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PubMed1986

The pH dependence of proton-deuterium exchange, hydrogen production and uptake catalyzed by hydrogenases from sulfate-reducing bacteria.

Different patterns have been found in the pH dependence of hydrogenase activity with enzymes purified from different species of Desulfovibrio. With the cytoplasmic hydrogenase from Desulfovibrio baculatus strain 9974, the pH optima in H2 production and uptake were respectively 4.0 and 7.5 with a higher activity in production than in uptake. The highest D2-H+ exchange activity was found also at pH 4.0 but the optima differed for the HD and the H2 components. Both similarly rose when the pH decreased from 9.0 to 4.5, but the rate of H2 evolution slowed whereas the HD evolution continued rising till pH values around 3.0 were reached. The H2 to HD ratio at pH above 4.5 was higher than one. With the periplasmic hydrogenase from Desulfovibrio vulgaris Hildenborough, the highest exchange activity was near pH 5.5, the same value as in hydrogen production. The periplasmic hydrogenase from Desulfovibrio gigas had in contrast the same pH optimum in the exchange (7.5-8.0) as in the H2 uptake. The ratio of H2 to HD was below one for both enzymes. These different patterns may be related to functional and structural differences in the three hydrogenases so far studied, particularly in the composition of their catalytic centers.

Cytoplasm↗
PubMed1992

A randomized controlled trial of early surgery in Duchenne muscular dystrophy.

We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.

Biopsy↗
PubMed1987

Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations.

We have introduced a therapeutic alternative to exenteration for locally advanced vulvovaginal cancer using surgery for the vulvar (external genital) phase of this disease presentation, combined with radiotherapy for the internal genital phase (with adequate overlap of fields to protect surgical margins). The rationale is that this approach treats the cancer and its dual regional spread patterns, while at the same time preserving the bladder and/or rectum, and should be associated with less morbidity and mortality than exenterative surgery. This report updates our experience with a total of 48 treated cases (37 primary cases and 11 cases of recurrent disease). Of the 37 primary cases, 20 were FIGO stage III, 4 were FIGO stage IV, and 3 other cases represented "field" cancers involving vulva and/or cervix and/or vagina. Utilizing a Life Table analysis, the 5-year survival for the primary cases was 75.6%. Published FIGO survival for stage III is 32% and for stage IV 10.5%. Life Table analysis projects a 62.6% survival for recurrent cases and an overall 72% 5-year survival for all 48 cases treated. With 48 patients treated, 48 bladders and 48 rectums were at risk for surgical removal had exenteration been employed. One patient had a total pelvic exenteration for local failure, and one had a posterior exenteration for local failure. One bladder and one rectum were lost to permanent diversion because of radiation injury. Thus, 5 of these major viscera were lost of the 96 total, and 91 (94.8%) were retained. Radiation therapy and surgical details have been reviewed relevant to local control and local failure and complications. The continuing evolution of treatment modifications of all modalities will be discussed. The apparent advantages of this combined therapeutic approach over exenterative surgery include high probability of bladder and/or rectal preservation, low primary mortality, low treatment morbidity, and very good results in cancer control.

Brachytherapy↗
PubMed1988

Red cell size heterogeneity during ontogeny.

To determine the manner in which erythrocyte changes occur during ontogeny, several red cell parameters were analyzed in fetuses, newborn infants, children, and adults. Although mean cell volume (MCV) and hemoglobin F (HbF) levels decreased as expected during in utero development, the coefficient of variation of red cell size (%CV), or red cell distribution width (RDW), increased from fetuses to newborn infants. In normal adults, the %CV was 15 (RDW was 13). The %CV in fetuses at 18-24 weeks gestation was 18, and it was 21 at term birth. High values for %CV or RDW indicate significant anisocytosis. Erythropoiesis at the time of birth is not a steady-state condition. Erythrocytes of a wide variety of sizes are present, with the appearance of new small cells on a background of older, larger red cells. This increased anisocytosis suggests that these new erythrocytes do not appear to be due to a smooth, continuous evolution of red cell size, but rather to discrete, perhaps clonal, changes.

Adolescent↗
PubMed1989

The therapeutic community: exploring the boundaries.

The past 20 years have demonstrated the effectiveness of therapeutic community (TC) treatment for drug abuse as it evolved in the United States. We now better understand the influence that psychodynamic features of TC treatment have on character disorder. Best perceived as a setting designed--as society is not--to encourage and support social learning, the TC has succeeded in modifying its programs and adapting self-help methods to serve drug abusers of all kinds and abusers of all drugs. Continued evolution of the TC depends upon development of its already-demonstrated capacity to affect disordered behaviour other than drug abuse. The growth of disordered populations in the United States and increasingly in Great Britain gives urgency to such future employment. Therapeutic communities and TC-like programs for non-drug abusers already exist. But widespread use depends upon strengthening the theoretical underpinnings of TC treatment and establishing closer working relationships between TC's and mainstream medical, mental health and social service institutions.

Humans↗
PubMed1978

Behavioral marriage therapy. III. The contents of Gurman et al. may be hazardous to our health.

This paper was written as a reply to a critique of behavioral marital therapy (BMT) by Gurman, Kniskern, and Knudson (6, 7). The reply is divided into four sections. First, the paper addresses the critics' comments on the conceptual model put forth by BMT, correcting and clarifying various misconceptions, and restating some of the basic ideological principles in the behavioral model. Second, the paper discusses behavioral change techniques and technology, along with extratechnological treatment considerations. Again, misrepresentations of BMT are corrected. Third, an analysis of the literature investigating the therapeutic efficacy of BMT is reviewed, and the conclusion is reached that BMT is demonstrably effective, at least for a substantial number of mildly to moderately distressed couples. Criticisms are made of the analysis of the same literature conducted by Gurman et al. We conclude that, contrary to the spirit of the paper by Gurman et al., BMT is a viable framework for conceptualizing and treating relationship problems and that the commitment of its adherents to experimental investigation promises continued evolution, refinement, and improvement.

Behavior Therapy↗
PubMed1992

DNA content in primary tumours and lymph node metastases in colorectal adenocarcinoma.

In 18 consecutive patients operated on for colorectal carcinoma of Dukes' stage C, the DNA patterns were determined in multiple samples of the primary tumours and in all detected lymph node metastases. Single-cell microspectrophotometry on Feulgen-stained smears of fine-needle aspirates was used. When the most aggressive DNA pattern was considered representative, 12 primary tumours (67%) were designated as aneuploid. The frequency of aneuploidy among the metastases was almost the same (63%). In 15 cases (83%) the DNA patterns displayed by the metastatic lymph nodes were also found in the corresponding primary tumour, while in the remaining three cases (17%) the DNA pattern in the lymph node metastases was not seen in any of the multiple samples from the primary tumour. The observed tumour DNA heterogeneity may reflect either the multicellular origin of the tumour cells or the continuous evolution and progression of a neoplasm of unicellular origin, and may partly explain the dissimilarities between the DNA patterns of the primary tumour and the lymph node metastases. Biopsy samples from a number of metastatic lymph nodes are therefore required to ensure representativeness and to permit an adequate analysis of the prognostic role of the DNA ploidy status in lymph node metastases from colorectal cancer.

Adenocarcinoma↗
PubMed2026

Coxsackievirus A6 on the rise: epidemiology, pathogenicity, evolutionary dynamics, and antiviral strategy.

SUMMARYIn recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.

Humans↗
PubMed1992

A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia.

A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.

Adult↗
PubMed1987

Psychoanalytic contributions to psychiatric nosology: forms of masochistic behavior.

This paper summarizes the major strengths and weaknesses of current psychiatric nosology, and then discusses various forms of masochistic behavior as one illustration of how psychoanalysis can contribute to the continuing evolution of psychiatric nosology. Masochistic behavior is separated into behavior in which there is a predominantly conscious link between pleasure and pain, and behavior in which that link is predominantly unconscious. Both categories are further separated into normal and pathological forms. The current diagnostic category of dysthymic disorder is then discussed, with consideration given to the contribution that psychoanalysis can make toward the clarification and delineation of this heterogeneous diagnostic category.

Depressive Disorder↗
PubMed2025

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Animals↗
PubMed1992

The computer-based medical record: current status.

At the turn of the century, neither hospitals nor physicians routinely kept clinical records. Since then, the medical record has gradually evolved. More recently, as society and medicine have become more complex and sophisticated, inadequacies of the paper medical record have become increasingly apparent. The computer-based medical record addresses many of the deficiencies of the paper record. Meanwhile, barriers to computer-based records have decreased; hardware has become more affordable, powerful, and compact, and software has been refined. Socially, the major payers for health care are demanding verification of the effectiveness and quality of care, information that involves data-intensive research. The electronic medical record promises to improve quality of care by providing point-of-care reminder and decision support tools as well as a database for substantiating the effectiveness of care. In conjunction with the growing integration of computers into all facets of life, government agencies, computer giants, and medical organizations are currently laying the groundwork for the development of standardized elements and formats for computer-based medical information systems. As part of the continuing evolution of the medical record, we foresee these forces culminating in the computerization of the clinical record. In this review, we briefly describe the developments that led us to this conclusion and describe computer-based clinical record systems in use in two family practice settings.

Decision Support Techniques↗
PubMed1992

The Science of Unitary Human Beings: a contemporary literature review.

This literature review identifies the origins of the Science of Unitary Beings, explores definitions of the main components of the conceptual framework and highlights the latest developments in its continual evolution. Examples of how nurse researchers and practitioners have interpreted these components and latest developments are given. The author shows that rather than being an obscure and esoteric framework, the Science of Unitary Human Beings has already had a considerable influence on nursing practice, education and research in North America. A prediction is made that in years to come the framework may begin to have the same impact in the United Kingdom.

Humans↗
PubMedDate not supplied

Cancer and environment.

The attention of scientists has been directed mostly to analyze the influence of the environment on tumor induction. However, the external environment can also enhance the reactivity of the host organism towards tumors, by activating several immune mechanisms. Moreover, the host organism is the first "foreign" environment with which tumor cells come into contact in a dynamic way, characterized by a continuous evolution.

Animals↗
PubMed1992

Ig V kappa family repertoire of plasma cells derived from autoimmune MRL mice.

V kappa gene family usage was determined in the resident in vivo-activated plasma cells of individual diseased MRL mice by using in situ hybridization. In this way, the entire autoimmune repertoire could be analyzed. Autoantibody levels and extent of glomerulonephritis were also measured, so that the severity of disease could be assessed. It was found that V kappa expression was highly variable from mouse to mouse. Some animals displayed a V kappa family repertoire similar to mitogen-stimulated cells and consistent with the size of the families. These animals tended to have lower disease indices. Other animals, which had higher disease indices, displayed considerable over- or underutilization of individual V kappa families. However, no particular V kappa families were repeatedly biased in their expression, as was found at the VH level with J558. Importantly, in the 10% of animals that expressed VH J558 exclusively, four or more V kappa families were expressed and multiple antiself specificities were produced. The data are most consistent with a number of J558 genes being expanded in a variety of self-specificities. However, because only VH J558 is expressed in these sicker animals, nonspecific polyclonal activation is highly unlikely. These results underscore the continuing evolution of the autoimmune repertoire, with considerable diversity at early stages followed by a highly selected repertoire in which a potential role for nonspecific polyclonal activation is virtually excluded.

Animals↗
PubMed1991

Surgical myocardial revascularization for the 1990s.

After two decades, coronary artery surgery remains a reliable mainstay in the treatment of select patients suffering from ischemic heart disease. However, surgical myocardial revascularization has undergone continuous evolution. Several trends have emerged, including increased use of autogenous artery for bypass conduit, extending indications to include patients with poor ventricular function or following recent myocardial infarction and new techniques, such as surgical angioplasty of the left main coronary artery.

Humans↗
PubMed1991

Education and credentialing of the gynecologic laser surgeon.

Gynecologic laser surgery involves the use and understanding of a number of different wavelengths (lasers) and their delivery systems. The educated laser surgeon understands the pros and cons of all the practical wavelengths, their tissue reactions, and their safety features. The laser surgeon may use a colposcope, hysteroscope, laparoscope, or laser handpiece in surgery. Few gynecologists have acquired the necessary expertise to perform laser surgery during residency training. For this reason, attendance at courses that include hands-on laboratory experience has been mandatory. Hospitals, not course directors, credential surgeons to perform laser operations in their operating rooms. The credentialing committee of the hospital must decide which surgeons have been properly trained for laser surgery. Objective criteria have been offered in this chapter in the effort to make the task easier and more fair. As the number of laser surgeons grows, the need for training courses may decrease, because if laser surgery is learned during the residency years, the demand for postgraduate training will decrease. On the other hand, since surgical laser evolution continues, the training center will continue to offer a valuable educational experience.

Credentialing↗