The use of the term vulnerability in acute care: why does it differ and what does it mean?

OBJECTIVE: Throughout health care literature, vulnerability is widely accepted as a potential issue for all patients yet the consensus on the meaning of and practical strategies to reduce or manage these 'harmful agents' in the clinical context are rarely offered. Three main themes emerge from the related literature which can be further refined into general terms of; social vulnerability--a person's basic statistical data in relation to their potential for illness; psychological vulnerability--the actual or potential harm to the identity of self and/or other emotional effects such as anxiety or stress caused by the ailment or treatment; and physical vulnerability--which refers to the actual physiological state where an individual is susceptible to further morbidity or mortality. SETTING: Acute care facilities. PRIMARY ARGUMENT: Although there is acknowledgment within the literature that individuals will experience some form of vulnerability when hospitalised, the complexity of what defines vulnerability for individuals causes further problems for patients and health professionals alike. CONCLUSIONS: This paper attempts to define vulnerability within the context of Western health care systems and raises the following issues: all states of vulnerability are accurate and appropriate in the context of the study or incidence alluded to, but further discussion and research is required to achieve a consensus to when, how, why and who is vulnerable. It is this recognition of the potentially differing classifications of vulnerability and the particular contexts that can be used that may assist nurses and other health care professionals with, not only problems associated with a patient's hospitalisation, but in the implementation of appropriate strategies to individual patient's cases.     

Intradermal capsaicin causes dose-dependent pain, allodynia, and hyperalgesia in humans.

BACKGROUND: Intradermal capsaicin is a human pain model that produces reliable pain and sensitization. This model facilitates controlled testing of analgesic efficacy via a crossover design while minimizing confounding variables in clinical pain states and retaining sufficient power with small samples. METHODS: To determine the lowest dose of capsaicin that produces consistent neurosensory measures, we administered 0.1, 1, 10, or 100 microg to healthy volunteers in a blinded manner (N = 19). Pain scores were recorded at 0, 5, 10, 15, and 60 minutes on a visual analog scale from 0 to 100. Areas and intensities of mechanical allodynia (foam brush stimulus) and pinprick hyperalgesia (von Frey test) were quantified at 15 and 60 minutes, as were flare areas. RESULTS: Capsaicin produced dose-dependent increases in spontaneous pain (p = .013), the area and intensity of mechanical allodynia (p = .006 and p < .001, respectively), the area and intensity of pinprick hyperalgesia (p = .010 and p = .014, respectively), and the flare area (p = .010). The 10 microg dose produced greater spontaneous pain than the 1 microg dose (p = .017). The 100 microg dose produced greater spontaneous pain than the 10 microg, but the difference was not statistically significant. CONCLUSION: The 10 and 100 microg capsaicin doses produced robust pain measures across a range of modalities, and lower doses produced minimal effects. Whereas most studies use 100 microg, using a lower dose is reasonable and may facilitate detection of subtle analgesic effects--particularly with nonopioid analgesics--and drugs can be tested in lower doses, minimizing adverse side effects.     

Effects of cholinergic modulation on serum insulin-like growth factor4 and its binding proteins in normal and diabetic subjects*

OBJECTIVE We wished to study alterations In serum Insulin-like growth factor-I (IGF-I) and its binding proteins in subjects with insulin dependent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation. In addition, we have Investigated whether cholinergic modulation exerts any effects on IGF-I secretion, Independently of any actions on GH secretory status. DESIGN All subjects received OH releasing hormone (GHRH) 1-44; 80 μg i.v.) alone and 60 minutes following 120mg of pyridostigmine orally or 200 mg of plrenzepine orally. The three tests were carried out In random order at least one week apart. Blood was sampled at 15-mInute Intervals over 120 minutes. PATIENTS Twelve male subjects with IDDM and no clinical evidence of complications were selected on the basis of HbA₁ levels to provide a wide range of metabolic control. SIX normal male subjects were also studied. MEASUREMENTS Serum IGF-I, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA₁ were measured before each study to provide measures of metabolic control. RESULTS Serum IGF-I and IGFBP-3 levels were significantly lower while serum IGFBP-I levels were significantly higher In the diabetic subjects. Plrenzepine had no effect on serum IGF-I, IGFBP-1 or IGFBP-3 In diabetic subjects but caused a significant Increase In serum IGF-I and IGFBP-3 levels in normal subjects. Pyridostigmine had no effect on IGF-I, IGFBP-1 or IGFBP-3 In either diabetic or normal subjects. IGFBP-1 levels were significantly correlated with fasting plasma glucose but no correlation was demonstrated between measures of diabetic control and serum IGF-I or IGFBP-3 levels In diabetic subjects, nor was there any correlation between OH responses to GHRH alone or after plrenzepine or pyridostigmine pretreatment and serum levels of IGF-I, IGFBP-1 or IGFBP-3. CONCLUSION These data confirm that subjects with IDDM have reduced serum IGF-I and IGFBP-3 and Increased IGFBP-1 levels, the latter being directly related to the fasting plasma glucose concentrations. The absence of any relation between changes In the IGF-I system and altered GH neuroregulation after cholinergic modulation suggests that changes In IGF-I are not the sole contributors to the altered GH neuroregulation which occurs In IDDM. We have also shown an acute stimulatory effect of pirenzepine on serum IGF-I and IGFBP-3 In normal subjects which Is not present in IDDM although the underlying mechanism Is unknown.     

Growth hormone deficiency and hypogonadism in a patient with multiple sclerosis

We describe the case of a 30-year-old female patient with a 7-year hisory of multiple sclerosis, who presented with an 18-month history of secondary amenorrhoea and vague symptoms which included poor sleep and impaired concentration. Endocrine investigations revealed hypogonadotrophic hypogonadism and GH deficiency, a probable consequence of a hypothalamic plaque. This is the first report of hypogonadotrophic hypogonadism and GH deficiency occuring in conjunction with multiple sclerosis. As such, it should raise suspicion of endocrine dysfunction occurring in a condition with such a vast spectrum of disability as multiple sclerosis.     

Patient and partner perceptions about preventing genital herpes transmission

Research over the past decade has provided a new understanding of genital herpes transmission and measures that can reduce transmission risk. It is unclear, however, how those affected by genital herpes access and interpret this information to make decisions about risk behaviours. This study measured how people with genital herpes and their partners perceived prevention methods, barriers and facilitating factors, and information sources. Formative evaluation was conducted, and survey data were collected from visitors to four websites (n=1849). Results suggest that the prevention messages of refraining from sex during disease outbreaks and condom use have had the greatest reach. Misconceptions about the potential role of suppressive antiviral therapy for genital herpes prevention persist among a substantial percentage of respondents. Accurate information concerning transmission between outbreaks, the effectiveness of condoms and the role of antiviral medication is critical in preventing the spread of genital herpes.     

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.      

The role of fibronectin in tumor implantation at surgical sites

Fibronectins are a family of glycoproteins with modular functional domains. They mediate cell-cell and cell-matrix interactions which are important in embryogenesis, wound healing, metastasis and other processes. We present data on the influence of fibronectin on wound implantation of a murine mammary carcinoma line, TA3Ha. Fibronectin used in these studies was derived from bovine plasma, human serum, human foreskin fibroblasts, and mouse embryo cultures. TA3Ha cells rarely form tumors in the liver of syngeneic mice when injected intravenously but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Wound implantation is markedly reduced when the cells are pre-exposed to 200 µg/ml bovine plasma fibronectin (13%, P = 0.007), human serum fibronectin (0%, P = 0.02), human cellular fibronectin (0%, P = 0.02), or mouse cellular fibronectin (0%, P = 0.04). Lung colonization is also reduced by these fibronectins. These effects are not due to a cytotoxic action of fibronectin, since intraperitoneally injected fibronectin-treated cells form ascites tumor as effectively as do control untreated cells. Local application of a solution containing 0.25 mg/ml mouse cellular fibronectin to the hepatic wound reduces the frequency of tumor implantation from 45% to 5% (1/21, P = 0.001). No tumor implantation inhibition is seen when only suspending medium or albumin in suspending medium is used. The mechanism by which topical application of fibronectin reduces hepatic wound implantation of tumor cells is unclear, but this finding raises an exciting possibility of preventing local recurrence of cancer.     

Functional evidence for a breast cancer growth suppressor gene on chromosome 17

Rearrangements or deletions of chromosome 17 are the most frequentlyobserved genetic changes identified in breast tumors. Molecularanalyses suggest that in addition to the p53 gene on 17p13.1there may be at least three other tumor suppressor genes onchromosome 17 involved in breast cancer. Regions of loss ofheterozygosity (LOH) identified on 17p13.3 and 17q12-qter occurfrequently in breast tumors, and the BRCA-1 gene has been mappedto 17q21 by genetic linkage analysis. Here we provide biologicalevidence for the presence of a growth suppressor gene(s) onchromosome 17 that results In the In vitro growth suppressionof the p53 wild-type MCF 7 breast cancer cell line. We haveIntroduced a normal chromosome 17 into MCF 7 cells by microcellmediatedchromosome transfer (MMCT), and demonstrate that cells growtharrest before 10 to 12 population doublings. In contrast, theintroduction of a normal chromosome 13 had no effect upon growthof these cells either In vitro or In vivo. These data providedirect functional evidence for the presence of a growth suppressorgene(s) on chromosome 17, which is not p53, and which may representone of several gene(s) that play a critical role in the developmentof breast cancer.     

Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen-nitrogen species

Surfactant protein A (SP-A), a member of the collectin family, selectively binds to Pneumocystis carinii and mediates interactions between pathogen and host alveolar macrophages in vitro. To test the hypothesis that mice lacking SP-A have delayed clearance of Pneumocystis organisms and enhanced lung injury, wild-type C57BL/6 (WT) and SP-A-deficient mice (SP-A(-/-)) with or without selective CD4(+)-T-cell depletion were intratracheally inoculated with Pneumocystis organisms. Four weeks later, CD4-depleted SP-A-deficient mice had developed a more severe Pneumocystis infection than CD4-depleted WT (P. carinii pneumonia [PCP] scores of 3 versus 2, respectively). Whereas all non-CD4-depleted WT mice were free of PCP, intact SP-A(-/-) mice also had evidence of increased organism burden. Pneumocystis infection in SP-A-deficient mice was associated histologically with enhanced peribronchial and/or perivascular cellularity (score of 4 versus 2, SP-A(-/-) versus C57BL/6 mice, respectively) and a corresponding increase in bronchoalveolar lavage (BAL) cell counts. Increases in SP-D content, gamma interferon, interleukin-4, interleukin-5, and tumor necrosis factor alpha in BAL fluid occurred but were attenuated in PCP-infected SP-A(-/-) mice compared to WT mice. There were increases in total BAL NO levels in both infected groups, but nitrite levels were higher in SP-A(-/-) mice, indicating a reduction in production of higher oxides of nitrogen that was also reflected in lower levels of 3-nitrotyrosine staining in the SP-A(-/-) group. We conclude that despite increases in inflammatory cells, SP-A-deficient mice infected with P. carinii exhibit an enhanced susceptibility to the organism and attenuated production of proinflammatory cytokines and reactive oxygen-nitrogen species. These data support the concept that SP-A is a local effector molecule in the lung host defense against P. carinii in vivo.