The indications for and timing of haemodialysis in critically ill patients with acute kidney injury in Johannesburg, South Africa.

Background: Acute kidney injury (AKI) is common among patients admitted to the intensive care unit (ICU). It is an independent risk factor for morbidity and mortality. The optimal timing of renal replacement therapy (RRT) remains unknown, resulting in a wide variation in observed current practices. There is a paucity of data on current practices within ICUs in South Africa. Objectives: To describe current practices in the timing of RRT in patients with AKI admitted to the ICU. The secondary objectives were to describe the patient characteristics, severity of illness scores, staging at initiation of RRT, outcome at ICU discharge, and to estimate and describe delays in the initiation of RRT. Methods: A retrospective, descriptive study was conducted in an adult academic ICU in Soweto from 1 January 2014 to 31 December 2015. Results: There were 2 152 ICU admissions over the 2 years. Less than a tenth of the patients (3.5%; n=76) required RRT and the majority had sepsis (83%). The most common indication for RRT was oliguria/anuria (50%; n=38), followed by worsening urea/creatinine (29%; n=22), metabolic acidosis (11.8%; n=9), refractory hyperkalaemia (5.3%; n=4), fluid overload (2.6%; n=2) and other (1.3%; n=1). More than half of the patients (55%; n=42) had RRT instituted on admission day (D0 ), while 45% (n=34) had RRT initiated after D0 (D1-21). RRT was initiated at stage 3 AKI in 90% and 94% of D0 RRT group and D1-21 RRT group, respectively. The median (interquartile range (IQR)) time to starting RRT was 4 (4) hours once the decision to initiate RRT was made. The composite outcome of death, RRT dependence and diuretic dependence at ICU discharge was 21% and there was no difference between the two groups (p=0.22). The ICU mortality was 3%. Conclusion: The sampled population was young, predominantly male and had post emergency surgery with a high burden of sepsis and HIV. The observed current threshold for RRT was late (stage 3 AKI with classic/emergent indications) with outcomes comparable with the reviewed literature. Contributions of the study: The present study adds insight into the practice of initiating RRT in patients admitted to the ICU with AKI. These data have previously not been described in the South African context. The patient population differed from the literature in that they were young, predominantly male and had post-emergency surgery with a high burden of sepsis and HIV.

LOPP chemotherapy as a first-line treatment for dogs with T-cell lymphoma.

BACKGROUND: The aim of this study was to describe the use of a lomustine (CCNU), vincristine, procarbazine and prednisolone (LOPP) protocol used for treatment of chemotherapy naive T-cell lymphoma patients and to describe the response rate, toxicity and disease-free interval compared historically to CHOP chemotherapy. MATERIALS AND METHODS: Retrospective case study of 31 dogs with naïve T-cell lymphoma treated with a lomustine (CCNU), vincristine, procarbazine and prednisolone (LOPP) protocol. RESULTS: Thirty-one dogs with T cell lymphoma were treated. The overall response rate was 97%. Of the 30 dogs that had a response to LOPP chemotherapy, the median disease free interval was 176 days (range 0-1745 days). The median overall survival time for this study group was 323 days (range 51-1758 days). All deaths in this study were attributable to lymphoma. CONCLUSION: LOPP chemotherapy for T cell lymphoma is well tolerated with a low toxicity profile and an excellent overall response rate. This protocol showed minimal toxicity and comparable disease free interval and survival times for canine high grade T cell lymphoma treated with CHOP.

Negative pressure wound therapy using a portable single-use device for free skin grafts on the distal extremity in seven dogs.

OBJECTIVE: Retrospective study to describe clinical experience with a portable single-use negative pressure wound therapy device after application of full-thickness meshed skin grafts to wounds on the distal extremities of seven dogs. METHODS: Seven dogs were treated with portable NPWT after receiving skin grafts; six as the result of tumour resection and one for traumatic injury. Medical records were reviewed and data recorded on patient signalment, cause and location of wound, surgical technique, application and maintenance of portable NPWT, graft survival and outcome, and complications encountered with the system. CLINICAL OUTCOMES: NPWT was provided for between 4 and 7 days. Five patients were discharged from hospital during the treatment period. Application and maintenance of the portable device was technically easy and no major complications were encountered. Minor complications consisted of fluid accumulation in the evacuation tubing. All dogs achieved 100% graft survival. CONCLUSIONS: Application and maintenance of the portable device was technically straightforward. All dogs receiving portable NPWT after transfer of a free skin graft to the distal extremity had a successful outcome.

Effectiveness of etoposide chemomobilization in lymphoma patients undergoing auto-SCT.

The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and G-CSF (5 µg/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (>2 × 10(6) CD34+ cells collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven percent of patients yielded at least 5 × 10(6) cells in 2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were $14 923 for good mobilizers and $27 044 for poor mobilizers (P<0.05). Using our data, we performed a 'break-even' analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34+ cell count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents.

A carotid stenosis model in canines.

A carotid stenosis model was developed in canines in order to study the effects of systemic blood pressure and hemodilution on cerebrovascular perfusion and metabolism during cardiopulmonary bypass in the setting of significant coexistent inflow stenosis. Under general anesthesia, through a low midline neck incision, the carotid sheath was entered and the carotid artery was isolated and retracted medially. The vertebral artery could be identified posterolaterally. After ligating the vertebral artery with a 00 silk tie, carotid stenosis was created by tying bilateral carotid arteries over an 18-gauge needle using a 00 silk tie. The needle was then removed, leaving a tight stenosis. To determine the degree of stenosis, arteriograms were performed, revealing high-grade lesions of greater than 90% stenosis in the carotid arteries and absence of flow through the vertebral arteries. Cerebral blood flow studies during cardiopulmonary bypass (CPB) were performed, revealing a significant decline. Carotid arteries were harvested at the conclusion of the experiments, revealing tight lesions on direct inspection. The mean gradient measured across stenotic segments was >25 mm Hg. In conclusion, a carotid stenosis model can be created successfully in dogs by ligating the vertebral arteries bilaterally and simply using the shaft of a needle to standardize the lumen size of the carotid arteries. We found the diameter of an 18-gauge needle sufficient to produce stenoses of greater than 90% as evidenced by arteriograms.

CYP2E1-mediated modulation of valproic acid-induced hepatocytotoxicity.

OBJECTIVES: To determine the cytotoxicity of valproic acid (VPA) and its metabolite, 4-ene-valproic acid (4-ene-VPA) in human hepatoblastoma cells (Hep G2), and to study the modulatory effect of cytochrome P450 2E1 induction in this model. METHODS: Cells were exposed to VPA or 4-ene-VPA in the presence of either ethanol (EtOH), or EtOH combined with disulphiram (DS). Some cells were exposed to alpha-fluoro-VPA or to alpha-fluoro-4-ene-VPA in the absence of CYP2E1 inducers. Apoptosis and necrosis were measured by analyzing 6000 cells per sample using transmission electron microscopy, while cytokine release and apoptosis were quantitated by ELISA. RESULTS: VPA + EtOH increased VPA cytotoxicity. 4-ene-VPA + EtOH significantly increased toxicity, while DS + EtOH significantly reduced this toxicity. Alpha-fluorinated analogues reduced cytotoxicity compared to the corresponding VPA compounds. Neither VPA nor alpha-fluorinated VPA increased the release of IL-6 or TNF-alpha in media. A significant increase in the release of TNF-alpha was observed in cells exposed to 4-ene-VPA that further increased with EtOH exposure. CONCLUSIONS: Cells exposed to 4-ene-VPA experience greater cytotoxicity than those treated with VPA. Cytochrome P450 2E1 inducers enhance toxicity in VPA-exposed cells, while alpha-fluorination of VPA diminishes cytotoxicity by directly interfering with the beta-oxidation of the 4-ene-VPA metabolite.

Regional left ventricular systolic function in humans during off-pump coronary bypass surgery.

BACKGROUND: Controversy exists as to whether off-pump CABG with local occlusion results in clinically significant myocardial ischemia during the occlusion period. This study was undertaken to delineate the effects of transient local coronary artery occlusion on regional systolic function. METHODS AND RESULTS: Eight consenting patients undergoing left internal mammary to left anterior descending coronary artery (LAD) bypass were instrumented with a left ventricular pressure catheter and 2 subepicardial cylindrical ultrasonic dimension transducers placed in the minor axis dimension in the region served by the LAD. A digital sonomicrometer was used to collect data before, during, and after coronary occlusion from which percent systolic shortening and pressure-dimension loops were derived. Measuring devices were removed immediately after the final time point. All patients tolerated the procedure well, and there were no complications. Average duration of local occlusion needed for CABG was 15.9+/-4.4 minutes (range, 12 to 26 minutes). Local occlusion was associated with a decrease in peak systolic shortening from 5.8+/-0.8% to 1.8+/-0.8%. In all cases, function returned to baseline after restoration of flow. Pressure-dimension loops confirmed these findings and no evidence of diastolic creep. Linear repression analysis of degree of stenosis versus change in segmental shortening revealed a significant inverse correlation. CONCLUSIONS: Local occlusion of the LAD resulted in a transient decrease in myocardial function during occlusion with complete recovery during reperfusion. This change was less significant with increasing degrees of coronary stenosis. These data suggest that local occlusion is not associated with permanent myocardial injury but that ischemic changes do occur that may be clinically significant, especially in patients with lesser degrees of coronary stenosis.

Autologous superficial femoral vein for aortic reconstruction in infected fields.

Autogenous reconstruction is one option available for patients with aortic graft infection or mycotic aneurysms. We reviewed our recent institutional experience with all patients undergoing aortic reconstruction using autologous superficial femoral vein (SFV). Between February 1995 and November 1997, eight patients (five with prosthetic aortic graft infection and three with mycotic aneurysms, including one ruptured mycotic aneurysm) underwent single-stage aortic reconstruction using autologous SFV. Therapy for graft infection included graft excision and replacement with aortobifemoral or aortofemoral (with subsequent cross femoral) grafts fashioned from the SFV. The two patients undergoing elective repair of mycotic aneurysms were treated with extensive SFV patches, and the patient with a ruptured mycotic aneurysm underwent SFV tube grafting. Autogenous reconstruction of the aorta using the SFV in infected fields shows promise for salvage of life and limb during early experiences and short-term follow-up. Morbidity and mortality rates compare favorably with those from existing series, reconstruction is anatomic, and reinfection potential is low. Long-term follow-up and more extensive experience with this technique are needed to establish its role relative to other conventional methods.

Intraoperative MIDCABG arteriography via the left radial artery: a comparison with Doppler ultrasound for assessment of graft patency.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting involving beating heart left internal mammary artery to left anterior descending coronary artery anastomoses are performed with increasing frequency. Controversy exists regarding the need for intraoperative assessment of graft patency. METHODS: We designed a technique to perform arteriography of the left internal mammary artery by using left radial artery access and standard fluoroscopy to evaluate patency in the operating room. The last 50 of 87 minimally invasive direct coronary artery bypass grafting operations were evaluated by intraoperative arteriography and Doppler ultrasound. Angiograms were performed by the surgeon and involved cannulation and direct injection of contrast medium into the origin of the left internal mammary artery via the left radial artery. RESULTS: Total procedure time was less than 15 minutes. No injuries to the left internal mammary artery were identified. Anastomotic occlusions were identified in 4 cases (8%), 2 of which involved sequential diagonal and left anterior descending anastomoses. These were corrected at the time of surgery with 2 cases requiring conversion to standard coronary artery bypass grafting. Qualitative assessment of grafts with Doppler ultrasound failed to definitively identify these occlusions. There were no deaths and no perioperative infarctions. CONCLUSION: Intraoperative arteriography of the left internal mammary artery can be performed by the surgeon, and a significant number of anastomotic problems may be identified and corrected by using this technique. Therefore, a 100% early graft patency rate may be attainable.

ENT day surgery in England and Wales--an audit by the Royal College of Surgeons (Eng.) Comparative Audit Service.

An audit of day surgery was carried out by the Royal College of Surgeons (Eng.) Comparative Audit service. Data from 121 respondents on over 3,962 day cases were analysed from both retrospective information and from prospective individual patient proformas. The day surgery rate is 31 per cent. The variability of facilities for day-surgery, the timing of lists, type of anaesthetic used and case-mix are discussed. Outcome and the reasons for admission to an overnight bed are analysed. The overall admission rate was found to be 2.8 per cent (range 0.6-19.5 per cent between consultants). Seventy per cent of ENT day-surgery was performed on morning lists which have a lower admission rate than afternoon lists. The main reasons for admission are vomiting 30 per cent, haemorrhage 20 per cent and inadequate recovery from anaesthetic 22 per cent. A more detailed analysis of reasons for admission were given for tonsillectomy, adenoidectomy, FESS, and grommets. Recommendations are given which might increase the scope of safe day-surgery and reduce admission rate.

Selective management of abdominal aortic aneurysms in a prospective measurement program.

PURPOSE: The purpose of this study was to clarify the treatment of patients with small abdominal aortic aneurysms (AAAs) less than 5 cm in diameter and those believed to be unfit for operation with AAAs 5 cm diameter or greater. METHODS: Four hundred ninety two patients with AAAs less than 5 cm when first seen were entered in a prospective measurement program by ultrasonography or computed tomography scan (exclusively after 1998) every 6 months. A decision regarding operative fitness was made when the AAA was 5 cm. Patients then underwent operation if fit or continued follow-up if their AAA was larger than 5 cm but they were unfit. A further group of 91 patients with aneurysms 5 cm or greater when first seen but unfit for repair were entered in the prospective measurement program. RESULTS: In the group with AAAs less then 5 cm at entry, operation was performed in 201 patients as a result of increase in AAA size to 5 cm or greater (157), AAA expansion of more than 0.5 cm in 6 months (24), or for other reasons (20). Of those with AAAs smaller than 5 cm at entry, 291 have not undergone operation at a mean follow-up of 42 months. Expansion was significantly related to aneurysm size at entry and was highest in the 4.5 to 4.9 cm group at 0.7 cm/year. In the group of patients deemed unfit for operation with 5 cm AAAs [as a graduate of the less than 5 cm group at entry (85 patients) or first seen with AAA greater than 5 cm (91 patients)], 10 ruptures have occurred. Of these patients with ruptured AAAs, six had AAAs between 5.0 and 5.6 cm. CONCLUSIONS: Because of the risk of rupture demonstrated in our series in AAAs 5 cm or slightly greater and the progressive increase in expansion to a mean of 0.7 cm/year in those AAAs between 4.5 and 4.9 cm at entry, recommendation for elective operation in patients with AAAs between 4.5 and 4.9 cm at entry, recommendation for elective operation in patients with AAAs between 4.5 and 5.0 cm should be strongly considered in a fit patient.

A single-step purification of biologically active recombinant human interleukin-5 from a baculovirus expression system.

Recombinant human interleukin-5 (rhIL-5) was expressed in baculovirus-infected insect cells and purified to homogeneity from the culture medium in a single chromatographic step. Beginning with a cDNA encoding the full-length precursor form of human IL-5, including the authentic secretory leader sequence, recombinant baculovirus-infected insect cells expressed high levels of rhIL-5 (5-15 mg/liter culture) of which > 90% was processed to the mature form and secreted into the culture medium. After removing cells by centrifugation, rhIL-5 was purified by first adjusting the culture medium to the calculated pI value of mature IL-5 (pI 7.44) and then passing the conditioned medium through tandem linked anion- and cation-exchange columns. The resulting pass-through fraction contained the rhIL-5 and was devoid of contaminating proteins. An optional hydrophobic-interaction chromatography step effectively concentrated the pure homodimeric N-glycosylated rhIL-5 with a high overall yield (> 90%). N-terminal amino acid sequence determination indicated that cleavage of the human IL-5 leader sequence in insect cells occurred between Ala19 and Ile20. Recombinant human IL-5 prepared by this procedure bound to the high-affinity IL-5 receptor present on an eosinophilic leukemia cell line and elicited a proliferative response in the IL-5-dependent murine B-cell line BCL1. This rapid and simple procedure for the expression and purification of mature rhIL-5 should therefore enable studies requiring large amounts of this cytokine.

Complications in ENT--a nationwide audit carried out in November 1992.

We report a prospective audit of complications following ENT surgery during November 1992 from 42 consultants across the United Kingdom. Complications were reported as codes, and results were analysed at the Royal College of Surgeons Comparative Audit Unit. A total of 174 complications were reported, giving an annualized complication rate per consultant of 5.7-7.0% (depending on whether only the most severe complication per patient is counted or all complications). This compares with an annual complication rate of 1.49% reported retrospectively for the year of 1991 by the same consultants.

The extracellular domain of the epidermal growth factor receptor. Studies on the affinity and stoichiometry of binding, receptor dimerization and a binding-domain mutant.

The binding of epidermal growth factor (EGF) or an EGF-like growth factor to the EGF receptor is the initial event which leads to receptor activation, and consequently the induction of cell growth. In order to study this binding interaction in detail, we produced the extracellular domain of the EGF receptor (EGFR) using the baculovirus expression system. Affinity-labeling and Western-blot analyses revealed that the baculovirus-infected insect cells secrete active EGFR extracellular domain relatively efficiently, however a significant amount of inactive EGFR extracellular domain is retained within the cells. The apparent dissociation constant (Kd) of the secreted EGFR extracellular domain for EGF and transforming growth factor alpha (TGF-alpha), as determined using an immobilized receptor binding assay, was approximately 200 nM. Interestingly, this Kd value is 30-40-fold lower than that of the full-length EGFR derived from detergent-solubilized A431 cell membranes. The stoichiometry of binding of the EGFR extracellular domain to EGF and TGF-alpha was examined by band-shift analysis on non-denaturing PAGE and was estimated to be 1:1. We have also shown, using sedimentation equilibrium analysis, that ligand binding induces significant dimerization of the EGFR extracellular domain. Finally, we carried out site-specific mutagenesis on the EGFR extracellular domain in order to define the ligand-binding region. We identified amino acid residues which are close to the binding site since they are common to the epitopes of several ligand-competitive monoclonal antibodies. However, these residues do not contribute directly to ligand binding since the affinity of the mutated EGFR extracellular domain for EGF and TGF-alpha was unaffected.

Royal College of Surgeons comparative ENT audit 1990.

The Royal College of Surgeons Comparative Audit Service was set up in 1990 so that surgeons could pool their audit data, to provide 'standards' with which to compare their own figures. A total of 405 consultant otolaryngologists were circularized in December 1991 inviting them to return data about their resources, workload, case-mix and complications, and about two specific audit topics-Myringoplasty and Carcinoma of the Larynx--for the calendar year 1990. A total of 65 consultants returned proformas with data on 52208 admissions and 31240 surgical procedures. The 'average' respondent admitted 829 patients in the year (19% of these day cases and 14% emergencies) and performed 744 surgical procedures with a mean complication rate of 1.39% using three theatre sessions per week. Cancelled theatre sessions per annum per consultant ranged from 0 to 71. The mean known success rate after myringoplasty was 65%, with hearing improvement in 53%. The 'average' ENT surgeon saw 3.5 new cases of invasive carcinoma of the larynx and treated 69% of these with radiotherapy alone, compared with 14% surgery alone. As well as allowing a profile to be drawn up of the 'average' respondent, this audit allowed individual consultants returning data to compare their own figures in detail with the pooled data, which were presented graphically at a meeting in April 1992.

Occult fever in surgical intensive care unit patients is seldom caused by sinusitis.

Febrile intensive care unit (ICU) patients were evaluated prospectively for sinusitis. Of 598 admissions, 26 patients with transnasal cannulas, ICU stays over 48 hours, and occult fevers were identified. These 26 underwent physical examinations and sinus computed tomographic (CT) scans. Maxillary centeses and cultures were done in patients with CT abnormalities. Patients with positive scans had nasal tubes removed and received decongestants. Scans were abnormal in 19 (73%). All patients with major CT changes had positive maxillary taps. Most infections were polymicrobial; enteric bacilli were common. Fever resolved with nonoperative care in 18 (95%) patients; in only 1 patient was fever primarily from sinusitis. Sinus CT scans are often abnormal in ICU patients with occult fevers and transnasal cannulas. Pneumatic otoscopy can serve as a screening tool. Most patients respond to nonoperative management. Remote infections are often present. Although radiographic nosocomial ICU sinusitis is common, it is seldom the sole source of fever or the proximate cause of significant morbidity.

Thoracoscopic transthoracic dorsal sympathectomy.

The authors report on the three patients who underwent thoracoscopic transthoracic dorsal sympathectomies by the techniques of minimal-access surgery learned from laparoscopic cholecystectomy. All three had histologic confirmation of removal of the sympathetic chain and have had an encouraging early postoperative result. The authors believe that thoracoscopic transthoracic dorsal sympathectomy can be accurately and safely performed and will become the method of choice for dorsal sympathectomy.

The selective management of small abdominal aortic aneurysms: the Kingston study.

The management of small abdominal aortic aneurysms less than 5.0 cm maximum diameter remains controversial particularly in patients who are medically fit. All patients referred with abdominal aortic aneurysms less than 5.0 cm maximum diameter were prospectively followed regardless of their fitness for operation. Two hundred sixty-eight patients had been entered into the study by December 31, 1988, and monitored until December 31, 1990, by at least two aneurysm sizings by ultrasonography, CT scanning, or both. The mean follow-up was 42 months. Operations were performed on 114 patients (if they were fit for operation) when the aneurysm reached 5.0 cm, expanded more than 0.5 cm in a 6-month period, or when the patient had significant occlusive disease requiring repair. In this group the mean annual increase in diameter was 0.9 cm. One hundred fifty-four patients were monitored without operation for a mean period of 42 months. One rupture occurred in this group. The average annual increase in diameter in the group not undergoing operation was 0.24 cm. This study supports a policy of observation for abdominal aortic aneurysms less than 5.0 cm in maximum diameter.