Incidence and risk factors for healthcare utilisation among patients discharged on outpatient parenteral antimicrobial therapy.

Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case-control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09-0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05-2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23-17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.

The dorsal skinfold chamber: A versatile tool for preclinical research in tissue engineering and regenerative medicine.

Previous human study suggested that fresh-frozen intervertebral disc allograft transplantation can relieve neurological symptoms and restore segmental kinematics. Before wide clinical application, research into the pathophysiology of the postoperative disc allograft is needed. One important question that remains to be answered in disc allografting is the healing process of the host-graft interface and the subsequent change of the endplates. With the goat model for lumbar disc allografting, histology, micro-computed tomography analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy mapping were applied to evaluate the healing of the host-graft interfaces, the remodelling of subchondral bone, and the changes of the bony and cartilaginous endplates after transplantation. It was found that healing of the host-graft interfaces started at 1.5 months and was completed at 6 months by natural remodelling. This bony remodelling was also noted in the subchondral bone area after 6 months. The bony endplate was well preserved initially, but was gradually replaced by trabecular bone afterwards; on the other hand, the cartilaginous endplate became atrophic at 6 months and nearly disappeared at the final follow-up. Collectively, after intervertebral disc allograft transplantation, bony healing and remodelling were seen which ensured the stability and mobility of the disc-transplanted segment, but the integrity of bony and cartilaginous endplates was gradually lost and nearly disappeared finally.

Lumbar intervertebral disc allograft transplantation: healing and remodelling of the bony structure.

Previous human study suggested that fresh-frozen intervertebral disc allograft transplantation can relieve neurological symptoms and restore segmental kinematics. Before wide clinical application, research into the pathophysiology of the postoperative disc allograft is needed. One important question that remains to be answered in disc allografting is the healing process of the host-graft interface and the subsequent change of the endplates. With the goat model for lumbar disc allografting, histology, micro-computed tomography analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy mapping were applied to evaluate the healing of the host-graft interfaces, the remodelling of subchondral bone, and the changes of the bony and cartilaginous endplates after transplantation. It was found that healing of the host-graft interfaces started at 1.5 months and was completed at 6 months by natural remodelling. This bony remodelling was also noted in the subchondral bone area after 6 months. The bony endplate was well preserved initially, but was gradually replaced by trabecular bone afterwards; on the other hand, the cartilaginous endplate became atrophic at 6 months and nearly disappeared at the final follow-up. Collectively, after intervertebral disc allograft transplantation, bony healing and remodelling were seen which ensured the stability and mobility of the disc-transplanted segment, but the integrity of bony and cartilaginous endplates was gradually lost and nearly disappeared finally.

MicroRNA-21 promotes proliferation of rat hepatocyte BRL-3A by targeting FASLG.

Rat liver regeneration (RLR) induced by partial hepatectomy involves cell proliferation regulated by numerous factors, including microRNAs (miRNAs). miRNA high-throughput sequencing has been established and used to analyze miRNA expression profiles. This study showed that 39 miRNAs were related to RLR through the analysis of miRNA high-throughput sequencing. Their role toward rat normal hepatocyte line BRL-3A was studied by gain- and loss-of-function analyses, and one of them, microRNA-21 (miR-21), obviously upregulated and promoted BRL-3A cell proliferation. Using bioinformatics to search for miR-21 targets revealed that Fas ligand (FASLG) is one of miR-21's target genes. A dual-luciferase report assay and Western blot assay showed that miR-21 directly targeted the 3'-untranslated region of FASLG and inhibited the expression of FASLG, which suggests that miR-21 promoted BRL-3A cell proliferation by reducing FASLG expression.

A cluster of chilblains in Hong Kong.

OBJECTIVE: To report a recent clustering of chilblain cases in Hong Kong. DESIGN: Case series. SETTING: A regional hospital and a social hygiene clinic in the New Territories West, Hong Kong. PATIENTS: Patients with a clinical diagnosis of chilblains in February 2008. RESULTS: Eleven patients with chilblains were identified; seven (64%) gave an antecedent history of prolonged exposure to cold. They all presented with erythematous or dusky erythematous skin lesions affecting the distal extremities, especially fingers and toes. Laboratory tests revealed elevated antinuclear antibodies titres in two, positive rheumatoid factor in two, presence of cold agglutinins in one, and a raised anti-DNA titre (>300 IU/mL) in one. Skin biopsies were performed in six patients, four of them showed typical histopathological features of chilblains. In the patient with systemic lupus erythematosus, features of vasculitis were suspected, and in the one with pre-existing juvenile rheumatoid arthritis, there were features of livedo vasculitis. In 10 (91%) of the patients, the skin lesions had resolved when they were last assessed (at the end of March 2008), but had persisted in the patient who had pre-existing systemic lupus erythematosus. CONCLUSION: The recent clustering of chilblains was possibly related temporally to the prolonged cold weather at the end of January to mid-February. In our series, most of the patients developed chilblains as an isolated condition and resolved spontaneously within a few weeks. Laboratory tests and skin biopsies for chilblains are not necessary, unless the condition persists, the diagnosis in doubt or an underlying systemic disease is suspected.

Conventional muscle-reflection approach versus mini-incision muscle-splitting approach in dynamic hip screw fixation.

PURPOSE: To compare the short-term results of conventional versus mini-incision approaches to dynamic hip screw (DHS) fixation. METHODS: 41 geriatric patients with either basal femoral neck or intertrochanteric fractures (Kyle types I to III) who underwent closed reduction and DHS fixation by a single surgeon were retrospectively reviewed. From January 2001 to June 2005, 6 men and 19 women aged 60 to 94 (median, 83) years underwent DHS fixation through a conventional muscle-reflection approach with a skin incision of 10 cm or more. From July 2005 to March 2006, 9 men and 7 women aged 67 to 95 (median, 81) years underwent DHS fixation through a mini-incision (4 cm) approach at the lower border of the lesser trochanter. Operating time, drain output and duration of drain placement, decrease in haemoglobin level and receipt of blood transfusions, deterioration in ambulation status, analgesic intake, duration of hospital stay, and bone healing time for the 2 groups were compared. An independent observer retrospectively assessed the fracture pattern, reduction quality, and bone healing time. RESULTS: Compared to patients in the conventional group, those in the mini-incision group had shorter operating times (50 vs 43 minutes, p=0.02), a higher proportion whose drain was removed within 24 hours (28% vs 69%, p=0.01), and consumed fewer dosages of oral analgesics within 48 hours (8 vs 5, p=0.001). Classification of the fracture pattern in 21 of 38 patients were consistent between the surgeon and observer. The Kappa value for agreement was 0.32, denoting marginal agreement (p=0.003). Reduction quality (p=0.66) and bone healing time (p=0.73) assessed by the observer were not significantly different between the 2 groups. CONCLUSION: The short-term clinical outcome of mini-incision DHS fixation for geriatric pertrochanteric fractures was favourable.

Selective induction of apoptosis in Hep 3B cells by topoisomerase I inhibitors: evidence for a protease-dependent pathway that does not activate cysteine protease P32.

Progress in the treatment of hepatocellular carcinoma (HCC), a common tumor worldwide, has been disappointing. Inhibitors of topoisomerases are being widely studied as potential inducers of tumor cell apoptosis. Our aims were to determine whether topoisomerase-directed drugs would induce apoptosis in a human HCC cell line (Hep 3B) and, if so, to investigate the mechanism. The topoisomerase I poison camptothecin (CPT) induced apoptosis of Hep 3B cells in a time- and concentration-dependent manner. In contrast, the topoisomerase II poison etoposide failed to induce apoptosis despite the apparent stabilization of topoisomerase II-DNA complexes. Unexpectedly, CPT-induced apoptosis in this cell type occurred without any detectable cleavage of poly(ADP-ribose) polymerase or lamin B, polypeptides that are commonly cleaved in other cell types undergoing apoptosis. Likewise, Hep 3B cell apoptosis occurred without a detectable increase in interleukin-1beta-converting enzyme (ICE)-like or cysteine protease P32 (CPP32)-like protease activity. In contrast, trypsin-like protease activity (cleavage of Boc-Val-Leu-Lys-chloromethylaminocoumarin in situ) increased threefold in cells treated with CPT but not etoposide. Tosyl-lysyl chloromethyl ketone inhibited the trypsin-like protease activity and diminished CPT-induced apoptosis. These data demonstrate that (a) apoptosis is induced in Hep 3B cells after stabilization of topoisomerase I-DNA complexes but not after stabilization of topoisomerase II-DNA complexes as measured by alkaline filter elution; (b) Hep 3B cell apoptosis occurs without activation of ICE-like and CPP32-like protease activity; and (c) a trypsin-like protease activity appears to contribute to apoptosis in this cell type.

Expansions and contractions in a tandem repeat induced by double-strand break repair.

Repair of a double-strand break (DSB) in yeast can induce very frequent expansions and contractions in a tandem array of 375-bp repeats. These results strongly suggest that DSB repair can be a major source of amplification of tandemly repeated sequences. Most of the DSB repair events are not associated with crossover. Rearrangements appear in 50% of these repaired recipient molecules. In contrast, the donor template nearly always remains unchanged. Among the rare crossover events, similar rearrangements are found. These results cannot readily be explained by the gap repair model of Szostak et al. (J. W. Szostak, T. L. Orr-Weaver, R. J. Rothstein, and F. W. Stahl, Cell 33:25-35, 1983) but can be explained by synthesis-dependent strand annealing (SDSA) models that allow for crossover. Support for SDSA models is provided by a demonstration that a single DSB repair event can use two donor templates located on two different chromosomes.

Mismatch repair-induced meiotic recombination requires the pms1 gene product.

The presence of multiple heterologies in a 9-kilobase (kb) interval results in a decrease in meiotic crossovers from 26.0% to 10.1%. There is also an increase from 3.5% to 11.1% in gene conversions and ectopic recombinations between the flanking homologous MAT loci. The hypothesis that mismatch repair of heteroduplex DNA containing several heterologies would lead to a second round of recombination has now been tested by examining the effect of a mutation that reduces mismatch correction. The repair-defective pms1-1 allele restores the pattern of recombination to nearly that seen in congenic diploids without the heterologies. Mismatch repair-induced recombination causes a significant increase in MAT conversions and ectopic recombination events with as few as two heterozygosities separated by 0.3-0.7 kb, but not when the mismatches are separated by greater than 1 kb. The frequency of these events depends on both the number and position of the heterozygosities relative to the flanking homologous MAT loci used to detect the events. The creation of recombinogenic lesions by mismatch repair in yeast could be analogous to the creation of recombinogenic lesions in dam- Escherichia coli. We suggest that the repair of heteroduplex DNA containing multiple mismatches may produce chromosomal rearrangements and gamete inviability when naturally polymorphic chromosomes undergo meiotic recombination.

Over-expression of FoxM1 stimulates cyclin B1 expression.

FoxM1 (previously named WIN, HFH-11 or Trident) is a Forkhead box (Fox) transcription factor widely expressed in proliferating cells. Various findings, including a recent analysis of FoxM1 knockout mice, suggest that FoxM1 is required for normal S-M coupling during cell cycle progression. To study the regulatory role of FoxM1 and its downstream regulatory targets, three stably transfected HeLa lines that display doxycycline (dox)-inducible FoxM1 expression were established. Over-expression of FoxM1 by dox induction facilitates growth recovery from serum starvation. Quantitation of cyclin B1 and D1 levels using flow cytometric, Western and Northern analyses reveals that elevated FoxM1 levels lead to stimulation of cyclin B1 but not cyclin D1 expression. Transient reporter assays in the dox-inducible lines and upon co-transfection with a constitutive FoxM1 expression plasmid suggest that FoxM1 can activate the cyclin B1 promoter.

Alexa dyes, a series of new fluorescent dyes that yield exceptionally bright, photostable conjugates.

Alexa 350, Alexa 430, Alexa 488, Alexa 532, Alexa 546, Alexa 568, and Alexa 594 dyes are a new series of fluorescent dyes with emission/excitation spectra similar to those of AMCA, Lucifer Yellow, fluorescein, rhodamine 6G, tetramethylrhodamine or Cy3, lissamine rhodamine B, and Texas Red, respectively (the numbers in the Alexa names indicate the approximate excitation wavelength maximum in nm). All Alexa dyes and their conjugates are more fluorescent and more photostable than their commonly used spectral analogues listed above. In addition, Alexa dyes are insensitive to pH in the 4-10 range. We evaluated Alexa dyes compared with conventional dyes in applications using various conjugates, including those of goat anti-mouse IgG (GAM), streptavidin, wheat germ agglutinin (WGA), and concanavalin A (ConA). Conjugates of Alexa 546 are at least twofold more fluorescent than Cy3 conjugates. Proteins labeled with the Alexa 568 or Alexa 594 dyes are several-fold brighter than the same proteins labeled with lissamine rhodamine B or Texas Red dyes, respectively. Alexa dye derivatives of phalloidin stain F-actin with high specificity. Hydrazide forms of the Alexa dyes are very bright, formaldehyde-fixable polar tracers. Conjugates of the Alexa 430 (ex 430 nm/em 520 nm) and Alexa 532 (ex 530 nm/em 548 nm) fluorochromes are spectrally unique fluorescent probes, with relatively high quantum yields in their excitation and emission wavelength ranges.

Cardiac Na+,K+-ATPase isoenzymes: sensitivity to prednisolone bisguanylhydrazone.

Prednisolone-3,20-bisguanylhydrazone (PBGH), a steroid derivative, has been shown to inhibit Na+,K+-ATPase isolated from guinea-pig heart or kidney in concentrations significantly lower than those required to inhibit the enzyme obtained from other sources. Because Na+,K+-ATPases obtained from guinea-pig heart or kidney are predominantly of the alpha isoform, the hypothesis that PBGH selectively inhibits the alpha isoform over alpha (+) isoform of the enzyme was tested. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the enzyme preparations revealed the presence of only the higher mobility, alpha isoform in guinea-pig heart and ferret kidney, whereas those from guinea-pig brain, dog brain and ferret heart showed both high and low mobility isoforms corresponding to alpha and alpha (+) isoforms. Na+,K+-ATPase obtained from the guinea-pig heart was most sensitive to PBGH and those isolated from ferret heart or ferret kidney had the lowest sensitivity. Enzyme preparations obtained from dog brain, dog heart or guinea-pig brain had intermediate sensitivity. This spectrum of enzyme sensitivity to PBGH was markedly different from that to ouabain. In ferret heart Na+,K+-ATPase, a low concentration of PBGH preferentially inhibited [3H]ouabain binding to the high affinity ouabain binding sites (alpha(+) isoform). These results indicate that PBGH is not a specific inhibitor of the alpha isoforms of Na+,K+-ATPase. Affinity of the enzyme for PBGH is determined by the species and tissue rather than isoforms of Na+,K+-ATPase.

Sex difference of antifertility effect by passively immunized monoclonal sperm antibodies.

Sperm-specific monoclonal antibodies (MS 204, MS 207, HS 11, and HS 63) that had been shown to inhibit fertilization of mouse oocytes in vitro were used to passively immunize male and female mice. In vitro and in vivo fertilization experiments were performed to compare the efficacy of resulting antifertility effects owing to the presence of circulating sperm antibodies. When the sperm from the antibody-treated mice were recovered for insemination, a partial inhibition of fertilization of mouse oocytes in vitro was observed. However, under the same antibody dose that effectively inhibits the in vivo fertilization of treated female mice the fertilization rate of the treated male was not significantly reduced, when they were mated with normal superovulated females followed by in vitro embryo culture. Similarly, on day 9 after mating with the antibody-treated males, the number of fetuses in mated females was not significantly different from that of the control. In contrast, when the antibody-treated females were mated with the proven fertile males, the number of fetuses was significantly reduced in response to the antibody treatment. When I-125-labeled monoclonal sperm antibodies were used to passively immunize male mice, the percentage of antibodies recovered from epididymis (relative to that of blood) was not much different from that of other organs, except for lower percentages detected in brain and testis. In treated females, oviduct and uterus revealed the presence of relatively high percentages of antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Building-associated pulmonary disease from exposure to Stachybotrys chartarum and Aspergillus versicolor.

The authors present an outbreak of disease associated with exposure to Stachybotrys chartarum and Aspergillus species. A courthouse and two associated office buildings had generated discomfort among employees for two years since initial occupancy. Multiple interventions had been unsuccessful An initial evaluation of 14 individuals identified three with potential asthma and three with symptoms consistent with interstitial lung disease. A clinical screening protocol to identify individuals who should be removed from work identified three likely and seven possible cases of building-related asthma. Detailed environmental and engineering assessments of the building identified major problems in mechanical system design, building construction, and operational strategies leading to excess moisture and elevated relative humidities. Moisture-damaged interior surfaces in both buildings were contaminated with S. chartarum, A. versicolor, and Penicillium species. Aspergillus species, especially A. versicolor, at concentrations of 10(1) to 10(4)/m3 dominated the indoor air under normal operating conditions. Bulk samples also revealed large quantities of Stachybotrys. A questionnaire survey of the three case and two control buildings documented between three- and 15-fold increases in symptoms. A nested case-control study suggested emphysematous-like disease in individuals meeting questionnaire definitions for cases. Replication of analysis strategies used in similar previous investigations suggested an association between worsening symptoms and decreased diffusing capacity of the lung. Performance on neuropsychological measures was similar for both cases and controls, although workers with symptoms reported increased levels of current but not past psychiatric symptomatology. Chemical analyses demonstrated the presence of satratoxins G and H. Cytotoxic laboratory analyses demonstrated the presence of agents with biological effectiveness in bulk materials. No association was seen between IgE or IgG antibodies and the presence of disease. This outbreak represents a likely human response to inhaled fungal toxins in indoor environments. Moisture indoors represents a public health issue currently inadequately addressed by building, health, or housing codes.

Clinical outcome of stent implantation in small coronary arteries using different types of coronary stents.

PURPOSE: We evaluated the results of stent placement in small coronary arteries. SUBJECTS: The subjects were divided into 2 groups: the first contained 911 lesions treated with stenting in the coronary arteries (stent group), and the second contained 1,203 background- and patient-matched lesions treated with balloon angioplasty (POBA group). There was no significant difference in the background of patients or lesions between the groups. A "small coronary artery" was defined as a coronary artery with a reference vessel diameter < 3.0 mm. RESULTS: There was no significant difference in incidence of acute myocardial infarction (AMI), coronary artery bypass grafting, or death between the groups. In the stent group, acute occlusion (0.8%) and subacute thrombosis (2.1%) occurred. The restenosis rate of 29.8% in the stent group was significantly lower than in the POBA group (38.2%; p < 0.01). The restenosis rate of 19.4% in stented vessels 3.0 mm diameter was significantly lower than in vessels < 3.0 mm diameter (29.8%; p < 0.01). The rate of restenosis was 22.9% for the Multi-Link stent, 24.4% for the NIR stent, 34.1% for the GFX stent, and 35.3% for the PS stent. The restenosis rate of 23.8% in stented vessels > 2.5 mm diameter and < or = 20 mm length was significantly lower than in vessels , < or = 2.5 mm diameter and > 20 mm length (32.7%; p < 0.01). Factors associated with restenosis, analyzed using a stepwise multivariate logistic regression model, included ostial lesions and post-procedural minimum lumen diameter. CONCLUSIONS: Stent implantation in vessels < 3.0 mm diameter using a newly designed coronary stent yielded favorable clinical results, while there was a high prevalence of restenosis, leading to diffused stenotic lesions, in vessels < 2.5 mm diameter.

Prognosis of acute pelvic fractures in elderly patients: retrospective study.

OBJECTIVE: To analyse the pattern of acute pelvic fractures, prognostic indicators, and intermediate-term functional outcome among elderly patients. DESIGN: Retrospective study. SETTING: Community-based hospital, Hong Kong. PATIENTS: Sixty patients older than 60 years who were admitted to hospital with acute pelvic fracture between 1 November 1993 and 31 December 1996. MAIN OUTCOME MEASURES: Review of medical records and X-ray assessment to determine the patients' demographic data, medical comorbidities, aetiology and mechanism of injury, associated injuries, and clinical outcome indicators such as complications, duration of hospital stay, ambulatory status, and 1- and 2-year mortality rates. RESULTS: The mean follow-up period was 29 months (range, 12 to 65 months). Eighty-seven percent of patients were women and the predominant fracture pattern was Tile A2. The leading cause of injury was low-energy fall injury (75%). The 1-year mortality rate was nearly 12%. Thirty-six percent of patients experienced a decline in ambulatory status. Twenty-five percent of superior rami fractures involved the low anterior column of the acetabulum. There was a high incidence of associated cardiovascular disorders. CONCLUSIONS: Pre-existing medical conditions and acetabular involvement are important adverse factors affecting postinjury ambulatory status. A significant decline in ambulatory status and a significant mortality rate at 1 year were found following pelvic fracture in elderly patients.