Change from transrectal to transperineal ultrasound-guided prostate biopsy under local anaesthetic eliminates sepsis as a complication.

Transrectal ultrasound-guided (TRUS) biopsy of the prostate is associated with increased risk of post-procedural sepsis with associated morbidity, mortality, re-admission to hospital, and increased healthcare costs. In the study institution, active surveillance of post-procedural infection complications is performed by clinical nurse specialists for prostate cancer under the guidance of the infection prevention and control team. To protect hospital services for acute medical admissions related to the coronavirus disease 2019 (COVID-19) pandemic, TRUS biopsy services were reduced nationally, with exceptions only for those patients at high risk of prostate cancer. In the study institution, this change prompted a complete move to transperineal (TP) prostate biopsy performed in outpatients under local anaesthetic. TP biopsies eliminated the risk of post-procedural sepsis and, consequently, sepsis-related admission while maintaining a service for prostate cancer diagnosis during the COVID-19 pandemic.

Assessment of RAdiopaque Patient IDentification Stickers (RAPIDS) for patient-scan correlation in a mass casualty incident.

PURPOSE: To qualitatively assess the legibility of radiopaque patient identification stickers and their effect on image quality. These stickers are intended for use as a part of a patient registration and identification pack utilized in a mass casualty incident (MCI), to prevent errors in correlating patients with their diagnostic imaging and reports. METHODS: Four different prototype designs of stickers with radiopaque identification numbers which are legible on radiographs and CT were created. These were affixed to head and thorax phantoms and scanned using standard imaging protocols. Images were reviewed qualitatively for legibility and the presence of image degradation due to the radiopaque sticker materials using Likert scales by four radiologists and four emergency physicians. RESULTS: All four prototypes were confidently legible on forehead, shoulder and sternum on CT on topogram and reconstructed images. Sticker positioning over the temple resulted in unreliable legibility on topogram. All prototypes were confidently legible on shoulder and sternum on CT and radiographs. Significant image degradation was reported on radiographs with sticker position over the sternum. The preferred anatomic position was the forehead. CONCLUSION: In a mass casualty incident, radiopaque patient identification stickers affixed to injured patients may help to ensure confidence in the correlation between patients and their imaging. Tested prototypes were found to be easily legible without substantial degradation of image quality. Preferred anatomical position and construction material was established. Consideration should be given to addition of such radiographic identity aides to MCI patient registration packs.

Cloning, chromosomal sublocalization of the human soluble aminopeptidase P gene (XPNPEP1) to 10q25.3 and conservation of the putative proton shuttle and metal ligand binding sites with XPNPEP2.

Human soluble ("cytosolic") aminopeptidase P (hsAmP) is an aminoacylprolyl hydrolase (EC 3.4.11.9) present in all tissues yet examined. hsAmP is related in terms of catalytic specificity to an ectoenzyme, membrane aminopeptidase P (hmAmP), which is largely limited in distribution to endothelia and brush border epithelia. Although both enzymes can degrade oligopeptides having N-terminal Xaa-Pro- moieties, hsAmP and hmAmP are of relatively low sequence homology. Recently, it has been shown that the two enzymes are not products of splice variants of the same gene. How hsAmP relates to hmAmP has clinical significance in that both can inactivate bradykinin, and AmP deficiency states have been described. The hmAmP gene (XPNPEP2) is disposed at chromosome Xq25, a disposition with clear meaning in terms of inheritance of hmAmP deficiencies. To further explore similarities and differences between hsAmP and hmAmP, the present study was begun to determine the chromosomal disposition of the hsAmP gene. Here we show that the gene is sublocalized on chromosome 10q25.3. We also show that hsAmP and hmAmP contain homologous blocks of sequence common to members of the "pita bread-fold" protein family, of which Escherichia coli methionine aminopeptidase is the prototype. The prototype is known to contain a proton shuttle and five divalent metal ligands, counterparts of which we identify in the homologous blocks of sequence in both hsAmP and hmAmP and compare to E. coli aminopeptidase.

An innovative approach to the medical management of the nursing home resident: the EverCare experience.

Providing quality medical care to the frail elderly who reside permanently in nursing homes is associated with a variety of problems and impediments. This article describes the solution devised by two geriatric nurse practitioners who created a program of care called EverCare. This program, now a Health Care Financing Administration (HCFA) demonstration project, incorporates the nurse practitioner in a collaborative relationship with the primary care physician to provide early detection and intervention for myriad health and medical problems found in the nursing home population and to enhance the care of the frail elderly overall.

HIV prevalence at reception into Australian prisons, 1991-1997.

OBJECTIVE: To measure the extent and outcome of HIV antibody testing at reception into Australian prisons. DESIGN: Cross-sectional survey at reception into prison. PARTICIPANTS AND SETTING: People received into Australian prisons from 1991 to 1997. MAIN OUTCOME MEASURES: Number of people tested for HIV infection and prevalence of diagnosed HIV infection. RESULTS: In 1991-1997, HIV antibody testing was carried out for 72% of prison entrants in Australia; the percentage tested declined significantly from 76% in 1991 to 67% in 1997 (P < 0.001). In New South Wales, the percentage of entrants tested at reception into prison dropped from almost 100% in 1991-1994 to 45% in 1997, whereas in the Northern Territory, South Australia and Western Australia the extent of testing increased significantly (P < 0.001). HIV prevalence was 0.2% among people received into Australian prisons in 1991-1997, and did not differ by sex. Most people with HIV infection (242/378; 64%) received into prison in 1991-1997 had been diagnosed at a previous entry; 136 people (36% of the total number of diagnoses) were newly diagnosed at reception into prison. CONCLUSIONS: A national monitoring system in place from 1991 indicates generally high rates of HIV antibody testing and a low prevalence of HIV infection among people entering Australian prisons. In each year, people not previously known to the prison health service to have HIV infection were received into prison, indicating continuing HIV infection in the population entering Australian prisons.

Collaboration of the nurse practitioner and physician in long-term care.

Collaboration between nurse practitioners and physicians in providing clinical care is a positive contribution not only for the clinicians involved, but also for health care consumers. The resident in the long-term care environment can benefit particularly when the nurse practitioner enters the setting as a primary care provider with the physician. The history of the term "collaboration" suggests its importance to the evolution of the nurse practitioner role. However, collaboration does not occur automatically among providers; it needs to be learned, consciously approached, and protected. The critical attributes of successful collaboration and impediments to its implementation are discussed.

Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in humans.

BACKGROUND: Pulmonary endothelium has metabolic functions including the conversion of angiotensin I to angiotensin II by angiotensin-converting ectoenzyme (ACE). In this study, we have validated an indicator-dilution technique that provides estimations of dynamically perfused capillary surface area (DPCSA) in humans, and we have characterized pulmonary endothelial ACE in vivo. METHODS AND RESULTS: In 12 adults, single-pass transpulmonary (one or both lungs) hydrolysis of the specific ACE substrate 3H-benzoyl-Phe-Ala-Pro (3H-BPAP) was measured and expressed as % metabolism (%M) and v=-ln(1-M). We also calculated Amax/Km, an index of DPCSA. %M (70.1+/-3.2 vs 67.9+/-3.1) and v (1.29+/-0.14 vs 1. 20+/-0.12) were similar in both lungs and the right lung, respectively, whereas Amax/Km//body surface area decreased from 2460+/-193 to 1318+/-115 mL/min per square meter. CONCLUSIONS: Pulmonary endothelial ACE activity can be assessed in humans at the bedside by means of indicator-dilution techniques. Our data suggest homogeneous pulmonary capillary ACE concentrations and capillary transit times (tc) in both human lungs, and similar tc within the normal range of cardiac index. Amax/Km in the right lung is 54% of total Amax/Km in both lungs, suggesting that Amax/Km is a reliable and quantifiable index of DPCSA in humans.

Cloning and tissue distribution of human membrane-bound aminopeptidase P.

Complementary DNA clones encoding human membrane-bound aminopeptidase P (AmP) were isolated by reverse transcription-polymerase chain reaction (RT-PCR) of human kidney and lung poly (A)+ RNA. Comparison of the human AmP sequence to that of the pig shows significant evolutionary divergence with only 83% amino acid sequence identity between the two species. Northern hybridization analysis and RT-PCR suggests that the soluble and membrane-bound forms of human AmP are products of two distinct genes or, through alternative splicing, have different C-terminal sequences.

The orally active ET(A) receptor antagonist (+)-(S)-2-(4,6-dimethoxy-pyrimidin-2-yloxy)-3-methoxy-3,3-diphe nyl-propionic acid (LU 135252) prevents the development of pulmonary hypertension and endothelial metabolic dysfunction in monocrotaline-treated rats.

Pulmonary hypertension is associated with endothelial dysfunction that may mediate or contribute to the disease process; among those abnormalities is an increase in circulating endothelin-1 levels. We investigated the effect of the orally active endothelin A receptor antagonist LU 135252 (LU) on the development of monocrotaline (MCT)-induced pulmonary hypertension and endothelial metabolic dysfunction. Rats were assigned to four groups by receiving a single dose of MCT or saline, followed by once-daily gavage with LU (50 mg/kg) or saline for 3 weeks. Plasma immunoreactive endothelin-1 levels doubled after MCT and were unaffected by LU therapy. The MCT-induced increase in right ventricular systolic pressure (72.5 +/- 15.9 mmHg) and hypertrophy (right ventricle/[left ventricle plus septum weight]; 0.58 +/- 0.08) were reduced by LU to 42.7 +/- 8.5 mmHg (P < .01) and 0.42 +/- 0.05 (P < .01), respectively. LU, however, did not modify MCT-induced pulmonary artery medial hypertrophy. Pulmonary vascular endothelial metabolic activity was evaluated in isolated lungs by measuring endothelium-bound angiotensin-converting enzyme activity using a synthetic angiotensin-converting enzyme substrate, 3H-benzoyl-phenylalanly-glycyl-proline. MCT reduced fractional 3H-benzoyl-phenylalanly-glycyl-proline hydrolysis (0.488 +/- 0.051, P < .01) which was normalized by LU therapy (0.563 +/- 0.050). LU treatment alone had no significant effect on any of these parameters. We conclude that the endothelin A antagonist LU reduces MCT-induced pulmonary hypertension and right ventricular hypertrophy and restores endothelial metabolic function. These results support the development of endothelin antagonists for the treatment of pulmonary hypertension and associated endothelial metabolic abnormalities.

The influence of xenotransplant immunogenicity and immunosuppression on host MHC expression in the rat CNS.

During the early stages following neural transplantation, host immune responses are initiated that are not normally found in the CNS including the induction of major histocompatibility antigens (MHC I and II). Previous laboratory findings have demonstrated prolonged survival of bovine chromaffin cells (BCC) in the rat CNS following transient immunosuppression with cyclosporin A (CSA) providing chromaffin cells are isolated from highly immunogenic passenger cells. To assess the influence of passenger and chromaffin cells on host MHC I and II expression, either BCC, nonchromaffin cell adrenal constituents (NCC), or adrenal medullary endothelial cells (EC) were implanted into the host. At 2 weeks postimplantation, robust BCC survival was obtained in CSA-treated animals. This correlated with low expression of MHC I at the host-graft border and the virtual absence of MHC II. Good BCC survival with reduced MHC I expression only was seen at 6 weeks postimplantation in animals transiently immunosuppressed (4 weeks). In contrast, poor survival was seen in the EC group (even with CSA treatment). In addition, marked MHC I and II expression was found in and around these grafts at 2 weeks, and was particularly intense in EC implanted animals. The results of this study suggest that nonchromaffin passenger cells in BCC preparations, most notably endothelial cells, can induce strong immune responses even in the presence of immunosuppression. Based on MHC staining, removal of these passenger cells can reduce host responses and improve long term survival of xenogeneic chromaffin cells in the CNS.

Endopeptidase 24.11 activity in the human prostate cancer cell lines LNCaP and PPC-1.

Human endopeptidase 24.11 (EP) occurs in greatest abundance on terminally differentiated prostate cells; thus, loss of EP could mark dedifferentiation of prostate epithelium. To identify laboratory models that would permit continuous work on the biochemistry and hormonal regulation of EP, we examined the well-differentiated LNCaP and poorly differentiated PPC-1 human prostate cancer cell lines. Ultrastructural analysis revealed that LNCaP secretes electron-dense material that resembles the particulate matter of seminal plasma, which is associated with endopeptidase activity. LNCaP medium contained EP activity while PPC-1 medium did not. Whether the apparent deletion of EP from the PPC-1 cell line is characteristic of poorly differentiated prostate adenocarcinoma is not yet clear. However, it may be relevant to the carcinogenic process that EP can limit growth of lung small carcinomas by inactivating cell growth-promoting bombesin-like peptides. Because bombesin has been identified in aggressive human prostate cancers, loss of EP in PPC-1 could represent a necessary step in transformation to aggressive phenotype. The combination of LNCaP and PPC-1, which offers well-differentiated and poorly differentiated cancer phenotypes, appears well suited to studying the relevance of EP in prostate cancer biology.

Subunit interactions of endothelial nitric-oxide synthase. Comparisons to the neuronal and inducible nitric-oxide synthase isoforms.

Endothelial nitric-oxide synthase (eNOS) is comprised of two identical subunits. Each subunit has a bidomain structure consisting of an N-terminal oxygenase domain containing heme and tetrahydrobiopterin (BH4) and a C-terminal reductase domain containing binding sites for FAD, FMN, and NADPH. Each subunit is also myristoylated and contains a calmodulin (CaM)-binding site located between the oxygenase and reductase domains. In this study, wild-type and mutant forms of eNOS have been expressed in a baculovirus system, and the quaternary structure of the purified enzymes has been analyzed by low temperature SDS-PAGE. eNOS dimer formation requires incorporation of the heme prosthetic group but does not require myristoylation or CaM or BH4 binding. In order to identify domains of eNOS involved in subunit interactions, we have also expressed eNOS oxygenase and reductase domain fusion proteins in a yeast two-hybrid system. Corresponding human neuronal NOS (nNOS) and murine inducible NOS (iNOS) fusion proteins have also been expressed. Comparative analysis of NOS domain interactions shows that subunit association of eNOS and nNOS involves not only head to head interactions of oxygenase domains but also tail to tail interactions of reductase domains and head to tail interactions between oxygenase and reductase domains. In contrast, iNOS subunit association involves only oxygenase domain interactions.

Implementing strategies to decrease risk of falls in older women.

1. Seventy-three percent of older women attending a fall prevention program made at least one low cost change in either their personal behavior or living environment to decrease their likelihood of falls. 2. Older women educated in small group sessions made more fall prevention changes than those educated individually. 3. When conducting a fall prevention program, having examples of safety devices available for participants to examine enhances the presentation.

Monocyte- and cytokine-induced downregulation of angiotensin-converting enzyme in cultured human and porcine endothelial cells.

We investigated the effects of monocytes on endothelial cell (EC) ectoenzyme activity. Coculture of human aortic ECs with human monocytes (2 x 10(5) monocytes per 2-cm2 well) led to a decrease in EC angiotensin-converting enzyme (ACE) activity (64.5 +/- 3.5% of control) but not aminopeptidase N, aminopeptidase P, and 5'-nucleotidase activities. Similar results were obtained using human umbilical vein EC-human monocyte and porcine aortic EC-porcine monocyte cocultures. The decrease in ACE activity was monocyte concentration and coculture time dependent, reaching a maximum of 65% decrease in activity at 120 hours. Monocyte-mediated reduction in ACE activity did not require cell to cell contact, since exposure of ECs to conditioned medium from cocultures (CCCM) or from monocyte cultures (MCM) produced a decrease in ACE activity similar to that observed in EC-monocyte cocultures. Exogenously added tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 alpha, two known secretory products of monocytes, simulated the effects of monocytes on ACE activity. Western blot analysis revealed a decrease in the amount of ACE protein in TNF-alpha-treated and CCCM-treated ECs compared with control ECs. Both TNF-alpha and IL-1 alpha were present in CCCM and MCM but not EC-conditioned medium. Incubation of the cocultures with a mixture of neutralizing antibodies against TNF-alpha and IL-1 totally abolished the monocyte-induced decrease in ACE activity. In conclusion, monocytes decrease ACE activity in cultured ECs through the release of cytokines such as TNF-alpha and IL-1.

Hypoxia sensitive neurons in the caudal hypothalamus project to the periaqueductal gray.

Previous studies have demonstrated that the caudal hypothalamus modulates the respiratory responses to hypoxia and hypercapnia. In addition, many of the neurons in this area have a basal discharge related to the cardiac and/or respiratory cycles and are stimulated by hypoxia or hypercapnia. The purpose of the present study was to determine if these hypothalamic neurons project to a known cardiorespiratory area, the periaqueductal gray in the rat. In a first set of experiments, rhodamine-tagged microspheres were injected into the periaqueductal gray (PAG) to determine the areas of the caudal hypothalamus that project to the PAG. These studies revealed that the caudal hypothalamus sends strong ipsilateral and weak contralateral projections to the PAG. In a second set of experiments, single unit recordings were made from neurons in the caudal hypothalamus; the basal discharge of these neurons were examined with signal averaging techniques. Each neuron (n = 79) was tested for a response to inhalation of a hypoxic (10% O2) and a hypercapnic (5% CO2) gas. Antidromic activation techniques were then used to determine if neurons in the caudal hypothalamus send projections to or through the PAG. Nineteen percent (n = 15) of the hypothalamic neurons studied could be activated from the PAG; approximately 53% (n = 8) of these were excited by hypoxia and 27% (n = 4) by hypercapnia. Most of these neurons tested (42 of 64 neurons) had a basal discharge related temporally to the cardiac and/or respiratory cycles. These findings suggest that a caudal hypothalamic to periaqueductal gray projection is involved in the integrated response to hypoxia.