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1.
Soc Sci Med ; 332: 116103, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37506485

ABSTRACT

Mandatory COVID-19 vaccination requirements for healthcare workers in the United States, instituted at the height of the pandemic to protect vulnerable patients and preserve the infrastructure of healthcare, nonetheless met with resistance by some members of the work force. As unprecedented numbers of employees sought religious accommodations, chaplain leaders were recruited by institutional leadership to adjudicate these requests, either alone or as part of a committee. This study reports results of a survey conducted from 6/1/2022 to 7/15/2022 with U.S. healthcare chaplains (n = 76) who were involved in the evaluation of coworker requests for religious exemption to the COVID-19 vaccine anytime during the pandemic until they accessed the survey. Chaplains were recruited online through national chaplaincy and ethics organizations. A mixed methods design facilitates integration of statistically significant associations with chaplains' in-depth reflections on their experience. Surveying the religious experts on the review committee affords a rare look into how the tension between the free exercise of religion in the workplace and the obligation to protect the public played out during the pandemic. The study further addresses a gap in research literature on the experience of chaplains during the pandemic and identifies unique features of moral injury experienced by a subset of healthcare providers. Chaplains largely perceived their involvement as promoting an ethical, informed process of review. Although all chaplains found this role stressful, high levels of meaning were protective against distress. Sources of distress identified included: ethical concern that granting exemptions would lead to the spread of the virus; inconsistencies in the review process; and, repeated exposure to coworkers' misunderstanding and political use of religious teachings. Featuring prominently in comments from chaplains was the difficulty navigating requests in the context of anti-science, anti-vaccine, and politically charged public discourse.

2.
Infect Control Hosp Epidemiol ; 34(10): 1094-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24018927

ABSTRACT

OBJECTIVE: To develop and validate a partially automated algorithm to identify surgical site infections (SSIs) using commonly available electronic data to reduce manual chart review. DESIGN: Retrospective cohort study of patients undergoing specific surgical procedures over a 4-year period from 2007 through 2010 (algorithm development cohort) or over a 3-month period from January 2011 through March 2011 (algorithm validation cohort). SETTING: A single academic safety-net hospital in a major metropolitan area. PATIENTS: Patients undergoing at least 1 included surgical procedure during the study period. METHODS: Procedures were identified in the National Healthcare Safety Network; SSIs were identified by manual chart review. Commonly available electronic data, including microbiologic, laboratory, and administrative data, were identified via a clinical data warehouse. Algorithms using combinations of these electronic variables were constructed and assessed for their ability to identify SSIs and reduce chart review. RESULTS: The most efficient algorithm identified in the development cohort combined microbiologic data with postoperative procedure and diagnosis codes. This algorithm resulted in 100% sensitivity and 85% specificity. Time savings from the algorithm was almost 600 person-hours of chart review. The algorithm demonstrated similar sensitivity on application to the validation cohort. CONCLUSIONS: A partially automated algorithm to identify potential SSIs was highly sensitive and dramatically reduced the amount of manual chart review required of infection control personnel during SSI surveillance.


Subject(s)
Algorithms , Infection Control/statistics & numerical data , Population Surveillance/methods , Surgical Wound Infection/diagnosis , Automation , Humans , Retrospective Studies , Sensitivity and Specificity , Time Factors , Workload
3.
Infection ; 41(1): 135-44, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23160837

ABSTRACT

PURPOSE: Community-acquired pneumonia (CAP) is the most common infection leading to hospitalization in the USA. The objective of this study was to evaluate management practices for inpatient CAP in relation to Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines to identify opportunities for antibiotic and health care resource stewardship. METHODS: This was a retrospective cohort study of adults hospitalized for CAP at a single institution from 15 April 2008 to 31 May 2009. RESULTS: Of the 209 patients with CAP who presented to Denver Health Medical Center during the study period and were hospitalized, 166 (79 %) and 43 (21 %) were admitted to a medical ward and the intensive care unit (ICU), respectively. Sixty-one (29 %) patients were candidates for outpatient therapy per IDSA/ATS guidance with a CURB-65 score of 0 or 1 and absence of hypoxemia. Sputum cultures were ordered for 110 specimens; however, an evaluable sample was obtained in only 49 (45 %) cases. Median time from antibiotic initiation to specimen collection was 11 [interquartile range (IQR) 6-19] h, and a potential pathogen was identified in only 18 (16 %) cultures. Blood cultures were routinely obtained for both non-ICU (81 %) and ICU (95 %) cases, but 15 of 36 (42 %) positive cultures were false-positive results. The most common antibiotic regimen was ceftriaxone + azithromycin (182, 87 % cases). Discordant with IDSA/ATS recommendations, oral step-down therapy consisted of a new antibiotic class in 120 (66 %), most commonly levofloxacin (101, 55 %). Treatment durations were typically longer than suggested with a median of 10 (IQR 8-12) days. CONCLUSIONS: In this cohort of patients hospitalized for CAP, management was frequently inconsistent with IDSA/ATS guideline recommendations, revealing potential targets to reduce unnecessary antibiotic and healthcare resource utilization.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Health Resources , Inpatients , Pneumonia/diagnosis , Pneumonia/drug therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Practice Guidelines as Topic , Practice Management, Medical/standards , Retrospective Studies , Risk Factors , Treatment Outcome
4.
Child Care Health Dev ; 37(6): 852-60, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22007985

ABSTRACT

BACKGROUND: The prevalence of Type 1 diabetes is increasing with more children and adolescents being diagnosed with this chronic condition. There has been an increasing focus in recent years on the transition through adolescence and supporting young people who have chronic health conditions, with the recognition that young people are at risk of dropping out of healthcare services following transfer from paediatric to adult services. To date, there have been limited evaluations of transition models. The purpose of this study is to evaluate one such model in diabetes, the 'Transition Pathway' via interviews with young people who have experienced it first-hand. The results are discussed in terms of understanding the unique needs of adolescents with regard to psychosocial developmental theory, and what this means for healthcare providers of transition/adolescent services. METHODS: Semi-structured interviews were carried out with 11 young people, two of whom returned a year later for a second interview. Qualitative analysis of these interviews using a 'Framework' approach enabled the data to be sorted according to initial themes. Following this, further analysis enabled the identification of 'super-ordinate' or overall themes. RESULTS: Six initial themes emerged from the data. These concerned the transition pathway process, the experience and organization of transfer, organization of services, information and education, the healthcare consultation and the need for services to be inclusive of all young people's needs. From these initial themes, two overall/super-ordinate themes were identified: the need for transition services to be developmentally appropriate and to be based around individual needs. The consultation experience was central to keeping young people engaged with adolescent healthcare services. CONCLUSION: Several key elements of adolescent/transition healthcare services have been proposed, one of which is training for professionals delivering the service. This study suggests that communication skills form a vital component of such training.


Subject(s)
Adolescent Development , Child Welfare , Diabetes Mellitus, Type 1/psychology , Patient-Centered Care/methods , Transition to Adult Care , Adolescent , Age Factors , Child , Female , Humans , Interview, Psychological , Male , Psychological Theory , Qualitative Research
5.
J Antimicrob Chemother ; 61(1): 177-82, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17999973

ABSTRACT

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Osteoarthritis/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Daptomycin/administration & dosage , Drug Administration Schedule , Female , Humans , Injections, Intravenous , Male , Middle Aged , Osteoarthritis/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , Treatment Outcome
7.
J Postgrad Med ; 51(1): 23-8; discussion 28-9, 2005.
Article in English | MEDLINE | ID: mdl-15793334

ABSTRACT

BACKGROUND AND AIMS: 30-day Percutaneous endoscopic gastrostomy (PEG) mortality of 8% (1992). Recent concerns suggest that mortality may have increased, prompting a comparison of current practice with that reported earlier. MATERIALS AND METHODS: Data regarding PEG insertion with relation to case mix, complications, 30-day mortality and associated risk factors, in 2002, in a British University Hospital was compared with that in 1992. Logistic regression analysis was used to determine factors independently predictive of 30-day mortality. RESULTS: In 2002, 112 patients (70% males, mean age 67.5 years; 1992: 63.6 years) underwent PEG. The 30-day mortality increased significantly from 8% (1992) to 22% (2002), P= 0.03. During this time, PEG insertion rate increased ten-fold, however, procedure-related mortality decreased from 2% to nil. In terms of percentage, the indications for PEG in 1992 and 2002 respectively were: cerebrovascular disease (33/25), head and neck tumours (16/24), motor neuron disease (27/11, P= 0.01). The proportion of PEGs for non-evidence-based indications increased from 16% in 1992 to 31% in 2002, P= 0.048. The number of PEGs placed radiologically increased (0/17, P= 0.02). Radiological patients received less antibiotic prophylaxis (P< 0.001) and had more PEG site infections than standard placement, P= 0.04. Multivariate analysis identified nil by mouth > or = 7 days or 11.4 (CI 3.2-41.7), albumin< or = 30 g/L or 12 (2.2-66.7) and > 1 cardiac factor or 5.1 (1.02-25.6) as independent predictors of 30-day mortality. CONCLUSIONS: The ten-fold rise in the PEG insertion rate has been accompanied by a three-fold rise in 30-day mortality. This may reflect a lowered threshold of PEG insertion. The risk factors identified may help decision-making in cases where the risk-benefit relationship is not clear-cut.


Subject(s)
Gastroscopy/mortality , Gastrostomy/mortality , Aged , Enteral Nutrition , Female , Gastrostomy/methods , Humans , Male , Middle Aged , Pneumonia/complications , Risk Factors , Serum Albumin/analysis , United Kingdom , Withholding Treatment
8.
Alcohol Clin Exp Res ; 26(1): 19-27, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11821650

ABSTRACT

BACKGROUND: The purpose of the present study was to determine whether alcohol-naïve rats selectively bred for alcohol preference or nonpreference differ in alcohol withdrawal severity using two sets of rat lines selectively bred for the same phenotype. METHODS: Alcohol-naïve male rats from the high alcohol drinking (HAD1) and low alcohol drinking (LAD1) rat lines and from the alcohol preferring (P) and nonpreferring (NP) rat lines received an intragastric infusion of alcohol (4.0 g/20.3 ml/kg; 25% v/v) or an equal volume of water once a day for 10 consecutive days. Alcohol withdrawal severity was assessed at using a behavioral rating scale and a radiant heat assay measured analgesia at 10, 12, 14, 16, 18, and 24 hrs following infusion of alcohol or water on days 1, 5, and 10 of treatment. RESULTS: Data were analyzed using body weight as a co-factor to correct for differences in body weight between the HAD1/LAD1 and P/NP lines. Acute (1 day) but not repeated alcohol treatment (5 or 10 days) produced mild behavioral signs of withdrawal in LAD1 but not in HAD1 rats. HAD1 and LAD1 rats showed alcohol-induced analgesia after 1 and 5 days of alcohol treatment that disappeared by day 10 in both lines. Repeated alcohol treatment (5 days) produced mild behavioral signs of withdrawal in NP but not in P rats. Neither P nor NP rats showed alcohol-induced analgesia after 1, 5, or 10 days of alcohol treatment. CONCLUSIONS: An inverse genetic association was found between alcohol preference and severity of alcohol withdrawal in two sets of rat lines selected for the same phenotype. The pattern of alcohol withdrawal that emerged over the course of the 10 days of alcohol treatment differed between the two lines selected for low alcohol drinking (LAD1 and NP), suggesting that unique sets of genes may influence alcohol withdrawal severity in the two lines.


Subject(s)
Alcohol Drinking/genetics , Substance Withdrawal Syndrome/genetics , Alcohol Drinking/blood , Animals , Male , Phenotype , Rats , Rats, Inbred Strains , Severity of Illness Index , Species Specificity , Substance Withdrawal Syndrome/blood
9.
Atherosclerosis ; 158(1): 1-12, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11500168

ABSTRACT

Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.


Subject(s)
Arteriosclerosis/physiopathology , Ascorbic Acid Deficiency/physiopathology , Ascorbic Acid/physiology , Endothelium, Vascular/physiopathology , Hyperglycemia/complications , Animals , Antioxidants/metabolism , Antioxidants/therapeutic use , Arteriosclerosis/etiology , Arteriosclerosis/prevention & control , Ascorbic Acid/therapeutic use , Ascorbic Acid Deficiency/etiology , Collagen/metabolism , Humans
10.
Evolution ; 55(1): 81-92, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11263748

ABSTRACT

Forms of reproductive isolation that act after copulation but before fertilization are potentially important components of speciation, but are studied only infrequently. We examined postmating, prezygotic reproductive isolation in three hybridizations within the Drosophila simulans species complex. We allowed females to mate only once, observed and timed all copulations, dissected a subset of the females to track the storage and retention of sperm, examined the number and hatchability of eggs laid after insemination, counted all progeny produced, and measured the longevity of mated females. Each of the three hybridizations is characterized by a different set of cryptic barriers to heterospecific fertilization. When D. simulans females mate with D. sechellia males, few heterospecific sperm are transferred, even during long copulations. In contrast, copulations of D. simulans females with D. mauritiana males are often too short to allow sperm transfer. Those that are long enough to allow insemination, however, involve the transfer of many sperm, but only a fraction of these heterospecific sperm are stored by females, who also lay fewer eggs than do D. simulans females mated with conspecific males. Finally, when D. mauritiana females mate with D. simulans males, sperm are transferred and stored in abundance, but are lost rapidly from the reproductive tract and are therefore used inefficiently. These results add considerably to the list of reproductive isolating mechanisms in this well-studied clade and possibly to the list of evolutionary processes that could contribute to their reproductive isolation.


Subject(s)
Biological Evolution , Drosophila/physiology , Fertilization , Hybridization, Genetic , Animals , Drosophila/anatomy & histology , Female , Genitalia/anatomy & histology , Life Expectancy , Male , Spermatozoa/physiology
11.
Neuropsychopharmacology ; 22(3): 240-50, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10693151

ABSTRACT

Seasonal changes in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations were assessed on multiple occasions in 103 free-ranging male rhesus macaques (Macaca mulatta). At the time of sampling subjects ranged between the ages of 2 and 6 years. CSF samples were collected between the hours of 0900 and 1600 throughout the Fall, Winter, and Spring from 1990 through 1994. Data were analyzed in a general linear mixed model with random intercepts. Results indicated that CSF 5-HIAA concentrations decreased with age. CSF 5-HIAA concentrations were significantly increased in the Fall (October and November), which is the height of the breeding season, with no evidence of differences between Winter and Spring. There was also some evidence that the seasonal variation in CSF 5-HIAA concentrations was blunted in younger, more immature subjects.


Subject(s)
Aging/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Macaca mulatta/cerebrospinal fluid , Seasons , Analysis of Variance , Animals , Male
12.
Evolution ; 54(6): 2028-37, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11209779

ABSTRACT

The postmating, prezygotic isolating mechanism known as conspecific sperm precedence (CSP) may play an important role in speciation, and understanding the mechanism of CSP is important in reconstructing its evolution. When a Drosophila simulans female mates with both a D. simulans male and a D. mauritiana male, the vast majority of her progeny are fathered by D. simulans, regardless of the order of mating. The dearth of hybrid progeny does not result from inviability of eggs fertilized by heterospecific sperm or from the relative inviability of heterospecific larvae. Instead, CSP apparently results from a prefertilization obstacle to heterospecific sperm. We identified two independent barriers to heterospecific fertilization, sperm displacement and incapacitation, whose action depends on the order of mating. When a D. simulans female mates first with a conspecific male, the seminal fluid from this mating incapacitates heterospecific sperm transferred two days later. This sperm incapacitation occurs with no change in the retention of stored sperm over time, but does not occur when the conspecific mating lasts for only 5 min. When the order of matings is reversed, the seminal fluid from the second mating physically displaces heterospecific sperm from storage, even if the conspecific copulation lasts only 5 min. Conspecific sperm are not susceptible to displacement by a second conspecific copulation, but are susceptible to interference by heterospecific sperm if the conspecific copulation is interrupted after 12 min. Curing the D. mauritiana males of their infection with the endosymbiont Wolbachia had no effect on CSP. Sperm displacement and incapacitation involve the same basic mechanisms seen in second-male sperm precedence within species, supporting the hypothesis that CSP is an evolutionary by-product of adaptations affecting sperm competition within species.


Subject(s)
Drosophila/physiology , Spermatozoa/physiology , Animals , Drosophila/anatomy & histology , Drosophila/microbiology , Female , Genitalia, Male/anatomy & histology , Male , Reproduction , Sexual Behavior, Animal/physiology , Spermatozoa/microbiology , Wolbachia/pathogenicity
13.
Nature ; 400(6743): 449-52, 1999 Jul 29.
Article in English | MEDLINE | ID: mdl-10440373

ABSTRACT

Females in almost all animal groups copulate with multiple males. This behaviour allows different males to compete for fertilization and gives females the opportunity to mediate this competition. In many animals and most insects, the second male to copulate with a female typically sires most of her offspring. In Drosophila melanogaster, this second-male sperm precedence has long been studied but, as in most species, its mechanism has remained unknown. Here we show, using labelled sperm in doubly mated females, that males can both physically displace and incapacitate stored sperm from earlier-mating males. Displacement occurs only if the second male transfers sperm to the female, and in only one of her three sperm-storage organs. Incapacitation can be caused by either fertile or spermless second males, but requires extended intervals between matings. Sperm from different males are not 'stratified' in the storage organs but mix freely. Many animal species may have multiple mechanisms of sperm competition like those observed here, and revealing these mechanisms is necessary to understand the genetic and evolutionary basis of second-male sperm precedence in animals.


Subject(s)
Drosophila/physiology , Spermatozoa/physiology , Animals , Cell Survival , Eye Color/genetics , Female , Fertilization/physiology , Green Fluorescent Proteins , Luminescent Proteins/genetics , Male , Models, Biological , Selection, Genetic , Sexual Behavior, Animal , Species Specificity
14.
Health Psychol ; 17(3): 285-9, 1998 May.
Article in English | MEDLINE | ID: mdl-9619479

ABSTRACT

Environmental stressors and stable individual differences in human behavior have both been implicated etiologically in injuries. Because stress-related injuries are difficult to study experimentally in humans, the authors examined injury incidence in a troop of 21 male and 15 female free-ranging rhesus macaques (Macaca mulatta) before, during, and after a 6-month group confinement. Individual differences in behavioral inhibition to novelty were assessed, using multiple, quantified observations of behavior by 3 independent raters during 3 previous years. Incidence and severity of medically attended injuries were ascertained from veterinary records over a 2-year study period. A 5-fold increase in the incidence of injuries was documented during confinement stress, and an interaction was found between the stressor and behavioral inhibition in the prediction of injury incidence. Highly inhibited animals had significantly higher injury rates during confinement, compared with their uninhibited peers, but equal or lower rates in the low stress periods that preceded and followed confinement. Inhibited individuals appeared to have been specifically targeted for violence during the group stressor but were protected under normative, more predictable conditions.


Subject(s)
Crowding , Inhibition, Psychological , Macaca mulatta/psychology , Stress, Psychological/complications , Violence/psychology , Accidents/statistics & numerical data , Adaptation, Psychological , Animals , Animals, Zoo/injuries , Animals, Zoo/psychology , Chi-Square Distribution , Disease Susceptibility , Female , Housing, Animal , Incidence , Macaca mulatta/injuries , Male , Population Surveillance , Social Adjustment , Temperament/classification , Trauma Severity Indices , Wounds and Injuries/epidemiology , Wounds and Injuries/etiology
15.
Nature ; 388(6643): 663-6, 1997 Aug 14.
Article in English | MEDLINE | ID: mdl-9262398

ABSTRACT

Traits that influence the interactions between males and females can evolve very rapidly through sexual selection or sexually antagonistic coevolution. Rapid change in the fertilization systems of independent populations can give rise to reproductive incompatibilities between populations, and may contribute to speciation. Here I provide evidence for cryptic reproductive divergence among three sibling species of Drosophila that leads to a form of postmating isolation. When a female mates with both a conspecific and a heterospecific male, the conspecific sperm fertilize the vast majority of the eggs, regardless of the order of the matings. Heterospecific sperm fertilize fewer eggs after these double matings than after single matings. Experiments using spermless males show that the seminal fluid of the conspecific male is largely responsible for this conspecific sperm precedence. Moreover, when two males of the same species mate sequentially with a female from a different species, a highly variable pattern of sperm precedence replaces the second-male sperm precedence that is consistently found within species. These results indicate that females mediate sperm competition, and that second-male sperm precedence is not an automatic consequence of the mechanics of sperm storage.


Subject(s)
Drosophila/physiology , Spermatozoa/physiology , Animals , Female , Fertilization , Male , Reproduction , Semen/physiology , Species Specificity
16.
Med Hypotheses ; 46(2): 119-29, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8692035

ABSTRACT

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.


Subject(s)
Arteriosclerosis/etiology , Hyperglycemia/complications , Scurvy/etiology , Animals , Arteriosclerosis/metabolism , Ascorbic Acid/metabolism , Collagen/metabolism , Diabetes Complications , Diabetes Mellitus/metabolism , Foam Cells/metabolism , Humans , Hyperglycemia/metabolism , Lipoprotein(a)/metabolism , Metaplasia , Models, Biological , Scurvy/metabolism
18.
Can J Physiol Pharmacol ; 53(4): 531-9, 1975 Aug.
Article in English | MEDLINE | ID: mdl-169974

ABSTRACT

Cell suspensions of normal adult rad adrenals have been prepared by trypsinization and incubated in Ham's nutrient mixture F10 containing horse serum, fetal calf serum, and lima bean trypsin inhibitor. In most experiments culture medium was not changed during incubation. In this system the number of cells fell to 50% after 2 days, then slowly declined to 20% after 1 month of incubation. A corticosterone (B) response was seen to as little as 5 muU of ACTH per millilitre, a concentration which is within the range found in normal rat serum. With maximal stimulation (100 mU ACTH/ml) the rate of accumulation was highest during the first 24 h then slowly decreased over the following 9 days. When in separate experiments ACTH was added after various times of incubation up to 3 weeks, there was a B response which continued for as long as 1 week after the ACTH was added; the later the time at which ACTH was added the lesser was the initial B response and the longer the lag period before a substantial response occurred. In cell suspensions in medium containing 5.0 mequiv. of K+ per litre, aldosterone content increased for approximately 24 h, then showed little or no change over the next 9 days. With increased K+ concentration, aldosterone was found in greater amounts and accumulation continued for longer periods, both without and with ACTH. This adrenal cell system appears suitable for long term study of factors affecting steroidogenesis.


Subject(s)
Adrenal Cortex Hormones/biosynthesis , Adrenal Glands/cytology , Cells, Cultured , Adrenal Glands/metabolism , Adrenocorticotropic Hormone/pharmacology , Aldosterone/metabolism , Animals , Cell Count , Corticosterone/metabolism , Culture Media , Cytological Techniques , In Vitro Techniques , Male , Potassium/pharmacology , Rats , Time Factors
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