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Stephen Hales: neglected respiratory physiologist.

Stephen Hales was an eminent early 18th century scientist and minister of the parish of Teddington near London. He is well known for his early work on blood pressure. However, he made many contributions to respiratory physiology. He clarified the nature of the respiratory gases, distinguishing between their free (gaseous) and fixed (chemically combined) forms, demonstrated that rebreathing from a closed circuit could be extended if suitable gas absorbers were included (to remove carbon dioxide), suggested a similar device as a respirator for noxious atmospheres, invented the pneumatic trough for collecting gases, measured the size of the alveoli, calculated the surface area of the interior of the lung, calculated the time spent by the blood in a pulmonary capillary, invented the U-tube manometer, and measured intrathoracic pressures during normal and forced breathing. Hale's work is remarkable for its emphasis on the "statical" method, i.e., meticulous attention to detail in measurement and careful calculations. In his later life he made important contributions in the area of public health. He was a trustee of the new colony of Georgia and willed his own library of books to the colony though their whereabouts is unknown. He deserves more recognition in the history of respiratory physiology.

England↗

The inventors.

Amongst Australian anaesthetists there have been many whose ingenuity and mechanical knowledge produced ingenious devices. Lidwill and Geoffrey Kaye come immediately to mind, and their contributions are well-described elsewhere. In this paper, two inventions with contrasting fates are described: the Grant Humidifier and the Komesaroff single-use analgesia device. Graham Grant's invention addressed the problem of rain-out in a most ingenious manner The device was compact, efficient and deserved greater commercial success, but a similar apparatus developed in New Zealand was better supported and captured most of the market. Grant has a degree in engineering, acquired before his medical degree, but David Komesaroff spent only a year in the Engineering Faculty before transferring to Medicine. Nevertheless, he has remained interested and in touch with technical matters, and has a number of other devices to his credit. Mention is briefly made of others: Stokes (of the suction bullet), Bill Cole (an early volatile specific vaporiser), Fisk (the paediatric ventilator) and Noel Cass (the Cass needle) These achievements are by no means the end of the road. Already an Australian-designed single-use laryngoscope is being manufactured and launched on both the national and international markets.

Anesthesiology↗

Compliance with and accuracy of daily self-assessment of peak expiratory flows (PEF) in asthmatic subjects over a three month period.

Serial peak expiratory flow (PEF) assessment has been proposed in the clinical evaluation of asthma. In subjects attending the asthma clinic of a tertiary care hospital, we wanted to assess: 1) compliance in performing PEF; and 2) accuracy of a PEF-diary. Twenty adult asthmatic subjects, all using inhaled steroids, were asked to assess their PEF in the morning and evening with a VMX instrument (Clement Clarke Int., Colombus, OH, USA). This instrument, which incorporates a standard mini-Wright peak flow meter, stores PEF data on a computer chip. Subjects were not informed that the values were being stored. The mean duration of PEF monitoring was 89 days (range 44-131 days). For the total of 20 subjects, it was estimated that 3,482 values should have been written down and stored on the VMX computer chip. Whilst 1,897 values (54%) were written down, only 1,533 (44%) were stored, 425 values being invented. Morning and evening values were stored on 34% of days; and values were stored at least once a day on 55% of days. The values written down corresponded precisely to stored values 90% of the time, and were within +/- 20 L 94% of the time. We conclude that: 1) compliance with daily peak expiratory flow assessments is generally poor in chronic stable asthmatic subjects assessed on two visits separated by a 3 month period; and 2) a substantial percentage of values (22%) is invented. The unsatisfactory compliance with peak expiratory flow monitoring in this group of asthmatics on inhaled steroids underlines the need for similar studies on peak expiratory flow monitoring as part of an action treatment plan, and in more severe and brittle asthmatics.

Administration, Inhalation↗

A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes.

BACKGROUND: Sequencing the genomes of multiple, taxonomically diverse eukaryotes enables in-depth comparative-genomic analysis which is expected to help in reconstructing ancestral eukaryotic genomes and major events in eukaryotic evolution and in making functional predictions for currently uncharacterized conserved genes. RESULTS: We examined functional and evolutionary patterns in the recently constructed set of 5,873 clusters of predicted orthologs (eukaryotic orthologous groups or KOGs) from seven eukaryotic genomes: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe and Encephalitozoon cuniculi. Conservation of KOGs through the phyletic range of eukaryotes strongly correlates with their functions and with the effect of gene knockout on the organism's viability. The approximately 40% of KOGs that are represented in six or seven species are enriched in proteins responsible for housekeeping functions, particularly translation and RNA processing. These conserved KOGs are often essential for survival and might approximate the minimal set of essential eukaryotic genes. The 131 single-member, pan-eukaryotic KOGs we identified were examined in detail. For around 20 that remained uncharacterized, functions were predicted by in-depth sequence analysis and examination of genomic context. Nearly all these proteins are subunits of known or predicted multiprotein complexes, in agreement with the balance hypothesis of evolution of gene copy number. Other KOGs show a variety of phyletic patterns, which points to major contributions of lineage-specific gene loss and the 'invention' of genes new to eukaryotic evolution. Examination of the sets of KOGs lost in individual lineages reveals co-elimination of functionally connected genes. Parsimonious scenarios of eukaryotic genome evolution and gene sets for ancestral eukaryotic forms were reconstructed. The gene set of the last common ancestor of the crown group consists of 3,413 KOGs and largely includes proteins involved in genome replication and expression, and central metabolism. Only 44% of the KOGs, mostly from the reconstructed gene set of the last common ancestor of the crown group, have detectable homologs in prokaryotes; the remainder apparently evolved via duplication with divergence and invention of new genes. CONCLUSIONS: The KOG analysis reveals a conserved core of largely essential eukaryotic genes as well as major diversification and innovation associated with evolution of eukaryotic genomes. The results provide quantitative support for major trends of eukaryotic evolution noticed previously at the qualitative level and a basis for detailed reconstruction of evolution of eukaryotic genomes and biology of ancestral forms.

Animals↗

[Research and development of beraprost sodium, a new stable PGI2 analogue].

A novel prostaglandin I2 (PGI2) analogue, beraprost sodium, is the first launched drug as an orally active PGI2. PGI2 was discovered in 1976, and has attracted much attention as a medicine for cardiovascular diseases such as strokes and heart attacks because of its potent antiplatelet and vasodilating effect. However, PGI2 is extremely unstable for the use as practical medicines. Thus, stable PGI2 analogues have been explored by a large number of researchers in the world. Just after the discovery of PGI2, we started a research on chemically and metabolically stable PGI2 derivatives with longer duration of action and less adverse reaction. We invented a novel class of stable PGI2, 5,6,7-trinor-4,8-inter-m-phenylenePGI2 analogues that have the phenol moiety instead of the enolether moiety of PGI2. Further efforts were devoted to enhance the efficacy of the PGI2 analogues and to eliminate their side effects, and an orally active analogue, beraprost sodium, was obtained. In order to establish the synthetic route of beraprost sodium, various novel processes were invented, including ortho-selective metalation of bromoanisoles by means of Grignard reagents, copper-catalyzed SN2' cyclization to prepare cyclopenta[b]benzofuran, and stereo-selective elongation of the omega-side chain by Prins reaction. Beraprost sodium inhibit platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen and arachidonic acid. It was shown that the drug has a potent antiplatelet effect both in vitro and ex vivo in human and several animal species. In clinical studies, beraprost sodium exerted a marked effect to improve arteriosclerosis obliterans. No serious adverse effects related with the drug have been reported. It was highly evaluated as an orally active PGI2 by pharmaceutical companies overseas as well, and now clinical trials are under way in U.S.A. and Europe.

Animals↗

Patterns of spelling in young deaf and hard of hearing students.

The study examined the invented spelling abilities demonstrated by kindergarten and first-grade deaf and hard of hearing students. The study included two parts: In Part 1, the researcher compared three groups (deaf, hard of hearing, and hearing) using posttesting only on the Early Reading Screening Inventory, or ERSI (Morris, 1998), and in part 2 collected and analyzed samples of the spelling of deaf students in a Total Communication program. Analysis showed that the deaf group performed significantly differently in three areas: concept of word, word recognition, and phoneme awareness ("invented spelling"; Read, 1971). The deaf group outperformed the hearing and hard of hearing groups in concept of word and word recognition. But in phoneme awareness, the deaf group performed significantly less well than the hearing group. Therefore, the deaf group's spelling was followed for 1 year. Deaf students' spelling patterns were not the same as those of hearing and hard of hearing students. Deaf students' spelling miscues were directly related to the cueing systems of lipreading, signing, and fingerspelling.

Achievement↗

Can SEE-2 children understand ASL-using adults?

Signing Exact English or SEE-2, is one of several invented sign systems currently being used with hearing-impaired children in the United States. The system parallels the morphology of written English and differs from American Sign Language both in terms of the configuration of many of the lexical signs and in grammatical word order. The current study investigated whether students accustomed to an invented sign system could comprehend ASL signed by deaf adults. One group of subjects was exposed to SEE-2 in their day school classrooms. The other group attended residential programs and was exposed to Signed English, PSE and ASL. Both groups observed three videotaped short stories and answered questions following each. Both groups answered approximately 25 percent of the written comprehension questions correctly; their mean scores did not differ significantly. Results of the study suggest that students exposed to SEE-2 and lacking experiences with deaf adults were able to comprehend ASL as well as their peers who attended residential schools.

Adolescent↗

Intellectual property law: a primer for scientists.

Intellectual property (IP) is a generic legal term for patents, copyrights, and trademarks, which provide legal rights to protect ideas, the expression of ideas, and the inventors and creators of such ideas. A patent provides legal protection for a new invention, an application of a new idea, discovery, or concept that is useful. Copyright provides legal protection from copying for any creative work, as well as business and scientific publications, computer software, and compilations of information. A trademark provides rights to use symbols, particular words, logos, or other markings that indicate the source of a product or service. A further method of benefiting from an invention is simply to keep it secret, rather than to disclose it a trade secret. IP impinges on almost everything scientists do. As scientists are paid to come up with ideas and aspire to patent and/or publish their work, the protection of ideas and of written works especially should be of interest and concern to all.

Biochemistry↗

The human mind: building bridges between neuroscience and psychiatry.

This essay proposes the existence of four unique behavioral characteristics that distinguish Homo sapiens from its nearest evolutionary kin, the great apes. These are inventiveness, capacity for language, curiosity, and self-reflection or self-analysis. Some would counterargue that none of these features are "unique" to humans. Examples would be given of animal "intelligence" involving at times surprising problem-solving abilities. Even "conversations" between humans and parrots might be cited. However, this is to misunderstand what the focus is in the article. This is not a thesis on the continuity or discontinuities of evolution. Every well-trained biologist learns about evolution and understands that the most complex human traits have some hint of related traits in nearest relatives. Rather, the emphasis of this article has been to select and emphasize certain distinctive aspects of human behavior that are the most important features distinguishing human "uniqueness." Uniqueness may be quantified by the number and complexity of processes within the four attributes presented in this article. While this may be an interesting mathematical exercise, the author would rather take it for granted that the outcome would be that humans are significantly more complex in each of the four features referred to than the great apes. For those in the mental health field, one would hope that this overview of the most highly evolved systems in human brain may provide a useful framework where creative therapeutic processes can be applied to the ultimate beneficiary, the client or patient. This article proposes that psychosis can be considered the impossibility of conflict resolution among the special neuronal assemblies that separately mediate feelings of attachment versus abandonment, security versus anxiety, calmness versus anger, fulfillment versus helplessness, and satisfaction of sexual needs. Given this model, the role of the therapist is to consider whether the client is in touch with the various equilibrium points in their current life situation or crisis. A questionnaire designed to help access information on these internal states may work better than an oral interview because it forces the client to reflect. How much conflict does the client feel in sorting out personal priorities? Does the client have any practice at resolving internal conflicts? If unpracticed, is the client likely to act out in destructive ways to self or others to resolve the pressure of internal conflicts? I am sure that we can all think of current well-publicized destructive acts in which one has to wonder precisely what model of mind the psychotherapists were using to assist the client. At a higher level, each human has the potential to be creative. Whether expressed as curiosity about the universe and nature or inventiveness, as in improving the quality of one's life or by the use of gifted language as in art and music, the therapist needs to determine how to assist the client into these kinds of self-defined fulfillments, which one hopes will reduce the other tensions of conflict resolution. There is no doubt that the journey for both the client and therapist will be challenging. Ultimately, the journey is the reward for both the client and therapist. In closing, the following quotation seems appropriate. Sydney Brenner (2002), a pioneer in molecular biology, reviewed a current book on the Science, Politics, and Ethics of the Human Genome Project (Sulston and Ferry 2002). He states, "What I found interesting in the account is that Sulston doesn't tell us anything about the genomes he has sequenced. What did he find there that excited him? What did he learn about genes, about life, about evolution, about worlds to come? It is the play of Hamlet without Hamlet" (p. 794).

Animals↗

The quest for market exclusivity in biotechnology: navigating the patent minefield.

A patent is a legal device that grants an inventor market exclusivity over a new invention or medication. Market exclusivity can mean tremendous economic rewards for the patent holder because it provides the inventor with a monopoly over the invention for the 20-year patent term. Obtaining a patent and retaining market exclusivity can be a treacherous process, especially in the arena of biotechnology patents. Scientific, legal, and practical considerations must be carefully weighed to best protect an inventor's rights. This article explores some common patenting pitfalls as well as emerging issues that are specific to the area of biotechnology patenting.

Biotechnology↗

Montrose M. Wolf (1935-2004).

Montrose Madison Wolf, who discovered the reinforcing power of adult attention for children and based on that discovery invented and named the nonviolent parenting procedure time-out; who discovered that absent speech and social development could be artificially created with operant conditioning techniques; who first engineered a token economy into a useful motivational system; who invented the good behavior game; who orchestrated the massive research program that developed and refined the Teaching-Family Model as a residential treatment solution for delinquent development; who reinvented field observation, repeated measurement, and single-subject research methods; who introduced and named the concept of social validity; and who led the founding of the discipline of problem-solving real-world research called applied behavior analysis, died of Huntington's disease on March 19, 2004, at his home in Lawrence, Kansas.

Child↗

Bringing care to the people: Lillian Wald's legacy to public health nursing.

Lillian Wald invented public health nursing in 1893, making this year the field's centennial. One of nursing's visionaries, Wald secured reforms in health, industry, education, recreation, and housing. This historical inquiry examines three of Wald's critical experiments, each of which illuminates the past of public health nursing and its contemporary dilemmas: invention of public health nursing itself, establishment of a nationwide system of insurance payments for home-based care, and creation of a national public health nursing service.

History, 19th Century↗

Costs and benefits of genomics patents.

Genomics patents are controversial on religious, ethical, legal, and economic grounds. An economic approach is desirable for valuing the patent system generally, and genomics patents in particular, in terms of its stated constitutional objective, which is to 'promote progress'. Several types of criticisms and warnings have been issued regarding the suitability of genomics inventions for patent protection; here these are evaluated in the context of more general concerns about the efficacy of the patent system. As with the patent system more generally, it is difficult to specify an alternative mechanism for producing inventions that has attributes (such as decentralized resource allocation, speed of therapeutic discovery, and financing by beneficiaries) that are predictable enough to serve as a benchmark against which to judge the current regime, which is dominated by genomics patents. The current patent regime can be expected to produce commercializable therapies reasonably reliably, while many proposed alternatives hearken back to a regime that did not produce commercializable therapies with as great speed or variety. Therefore, the onus appears to lie on the critics to create a model with the desirable properties of the patent system, but with fewer of its acknowledged weaknesses, such as 'monopoly' pricing and 'patent thickets'.

Costs and Cost Analysis↗

The evolution of inhaler technology.

Historically, the evolution of inhalation therapy can be traced to India 4000 years ago. The antecedents of contemporary inhalation therapy, however, began in the nineteenth-century industrial age with the invention of the glass bulb nebulizer. From there, inhaler technology evolved along two pathways characterized by refinements in existent nebulizer technology and the invention of a portable inhalation device, the metered-dose inhaler (MDI). More recently, growing recognition of problems associated with MDI use (chiefly, its reliance on coordinated patient inhalation and actuation technique) led to modifications in the MDI itself with auxiliary devices (spacers) and the development of new inhaler systems--dry powdered inhalers (DPIs) and the breath-actuated metered-dose inhaler (BAI-MDI).

Asthma↗

Rene Theophile Hyacinthe Laënnec (1781-1826): the man behind the stethoscope.

Rene Theophile Hyacinthe Laënnec (1781-1826) was a French physician who, in 1816, invented the stethoscope. Using this new instrument, he investigated the sounds made by the heart and lungs and determined that his diagnoses were supported by the observations made during autopsies. Laënnec later published the first seminal work on the use of listening to body sounds, De L'auscultation Mediate (On Mediate Auscultation). Laënnec is considered the father of clinical auscultation and wrote the first descriptions of bronchiectasis and cirrhosis and also classified pulmonary conditions such as pneumonia, bronchiectasis, pleurisy, emphysema, pneumothorax, phthisis and other lung diseases from the sounds he heard with his invention. Laënnec perfected the art of physical examination of the chest and introduced many clinical terms still used today.

France↗

[Studies on treatment of fatty liver with traditional Chinese medicine].

Great progress has been made in the study of fatty liver with integrated traditional Chinese and western medicine in aspects of diagnosis, treatment and experimental study, etc. Most researches were designed to utilize diagnostic or model replicating method of western medicine to observe the effects or investigate the action mechanism of compound recipe, single Chinese herb or effective ingredients of Chinese herbs on fatty liver. According to the pathological mechanism of traditional Chinese medicine (TCM), fatty liver is characterized by deficiency in nature and repletion in appearance, which involves three Zang viscera such as liver, spleen and kidney and manifests as spleen Qi deficiency, liver and kidney deficiency, phlegm and dampness heaping internally, and Qi stagnation and blood stasis. This facilitates us to use specific recipe or modified recipe to treat fatty liver from the points of integrated traditional Chinese and western medicine and combining syndrome differentiation with disease differentiation. With gratifying achievement, this kind of approach has been the mainstream of the research on fatty liver and many researchers have reached an agreement on this point domestically. Spleen Fortifying and Blood Invigorating Recipe (SFBVER in brief, invented by our institute) can significantly improve the B ultrasound outcome of the liver in patients with fatty liver, with significant difference in B ultrasound scoring between pre-and post-treatment. It can alleviate the patients' symptoms, improve or regain liver function, decrease waist/buttocks ratio and the content of triglyceride and cholesterol in blood. SFBVER is superior to Dongbao Gantai Recipe in general effective rate. Experimental study also reveals that SFBVER can alleviate CCl(4) induced liver cell fatty degeneration and the inflammatory cell infiltration in rats, decrease the activities of ALT and AST, lower the content of triglyceride in liver, recover SOD activity in liver to normal level. The overall efficacy of SFBVER is superior to that of Dongbao Gantai Recipe. Further correlated study should be focused on inventing new preparation of traditional Chinese medicine and investigating its action mechanism with the guiding of the theory of TCM and referring to the latest discovery in fatty liver research in modern medicine.

Drug Therapy, Combination↗

[History and current state of moxibustion].

Moxibustion is an important invention of the Chinese nation, which originated as early as in the clan commune period of the primitive society. The literature records on moxibustion can be traced back to the Warring States Period (475 B.C. to 221 B.C.). Doctors through the ages made considerable progress and published a great number of books on moxibustion. Moxibustion has been applied in treating a great range of diseases. Since the 1950s, the treatment scope of moxibustion has been expanded, and the therapeutic methods of moxibustion are becoming increasingly rich and varied, and great progress in research on the mechanism of moxibustion has been made. Moxibustion was once popular in Europe after its dissemination to the West in the seventeenth century, and the practitioners invented some new methods of moxibustion. Japan is the country in the West where fruitful efforts have been made in research on moxibustion. In modern times, moxibustion has been used for health protection, and the scientists are paying great attention to the experimental research on moxibustion.

China↗

Hospitals without walls: trustees reach out to the community. Interview by Karen Gardner.

"A futurist is someone who either predicts or invents the future, and I really try to do both," says Leland R. Kaiser, Ph.D., president of Kaiser & Associates, Brighton, CO, and associate professor, University of Colorado at Denver School of Business. Kaiser--a former hospital trustee--says, "When you're inventing the future, you're using a vision of how you would like to see the organization be in the future, and then you help the organization achieve that." Kaiser concentrates on helping institutions achieve a vision that has been formed by his many years of health care and management experience as well as an extraordinary sensitivity to the needs of communities and the potential that the United States health care system has to address those needs. Futurist Kaiser recently spoke with Trustee editor Karen Gardner about his vision of health care delivery, the central role that trustees must play in order to realize that vision, and the promise of a truly community-based health care system.

Chief Executive Officers, Hospital↗