Emergencies in continuous dialysis patients: diagnosis and management

The number of patients undergoing long-term hemodialysis and peritoneal dialysis is growing in the United States. To provide adequate emergent care to these patients emergency physicians must understand the alterations in normal physiologies present in these patients and how this may affect care. Cardiovascular disease and infection (especially Staphylococcus aureus sepsis) are the leading causes of death among dialysis patients. These patients are also subject to a significantly higher incidence of life-threatening electrolyte disturbances, particularly hyperkalemia and hypercalcemia, than the general population. Suicide, cardiac tamponade, intracranial hemorrhage, bleeding disorders, and bowel infarction are also much more frequent. The inability of dialysis patients to excrete drugs, metabolites, toxins, and fluids significantly alters their responses to common emergencies and should directly influence their care. Failure to recognize these differences in physiology may result in the use of standard forms of emergency therapy that may compound, rather than treat, the underlying disorder. Although most dialysis patients who come into an emergency department have conditions that can, and should, be managed by their nephrologist, the presence of a life threatening emergency requires prompt, appropriate therapy by the emergency physician.     

Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British South Asians with hypertension

BACKGROUND: People from British South Asian communities have an increased risk of mortality from coronary heart disease (CHD). Doxazosin, a selective alpha(1)-adrenergic blocker, in addition to lowering blood pressure, has been shown to have positive effects on glucose metabolism and lipid profiles in patients with hypertension. AIM: We studied doxazosin (1-8 mg) and bendrofluazide (2.5 mg) in patients of British South Asian origin with existing mild to moderate hypertension (doxazosin n = 78; bendrofluazide n = 82), to compare their effects on glucose and lipid metabolism in this group. DESIGN OF STUDY: A 34-week randomised, double-blind, parallel-group, multicentre study. SETTING: Primary care in the UK. METHOD: All doxazosin patients started with an initial dose of 1 mg once daily, titrated to a maximum 8 mg once daily if diastolic blood pressure was >90 mmHg or was not <5 mmHg of the baseline value. The primary efficacy variables were mean glucose and total cholesterol concentrations at week 21. RESULT: Doxazosin reduced glucose, total cholesterol, low-density lipoprotein-cholesterol and triglycerides and increased high-density lipoprotein-cholesterol. There were significant differences between doxazosin and bendrofluazide for glucose concentrations at week 21 (P = 0.029) and week 34 (P = 0.015), total cholesterol at week 21 (P = 0.048) and triglycerides at week 21 (P = 0.047) and week 34 (P = 0.009). There was no significant difference in blood pressure lowering between the two treatments. CONCLUSION: Doxazosin exhibits beneficial effects on glucose concentrations and lipid profile, in particular in lowering triglyceride concentrations in British South Asians. Whether these desirable characteristics translate to improved overall cardiovascular risk requires formal evaluation.     

Cognitive and adaptive outcome in low-grade pediatric cerebellar astrocytomas： evidence of diminished cognitive and adaptive functioning in National Collaborative Research Studies （CCG 9891/POG 9130）.

PURPOSE： Clinicians often assume that children with posterior fossa tumors are at minimal risk for cognitive or adaptive deficits ff they do not undergo cranial irradiation. However, small case series have called that assumption into question, and have also suggested that nonirradiated cerebellar tumors can cause location-specific cognitive and adaptive impairment. This study （1） assessed whether resected but not irradiated pediatric cerebellar tumors are associated with cognitive and adaptive functioning deficits, and （2） examined the effect of tumor location and medical complications on cognitive and adaptive functioning. PATIENTS AND METHODS： The sample was composed of 103 children aged 3 to 18 years with low-grade cerebellar astroeytomas, who underwent only surgical treatment as part of Children＇s Cancer Group protocol 9891 or Pediatric Oncology Group protocol 9130. The sample was divided into three groups based on primary tumor location： vermis, left hemisphere, or right hemisphere. Data were collected prospectively on intelligence, academic achievement, adaptive skills, behavioral functioning, and pre-, peri-, and postsurgical medical complications. RESULTS： The sample as a whole displayed an elevated risk for cognitive and adaptive impairment that was not associated consistently with medical complications. Within this group of children with cerebellar tumors, tumor location had little effect on cognitive, adaptive, or medical outcome. CONCLUSION： We did not replicate previous findings of location-specific effects on cognitive or adaptive outcome. However, the elevated risk of deficits in this population runs contrary to clinical lore, and suggests that clinicians should attend to the functional outcomes of children who undergo only surgical treatment for cerebellar tumors.     

Low dose short duration pulsed electromagnetic field effects on cultured human chondrocytes: An experimental study

Background:

Pulsed electromagnetic field (PEMF) is used to treat bone and joint disorders for over 30 years. Recent studies demonstrate a significant effect of PEMF on bone and cartilage proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors. The aim of this study is to assess if PEMF of low frequency, ultralow field strength and short time exposure have beneficial effects on in-vitro cultured human chondrocytes.

Materials and Methods:

Primary human chondrocytes cultures were established using articular cartilage obtained from knee joint during joint replacement surgery. Post characterization, the cells were exposed to PEMF at frequencies ranging from 0.1 to 10 Hz and field intensities ranging from 0.65 to 1.95 μT for 60 min/day for 3 consecutive days to analyze the viability, ECM component synthesis, proliferation and morphology related changes post exposure. Association between exposure doses and cellular effects were analyzed with paired''t’ test.

Results:

In-vitro PEMF exposure of 0.1 Hz frequency, 1.95 μT and duration of 60 min/day for 3 consecutive days produced the most favorable response on chondrocytes viability (P < 0.001), ECM component production (P < 0.001) and multiplication. Exposure of identical chondrocyte cultures to PEMFs of 0.65 μT field intensity at 1 Hz frequency resulted in less significant response. Exposure to 1.3 μT PEMFs at 10 Hz frequency does not show any significant effects in different analytical parameters.

Conclusions:

Short duration PEMF exposure may represent a new therapy for patients with Osteoarthritis (OA).     

Predictors of incident atrial fibrillation and influence of medications: a retrospective case�Ccontrol study

Background

Atrial fibrillation (AF) is a common condition, associated with raisedmortality and risk of majormorbidity, and is predicted to increase due to an aging population.

Aim

To update earlier research of AF predictors using UK data.

Design and setting

Case–control analysis of adults aged 18 years and older with a diagnosis of AF in practices registered with the General Practice Research Database (GPRD) in the UK.

Method

Using the GPRD, a case.control analysis was performed using logistic regression to compare 55 412 incident AF cases to 216 400 controls, for medical history and prior use of drugs. The association between time since start of diagnosis or drug use and AF risk was summarised using Spline regression.

Results

The following were confirmed as risk factors for AF: heart failure (risk ratio [RR] 2.91 [95% CI = 2.59 to 3.27]); ischaemic heart disease (IHD) (RR 2.00 [95% CI = 1.78 to 2.24]); hypertension (RR 2.60 [95% CI = 2.32 to 2.92]); hyperthyroidism (RR 1.56 [95% CI = 1.39 to 1.75]); being a heavy drinker (RR 1.43 [95% CI = 1.27 to 1.60]); cerebrovascular accident (RR 1.48 [95% CI = 1.32 to 1.66]); and obesity (bodymass index ≥30 kg/m² RR 1.29 [95% CI = 1.15 to 1.45]). Current use of oral glucocorticoids (RR 1.62 [95% CI = 1.44 to 1.82]) and of beta-2 agonists (RR 1.30 [95% CI = 1.16 to 1.46]) were identified as significant risk factors, and statins (RR 0.82 [95% CI = 0.73 to 0.92]) as a significant protective factor. No effect was found for current use of bisphosphonates (RR 0.95 [95% CI = 0.85 to 1.07]), renin.angiotensin.aldosterone system (RAAS) agents (RR 1.04 [95% CI = 0.93 to 1.17]), or xanthine derivatives (RR 1.09 [95% CI = 0.97 to 1.22]). Spline regression analysis found the effect of heart failure, IHD, use of oral glucocorticoids, and use of statins on the likelihood of developing AF was sustained over a number of years.

Conclusion

These findings update the risk factors that are associated with AF, and confirmthe protective properties of statins and the risks of beta-2 agonists in developing AF, but not the supposed protective qualities of glucocorticoids and RAAS agents.     

Ex-vivo evaluation of gene therapy vectors in human pancreatic （cancer） tissue slices

AIM： To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions.
METHODS： Human pancreatic tissue samples （malignant and normal） were obtained from surgical specimens and processed immediately to tissue slices. Tissue slices were cultured ex vivo for 1-6 d in an incubator using 95% 02. Slices were subsequently analyzed for viability and morphology. In addition the slices were incubated with different viral vectors expressing the reporter genes GFP or DsRed. Expression of these reporter genes was measured at 72 h after infection.
RESULTS： With the Krumdieck tissue slicer, uniform slices could be generated from pancreatic tissue but only upon embedding the tissue in 3% low melting agarose. Immunohistological examination showed the presence of all pancreatic cell types. Pancreatic normal and cancer tissue slices could be cultured for up to 6 d, while retaining viability and a moderate to good morphology. Reporter gene expression indicated that the slices could be infected and transduced efficiently by adenoviral vectors and by adeno associated viral vectors, whereas transduction with lentiviral vectors was limited. For the adenoviral vector, the transduction seemed limited to the peripheral layers of the explants.
CONCLUSION： The presented system allows reproducible processing of minimal amounts of pancreatic tissue into slices uniform in size, suitable for pre-clinical evaluation of gene therapy vectors.     

Debridement arthroscopy. 10-year followup.

The treatment of osteoarthritis of the knee is a difficult problem. In the senior author's opinion, nonaggressive arthroscopic debridement of the knee is an effective procedure to relieve pain and restore function in patients with osteoarthritis of the knee. A subjective telephone interview of patients done 10 or more years after arthroscopic debridement evaluated the long term results of this treatment in patients with osteoarthritis of the knee. The patients all were candidates for total knee replacement who selected arthroscopy as a temporizing procedure. Of the 191 knees in patients undergoing arthroscopic debridement, 77 patients (91 knees) were contacted for followup. Sixty-seven percent of the 91 knees did not have total knee arthroplasty at an average of 13.2 years followup. The Tegner activity score averaged 3.5 and patient satisfaction averaged 8.6 on a 0 to 10 scale. Twenty-one patients (30 knees) or (33%) had total knee arthroplasty at an average of 6.7 years. Seven of these had total knee arthroplasty within 2 years of arthroscopic debridement. Six of these seven knees had Outerbridge Grade 4 articular cartilage changes and clinically significant meniscus tears. Seven of the 19 knees (37%) with Outerbridge Grade 4 changes in 80% of one knee compartment did not require total knee arthroplasty after greater than 10 year followup. The difficulties in long term followup in this patient population is evident, yet the number of patients who had a functional lifestyle after arthroscopic debridement was notable.     

The effect on the safety of intravenous immunoglobulin of testing plasma for antibody to hepatitis C

BACKGROUND: The safety of intravenous immunoglobulin (IGIV), manufactured from units testing negative for antibody to hepatitis C virus (anti-HCV), was investigated. STUDY DESIGN AND METHODS: A study involving five chimpanzees was performed to determine whether the safety of IGIV would be compromised if units of plasma that reacted for anti-HCV were withheld from pools from which IGIV is manufactured. In the first phase of the experiment, two chimpanzees were infused with 25 mL per kg of unprocessed, pooled plasma from 2887 donors who did not react for anti-HCV in single-antigen (c100-3) enzyme-linked immunosorbent assays. In the second phase, each of three chimpanzees was infused with 1000 mg per kg of IGIV manufactured from the same plasma units. The immunoglobulin was made by seven United States- licensed manufacturers, each using its own approved method. Each chimpanzee received an equal dose of each manufacturer's IGIV. RESULTS: The two chimpanzees that received anti-c100-3-nonreactive, unprocessed pooled plasma became infected with HCV. The three chimpanzees infused with IGIV did not show any evidence of infection with HCV 15 months after inoculation. Two of these animals were challenged with human non- A,non-B hepatitis-infectious plasma, and both subsequently showed evidence of HCV infection. CONCLUSION: These studies demonstrate that, as determined by infectivity for chimpanzees, 1) the withholding of plasma units that react for anti-c100-3 from pools from which plasma products are manufactured does not render the source material noninfectious, and 2) the safety of IGIV manufactured from such plasma pools is not compromised by withholding the units that react for anti- c100-3.