Hip fractures, preceding distal radius fractures and screening for osteoporosis: should we be screening earlier? A minimum 10-year retrospective cohort study at a single centre.

UNLABELLED: Both men and women who sustain a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. Our study implies that these patients may not necessarily constitute a group in which osteoporosis screening is warranted. INTRODUCTION: People who sustain a distal radius fracture run an increased risk of sustaining a subsequent hip fracture. However, many institutions only screen for osteoporosis at the time of a hip fracture. We aimed to determine the true incidence of preceding distal radius fractures in an Asian population of patients with a hip fracture aged 60 years or older and whether screening for osteoporosis earlier would be beneficial. METHODS: We reviewed 22 parameters of 572 patients aged 60 years or older admitted after sustaining a hip fracture over a 3-year period. This included the occurrence or absence of a distal radius fracture in the 10 years preceding their hip fracture. RESULTS: Twenty-nine patients (5 %) had a fracture of the distal radius in the preceding decade. Univariate analyses suggested that hip fracture patients who had preceding distal radius fractures were older, female, have lower mean haemoglobin levels, and right-sided hip fractures. Of these factors, only age was found to have significant predictive value in a multivariate analysis. CONCLUSIONS: A number of institutions have started to screen for osteoporosis when a patient presents with a fracture of the distal radius because these patients may have an increased risk of a subsequent hip fracture. Our study implies that this may not be warranted. Implementing such a screening service from both cost and resource utilization point of view must be studied prospectively and in greater detail considering earlier screening may only be beneficial to a very small percentage of patients.

Statistical atlas-based morphological variation analysis of the asian humerus: towards consistent allometric implant positioning.

PURPOSE: Positioning existing humeral implants into Asian patients poses significant challenges due to the inconsistent statistical shapes between Western population and Asian population. Current humeral orthopedic fixation devices and implants have a generic shape and are not designed for Asian patients who exhibit different sizes and shapes compared to their Western counterparts for which present day designs have been based on. To address this problem, it is necessary to develop Asian-specific implants that accommodate the morphology of Asian humeri. Existing morphological studies of humeri in Asian populations are rare and most previous analyses are either based on the manual measurement of dry bones or the use of dual energy X-ray absorptiometry scans. The purpose of this pilot morphological study is to explore the characteristics of Asian humeri using statistical atlas-based analysis. METHODS: Forty-four CT scans of normal upper limbs were obtained from the National University Hospital, Singapore and used to construct statistical humerus atlases. The atlases were subsequently used to study the morphology of the humeri in an Asian population. Humeral shapes of different patient clusters were analyzed based on statistical shape models. Comparison between different clusters was conducted with regard to centerline, length, width and surface curvature. RESULTS: The statistical humerus atlases reflected the mean shape and modes of variation of humeri in an Asian population. Analyses based on these atlases indicated that curvature and shape of the internal humeral canal were similar in males and females while humeral length and width were greater in males. Most importantly, surface curvatures were explicitly different between clusters. CONCLUSION: Morphologic analysis based on statistical atlases is novel and useful to characterize the Asian humerus. The humerus demonstrates gender-specific morphology. This unique approach provides information that is useful to the clinician and biomedical engineer, not only in the modification of current or design of future humeral implants, but also in the precise dynamic positioning of Asian-specific humeral implants to Asian patients. Our findings support the need for further development of humeral implants, curvilinear robotics, and the questioning of whether gender-specific devices are necessary.

Synergistic effects of epidermal growth factor (EGF) and insulin-like growth factor I/somatomedin C (IGF-I) on keratinocyte proliferation may be mediated by IGF-I transmodulation of the EGF receptor.

The epidermal growth factor (EGF) receptor pathway is an important mediator of keratinocyte growth in vitro and both receptor and ligand components of this pathway are abnormally expressed in hyperproliferative epidermis. The purpose of this study was to examine interactions between the EGF receptor pathway and the insulin-like growth factor I/somatomedin C (IGF-I) receptor pathway in modulating the growth of cultured normal human keratinocytes. Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could. IGF-I or high-dose insulin transmodulates keratinocyte EGF receptor expression via the IGF-I receptor in a dose- and time-dependent manner, increasing EGF receptor binding an average of 1.8 times up to a maximum of fourfold without altering EGF binding affinity. Staining of normal human epidermis with an IGF-I receptor specific monoclonal antibody demonstrates that IGF-I receptors localize to the basal proliferative cell compartment, suggesting that IGF-I receptor and EGF receptor pathway interactions may play a role in the regulation of epidermal growth and in the pathogenesis of hyperproliferative skin diseases.

Increased dermal expression of platelet-derived growth factor receptors in growth-activated skin wounds and psoriasis.

Platelet-derived growth factor (PDGF) is a potent mitogenic and chemotactic factor for fibroblasts and other cell types. PDGF effects are mediated by binding of PDGF to dimeric PDGF receptors possessing intrinsic tyrosine kinase activity. We examined the expression pattern of PDGF receptors in cryostat sections of normal and growth-activated human skin using a monoclonal antibody, PR7212, specific for the beta subunit of the PDGF receptor. PDGF receptors were expressed at low levels in normal skin, with only occasional staining of dermal connective tissue cells. In contrast, PDGF receptor expression was greatly elevated in the dermis of growth-activated skin from 15 chronic wounds and 10 psoriatic lesions. PDGF receptors were increased in dermal fibroblasts and in dermal blood vessels in both conditions. Immunoblot analysis confirmed the increased expression of beta-subtype PDGF receptors in psoriatic lesional tissue. PDGF receptors were not detected in normal or growth-activated epidermis. Differential expression of PDGF receptors could regulate increased proliferation of vascular and connective tissue cells observed in psoriasis and chronic wounds.

Advance directives for seriously ill hospitalized patients: effectiveness with the patient self-determination act and the SUPPORT intervention. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: To assess the effectiveness of written advance directives (ADs) in the care of seriously ill, hospitalized patients. In particular, to conduct an assessment after ADs were promoted by the Patient Self-Determination Act (PSDA) and enhanced by the effort to improve decision-making in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), focusing upon the impact of ADs on decision-making about resuscitation. DESIGN: Observational cohort study conducted for 2 years before (PRE) and for 2 years after (POST) the PSDA, with a randomized, controlled trial of an additional intervention to improve decision-making after PSDA (POST+SUPPORT). SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 9105 seriously ill patients treated in five teaching hospitals. INTERVENTIONS: The PSDA mandated patient education about ADs at hospital entry and documentation of ADs in the medical record. The SUPPORT intervention, in addition, provided a nurse to facilitate communication among patients, surrogates, and physicians about preferences for and outcomes of treatment alternatives and, when clinically appropriate, to encourage completion and utilization of ADs. MEASUREMENTS: Interviews were conducted with patients, surrogates, and attending physicians about awareness, completion, and impact of ADs. Medical records were reviewed for discussion about preferences concerning resuscitation, timing and writing of "Do Not Resuscitate" (DNR) orders, evidence of ADs, and the use or forgoing of resuscitation at the time of death. RESULTS: In the three cohorts, PRE, POST, and POST+SUPPORT, average age was 63. One-quarter of patients died during the initial hospitalization, one-half were dead within 6 months, and one-half were unconscious for their last 3 days. Before the PSDA (PRE), 62% were familiar with a living will, and 21% had an AD. These rates were similar for the POST and POST+SUPPORT cohorts. Just 36 (6%) of these directives were mentioned in the medical records for PRE, but a stable 35% were documented for POST, and POST+SUPPORT had an increasing rate averaging 78% (P < .001). As previously reported for PRE patients, the POST patients with and without ADs had no significant differences in the rates of medical record documentation of discussions about resuscitation (33% vs 38%, POST without AD vs POST with AD), DNR orders among those who wanted to forgo resuscitation (54% vs 58%), and attempted resuscitations at death (17% vs 9%). The POST+SUPPORT patients had similar results, with no evidence that the intervention enhanced the effect of ADs on these three measures of resuscitation decision-making. Patients with ADs more often reported that preferences about resuscitation were discussed with a physician (e.g., for POST patients, 30% for those with no AD and 43% for those with an AD, P < .05). Only 12% of patients with ADs had talked with a physician when completing the AD. Only 42% reported ever having discussed the AD with their physician. By the second study week, only one in four physicians was aware of patients' ADs. CONCLUSIONS: In these seriously ill patients, ADs did not substantially enhance physician-patient communication or decision-making about resuscitation. This lack of effect was not altered by the PSDA or by the enhanced efforts in SUPPORT, although these interventions each substantially increased documentation of existing ADs. Current practice patterns indicate that increasing the frequency of ADs is unlikely to be a substantial element in improving the care of seriously ill patients. Future work to improve decision-making should focus upon improving the current pattern of practice through better communication and more comprehensive advance care planning.

The illusion of end-of-life resource savings with advance directives. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: Would increasing the documentation of advance directives (ADs) lead to a reduction in resource utilization? We examined this question by conducting three secondary analyses: (1) we tested for a change in resource use among those who died in the hospital at a time before and after an intervention that increased the documentation of ADs in the medical record; (2) we replicated analyses of published studies that reported an association of chart documentation of ADs and hospital resource use; and (3) we examined whether a potential explanation of the observed association is biased documentation of ADs among patients who have completed an AD. DESIGN: Replication of analysis of previous published studies using data from a prospective cohort study and block-randomized controlled trial. SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 9105 seriously ill patients were enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), including 4301 patients in the 2 years (1989-91) before the Patient Self-Determination Act (PSDA) and 4804 in the 2 years (1992-94) after the PSDA implementation, with 2652 patients receiving the intervention and 2152 serving as controls. INTERVENTIONS: The SUPPORT intervention provided a nurse to facilitate communication among patients, surrogates, and physicians about preferences for and outcomes of treatments. Documenting existing advance directives was also one of this nurse's tasks. The Patient Self-Determination Act required that health care institutions inquire about and document existing advance directives at the time of hospital admission. MEASUREMENT: Hospital resource use was derived from the Therapeutic Intensity Scoring System and hospital length of stay, converted into 1994 dollars. RESULTS: Chart documentation of existing advance directives at the time of study admission increased with both the PSDA and the SUPPORT intervention. We found that intervention patients were more likely to have pre-existing ADs documented. Despite this increase, there was no corresponding change in hospital resource use for those who died during the enrollment hospitalization. Replication of analyses from published studies using data from the block randomized controlled trial found that ADs documented by the third day of serious illness were associated with a 23% reduction in hospital resource use among control patients ($21,284 with ADs documented compared with $26,127 without, 95% CI 1-48% reduction). However, this association was not observed among intervention patients, who had more pre-existing ADs documented in the medical record. Intervention patients with early documentation of ADs showed a trend toward greater cost ($28,017 compared with $24,178 among those without AD documentation, 95% CI 0-25% increase). The rate of documentation and characteristics of those with documentation differed between control and intervention patients. Intervention patients were more likely (as reported by patient or surrogate interview) to have ADs documented in the medical record by the third day (55% vs 32%, P < .001). In contrast to intervention patients, control patients who were older, less wealthy, less educated, more likely to prefer to forgo CPR, and more likely to want life-sustaining treatment limited had their ADs documented. These associations were not found among intervention patients when comparison was made between those with and those without an AD documented in the medical record. CONCLUSION: Increasing the documentation of pre-existing ADs was not associated with a reduction in hospital resource use. ADs documented without further intervention by the third day of a serious illness were associated with decreased hospital resource use. However, we did not find this association with an intervention that increased AD documentation. One potential explanation of these findings is that classification of those with an AD was based on cha

Do advance directives provide instructions that direct care? SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: To evaluate whether the lack of effect of advance directives (ADs) on decision-making in SUPPORT might arise, in part, from the content of the actual documents. DESIGN: Advance directives placed in the medical records were abstracted for date of completion and content of additional written instructions. We examined directives with instructions to forgo life-sustaining treatment in the current state of health to determine whether care given was consistent with preferences noted in those directives. SETTINGS: Five teaching hospitals in the United States. PATIENTS: A total of 4804 patients with at least one of nine serious illnesses were admitted to five teaching hospitals in the 2 years following implementation of the Patient Self-Determination Act. Patients were part of a randomized controlled trial to improve decision-making and outcomes. RESULTS: From the medical records of 4804 patients, a total of 688 directives were collected from 569 patients. The majority of these directives (66%) were durable powers of attorney; in addition, 31% were standard living wills or other forms of written instructions (3%). Only 90 documents (13%) provided additional instructions for medical care beyond naming a proxy or stating the preferences of a standard living will. Only 36 contained specific instructions about the use of life-sustaining medical treatment, and only 22 of these directed forgoing life-sustaining treatment in the patient's current situation. For these, the treatment course was consistent with the instruction for nine patients. In two cases, patients may have changed an inconsistent directive after discussion with hospital staff. CONCLUSION: Advance directives placed in the medical records of seriously ill patients often did not guide medical decision-making beyond naming a healthcare proxy or documenting general preferences in a standard living will format. Even when specific instructions were present, care was potentially inconsistent in half of the cases.

Morphometric study of hepatic ultrastructure in alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis.

We undertook a morphometric analysis of hepatocellular organelles in an attempt to correlate their changes with the clinical stages of patients with alcoholic hepatitis. Although hepatic ultrastructural alterations did not correlate with disease severity, we found significant differences between patient and control groups in the measured parameters of non-organelle cytoplasm, mitochondria, SER, RER, glycogen, and lipid.

Mycotic aneurysm of the thoracic aorta caused by Clostridium septicum.

We describe a case-of a 78-year-old man who presented with a mycotic aneurysm of the thoracic aorta caused by Clostridium septicum and underwent successful resection. There are only 3 cases of mycotic aneurysms caused by Clostridium septicum reported in the literature. Clostridium septicum infections have been shown to have a high association with gastrointestinal and hematologic malignancies. All patients with Clostridium septicum infections, therefore, require a search for gastrointestinal lesions, as they may represent a source of persistent bacteremia. This patient had no malignant lesions but did have multiple benign sigmoid polyps.

Mitral valve myxoma.

Cardiac myxomas arising from the mitral valve are extremely rare. We describe the case of an asymptomatic 49-year-old woman who was found to have a 3.6 x 4.0-cm myxoma originating from the atrial side of the anterior mitral leaflet. The lesion was successfully treated by surgical excision and mitral valve replacement. A review of the literature regarding this rare lesion is presented.

Adenocarcinoma arising within a testicular metastasis.

Teratoma with malignant transformation is defined as the emergence of a non-germ cell tumor from a teratoma. Although extremely rare in extraovarian sites, cases have been reported that involve primary extragonadal germ cell tumors with transformation to variants of sarcoma. We report a 54-year-old man who was found to have adenocarcinoma arising within a mature teratomatous retroperitoneal metastasis 15 years after treatment of a nonseminomatous testicular germ cell tumor. The tumor was successfully excised and he remains without evidence of disease.

Elective aortic surgery with minimal banked blood.

It has been a historical supposition that aortic surgery, even in an elective setting, has been associated with the transfusion of large amounts of blood products. We feel that this assumption is now dated, and in fact far fewer patients now receive allogenic blood products. To assess this assumption, we carried out a retrospective chart review of all patients who underwent elective aortic surgery over an 18-month period from April 1994 to October 1995. Factors analyzed included type of procedure, blood loss, amount of Cell Saver blood replaced, need for autologous blood transfusion, and need for allogenic blood transfusion. Sixty-seven patients underwent elective aortic surgery with either an aortic tube graft (23), an aortobiiliac graft (25), or an aortobifemoral graft (19). The male:female ratio was 48:19, with a mean age of 67 years (range, 42-85 years). Mortality and morbidity were 4.4 per cent and 8.9 per cent, respectively. The average blood loss per patient was 770 cc. Cell saver was used in 65 patients, with the average amount of blood returned being 542 cc. Overall, 73 per cent of patients did not require allogenic blood transfusion, and 58 per cent did not need any type of transfusion. Of those who stored autologous blood prior to operation, none required allogenic blood perioperatively. With the new advances in autologous blood transfusion both by predeposit and salvage transfusion, we have greatly reduced the need for transfusion of allogenic blood products in patients undergoing major aortic surgery. This is reassuring, and although increasing short-term cost, will reduce the morbidity-infectious, noninfectious, and immunologic-associated in prior decades with allogenic blood transfusions. We strongly recommend the use of Cell Saver techniques, and also, where possible, patients should be encouraged to donate their own blood prior to major aortic procedures for future transfusion.

Comparison of two concentrations of amphotericin B bladder irrigation in the treatment of funguria in patients with indwelling urinary catheters.

The efficacy of amphotericin B bladder irrigation at two concentrations was studied. Patients with funguria (> or =15,000 colony-forming units of yeast per milliliter of urine), an indwelling urinary catheter, and a physician order for amphotericin B continuous bladder irrigation were randomly assigned to receive 10 or 50 mg of amphotericin B per liter of sterile water as a continuous irrigation for 72 hours at the rate of 42 mL/hr. Before the bladder irrigation began, the indwelling catheter was changed to a three-way catheter. Repeat urine cultures were performed 24 hours after the irrigation was discontinued. A total of 28 patients were enrolled from November 1993 to May 1995. The rate of eradication of the infection was 100% in the 50-mg/L group and 67% in the 10-mg/ L group. Subject enrollment was stopped prematurely because all the treatment failures occurred in the 10-mg/L group. Dose was the only variable significantly associated with outcome. Bladder irrigation with amphotericin B was more effective when the drug concentration was 50 mg/L rather than 10 mg/L.

Time-resolved ion flux measurements in pulsed, electron-beam-generated plasmas.

Time-resolved ion flux and energy distributions were measured at an electrode located adjacent to pulsed, electron-beam-generated plasmas in argon and oxygen. Temporal variations in the incident Ar+, O+, and O(2)+ energy and flux were correlated to changes in the electron temperature and plasma density. The decay time of the oxygen plasma is found to be shorter than that of the argon plasma, which is understood by considering the different loss mechanisms of each ion species.

A study comparing the immunologic responses of swine to pseudorabies viral antigens based on the ELISA, serum virus neutralization, and latex agglutination tests.

A study of pseudorabies virus (PRV)-vaccinated pigs comparing the immune responses detected by the latex agglutination test (LAT) with responses detected by other routine tests for pseudorabies antibodies indicated that LAT was more sensitive than either the enzyme-linked immunosorbent assay (ELISA) or the serum virus neutralization test (SVNT). The LAT detected antibodies sooner than ELISA and SVNT in unvaccinated pigs after challenge with virulent PRV. The specificities of the 3 tests were found to be near 100%. The LAT is a good alternative to SVNT or ELISA for detection of PRV-specific antibodies.

In vitro activity of four antimicrobial agents against North American isolates of porcine Serpulina pilosicoli.

Porcine colonic spirochetosis is a nonfatal diarrheal disease that affects pigs during the growing and finishing stages of production. The disease is caused by Serpulina pilosicoli, a newly recognized species of pathogenic intestinal spirochete. Antimicrobial therapy aimed at reducing the infection may be helpful in controlling spirochetal diarrhea. In this study, the in vitro antimicrobial susceptibilities of the reference isolate S. pilosicoli P43/6/78 from the United Kingdom and 19 field isolates obtained from pigs in Canada (n = 5) and the United States (n = 14) were determined against the antimicrobial agents carbadox, gentamicin, lincomycin, and tiamulin, all of which are commonly used for control of the related pathogenic intestinal spirochete S. hyodysenteriae. Additionally, the susceptibility or resistance of each isolate against each antimicrobial agent was estimated on the basis of available data on the in vitro antimicrobial susceptibility breakpoints of S. hyodysenteriae. Each isolate was identified on the basis of phenotypic and genotypic markers, and the minimum inhibitory concentration of each antimicrobial agent was determined by the agar-dilution method. All the isolates were susceptible to carbadox and tiamulin. The percentages of isolates susceptible, intermediate, and resistant to lincomycin were 42.1%, 42.1%, and 15.8%, respectively. Slightly less than half of the isolates (47.4%) were susceptible to gentamicin, and the remainder (52.6%) were resistant. Implementation of rational control measures to reduce infection by S. pilosicoli should improve overall health and productivity in swine herds.

Pseudorabies virus latency and reactivation in vaccinated swine.

Latency and reactivation of pseudorabies virus in swine was studied. Thirty-one pigs were assigned to 5 groups and were given 1 of 4 vaccines; 10 remained unvaccinated controls. All pigs were then challenge exposed with a sublethal dose of virulent pseudorabies virus. One hundred one days after challenge exposure, all pigs were treated with dexamethasone to reactivate the virus. Virus-positive tonsil and nasal mucus isolates were recovered from 29 of the 31 pigs over a 12-day period. Frequency and duration of virus-positivity were significantly (P less than 0.05) and consistently lower among vaccinated pigs than among the unvaccinated controls. It was concluded that vaccination before challenge exposure had little or no effect on the rate of establishment of virus latency, but that vaccination reduced shedding after subsequent reactivation of the virus.

Survival of pseudorabies virus in aerosol.

The survival of pseudorabies virus in an aerosol was studied under different environmental conditions of temperature and relative humidity. Pseudorabies virus decayed logarithmically with mean half-lives of 17.4 (85% relative humidity, 22 C), 18.8 (25% relative humidity, 22 C), 27.3 (85% relative humidity, 4 C), 36.1 (55% relative humidity, 22 C), and 43.6 (55% relative humidity, 4 C) minutes. Virus survival was significantly improved in environments at 55% relative humidity, compared with those at 85% relative humidity (P = 0.017). Rates of survival were improved in environment at 4 C in comparison with those at 22 C. Results suggest that, under the best conditions of this study, the infectivity of pseudorabies virus in an aerosol decreases by 50% in less than 1 hour.

Influence of temperature and age on the recovery of pseudorabies virus from houseflies (Musca domestica).

In laboratory experiments, pseudorabies virus was readily recovered from within the body of houseflies (Musca domestica L) that had ingested the virus. Age of the fly and ambient temperature affected the rate of virus inactivation within the houseflies. Virus half-life in 3-day-old flies was 6.36 hours vs 2.81 hours in flies 8 or 13 days old. Half-life in 5-day-old flies was 12.92 hours at 10 C, 5.95 hours at 20 C, and 2.69 hours at 30 C. Virus half-life in dead flies was 9.06 hours at 10 C, 4.28 hours at 20 C, and 1.71 hours at 30 C. The data did not provide any evidence of virus replication in either living or dead flies.

Treatment of anaemia in the polytrauma Jehovah's Witness.

The management of Jehovah's Witnesses can prove quite challenging to the surgeon who routinely uses blood and blood products in the treatment of anaemia and hypovolaemia. The medical and legal dilemmas are exacerbated when the patient has a critically low haemoglobin level or has suffered life-threatening blood loss following polytrauma. It is essential that the treating physician should have some knowledge and understanding of the beliefs of the Jehovah's Witness in order to effectively minimise and treat blood loss. This paper reviews the ethical and medicolegal aspects involved, as well as alternatives to allogenic blood products in the treatment of anaemia in the polytrauma Jehovah's Witness patient.