Development and validation of an instrument for procedure-related death notification.

BACKGROUND: Anaesthesia-related mortality is an important, potentially avoidable cause of perioperative mortality. A procedure-related death notification (PRDN) instrument is completed by relevant medical practitioners after a procedure-related death and is used to audit practice and identify areas of care that require improvement. It is also used in medicolegal investigations when establishing cause of death, and in the case of litigation. The current South African (SA) PRDN instrument, designated the GW7/24 form, contains both surgical and anaesthetic sections and is considered to be outdated, inadequate and in need of revision. OBJECTIVES: To develop and validate a revised anaesthetic section of the SA PRDN instrument that can be used for procedure-related deaths in future and be used to update the GW7/24 form for epidemiological, forensic or academic use. METHODS: Lynn's two-stage model was utilised. After an extensive literature review, a provisional PRDN instrument was developed. This provisional instrument was debated and reviewed at a peer group discussion in which 6 local experts took part. These experts were anaesthetic and forensic pathology specialists who specifically have expert knowledge on procedure-related deaths. A revised PRDN instrument was developed, which was then rated by 8 national experts using a Likert scale. The content validity index (CVI) for each item and for the instrument as a whole was then established. Items with a CVI <0.88 were removed to formulate the final PRDN instrument. RESULTS: The provisional PRDN instrument consisted of 14 domains and 66 items. The revised PRDN instrument consisted of 13 domains and 65 items, of which 3 items with a CVI <0.88 were removed. The final PRDN instrument, after minor revisions based on suggestions from the 8 national experts, consisted of 18 domains and 79 items. Every item on the form was declared relevant and important by the national experts, with the final instrument scoring an overall CVI of 1. CONCLUSIONS: A comprehensive, updated and validated anaesthetic section of the SA PRDN instrument was developed. This could be used as a government and anaesthesiology society-endorsed template when updating the current GW7/24 form.

Critical Care Society of Southern Africa adult patient blood management guidelines: 2019 Round-table meeting, CCSSA Congress, Durban, 2018.

The CCSSA PBM Guidelines have been developed to improve patient blood management in critically ill patients in southern Africa. These consensus recommendations are based on a rigorous process by experts in the field of critical care who are also practicing in South Africa (SA). The process comprised a Delphi process, a round-table meeting (at the CCSSA National Congress, Durban, 2018), and a review of the best available evidence and international guidelines. The guidelines focus on the broader principles of patient blood management and incorporate transfusion medicine (transfusion guidelines), management of anaemia, optimisation of coagulopathy, and administrative and ethical considerations. There are a mix of low-middle and high-income healthcare structures within southern Africa. Blood products are, however, provided by the same not-for-profit non-governmental organisations to both private and public sectors. There are several challenges related to patient blood management in SA due most notably to a high incidence of anaemia, a frequent shortage of blood products, a small donor population, and a healthcare system under financial strain. The rational and equitable use of blood products is important to ensure best care for as many critically ill patients as possible. The summary of the recommendations provides key practice points for the day-to-day management of critically ill patients. A more detailed description of the evidence used to make these recommendations follows in the full clinical guidelines section.

A novel computed tomography guided, transcutaneous approach to treat refractory autophony in patients with a patulous Eustachian tube - a case series.

BACKGROUND: Patulous Eustachian tube is a benign but notoriously difficult condition to treat successfully. Symptoms include autophony of voice and breathing, and aural fullness. METHODS: This paper presents a series of 8 patients (12 ears) for whom a novel computed tomography guided injection of silicone elastomer suspension implant (Vox) was used to treat patulous Eustachian tube. This is the largest and only series in the current literature using this technique. RESULTS: The combined complete and partial symptom resolution rate was 91 per cent. Complications related to the procedure are described. The pros and cons of this novel approach are also discussed in relation to traditional endoscopic transnasal techniques. CONCLUSION: Computed tomography guided injection of Vox for the treatment of patulous Eustachian tube is suggested to be a feasible alternative to endoscopic transnasal approaches, particularly for refractory cases.

THE EFFECT OF ETHNICITY ON THE INCIDENCE OF POSTOPERATIVE NAUSEA AND VOMITING IN MODERATE TO HIGH RISK PATIENTS UNDERGOING GENERAL ANESTHESIA IN SOUTH AFRICA: A CONTROLLED OBSERVATIONAL STUDY.

BACKGROUND: We conducted this prospective controlled observational study to compare the effect of ethnicity on the risk of postoperative nausea and vomiting (PONV) between moderate to high-risk African and non-African patients undergoing general anesthesia. METHODS: Using Apfel score risk factors and predicted length of surgery (>30 minutes), 89 moderate to high risk patients undergoing general anesthesia were recruited in a university hospital between March 2009 and November 2010. Thirty patients in the non-African group and 59 patients in the African group were allocated using an ethnicity self identification questionnaire. Intraoperative anesthesia was standardized. PONV was assessed at 0 minutes, 15 minutes, 90 minutes, 180 minutes, and 24 hours. Generalized linear mixed effects models was used to determine the effect of ethnicity on PONV. RESULTS: Despite similar Apfel scores, cumulative incidence of postoperative nausea was higher in the non-African group at 0 minutes (46.67% vs 22.03%, P = 0.019), 15 minutes (70% vs 23.73%, p<0.001) and 90 minutes (36.67% vs 16.95%, P = 0.04). The non-African group had more episodes of vomiting over 24 hours (13.33% vs 1.69%, P = 0.055). Non-Africans had a 25 times higher reported nausea incidence than Africans over 24 hours. CONCLUSION: The incidence of PONV in non-Africans is significantly higher than in Africans. Non-African ethnicity is an independent risk factor for PONV. Current risk prediction models may be limited in multi-ethnic populations and further investigations are warranted to examine ethnicity as a risk factor.

Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV.

BACKGROUND/AIM: Hepatitis C virus (HCV) is a major threat as almost 3% of the world's population (350 million individual) and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi), a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR), scavenger receptor class B type 1 (SR-B1), and Claudin1 (CLDN1). Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection. RESULTS: In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR), which resulted in a significant decrease in HCV viral copy number. CONCLUSION: From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.

High levels of multidrug resistance in clinical isolates of Gram-negative pathogens from Nigeria.

In Nigeria, quinolones and ß-lactam antibiotics are widely used to treat bacterial infections. This study aimed to identify the prevalence of resistance to these drugs and to determine the mechanisms of resistance to these agents. In total, 134 non-duplicate, Gram-negative enteric isolates of 13 species from different hospitals were investigated for susceptibility to a panel of antibiotics, carriage of plasmid-mediated quinolone and ß-lactam resistance genes, production of extended-spectrum ß-lactamases (ESBLs), and mutations within topoisomerase genes. The level of resistance to all antibiotics tested was extremely high, with minimum inhibitory concentrations for 90% of the organisms (MIC(90) values) of ≥ 256 µg/mL for all drugs. Of the 134 isolates, 92 had mutations within the quinolone resistance-determining region (QRDR) of gyrA or within gyrA and parC. In addition, the plasmid-mediated quinolone resistance genes qnrA, qnrB, aac(6')-Ib-cr and qepA were identified. The qnrD allele, which has previously only been found in Salmonella isolates from China, was identified in two Proteus isolates and one Pseudomonas isolate. Of the 134 isolates, 23 (17.2%) carried aac(6')-Ib-cr, 11 (8.2%) carried a qnr variant and 5 (3.7%) were positive for qepA. Twenty-eight isolates (20.9%) produced ESBL variants, with a CTX-M variant being carried by 25 isolates (18.7%). In addition, six isolates (4.5%) carried ampC variants [ACT-1 (1 isolate), DHA-1 (4 isolates) and CMY-2 (1 isolate)]. This study demonstrates a very high level of multidrug resistance amongst Gram-negative enteric bacilli isolated from different sites from patients in Nigerian hospitals as well as the presence of a variety of plasmid-associated resistance genes, including some identified from Africa for the first time.

Cardiac and kidney hormones cure up to 86% of human small-cell lung cancers in mice.

BACKGROUND: Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, and the kidney hormone urodilatin have anticancer effects in vitro. MATERIALS AND METHODS: These cardiac hormones and urodilatin were infused subcutaneously for 28 days with weekly fresh hormones since they lose biological effects at body temperature for more than a week at 0.3 nm kg(-1) body weight in athymic mice bearing human small-cell lung carcinomas. RESULTS: Long acting natriuretic peptide, vessel dilator, kaliuretic peptide, atrial natriuretic peptide and urodilatin eliminated 86%, 71%, 57%, 43% (P < 0.001 for the cardiac hormones) and 25% (P < 0.05; urodilatin) of the human small-cell lung carcinomas. The treated small-cell lung carcinomas that were not cured grew rapidly, similar to the untreated controls, whose volume was 7 fold larger in 1 week, 18-fold increased in 2 weeks, 39-fold increased in 3 weeks, 63-fold increased in 1 month and 97-fold increased in volume in 6 weeks. One vessel dilator treated small-cell lung carcinoma animal developed a large tumour (8428 mm3 volume) on treatment and this tumour was eliminated with utilizing atrial natriuretic peptide and then long acting natriuretic peptide sequentially. CONCLUSIONS: Four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas in athymic mice. Urodilatin can also eliminate small-cell lung carcinomas but at a lower cure rate of 25%. Unresponsive lesions can be eliminated by utilizing different hormones synthesized by the atrial natriuretic peptide gene in a sequential manner.

Antibiotic susceptibility patterns of Pseudomonas aeruginosa to available antipseudomonal drugs in Ibadan, Nigeria.

Pseudomonas aeruginosa has been reported to be a leading cause ofnosocomial infections. Resistance of this notorious bacterium to commonly used antimicrobial agents is becoming an increasing clinical problem and a recognized public health threat because there are limited number of antimicrobial agents including the antipseudomonal penicillins, cephalosporins, carbapenems, aminoglycosides and fluoroquinolones with reliable activity against it. This study was therefore carried out, using Bauer-Kirby method, to determine the antibiotic susceptibility patterns of Pseudomonas aeruginosa isolates from in-patients and out-patients attending the University College Hospital, Ibadan in Nigeria between June 2004 and May 2006. The isolation rate of Pseudomonas aeruginosa in clinical specimens was found to be 16.8% with the highest occurrence of 41.9% in ear swab followed by 39.3% occurrence in wound swab. The susceptibility pattern showed that 78.3% were sensitive to amikacin and 72.0% to ciprofloxacin. The isolates from the in-patients showed higher resistance to all the antibiotics tested than the isolates from the out-patients, most especially amikacin and ciprofloxacin. However, no consistent antibiotic susceptibility pattern could be established for this pathogenic bacterium based on sources. In conclusion, the Pseudomonas aeruginosa species harboured by in-patients showed higher rates of antibiotic resistance than those of the out-patients. Also amikacin and ciprofloxacin were the two antibiotics found to be most potent against this pathogen.

Urodilatin and four cardiac hormones decrease human renal carcinoma cell numbers.

BACKGROUND: Mortality from renal-cell cancer remains a significant problem with an estimated 12,600 deaths in the United States in 2005 even with current treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide and kaliuretic peptide have significant anti-cancer effects in breast, pancreatic, prostate and colon adenocarcinomas. MATERIALS AND METHODS: These four peptide hormones plus brain natriuretic peptide (BNP), C-natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney by a different post-translational processing of the atrial natriuretic peptide prohormone, were evaluated for their anti-cancer effects in renal carcinomas. RESULTS: Dose-response curves revealed a significant (P < 0.0001) decrease in human renal carcinoma cells with each 10-fold increase in concentration from 1 microm to 100 microm of five of these peptide hormones. There was an 81%, 74%, 66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and long-acting natriuretic peptide, respectively (P < 0.0001 for each), whereas BNP had no effect and CNP decreased renal cancer cell number by 10% (P = 0.04) at their 100 microm concentrations. Three days after treatment with these peptide hormones, the cancer cells began to proliferate again. The four cardiac hormones and urodilatin decreased DNA synthesis from 65-84% (P < 0.00001), whereas BNP and CNP decreased DNA synthesis 3% and 12% (both non-significant). Western blots revealed for the first time natriuretic peptide receptors (NPR)-A, -B and -C were present in the renal cancer cells. CONCLUSIONS: These results indicate that urodilatin and the four cardiac hormones have potent anti-cancer effects by eliminating up to 81% of renal carcinoma cells within 24 h of treatment.

Low urine pH is associated with reduced indinavir crystalluria in indinavir-treated HIV-infected individuals.

Indinavir is a potent HIV-1 protease inhibitor included in current antiretroviral therapeutic regimens. It is associated with renal and urological complications ascribed to indinavir crystalluria. We have previously reported that indinavir crystalluria is frequently observed soon after initiation of therapy. In a cohort of 54 asymptomatic indinavir-naive HIV-1-infected individuals during their first year of treatment with indinavir, approximately 25% of urinalyses (U/A) contained indinavir crystals. Because the determinants of the crystalluria are unknown, we examined the relationship between urine specific gravity (SG) and pH, singly and in combination, and indinavir crystalluria in these subjects. A total of 579 U/A were obtained from the study subjects at their scheduled monthly outpatient medical assessments. The frequency of indinavir crystalluria was lower in U/A with lower pH, irrespective of the SG. Conversely, U/A with high pH (> or = 6.0) had a higher frequency of indinavir crystalluria, which was further influenced by the urine SG. As a result, nearly half of the U/A (46.7%) with high pH (> or = 6.0) and intermediate-high SG (> or = 1.015) contained indinavir crystals. In conclusion, the frequency of indinavir crystalluria in asymptomatic HIV-1 infected individuals during their first year of treatment with indinavir was markedly influenced by the urine pH and SG. Our findings suggest that low urine pH may have a protective effect against indinavir crystalluria across the entire range of urine SG.

Four peptide hormones' specific decrease (up to 97%) of human prostate carcinoma cells.

BACKGROUND: Mortality from prostate cancer remains a significant problem with current treatment(s), with an expected 30 350 deaths from prostate cancer in 2005. Long-acting natriuretic peptide, vessel dilator, kaliuretic peptide and atrial natriuretic peptide have significant anticancer effects in breast and pancreatic adenocarcinomas. Whether these effects are specific and whether they have anticancer effects in prostate adenocarcinoma cells has not been determined. MATERIALS AND METHODS: These peptide hormones were evaluated to determine if they have specific anticancer effects in human prostate adenocarcinomas. RESULTS: Dose-response curves revealed a significant (P < 0.05) decrease in human prostate cancer number with each tenfold increase in the concentration from 1 microM to 1000 microM (i.e. 1 mM) of these four peptide hormones. There was a 97.4%, 87%, 88% and 89% (P < 0.001 for each) decrease in prostate cancer cells secondary to vessel dilator, long-acting natriuretic peptide, kaliuretic peptide and atrial natriuretic peptide, respectively, at their 1-mM concentrations within 24 h, without any proliferation in the 3 days following this decrease. These same hormones decreased DNA synthesis from 68% to 89% (P < 0.001). When utilized with their respective antibodies their ability to decrease prostate adenocarcinoma cells or inhibit their DNA synthesis was completely blocked. Western blots revealed that for the first time natriuretic peptide receptors (NPR) A- and C- were present in prostate cancer cells. CONCLUSIONS: These results indicate that these peptide hormones' anticancer effects are specific. Furthermore, they have very potent effects of eliminating up to 97% of prostate cancer cells within 24 h of treatment.

Five cardiac hormones decrease the number of human small-cell lung cancer cells.

BACKGROUND: Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones' effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small-cell lung cancer. METHODS AND MATERIALS: These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small-cell lung cancer cells in culture for 24, 48, 72, and 96 h. RESULTS: Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by 63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P < 0.05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10 microM concentrations. Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A- and C- were present in these cancer cells. CONCLUSIONS: Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.

Tuberculoma of the eye; a case report.

A case of tuberculoma of the eye is reported occurring in a 3-year-old girl. Clinically presenting as a case of leucocoria a pre-operative diagnosis of retinoblastoma was made, necessitating enucleation of the eye. Post-operatively a diagnosis of intraocular tuberculosis was made. The differential diagnosis is discussed and the importance of inclusion of intraocular tuberculoma in the differential diagnosis of retinoblastoma is stressed.

The radial intercepts method for measuring bronchial mucous gland volume.

A new linear method, the radial intercepts method, has been introduced for quantitating the components of the bronchial wall. The method is an adaptation of Rosiwal's (1898) original linear measurement technique, but unlike Rosiwal's the radial intercepts method takes measurements along radii at regular sectoral intervals. The method is reproducible and, from its high correlation with the standard planimetric, cut-weigh, and point-count techniques for quantifying bronchial wall components (Bedrossian, Anderson and Foraker, 1971), it is concluded that the method is reliable.