Calciphylaxis--a topical overview.

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.

Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats.

Gestational stress (GS) produces profound behavioural impairments in the offspring and may permanently programme hypothalamic-pituitary-adrenal (HPA) axis function. We investigated whether or not GS produced changes in the maternal behaviour of rat dams, and measured depression-like behaviour in the dam, which might contribute to effects in the progeny. We used the Porsolt test, which measures immobility in a forced-swim task, and models depression in rodents, while monitoring maternal care (arched-back nursing, licking/grooming, nesting/grouping pups). Pregnant rats underwent daily restraint stress (1 h/day, days 10-20 of gestation), or were left undisturbed (control). On post-parturition days 3 and 4, dams were placed into a swim tank, and time spent immobile was measured. GS significantly elevated immobility scores by approximately 25% above control values on the second test day. Maternal behaviours, in particular arched-back nursing and nesting/grouping pups, were reduced in GS dams over post-natal days 1-10. Adult offspring showed increased immobility in the Porsolt test, and also hypersecreted ACTH and CORT in response to an acute stress challenge. These data show that GS can alter maternal behaviour in mothers, and this might contribute to alterations in the offspring. GS may be an important factor in maternal post-natal depression, which may in turn detrimentally effect the offspring because depressed mothers do not sufficiently care for their offspring.

Retrospective analysis of detomidine infusion for standing chemical restraint in 51 horses.

OBJECTIVE: To assess the effectiveness of a detomidine infusion technique to provide standing chemical restraint in the horse. DESIGN: Retrospective study. ANIMALS: Fifty-one adult horses aged 9.5 ± 6.9 years (range 1-23 years) and weighing 575 ± 290.3 kg. METHODS: Records of horses presented to our clinic over a 3-year period in which a detomidine infusion was used to provide standing chemical restraint were reviewed. Information relating to the types of procedure performed, duration of infusion, drug dosages and adjunct drugs administered was retrieved. RESULTS: Detomidine was administered as an initial bolus loading dose (mean ±â€ŠSD) of 7.5 ± 1.87 µg kg-1. The initial infusion rate was 0.6 µg kg-1 minute-1, and this was halved every 15 minutes. The duration of the infusion ranged from 20 to 135 minutes. Twenty horses received additional detomidine or butorphanol during the procedure. All horses undergoing surgery received local anesthesia or epidural analgesia in addition to the detomidine infusion. A wide variety of procedures were performed in these horses. CONCLUSIONS: Detomidine administered by infusion provides prolonged periods of chemical restraint in standing horses. Supplemental sedatives or analgesics may be needed in horses undergoing surgery. CLINICAL RELEVANCE: An effective method that provides prolonged periods of chemical restraint in standing horses is described. The infusion alone did not provide sufficient analgesia for surgery and a significant proportion of animals required supplemental sedatives and analgesics.

Effect of process parameters upon the dopamine and lipid peroxidation activity of selected MIG welding fumes as a marker of potential neurotoxicity.

There is growing concern over the neurotoxic effects of chronic occupational exposure to metal fume produced by welding. Elevated iron and manganese levels in the brain have been linked to an increase in lipid peroxidation, dopamine depletion and predisposition to the development of a Parkinson's type condition in advanced cases. Chemical and toxicological analysis of selected welding fumes, generated by model processes, were used in order to evaluate their potential to release solutes that promote oxidation of dopamine and peroxidation of brain lipids in cell free assays. This study compared the effect of shield gas, electrode type and voltage/currect upon the dopamine and brain lipid peroxidation potential of selected welding fume, obtained from metal inert gas (MIG) welding systems. Overall, fume extracts were found to enhance dopamine oxidation and inhibit lipid peroxidation. Significant differences were also found in the oxidising potential of fume generated under differing process conditions; it may therefore be possible to determine the potential neurotoxicity of fumes using this system.

Primary peripheral T cell lymphoma of the endometrium.

A case of a primary peripheral T cell lymphoma arising in the endometrium is presented. Primary lymphomas of the female genital tract are rare, with endometrial lymphomas and those of T cell type being rarer still. Extensive investigations revealed no other sites of disease and the patient was treated by hysterectomy and chemotherapy. She remains well 33 months later. We believe that this case is exceptionally unusual.

The observation unit: a new interface between inpatient and outpatient care.

PURPOSE: Observation units for patients who present to emergency departments with chest pain have become common. We describe our 3-year experience with a multipurpose observation unit in which chest pain accounts for only a minority of patients' presenting clinical syndromes. SUBJECTS AND METHODS: We analyzed the effects of a 12-bed observation unit on inpatient admissions for common clinical syndromes, as well as its overall effects on inpatient medical admissions during its first 3 years of operation (1996 to 1998) compared with the 3 years preceding its creation (1993 to 1995). RESULTS: Among 7,507 patients admitted to the observation unit in 1996 to 1998, 6,334 (85%) were discharged home within 23 hours. Total inpatient medical admissions fell by a similar number (n = 5,366) during the 3 years of operation of the observation unit when compared with the 3 preceding years (39,569 admissions in 1996 to1998 versus 44,935 in 1993 to 1995). Analysis of local area trends suggested that the use of the observation unit contributed to reduced hospital admissions, rather than vice versa. CONCLUSION: Observation units can serve patients with diverse clinical syndromes and may reduce inpatient admissions. This novel "point of care" deserves further evaluation.

Teaching residents evidence-based medicine skills: a controlled trial of effectiveness and assessment of durability.

OBJECTIVES: To measure the effectiveness of an educational intervention designed to teach residents four essential evidence-based medicine (EBM) skills: question formulation, literature searching, understanding quantitative outcomes, and critical appraisal. DESIGN: Firm-based, controlled trial. SETTING: Urban public hospital. PARTICIPANTS: Fifty-five first-year internal medicine residents: 18 in the experimental group and 37 in the control group. INTERVENTION: An EBM course, taught 2 hours per week for 7 consecutive weeks by senior faculty and chief residents focusing on the four essential EBM skills. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was performance on an EBM skills test that was administered four times over 11 months: at baseline and at three time points postcourse. Postcourse test 1 assessed the effectiveness of the intervention in the experimental group (primary outcome]; postcourse test 2 assessed the control group after it crossed over to receive the intervention; and postcourse test 3 assessed durability. Baseline EBM skills were similar in the two groups. After receiving the EBM course, the experimental group achieved significantly higher postcourse test scores (adjusted mean difference, 21%; 95% confidence interval, 13% to 28%; P < .001). Postcourse improvements were noted in three of the four EBM skill domains (formulating questions, searching, and quantitative understanding [P < .005 for all], but not in critical appraisal skills [P = .4]). After crossing over to receive the educational intervention, the control group achieved similar improvements. Both groups sustained these improvements over 6 to 9 months of follow-up. CONCLUSIONS: A brief structured educational intervention produced substantial and durable improvements in residents' cognitive and technical EBM skills.

Narrowband TL-01 phototherapy for patch-stage mycosis fungoides.

BACKGROUND: Although patch-stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UV-B, photochemotherapy, topical nitrogen mustards, electron-beam therapy) are similar, there is concern regarding their potential adverse effects. Narrowband or TL-01 UV-B phototherapy (311 nm), in use for more than 10 years, is more effective than broadband UV-B for the treatment of psoriasis, with an efficacy approaching that of psoralen UV-A. This open study assesses TL-01 as an alternative therapy for patch-stage MF. OBSERVATIONS: Eight white patients (4 men, 4 women; age range, 66-83 years) with histologically proven patch-stage MF received TL-01 phototherapy 3 times weekly using a standard protocol. Complete clearance of MF was achieved in 6 cases in a mean of 9 weeks or 26 treatments (range, 20-37 weeks) and 4 patients have had prolonged remissions. Mean duration of clinical improvement has been 20 months (range, 11-40 months). Partial response to TL-01 or poor histologic improvement was associated with rapid relapse. CONCLUSIONS: TL-01 is an effective, convenient therapy that may have less risk of long-term adverse effects than current alternatives. Although larger prospective studies are necessary, for some patients intermittent courses of TL-01 may offer effective long-term therapy.

Study design and outcomes in out-of-hospital emergency medicine research: a ten-year analysis.

OBJECTIVE: Lack of rigorous study design and failure to follow diverse patient outcomes have been identified as critical gaps in the medical research literature. This study sought to determine whether similar gaps exist in the literature for out-of-hospital interventions. METHODS: A computerized MEDLINE search was conducted for the ten-year period 1985 through 1994 using the MeSH terms "emergency medical services," "prehospital," and "transportation of patients." Using a standard abstraction form, two investigators independently analyzed articles meeting these inclusion criteria: original research evaluating an out-of-hospital intervention and measuring a patient outcome. Study design was categorized in order of scientific rigor, moving from case series to randomized trial. Measures of outcomes were classified into the six Ds: death, disease, discomfort, disability, dissatisfaction, and debt (cost). RESULTS: Interobserver agreement was high (kappa = 0.80). For the ten-year period, 3,686 titles, 1,454 abstracts, and 373 articles were examined serially; all 285 studies meeting inclusion criteria were analyzed. Case series (44%) was the most frequently used design, while only 15% were randomized trials. The majority of the studies were retrospective (53%). A single outcome was assessed in 45% of the articles; 41% measured two outcomes, 13% three outcomes, and 1% four outcomes. Death and disease were the most common outcomes evaluated. Disability, debt, discomfort, and dissatisfaction were infrequently measured. CONCLUSION: Studies of out-of-hospital emergency medical interventions are limited in the scientific rigor of study design and the diversity of patient outcomes measured. To adequately assess the effectiveness of out-of-hospital care, efforts should be directed toward strengthening study designs and examining the full range of patient outcomes.

How does colorectal cancer present? Symptoms, duration, and clues to location.

OBJECTIVE: Most colorectal cancers still present with symptoms because screening, although effective, is not yet widely practiced. A careful history and physical examination are still the usual methods for suspecting colorectal cancer and ordering appropriate investigation. Therefore, we studied the symptoms, duration, and clues to location of colorectal cancer. METHODS: We reviewed both hospital and office records for 204 consecutive patients with colorectal cancer, first diagnosed after symptoms, at one regional referral center from 1983-87. We abstracted data on demographic characteristics, presence and duration of 15 symptoms, and characteristics of the tumors. RESULTS: The 194 patients included in the study were similar to those with colorectal cancer described elsewhere in terms of age, gender, and tumor location (58% distal to the splenic flexure), and stage (56% stage A or B). The most common symptoms were rectal bleeding (58%), abdominal pain (52%), and change in bowel habits (51%); the majority had anemia (57%) and occult bleeding (77%). The median duration of symptoms (from onset to diagnosis) was 14 wk (interquartile range 5-43). We found no association between overall duration of symptoms and the stage of the tumor. Patient age, gender, and proximal cancer location were also not associated with a longer duration of symptoms before diagnosis. We developed a rule for predicting a distal location of cancer using multiple logistic regression. Independent predictors were (odds ratio [95% CI]): Hb (1.34 for each g/dl [1.16-1.54]); rectal bleeding (3.45 [1.71-6.95]); constipation (3.16 [1.38-7.24]); and proximal symptoms (at least one of anorexia, nausea, vomiting, abdominal pain, or fatigue) (0.48 [0.20-1.02]). The rule had sensitivity of 93% and a specificity of 47%, with an area under the ROC curve of 0.79. CONCLUSIONS: Until prevention of colorectal cancer is more common, we must continue to rely on clinical findings for detecting this cancer. Our results will remind physicians to keep colorectal cancer on the differential diagnosis of "chronic" gastrointestinal symptoms, and our decision rule may prompt earlier investigation with colonoscopy.

Malignant mesothelioma of the tunica vaginalis: a case with an unusually indolent course following radical orchidectomy and radiotherapy.

Malignant mesothelioma (malignant adenomatoid tumour) of the tunica vaginalis testis is a very rare neoplasm with highly aggressive biological behaviour. Treatment is difficult, and widespread local invasion and/or metastatic disease at presentation are associated with a poor prognosis. In this case report we describe for the first time a patient who, despite presenting with locally advanced disease, remains well 10 years after diagnosis and treatment with radical orchidectomy and high dose radiotherapy.

New thoughts on cardiopulmonary resuscitation.

The results of cardiopulmonary resuscitation (CPR) have been distressingly poor when one considers the amount of research in this field since 1960. Accordingly, some improvements to present protocols have been suggested. Some of the suggestions can be applied by practicing veterinarians to increase the success rate for external chest massage. In addition, veterinarians are encouraged to switch to internal cardiac massage early in the resuscitation period.

Cell reactions to dielectrophoretic manipulation.

The phenomenon of dielectrophoretic particle manipulation holds promise for many biotechnology applications, including cell sorting. In our system cell manipulation normally involves transient exposure (15 minutes) to radio-frequency AC electric fields generated using planar microelectrodes. The present study was designed to investigate the range of acute effects of dielectrophoretic manipulation on the normal physiology of isolated cells. Cells were suspended in isoosmotic Mannitol and exposed to a 5 MHz, 21 V (peak to peak) electric field with 100 micrometer gap electrodes. Cells were assigned to three experimental groups; non-exposed controls, exposed cells processed immediately after cessation of the field, and exposed cells processed after a time delay. SEM observations of spread cells cultured on the devices showed no apparent acute effects of field exposure on cell morphology. Cell-doubling rates in exposed cells subsequent to field-exposure or transient incubation in mannitol were no different from control cells. An MTT 'mitochondrial stress' assay indicated no alteration in the rate of oxidative respiration in exposed cells 0.5 hour after exposure to the field. Western blot analysis indicated upregulation of fos protein in cells 0.5 hour after field-exposure, which was confirmed using densitometry. Reverse transcription of cellular mRNA followed by PCR amplification, polyacrylamide gel electrophoresis and autoradiography of cDNA banding revealed differential gene expression between controls and exposed cells processed immediately after cessation of the field. Differential gene expression persisted in exposed cells at least 0.5 hours after removal from the field. Observations indicated that temperature fluctuation in the mannitol solution was minimal, suggesting that upregulated mRNA may not have been related to thermally-induced heat shock protein. The present study has indicated that exposure to AC fields during dielectrophoretic cell manipulation is associated with upregulation of the intermediate-early gene cfos and also transcription of other as yet unidentified genes. These transcriptional events were not manifest as gross changes in cell morphology or cell-cycle dynamics.