Circulating markers of endothelial activation in canine parvoviral enteritis.

ABSTRACT: Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation. Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3-8.3]) and CRP higher (134 [IQR: 85-195]) compared to controls (8.0 [IQR: 6.9-10.3], p = 0.008; 1 [IQR: 0-7], p < 0.001). No significant difference was found for VCAM- 1 and HMGB-1. A strong correlation was identified between VCAM-1 and segmented neutrophil count (r = 0.612, p < 0.001). Despite the presence of systemic inflammation in CPV enteritis, evidenced by high CRP concentrations, our results suggest circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 failed to show an increase. Endothelial activation with subsequent leukocyte adhesion and transmigration through the endothelium may be affected in CPV enteritis and these findings require further investigation.

Age estimation from anterior cervical vertebral ring apophysis ossification in South Africans.

Age estimation in living individuals around the age of 18 years remains a difficult challenge. In this study, the anterior inferior vertebral ring apophysis development of cervical vertebrae C2, C3, and C4 of 496 white and 478 black South African individuals aged between 15 and 22 years was assessed from cephalometric radiographs. Apophysis development was scored according to a four-stage scoring system. Ancestry and sex differences in apophysis maturation were assessed and likelihood values determined for individuals in each population group being 18 years, based on developmental stages. Regression equations were developed for each ancestry and sex group. The results indicated that the median ages for attainment of stages 0, 1, and 2 were below the 18-year threshold for all ancestry and sex groups. Additionally, WSA males and BSA females attained stage 3 for C2, and WSA females attained stage 3 for C2, C3, and C4, below the 18-year threshold. The presence of stage 0 for black and white males in all three observed vertebrae and stage 1 for black males for C2, C3, and C4, white females for C2 and C3, and white males for C4 indicates an age below 18 years (with a 95% or higher probability). The results indicate that anterior inferior apophysis ossification stages of C2, C3, and C4 can be used as a reliable indicator to determine the likelihood of being 18 years of age at a 95% confidence index level. Apophysis development provides a valuable addition to the methods that can be used to assess age in the adolescent years.

Estimating age and the probability of being at least 18 years of age using third molars: a comparison between Black and White individuals living in South Africa.

Third molar development of 705 White and 563 Black South African individuals aged between 15 and 25 years was assessed from panoramic radiographs obtained from the School of Dentistry, University of Pretoria, South Africa. The maxillary and mandibular left third molars were scored according to a ten-stage scoring system. Ancestry and sex differences in dental maturity were assessed, and the likelihood of an individual being 18 years of age was determined for each developmental stage. Statistically significant differences were noted among ancestry groups for most developmental stages, with South African Black individuals consistently maturing earlier than the White individuals. Statistically significant differences were noted among sex groups for some of the stages, mostly those near the final stages of root development. The results indicate that male third molars completed their development faster than that of females. The likelihood of an individual being 18 years of age based on the third molar development stage for the maxilla and mandible on its own was also determined. Combined likelihood results, for the maxillary and mandibular left third molars for stage H, increased the likelihood of being 18 years to 95% for all the studied ancestry and sex groups.

Preoperative fasting times: Prescribed and actual fasting times at Universitas Hospital Annex, Bloemfontein, South Africa.

BACKGROUND: Guidelines recommend a preoperative fasting period of 6 hours for solid food and 2 hours for clear fluids. Because of fixed meal times and imprecise operation starting times, patients often fast for an extended period of time. OBJECTIVE: To investigate the prescribed preoperative fasting times, and the actual duration of fasting, compared with the internationally accepted fasting times for solid food and clear fluids. METHODS: Patients (N=105) aged 14 - 60 years, who were scheduled for elective surgery in the morning session (list starting time 07h00), were included in this prospective study. On arrival in theatre, all patients were asked when they last ate and drank. Anaesthetic records were used to determine the prescribed fasting times and operation starting times. RESULTS: For solids, patients were most frequently prescribed to start fasting from 22h00 to 00h00 (53.3% and 39.1%, respectively). No patient fasted <8 hours. The median duration of fasting was 14 hours and 45 minutes (range 9 hours and 45 minutes - 19 hours and 5 minutes). For fluids, patients were most frequently prescribed to start fasting from 05h00 (46.7%), 00h00 (27.6%) and 22h00 (7.6%). In practice, no patient ingested fluids after 22h30 or <9 hours preoperatively. The median fasting time for oral fluids was 13 hours and 25 minutes (range 9 hours and 37 minutes - 19 hours and 5 minutes). CONCLUSION: Most patients started fasting too early preoperatively, consequently withholding food and oral fluids for longer than recommended. An increased awareness regarding complications of unnecessarily long fasting times, and interventions to correct this problem, is required.

Assessment of the variability in the dimensions of the intact pelvic canal in South Africans: A pilot study.

Cephalopelvic disproportion is common among Africans and is a major cause of maternal and perinatal mortality and morbidity. As the dimensions of the pelvis may vary between populations and according to stature and age, they need to be considered during childbirth and also in the planning and performance of pelvic and perineal procedures. The aim of this study was to assess the possible variations in the dimensions of the intact pelvic canal in South Africans and their implications. Eighty intact cadaver pelves, belonging to 40 white South Africans (20 males and 20 females) and 40 black South Africans (20 males and 20 females) were used for both metric and geometric morphometric analyses. Pelvic inlet shapes did not differ significantly between groups but pelvic inlet and midpelvic dimensions were the greatest in white South Africans and females. The pubic symphyseal length was the greatest in white males and the smallest in black females, resulting in a smaller pelvic cavity anteriorly than for white females. Pelvic outlet shapes varied significantly between sexes in white South Africans and between white and black males. Females presented with the greatest dimensions. Black South African females presented with an elongated anteroposterior outlet diameter. Certain transverse pelvic diameters correlated positively with age in white males and with height in females. In planning childbirth options, the smaller pelvic inlet of black females and stature-dependent diameters should be considered. Pelvic and perineal surgery may be technically more challenging because of smaller pelvic dimensions in black South Africans, especially in males.

Preoperative fasting times: Prescribed and actual fasting times at Universitas Hospital Annex, Bloemfontein, South Africa

Background. Guidelines recommend a preoperative fasting period of 6 hours for solid food and 2 hours for clear fluids. Because of fixed meal times and imprecise operation starting times, patients often fast for an extended period of time.Objective. To investigate the prescribed preoperative fasting times, and the actual duration of fasting, compared with the internationally accepted fasting times for solid food and clear fluids.Methods. Patients (N=105) aged 14 - 60 years, who were scheduled for elective surgery in the morning session (list starting time 07h00), were included in this prospective study. On arrival in theatre, all patients were asked when they last ate and drank. Anaesthetic records were used to determine the prescribed fasting times and operation starting times. Results. For solids, patients were most frequently prescribed to start fasting from 22h00 to 00h00 (53.3% and 39.1%, respectively). No patient fasted <8 hours. The median duration of fasting was 14 hours and 45 minutes (range 9 hours and 45 minutes - 19 hours and 5 minutes). For fluids, patients were most frequently prescribed to start fasting from 05h00 (46.7%), 00h00 (27.6%) and 22h00 (7.6%). In practice, no patient ingested fluids after 22h30 or <9 hours preoperatively. The median fasting time for oral fluids was 13 hours and 25 minutes (range 9 hours and 37 minutes - 19 hours and 5 minutes).Conclusion. Most patients started fasting too early preoperatively, consequently withholding food and oral fluids for longer than recommended. An increased awareness regarding complications of unnecessarily long fasting times, and interventions to correct this problem, is required

Validation of transition analysis as a method of adult age estimation in a modern South African sample.

The use of advanced statistical methods, such as transition analysis, has transformed adult age estimation into a systematically and statistically appropriate practice. The method developed by Boldsen and colleagues (2002) uses 36 features from the cranial sutures, pubic symphysis and auricular surface to calculate maximum likelihood point estimates and 95% confidence intervals, using the ADBOU computer software. However, when using the method in a geographically and contextually distinct sample, such as South Africa, accuracy and precision is of concern. This study aimed to test the repeatability, accuracy and precision of the transition analysis method, using the ADBOU computer software, on a South African sample. Age estimations were generated, for 149 black individuals from the Pretoria Bone Collection, using three individual components as well as different combinations of components and prior distributions (uniform and informative). The informative prior distributions represented both an archaeological and a forensic context. Cohen's kappa statistic uncovered some failings in the scoring procedure. While the accuracy compared favourably with existing methods, the method lacked satisfactory precision. Although combining the components improved accuracy and precision, removing the cranium from the combination was beneficial in some instances. The influence of population variation was observed in the scoring procedure, reference sample and the prior distributions. Validity may be improved for a South African sample by adding age-related components that have been developed on a relevant population. A prior distribution based on South African mortality rates might also be beneficial.

Age estimation from the acetabulum in South African black males.

Anthropologists are constantly seeking to improve methods for age estimation in the human skeleton. A new method was introduced about a decade ago that assesses the morphological changes that take place in the acetabulum as an individual ages. The pelvis is usually well preserved in forensic cases, which makes this method potentially valuable as an adult age indicator. This method employs seven variables, each with its own set of phases. To test the accuracy and reliability of this method, 100 black South African male acetabula from the Pretoria Bone Collection were assessed based on the criteria described in the original study. Box plots and transition curves were constructed to establish whether progression with age was visible and how it could possibly be modelled. Inter-observer reliability was also assessed by making use of Fleiss's Kappa statistic. Five specimens were used as out-of-sample examples for which maximum likelihood (point) estimates were calculated. The results demonstrated that middle and older individuals' age estimates were vastly underestimated. Inter-observer repeatability was poor, which suggested that the classification system most likely needs to be modified. A discussion and recommendation is given for improvement of reliability and repeatability of this method.

Assessment of skeletal changes after post-mortem exposure to fire as an indicator of decomposition stage.

Forensic anthropologists are tasked with interpreting the sequence of events from death to the discovery of a body. Burned bone often evokes questions as to the timing of burning events. The purpose of this study was to assess the progression of thermal damage on bones with advancement in decomposition. Twenty-five pigs in various stages of decomposition (fresh, early, advanced, early and late skeletonisation) were exposed to fire for 30 min. The scored heat-related features on bone included colour change (unaltered, charred, calcined), brown and heat borders, heat lines, delineation, greasy bone, joint shielding, predictable and minimal cracking, delamination and heat-induced fractures. Colour changes were scored according to a ranked percentage scale (0-3) and the remaining traits as absent or present (0/1). Kappa statistics was used to evaluate intra- and inter-observer error. Transition analysis was used to formulate probability mass functions [P(X=j|i)] to predict decomposition stage from the scored features of thermal destruction. Nine traits displayed potential to predict decomposition stage from burned remains. An increase in calcined and charred bone occurred synchronously with advancement of decomposition with subsequent decrease in unaltered surfaces. Greasy bone appeared more often in the early/fresh stages (fleshed bone). Heat borders, heat lines, delineation, joint shielding, predictable and minimal cracking are associated with advanced decomposition, when bone remains wet but lacks extensive soft tissue protection. Brown burn/borders, delamination and other heat-induced fractures are associated with early and late skeletonisation, showing that organic composition of bone and percentage of flesh present affect the manner in which it burns. No statistically significant difference was noted among observers for the majority of the traits, indicating that they can be scored reliably. Based on the data analysis, the pattern of heat-induced changes may assist in estimating decomposition stage from unknown, burned remains.

Medication adherence, self-care behaviour and knowledge on heart failure in urban South Africa: the Heart of Soweto study.

BACKGROUND: There is a paucity of data on treatment adherence in patients with chronic heart failure (CHF) in Africa. METHODS: We examined the pattern of treatment adherence, self-care behaviour and treatment knowledge in 200 consecutive patients with CHF attending the Chris Hani Baragwanath Hospital, Soweto, South Africa via a combination of questionnaire (100%, n = 200) and pill count (41%, n = 82). RESULTS: Mean age was 56 +/- 14 years, 157 were black African (79%) and 109 (55%) were male. CHF-specific treatment included loop diuretics (93%), beta-blockers (84%), ACE inhibitors (74%), spironolactone (64%) and cardiac glycosides (24%); mean number of medications was 6 +/- 2. Overall, 71% (58 of 82) adhered to their prescribed CHF regimen and individual medication adherence ranged from 64 to 79%. Behavioural adherence varied from 2.5 to 98%. Patient treatment knowledge was poor; 56% could not name medication effects or side effects. However, an average knowledge score of 69% was achieved on 10 questions concerning CHF management. CONCLUSION: As in other regions of the world, non-adherence to complex CHF treatment is a substantial problem in Soweto. Our data confirm the need for a dedicated CHF management programme to optimise CHF-related outcomes in a low-resource environment.

Pharmacokinetic and glucodynamic variability: assessment of insulin glargine, NPH insulin and insulin ultralente in healthy volunteers using a euglycaemic clamp technique.

AIMS/HYPOTHESIS: This single-dose, double-blind, randomised, parallel-group study evaluated the reproducibility in systemic exposure and glucodynamic effect of insulin glargine, NPH insulin (NPH) and insulin ultralente (ultralente) using the manually adjusted euglycaemic clamp technique. METHODS: In total, 36 healthy volunteers received two consecutive s.c. injections (0.4 IU/kg) of glargine, NPH or ultralente with a wash-out period of 7 days between treatments. RESULTS: In healthy volunteers, glargine presented well-reproduced flat concentration profiles and no pronounced peaks in activity. NPH, by contrast, showed well-defined peaks in concentration and glucose disposal, while ultralente had highly variable profiles. Within-subject variability (ANOVA) for insulin exposure over 24 h was 15% for glargine and 19% for NPH, compared with 67% for ultralente (p<0.05, glargine and NPH vs ultralente). The 49% within-subject variability in total glucose disposal (glucose infusion rate [GIR]-AUC0-24 h) with ultralente was about twice as large as the 22% with NPH (p<0.05), but was intermediate with glargine at 31% (p=NS). By contrast, variability in the diurnal time-action profile (SD of diurnal day-to-day differences in GIR) for glargine was 30% (p<0.05) and 50% (p<0.05) less than with NPH and ultralente, respectively. No serious adverse events were reported. CONCLUSIONS/INTERPRETATION: Although representing insulins of different profiles, glargine and NPH showed a high and similar reproducibility of total absorption and glucodynamic effect, whereas ultralente proved to have poor reproducibility. However, while NPH yields peaks in concentration and activity, glargine shows flat and non-fluctuating profiles resulting in less variation in day-to-day 24-h activity.

Biotransformation of insulin glargine after subcutaneous injection in healthy subjects.

OBJECTIVE: It is important to establish pharmacokinetic or pharmacodynamic differences between novel insulin analogues and human insulin. This study examined the primary metabolic degradation products of insulin glargine (LANTUS) in humans. DESIGN: In this single dose, open-label study, insulin glargine was administered subcutaneously at a dose of 0.6 IU/kg; placebo was administered to one control subject. PATIENTS: Four healthy male subjects, plus one control subject, aged 18-50 years were enrolled in this study. MEASUREMENTS: Following insulin glargine administration, blood glucose levels were clamped at the subjects' fasting concentration for 6 h and the amount of 20% glucose infused to maintain this baseline concentration was recorded. Metabolite profiling was performed in plasma and injection site tissue using HPLC and radioimmunoassay (RIA). Pharmacokinetics were evaluated by RIA of serum and plasma immunoreactive insulin levels. The primary pharmacodynamic measure was the glucose infusion rate (GIR). Safety was evaluated by measuring blood glucose concentrations during the clamp and adverse events were observed by the investigator or reported by the subject. RESULTS: Metabolic profiling revealed a clear pattern: insulin glargine is metabolised by sequential cleavage at the carboxy terminus of the B chain, to yield products M1 and M2, which are both structurally similar to human insulin. These degradation products are present both at the injection site and in plasma. CONCLUSION: Thus, during treatment with a subcutaneous injection of insulin glargine, metabolic degradation is likely to be initiated at the injection site and continued within the circulatory system.

Equipotency of insulin glargine and regular human insulin on glucose disposal in healthy subjects following intravenous infusion.

The absolute glucose disposal of insulin glargine (Lantus) was compared to that of regular human insulin in healthy subjects (n=20) using the euglycaemic clamp technique in a single-dose, double-blind, randomized, two-way crossover design. Subjects received 30-minute intravenous infusions of insulin glargine (0.1 IU/kg) or human insulin (0.1 IU/kg) and a 20% glucose solution infused at a variable rate to maintain euglycaemia at the subject's baseline glucose level. At equal baseline blood glucose levels (4.42 mmol/l [range, 4.00-5.16 mmol/l] and 4.42 mmol/l [range, 4.01-4.94 mmol/l], respectively), the area under the glucose infusion rate (GIR) time curves from 0-6 hours (AUC(0-6h)) was within the bioequivalence range (insulin glargine, 663.92 mg/kg; human insulin, 734.85 mg/kg). Both the time to maximum GIR and the suppression of serum C-peptide were similar with insulin glargine and human insulin. The resulting maximum serum insulin concentrations (Cmax) were 151.16 microIU/ml and 202.23 microIU/ml, and the time to Cmax (Tmax) was 30 minutes (the duration of the infusion). The observed differences in the Cmax (the mean value for insulin glargine was about 25% lower than that of human insulin) could be explained by lower cross-reactivity of insulin glargine in the human insulin radioimmunoassay. The employed intravenous route, though definitely not the intended clinical use of insulin glargine, provided the clinical evidence in healthy subjects that on a molar basis insulin glargine is equipotent to regular human insulin regarding glucose disposal.

Lithogenic risk factors in the urine of black and white subjects.

OBJECTIVE: To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. SUBJECTS AND METHODS: The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. RESULTS: Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). CONCLUSION: Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.

Epidemiology and control of schistosomiasis mansoni in communities living on the Cuando River floodplain of East Caprivi, Namibia.

The Cuando River area of eastern Caprivi, Namibia, is highly endemic for Schistosoma mansoni whereas S. haematobium transmission, due to the scarcity of its intermediate host snail, Bulinus africanus, does not occur. Chemotherapy (6-monthly blanket treatments with praziquantel) combined with focal mollusciciding (monthly application of niclosamide) was used in a project in the area to control the disease. Although as many adults and pre-school children as possible were tested and treated, the project concentrated largely on school-age children. It took 3 years for prevalence to decline from > 80% to 20% because of a lack of proper sanitary facilities and piped water supplies and high rates of absenteeism and re-infection. However, intensity of infection decreased more rapidly, from an arithmetic mean of > 200 to < 5 eggs/g faeces. Hepatomegaly was common among school children when the project started but could be seen in only a small percentage of them after 3 years of control. Neither the bovine schistosome, S. mattheei, nor the lechwe schistosomes, S. margrebowiei and S. leiperi, were observed in the excreta of humans living in the area.

Trends in human immunodeficiency virus (HIV) infection among a patient population of an inner-city emergency department: implications for emergency department-based screening programs for HIV infection.

Personnel of inner-city emergency departments (EDs), which are frequently the only source of medical care for many patients, may be in a unique position to detect human immunodeficiency virus (HIV) infection earlier than personnel at other recommended screening sites. To assist development of ED-based screening strategies for HIV infection, we undertook a serosurvey of HIV infection in adult patients attending an ED during a 6-week period in 1992 using an identity-unlinked technique and compared our findings with data collected similarly in 1988. Of 1,606 patients, 183 (11.4%) were HIV-positive, compared with 6.0% in 1988. Seroprevalence rates of HIV infection among patients only at risk of heterosexual transmission increased more than fourfold (7% to 30.3%). CD4+ cell counts were higher in those patients with undiagnosed HIV infection than in those with known HIV infection. Targeting minority patients aged 25-44 years, intravenous drug users, and those patients at heterosexual risk would have identified 87% of patients with new HIV infection, while requiring screening of 41% of the study sample. Targeted voluntary screening programs in certain EDs would likely detect significant numbers of new early HIV infections.

The use of tricure glass ionomer cement as an apical sealant after apicoectomy.

The adaptation and sealing ability of a tricure glass ionomer material (Vitremer), used in a retrograde cavity was assessed and compared with amalgam. Fifty single-rooted, extracted teeth were prepared and filled endodontically. All teeth underwent root resection and retrograde cavities were prepared. The teeth were divided into two groups. One group of 10 teeth received a layer of varnish and an amalgam filling in a retrograde cavity, while the other group of 40 teeth received a layer of primer and a glass ionomer filling. All the teeth were placed in an aqueous solution of Procion Brilliant Blue for 7 days whereafter ground sections were prepared. Micro leakage was determined according to the extend of dye penetration using an image analysis system. The results showed that significantly less dye penetration was observed in teeth filled with the glass ionomer cement than in those with the amalgam.