cost of assay will continue to decline and that the principle of unsolicited testing will be expanded in the future to include procedures not presently in the profile.It is predicted that in the relatively near future almost all of the laboratory procedures that a clinician could conceivably request will have been done prior to his examination of the patient.     

Two Years of PKU Testing in California—The Role of the Laboratory

A cooperative phenylketonuria screening program involving private nongovernmental laboratories, individual physicians and local and state health departments has been in operation for two years. The system has evolved to the point where practically all newborns are tested. The accuracy of laboratory work has been verified by an ongoing evaluation program which has resulted in continual improvement in level of performance. There are two areas in which some beneficial changes might be considered. One is the reduction of costs of the testing and follow-up by increasing volume and centralization of work. The other is greater cooperation of the medical community in collecting the data necessary to evaluate the program and expedite the final diagnosis.     

Metastasizing keratoacanthomas? The difficulties in differentiating keratoacanthomas from squamous cell carcinomas

The problem in diagnosis of keratoacanthoma versus squamous cell carcinoma has been reviewed, and 13 patients are presented to illustrate the difficulties in differentiating between these two lesions. If the pathologist is in doubt, the lesion should be called "probable keratoacanthoma, but squamous cell carcinoma cannot be ruled out." We should all be aware that even the most careful pathologist, using all the information and material available, may still erroneously diagnose a lesion as a benign keratoacanthoma--one which, if inadequately treated, may metastasize or recur as a squamous cell carcinoma. Therefore, it is important for the clinician to treat most keratoacanthomas by adequate removal and close follow-up.     

A clinician's personal view of assisted reproductive technology over 35 years

This invited presentation is intended to cover clinical developments in the evolution of assisted reproductive technology (ART), a process which was attempted during the 1940's and 50's and culminated in the first fruition in 1978. The first in vitro fertilisation (IVF) child ensued following the partnership by a scientist with a focussed ambition (Nobel laureate Robert Edwards) joining with the gynaecologist who introduced laparoscopy to Britain in the late 60's (Patrick Steptoe). My journey commenced in 1976 as a clinician who became immersed in the embryological and endocrinological science, whence most progress in ART emanates, and continued into a medical directorship position from which this personal view is documented. Several clinical advances have been important developments in the understanding and management of sub-fertile patients. However evolution of the various laboratory sciences has been the major key essential to meeting both the immediate as well as the long-term needs for human reproduction. The future requires a much better understanding and control over gametogenesis and a laboratory process which much more closely duplicates intrinsic reproductive physiology, avoiding gamete and embryo exposure to the atmosphere.This invited presentation is intended to cover clinical developments in the evolution of assisted reproductive technology (ART), a process which was attempted during the 1940's and 50's and culminated in the first fruition in 1978. The first in vitro fertilisation (IVF) child ensued following the partnership by a scientist with a focussed ambition (Nobel laureate Robert Edwards) joining with the gynaecologist who introduced laparoscopy to Britain in the late 60's (Patrick Steptoe). My journey commenced in 1976 as a clinician who became immersed in the embryological and endocrinological science, whence most progress in ART emanates, and continued into a medical directorship position from which this personal view is documented. Several clinical advances have been important developments in the understanding and management of sub-fertile patients. However evolution of the various laboratory sciences has been the major key essential to meeting both the immediate as well as the long-term needs for human reproduction. The future requires a much better understanding and control over gametogenesis and a laboratory process which much more closely duplicates intrinsic reproductive physiology, avoiding gamete and embryo exposure to the atmosphere.     

Witch's chin: a progressive, three-step technique

Witch's chin is an unpleasant aesthetic defect characterized by ptosis of premental tissue and a deep submental fold, which may be exaggerated by hyperprojection of the mandible. These three elements determine the different degrees of deformity; therefore, the ideal treatment should be directed to one, two, or all three of them. Despite unanimity on the surgical approach of the defect, a large variety of techniques have been proposed by various authors. The need to use a technique suitable for different clinical pictures, characterized by a progressive surgical aggression, as usually performed in this practice, has led to standardize a technique to correct witch's chin, by means of three progressive steps, depending on the degree of deformity. The advantage of this procedure is that once a good result has been achieved, the subsequent steps may be omitted. The technique has been successfully performed in five patients, and the mean follow-up is 12 months. Figures from two representative cases are presented.     

Prolonged statin administration does not act on the cell-mediated immunity of HIV-infected dyslipidemic patients treated with a steady and effective highly active antiretroviral therapy. A two-year prospective study of statin versus fibrate administration

OBJECTIVE: To assess whether statin administration for HIV-associated hyperlipidemia has long-term effects on immune recovery (as expressed by the trend of mean CD4+ lymphocyte count), in patients on a virologically-active HAART regimen since 12 months or more. METHODS: Single-centre, open-label, prospective study of 301 hyperlipidemic patients treated with statins (99 cases, with a predominant hypercholesterolemia), fibrates (116 subjects, when hypertriglyceridemia prevailed), or a isolated dietary/exercise program (86 patients, used as a control group). Neither epidemiological nor clinical, virological, or immunological differences were detected among the three study groups at baseline. During the subsequent follow-up, patients were excluded from evaluation should virological efficacy was not maintained, and/or initial hypolipidemic therapy was modified or interrupted for any reason. RESULTS: The quarterly assessment of mean CD4+ lymphocyte count did not disclose any statistically significant difference among the three study groups, since baseline and until at least 24 consecutive months of follow-up. Our data tend to exclude relevant in vivo negative activities of statins on immune system recovery of HIV-infected individuals who undergo a virologically effective HAART treatment. CONCLUSIONS: Multiple, pleiotropic features have been attributed to both statins and fibrates, and also apparently significant effects on laboratory markers of HIV disease progression have been recently claimed or expected. Despite some preliminary in vitro and ex-vivo models, both the main hypolipidemic classes administered for the management of HIV-related dyslipidemia (both statins and fibrates) do not seem to act significantly on clinical immune response of patients successfully treated with HAART. Multifactorial pathways are expected to interact with the cell-mediated immune system of HIV-infected patients undergoing successful HAART, and further studies are needed to elucidate whether more subtle immune effects might be prompted by a long-term administration of hypolipidemic drugs in this speciasl setting.     

Literature Review of 2-D Laboratory Experiments in NAPL Flow,Transport, and Remediation

The migration of nonaqueous phase liquid (NAPL) contaminants in the subsurface results in a complex multiphase environment due in part to heterogeneity in both the soil and fluid saturations. To accurately predict the flow, transport, and remediation of NAPL contaminants, research has focused on laboratory and numerical modeling of the subsurface environment. Within this research, 2-D laboratory model are advantageous due to the fact that the capillary, viscous, and buoyancy forces found in the subsurface environment can be reproduced. Thus, they can be used to study flow and transport, test and develop remediation technologies, and verify numerical models. However, to date a comprehensive review of the 2-D experimental work has not been compiled. The review presented in this article should be of interest to geohydrologists, engineers and scientists involved in both applied and research aspects of NAPL-contaminated aquifers.     

Treatment of psoriasis with orally administered 8-methoxypsoralen and long-wavelength ultraviolet radiation.

Between May 1976 and September 1977, 51 patients with severe psoriasis were treated with orally administered 8-methoxypsoralen followed by exposure to high-intensity long-wavelength ultraviolet radiation. Clearing of psoriasis occurred in 40 patients (78%) and marked improvement in 5 (10%). Of the remaining patients three (6%), who had generalized erythroderma, failed to respond to this therapy. The mean number of treatments required for clearing was 37.5. No serious side effects were noted clinically, by ophthalmologic examination or by laboratory testing. This therapy has some advantages over conventional types of treatment now used for severe psoriasis, but also has limitations. It appears to be an effective method of treatment for ambulatory patients. Further long-term follow-up studies are required to evaluate its side effects.     

Genetic screening for the next decade: application of present and new technologies.

Molecular genetic technology is diffusing from the research laboratory to the clinical laboratory, where it has already begun to influence prenatal diagnosis and counseling. In the very near future, this technology will be applied more generally, using population-based screening strategies. Pilot programs are beginning to evaluate the technical feasibility and efficacy of recombinant DNA techniques for newborn screening follow-up. DNA-based population screening is being considered for heterozygous carriers of an autosomal recessive disorder such as cystic fibrosis in order to identify carrier couples at risk of having an affected child. We will review the current DNA methodologies in the context of three genetic disorders: sickle-cell disease, Duchenne muscular dystrophy, and cystic fibrosis. We will then consider the requirements for implementation of these new technologies. We will conclude that implementation will require two key factors: machines and people. Machines are required to automate molecular genetic procedures, which are currently personnel-intensive, so that the expense can be reduced and the procedures made more cost-effective. The people who are required are health professionals knowledgeable in the clinical aspects of the target disorders, as well as in the DNA laboratory testing. These professionals will be able to facilitate sample acquisition and information exchange among the laboratory, the primary health care provider, and the families requesting consultation.     

Computer-based Hypertension Clinic Records: A Co-operative Study

A computer-based medical record system has been developed to help with research into hypertension and the management of patients with hypertension. Standard medical records are replaced by data collection forms and case notes printed by the computer. A computer-generated document for recording information at follow-up visits contains an up-to-date summary of the important clinical features with warnings of risk factors. A blood-pressure graph and a letter for the general practitioner are produced on request. The system has been used in three clinics for two years and is being tested in general practice. Information on 900 newly-referred patients has been recorded and at present data on 30 to 40 new patients and 160 follow-up visits are added each month.     

The pathophysiology of severe falciparum malaria

By the end of the 1940s, the clinical and pathological features of severe falciparum malaria had been well described by military physicians and pathologists working in theatres of war where the disease was endemic. From that time serious efforts were made to discover the pathophysiology of the severe manifestations of malaria because an understanding of these mechanisms forms an important basis for the clinical management of affected patients. Recently, after a period of neglect, there has been a revival of interest in malaria as a subject for clinical and laboratory research. In this article, Rodney Phillips and David Warrell review aspects of that work and attempt to unravel the mysteries of the pathophysiology of severe malaria in man.     

Overlooked post-translational modifications of proteins in Plasmodium falciparum: N- and O-glycosylation -- a review

Human malignant malaria is caused by Plasmodium falciparum and accounts for almost 900,000 deaths per year, the majority of which are children and pregnant women in developing countries. There has been significant effort to understand the biology of P. falciparum and its interactions with the host. However, these studies are hindered because several aspects of parasite biology remain controversial, such as N- and O-glycosylation. This review describes work that has been done to elucidate protein glycosylation in P. falciparum and it focuses on describing biochemical evidence for N- and O-glycosylation. Although there has been significant work in this field, these aspects of parasite biochemistry need to be explored further.     

Statistical evaluation of field and laboratory investigations into applied growth regulator effects: An editorial comment

Statistical aspects of a field and laboratory investigation involving the use of plant growth regulators are described. The design and recording of a field trial on carrots are discussed, with special reference to those points where compromise is necessary between the ideal statistical arrangement and the constraints involved in a practical field trial. The results of the field trial were analysed in detail to examine the assumptions underlying the statistical methods used, and these assumptions were shown to be satisfied.The laboratory investigation included a comparison of different methods of taking samples for sugar determinations. The standard method of bulking samples from different roots was as satisfactory in practice as the more laborious method of sampling individual roots. There was more variation between samples than between different determinations on the same sample.The consequences of these results are discussed, not only in terms of this trial but also for what might be expected in other trials with plant growth regulators. The advantages of close collaboration between plant physiologist and statistician are emphasised. Editorial note: This paper has been prepared to assist potential contributors working on applied aspects of plant growth regulators. This has been inspired by the fact that a number of submitted papers dealing with growth regulator field experimentation have been unacceptable, not because of the basic rationale, but because the experimental design has not been sound enough to support the conclusions reached.     

Ecology and genetics of tropical rhizobia species

Biological nitrogen fixation (BNF) technology with special reference to Rhizobium-legume symbiosis is growing very rapidly with the hope of combatting world hunger by producing cheaper protein for animal and human consumption in the Third World. One can see rapid progress made in the biochemistry and molecular biology of symbiotic nitrogen fixation in general; however, less progress has been made on the ecological aspects despite the fact that an enormous amount of literature is available on inoculation problems and on agronomic aspects of symbiotic nitrogen fixation. So far most information on Rhizobium concerns fast-growing rhizobia and their host legume. Although it is essential that food production using BNF technology should be maximized in the Third World, the least work has been done on slow-growing rhizobia, which are generally found in tropical and sub-tropical soils. The majority of the developing countries are in tropical and sub-tropical regions. Except for R. japonicum, a microsymbiont partner of soybean (Glycine max), the majority of the slow-growing rhizobia belong to the cowpea group, and we refer to cowpea rhizobia as tropical rhizobia species. In this review we have tried to consolidate the recent progress made on ecology and genetics of tropical rhizobia. By using recombinant DNA technology techniques it is expected that super strains of rhizobia with desirable characteristics can be produced. One must evaluate the efficiency and effectiveness of these genetically manipulated laboratory strains under field conditions. In conclusion, if one aims at combatting hunger in the Third World using BNF technology, an intensive research programme on fundamental and applied aspects of tropical rhizobia species is suggested. This involves close cooperation between molecular biologists and microbial ecologists.     

The alliance in mental health care: conceptualization,evidence and clinical applications

The concept of alliance reflects the collaborative relationship between a clinician and a patient, defined as consisting of three elements: a) the agreement on the goals of treatment; b) the agreement on a task or series of tasks; c) the development of a bond. Although much of the theory and research on the alliance comes from the domain of psychotherapy, the concept is applicable to any practice involving a person seeking help and a socially sanctioned healer. An extensive research evidence suggests that the alliance (typically measured at the third or fourth session) is a robust predictor of the outcomes of various forms of psychotherapy, even when prior symptom improvement and other factors are considered. Both the clinician and the patient bring to the therapy situation different capacities to form an alliance. Factors concerning the patient include, among others, the diagnosis, attachment history and style, motivation, and needs for affiliation. However, the benefits of the alliance have been found to be mostly due to the therapist's contribution, in particular his/her facilitative interpersonal skills, including verbal fluency, communication of hope and positive expectations, persuasiveness, emotional expression; warmth, acceptance and understanding; empathy, and alliance rupture-repair responsiveness. Placebo studies have allowed to experimentally manipulate aspects of the relationship between a therapist and a patient in non-psychotherapy contexts. In these settings, two components of the relationship have emerged: an emotional one (involving being cared for and understood by the clinician) and a cognitive one (including the belief in the competence of the therapist to select and administer an effective treatment). Here we propose a model that describes three pathways through which the alliance creates benefits, named CARE (caring, attentive, real and empathic), EXPECTANCY, and SPECIFIC. Although research and clinical attention have mostly focused on the alliance between a clinician and a patient in face-to-face interactions, there is preliminary evidence concerning the alliance between patients and other clinic staff, systems of care, or the program in Internet-mediated services. These new research areas clearly require further development.     

Diagnosis of active tuberculosis in a university hospital

Active tuberculosis was diagnosed in 100 patients at Sunnybrook Medical Centre during the five-year period 1968-72. These cases were studied to find out if any delay had taken place in establishing the diagnosis and starting treatment. Delay was found most frequently when patients presented with atypical disease or when microbiological investigations were negative or misinterpreted. However, in nine patients with positive Ziehl-Neelsen smears the diagnosis was delayed more than one week. Usually such delays were caused by a failure to send specimens promptly for examination for acid-fast bacilli. Lack of communication between the laboratory and the clinician was found to be responsible for delays in starting treatment in several patients. It is essential that the clinician in a general hospital be alert to the possibility of tuberculosis and that there be close cooperation between the clinical staff and the diagnostic services.     

Cardiomyocytes from human embryonic stem cells: more than heart repair alone

One of the most-exciting and controversial discoveries of the last decade has been the isolation of embryonic stem cells from human embryos. The capacity of these cells to form all somatic cell types in the human body has captured the imagination of researcher and clinician alike, the perspectives that they represent for cell replacement therapies in multiple chronic disorders being used to justify the use of embryos for this purpose. However, there is a gradual realization that cell therapies are in the far future and some find that the other, more immediately applicable, types of research give less justification for the use of embryos. Here, cardiomyocytes derived from human embryonic stem cells are discussed. The research opportunities created by having human heart cells available routinely in the laboratory are explored and the types of questions that can be addressed are placed in the context of alternative cell and animal models.     

Dynamic modelling of high biomass density cultivation and biohydrogen production in different scales of flat plate photobioreactors

This paper investigates the scaling‐up of cyanobacterial biomass cultivation and biohydrogen production from laboratory to industrial scale. Two main aspects are investigated and presented, which to the best of our knowledge have never been addressed, namely the construction of an accurate dynamic model to simulate cyanobacterial photo‐heterotrophic growth and biohydrogen production and the prediction of the maximum biomass and hydrogen production in different scales of photobioreactors. To achieve the current goals, experimental data obtained from a laboratory experimental setup are fitted by a dynamic model. Based on the current model, two key original findings are made in this work. First, it is found that selecting low‐chlorophyll mutants is an efficient way to increase both biomass concentration and hydrogen production particularly in a large scale photobioreactor. Second, the current work proposes that the width of industrial scale photobioreactors should not exceed 0.20 m for biomass cultivation and 0.05 m for biohydrogen production, as severe light attenuation can be induced in the reactor beyond this threshold. Biotechnol. Bioeng. 2015;112: 2429–2438. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Peiodicals, Inc.     

Behavioral evaluation of microwave irradiation

Establishing safe exposure levels for microwave irradiation is important since new, more powerful emitters are developed and the potential for accidental exposure is increasing. Analysis of the behavior of exposed laboratory animals has proven to be an accurate and repeatable metric for assessing the effects of microwave irradiation. Determining the specific absorption rate (SAR) at which an animal will cease an ongoing behavior has proven useful in the development of safe exposure levels for humans. Behaviors that have been used are simple tasks, and the point at which behavior changes significantly or ceases has often been referred to as “work stoppage.” The tasks have been used to evaluate the overwhelming effects of heating produced by microwave irradiation. Both whole‐body exposures and partial‐body exposures with hotspots have been evaluated. Recent studies have suggested that microwave effects on specific cognitive aspects of behavior such as attention, learning, memory, discrimination, and time perception may occur at SAR levels far below the SARs needed to cause work stoppage. New research studies are underway to evaluate microwave‐induced cognitive effects. Bioelectromagnetics 20:64–74, 1999. Published 1999 Wiley‐Liss, Inc.     

Non-Invasive Prenatal Chromosomal Aneuploidy Testing - Clinical Experience: 100,000 Clinical Samples

Objective

As the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries. The objective of this study is to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT.

Study Design

The study includes plasma samples collected from patients with high-risk pregnancies in our CLIA–licensed, CAP-accredited laboratory between August 2012 to June 2013. Samples were assessed for trisomies 13, 18, 21 and for the presence of chromosome Y-specific DNA. Sample data and ad hoc outcome information provided by the clinician was compiled and reviewed to determine the characteristics of this patient population, as well as estimate the assay performance in a clinical setting.

Results

NIPT patients most commonly undergo testing at an average of 15 weeks, 3 days gestation; and average 35.1 years of age. The average turnaround time is 4.54 business days and an overall 1.3% not reportable rate. The positivity rate for Trisomy 21 was 1.51%, followed by 0.45% and 0.21% rate for Trisomies 18 and 13, respectively. NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age ≥35 undergoing amniocentesis. In this population 3519 patients had multifetal gestations (3.5%) with 2.61% yielding a positive NIPT result.

Conclusion

NIPT has been commercially offered for just over 2 years and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients. The accuracy and NIPT assay positivity rate are as predicted by clinical validations and the test demonstrates improvement in the current standard of care.