Anomalous Cosmic Rays and Heliospheric Energetic Particles.

We present a review of Anomalous Cosmic Rays (ACRs), including the history of their discovery and recent insights into their acceleration and transport in the heliosphere. We focus on a few selected topics including a discussion of mechanisms of their acceleration, escape from the heliosphere, their effects on the dynamics of the heliosheath, transport in the inner heliosphere, and their solar cycle dependence. A discussion concerning their name is also presented towards the end of the review. We note that much is known about ACRs and perhaps the term Anomalous Cosmic Ray is not particularly descriptive to a non specialist. We suggest that the more-general term: "Heliospheric Energetic Particles", which is more descriptive, for which ACRs and other energetic particle species of heliospheric origin are subsets, might be more appropriate.

Water-wise hand preparation - the true impact of our practice: A controlled before-and-after study.

BACKGROUND: South Africa (SA) and other countries worldwide are experiencing extreme drought conditions. Since the start of the drought in SA, many ways of saving water have been proposed and innovative water-saving mechanisms have become part of the lives of communities. We investigated water use during surgical scrubbing procedures and possible interventions to reduce water consumption. OBJECTIVES: To compare water use during surgical hand preparation before and after the implementation of specific water-saving interventions. METHODS: This was a non-randomised controlled study, following a before-and-after design, of orthopaedic theatre personnel scrubbing for surgical cases at Tygerberg Hospital, Cape Town. A control (CON) group (n=32) was established to observe standard practice for baseline measurements including total amount of water used, wash time and water flow rate during surgical hand preparation. After this, three interventions were randomly assigned to a single theatre each, where the same variables were measured. Intervention AS entailed using an alcohol scrub (n=18), intervention SN (n=12) had a dedicated assistant to open and close taps during scrubbing, and intervention SW (n=12) made use of adjusted tap levers to allow the surgeon to open and close taps more easily. Analysis of variance was used to detect global differences between groups, and Tukey's post hoc test was performed to detect differences between groups. RESULTS: Significant differences in water use (p<0.001), wash time (p<0.001) and water flow rate (p<0.001) were observed between the four groups. On average, the AS group used the least water per scrub (mean (standard deviation) 0.82 (1.43) L), which was significantly less than the CON (5.56 (1.79) L; p<0.001) and SN (2.29 (0.37) L; p=0.002) groups. The amount of time spent per scrub was significantly less in the AS group than all the other groups (p<0.05 for all comparisons), with no significant differences observed between the CON, SN and SW groups independently. The SW group had the lowest mean water flow rate (0.73 (0.22) L/min), which was significantly lower than the CON group (2.19 (0.84) L/min; p<0.001). The flow rate of the SN group (1.36 (0.66) L/min) was also significantly lower than that of the CON group (p=0.005). CONCLUSIONS: Water use during surgical hand preparation can easily be reduced by implementing easy and effective interventions. The practicality of interventions may differ between institutions, and their acceptance by surgical staff is important to ensure compliance. However, ensuring that alternative scrubbing options are available to surgical staff would equate to substantial savings over time.

Closed traction reduction of cervical spine facet dislocations: compelled by law

Background. Following a 2015 ruling, the South African (SA) Constitutional Court obligates closed reduction of cervical facet dislocations sustained through low-energy injury mechanisms, within 4 hours of injury. Closed traction reduction of cervical facet dislocations requires specific equipment and expertise, which have limited availability in SA.Objectives. To review the time delays, delaying factors and success rate of closed reductions of cervical facet dislocations in a tertiary-level orthopaedic department and training facility, and to consider the feasibility of such a reduction within 4 hours after injury.Methods. The clinical records and imaging screens of patients presenting with cervical facet dislocations to an academic training hospital between November 2008 and March 2016 were retrospectively reviewed, with specific attention to demographic information, mechanism of injury, time delays from injury to treatment and factors resulting in delay, as well as the success rate in closed cervical reduction.Results. Ninety-one patients with cervical dislocation presented during the study period, of whom 69 were included for further review. The mean age at presentation was 37.6 (range 18 - 65) years. Successful reduction was achieved in 71% (n=49) of cases, with a median delay time from injury to reduction of 26 (interquartile range (IQR) 19.50 - 31.75) hours. Only 1 patient of 69 patients received successful reduction within 6 hours after injury. Neurological improvement was noticed in 5 of 53 patients with neurological deficit ­ after successful reduction. Two patients improved with two American Spinal Injury Association (ASIA) grades (from A to C), and 2 improved with one ASIA grade (from A to B and D to E).Conclusions. Successful reduction of a cervical facet dislocation within 4 hours presents a challenge to healthcare infrastructure globally. The relative scarcity of this type of injury (91 cases during 8 years in a tertiary referral hospital) prevents district-level clinicians from readily acquiring a level of experience to confidently perform closed reduction of these injuries, unless very specific training and support are provided towards this end

Medicinal plants cultivated in Bapedi traditional healers homegardens, Limpopo Province, South Africa.

BACKGROUND: Plants used for medicinal purposes are very common feature in Bapedi traditional healer's home-gardens, but information about their diversity and application is not available. MATERIALS AND METHODS: To investigate medicinal plants found in Bapedi healer's home-gardens, 51 traditional health practitioners were interviewed using a semi-structured questionnaire in 17 municipalities of the Limpopo Province of South Africa, during the first half of 2013. RESULTS: A total of 43 plant species (67.4% indigenous and 32.5% exotics) from 32 families, mostly from the Asteraceae and Apocynaceae (9.3% each) were documented. Species cultivated in home-gardens were used to treat three major groups of ailments that include sexually transmitted infections (44.1%), chronic diseases of life style (44.1%) and reproductive ailments (32.5%). The exotics Catharanthus roseus (54.9%) and Carica papaya (15.6%) was the most cultivated. Threatened (11.6%) and protected (6.9%) species are also present in home-gardens, mostly due to their unavailability in natural areas. CONCLUSION: This study concludes that the practice of cultivating medicinal plant species in home-gardens is a positive development that in the long term will sustain both species and accompanying indigenous knowledge, as well as preserve the cultural identity of the Bapedi.

Exotic and indigenous problem plants species used, by the Bapedi, to treat sexually transmitted infections in Limpopo Province, South Africa.

BACKGROUND: The ethnic usage of exotics and indigenous problem plants is a highly debated topic, as legislative requirements over-shadow their potential medicinal value, particularly to treat sexually transmitted infections (STIs). Limited information exists regarding their medicinal value among the Bapedi. OBJECTIVES: To ascertain the importance of exotics and indigenous problem plants in the treatment of STIs, a major global primary health care challenge. METHODS: A field observation and semi-structured questionnaire focussing on species diversity, types of STIs treated and medicinal preparation as well as application was used to collect data from 34 traditional healers. RESULTS: Seven exotics and three indigenous problem species were identified. These species were used to treat four STIs; with Catharanthus roseus illustrating its dominance in the treatment of gonorrhoea. Some medicinal species used by Bapedi traditional healers have been validated through scientific research or through their extensive use by various cultures in South Africa and other parts of Africa. To the best of our knowledge Alternanthera pungens, Caesalpinia decapetala, Cinnamomum verum, and Citrullus lanatus are reported for the first time in the treatment of the investigated STIs. CONCLUSIONS: Exotic and indigenous problem species constitute an important component of the STIs treatment protocol. Their utilization by Bapedi cautions against the narrow-minded approach of indiscriminate eradication, as these species can play a significant role in the primary health care needs of socio-economic vulnerable people.

The long-term variability of cosmic ray protons in the heliosphere: A modeling approach.

Galactic cosmic rays are charged particles created in our galaxy and beyond. They propagate through interstellar space to eventually reach the heliosphere and Earth. Their transport in the heliosphere is subjected to four modulation processes: diffusion, convection, adiabatic energy changes and particle drifts. Time-dependent changes, caused by solar activity which varies from minimum to maximum every ∼11 years, are reflected in cosmic ray observations at and near Earth and along spacecraft trajectories. Using a time-dependent compound numerical model, the time variation of cosmic ray protons in the heliosphere is studied. It is shown that the modeling approach is successful and can be used to study long-term modulation cycles.

Sexually transmitted infections and their diagnoses: Bapedi experience.

BACKGROUND: The global burden of sexually transmitted infections (STIs) is a major concern to the World Health Organization (WHO). OBJECTIVE: To document STIs treated by Bapedi traditional healers and their methods of diagnoses in the Limpopo Province, South Africa. METHODS: A semi-structured questionnaire with closed and open-ended questions was used to collect data from 34 traditional healers, during a face-to-face interview. RESULTS: Five seemingly dissimilar STIs; gonorrhoea, chlamydia, HIV/AIDS, nta (Bapedi-terminology) and syphilis were identified as being treated by Bapedi traditional healers. With the exclusion of HIV/AIDS, all STIs are known by healers via their vernacular names. Not all of the recorded STIs are treated by all the questioned traditional healers. Generally, diagnosis of these infections was based primarily on the presentation of symptoms and certain behavioural traits; mostly unprotected sexual intercourse with multiple partners. CONCLUSION: The current study concludes that Bapedi traditional healers play an important role in the treatment STIs in the Limpopo Province. Of concern is their diagnosis which is based primarily on the presentation of symptoms and behavioural traits, which are not always accurate indicators. Thus, to make their contribution to the treatment and management of STIs beneficial, they have to receive elementary training in diagnostic methods particularly for HIV/AIDS.

Ethnobotanical survey of medicinal plants used by Bapedi healers to treat diabetes mellitus in the Limpopo Province, South Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Bapedi phytomedicine employ a range of plant species to treat diabetes mellitus (DM). Existing literature partially support the use of certain species for this purpose. AIM OF THE STUDY: To report on Bapedi medicinal plants employed to treat DM. MATERIALS AND METHODS: A semi-structured questionnaire was employed to conduct a survey on medicinal plants used by Bapedi traditional healers in their DM management protocol. Fifty-two traditional healers from 16 municipalities, covering three districts, were interviewed during the first half of 2011. RESULTS: A total of 24 plant species belonging to 20 families, mostly from the Asteraceae (13%), Cucurbitaceae and Sapotaceae (8%), were used to treat diabetes mellitus. Plant parts mostly preferred were roots and leaves. A decoction of these is most commonly used to make extracts, which are then taken orally for a period of one week. Mimusops zeyheri (29%), Helichrysum caespititium (25%), Plumeria obtusa (21%), Aloe marlothii subsp. marlothii, Hypoxis iridifolia and Moringa oleifera (17% each), were repeatedly mentioned by the traditional healers as most used for the management of diabetes mellitus in the study area. Plumeria obtusa and Momordica balsamina are exclusively used to treat diabetes mellitus, and only in the Sekhukhune District. CONCLUSION: It is concluded that Bapedi traditional healers do have a basic understanding of the causes and remedial action required in the treatment of diabetes mellitus.

Histological assessment of SJL/J mice treated with the antioxidants coenzyme Q10 and resveratrol.

The muscular dystrophies (MDs) are genetic disorders of muscle degeneration due to mutations in genes that encode a wide variety of proteins. Dysferlinopathy are characterized by the absence of dysferlin in skeletal muscle and an autosomal recessive mode of inheritance. Both histological and ultrastructural pathology have been well established in dysferlinopathy patients and dysferlin-deficient animal models. To our knowledge the effect of antioxidant supplementation on this level has not been described previously. This article therefore focuses on the histopathology to reveal the effect of antioxidant supplementation. The study aimed to determine, at cellular level, the histopathological changes in the SJL/J mouse model following a 90 day trial with antioxidant supplementation. Markedly reduced inflammatory insult in the more affected quadriceps muscles of animals treated with high doses of CoQ10 and a combination of resveratrol/CoQ10 were observed. The outcome provides evidence that high doses of antioxidant supplementation resulted in decreased dystrophic markers and enhanced tissue integrity at cellular level.

Comparative bioavailability of two once-daily tramadol HCl 200 mg extended-release products in healthy volunteers.

An open-label, randomized, 2-way crossover study was conducted to compare the pharmacokinetics of Tramadol Contramid OAD 200 mg tablets and Monocrixo L.P. 200 mg capsules following single-dose administration under fasting conditions in 30 healthy adult volunteers. Serial blood samples were collected at predefined time points over 48 hours post-dose and racemic tramadol and O-desmethyltramadol concentrations in plasma were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Results were compared using an analysis of variance (ANOVA) and the bioequivalence determination was based on the 90% confidence intervals for C(max), AUC(0-t) and AUC(0-infinity). Although the two products were determined to be bioequivalent with respect to C(max) and AUC, the time to reach peak tramadol concentrations was significantly earlier for Tramadol Contramid OAD (6 hours vs. 10 hours). A mean tramadol concentration of 100 ng/ml was attained within 1 hour for Tramadol Contramid OAD compared with > 4 hours for Monocrixo L.P. Both products were well tolerated.

Effect of renal impairment on the pharmacokinetics of eslicarbazepine acetate.

OBJECTIVE: Antiepileptic drugs are often used in patients with some degree of renal impairment. The objective of this study was to evaluate the effect of renal function on the pharmacokinetics of eslicarbazepine acetate (ESL, formerly known as BIA 2-093), a new antiepileptic drug under clinical development. METHODS: ESL pharmacokinetics following 800 mg single dose was characterized in subjects with normal renal function (n=8, control group), and in patients with mild renal impairment (n=8), moderate renal impairment (n=8), severe renal impairment (n=8), and end-stage renal disease requiring hemodialysis (n=8). RESULTS: ESL suffered extensive first-pass hydrolysis to eslicarbazepine (S-licarbazepine), the main active metabolite. While eslicarbazepine Cmax did not significantly differ between the different groups, the extent of systemic exposure, assessed by AUC, increased when renal function decreased. Eslicarbazepine CL/F and CLR were, respectively, 3.40 l/h and 1.04 l/h (17.3 ml/min) in the control group, and 2.10 l/h (35.0 ml/min) and 0.61 l/h (10.2 ml/min) in the mild, 1.60 l/h (26.7 ml/min) and 0.22 l/h (3.7 ml/min) in the moderate, and 1.33 l/h (21.2 ml/min) and 0.09 l/h (1.5 ml/min) in the severe renal impairment groups. Although the total amount of eslicarbazepine recovered in urine until 72 h post-dose was similar in the control and mild renal impairment groups, a decrease was found in the moderate and severe renal impairment groups. Major metabolites recovered in urine were eslicarbazepine and its glucuronide form. Clearance of minor metabolites (R-licarbazepine, oxcarbazepine and their glucuronides) was also dependent on renal function. In patients with end-stage renal disease, dialysis was effective in removing the ESL metabolites from the circulation. CONCLUSIONS: ESL metabolites are excreted primarily by renal route and their clearance is dependent on renal function. ESL dosage adjustment may be necessary in patients with a creatinine clearance <60 ml/min.

Pharmacokinetics of eslicarbazepine acetate in patients with moderate hepatic impairment.

OBJECTIVE: To evaluate the effect of moderate liver impairment on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093, ESL), a novel voltage-gated sodium channel blocker currently in clinical development. METHODS: The pharmacokinetics of ESL following an administration regimen of 800 mg once-daily for 8 days was characterized in patients with moderate liver impairment (n = 8) and in subjects with normal liver function (n = 8, control group). RESULTS: Eslicarbazepine acetate was rapidly and extensively metabolized by first-pass metabolism to its main active metabolite, eslicarbazepine (S-licarbazepine). There were more subjects with measurable plasma concentrations of the parent drug (ESL) in the hepatic impairment group than in the control group, suggesting that first-pass metabolism was slightly decreased by liver impairment. However, ESL plasma concentrations remained very low, representing only about 0.01% of total systemic exposure. No differences in the pharmacokinetics of eslicarbazepine or its metabolites were found between the hepatic impairment and control groups. Urinary excretion of eslicarbazepine and its glucuronide form was similar in the liver impaired and control subjects. The sum of drug moieties recovered in the urine corresponded to 91% of the administered dose in the control group and to 84% of the administered dose in the liver impairment group. CONCLUSION: The pharmacokinetics of ESL was not affected by moderate hepatic impairment. Therefore, patients with mild to moderate liver impairment treated with ESL do not require dosage adjustment.

Humalog Mix25 improves 24-hour plasma glucose profiles compared with the human insulin mixture 30/70 in patients with type 2 diabetes mellitus.

OBJECTIVE: To compare the effects of Humalog Mix25 (Humalog Mix75/25 in the USA) (Mix25) and human insulin 30/70 (30/70) on the 24-hour inpatient plasma glucose (PG) profile in patients with type 2 diabetes mellitus (T2DM). DESIGN: A randomised, open-label, 8-week crossover study. Study insulins were injected twice daily, 5 minutes before breakfast and dinner. SETTING: Four-week outpatient (dose-adjustment) treatment phase, and 3-day inpatient (test) phase. PATIENTS: Twenty-five insulin-treated patients with T2DM (ages 40-66 years), mean (+/- standard error of the mean) (SEM) HbA1c 7.7% +/- 0.23%, and body mass index (BMI) 29.3 +/- 0.83 kg/m2. OUTCOME MEASURES: 24-hour PG profiles, PG excursions after meals, PG area under the curve (AUC), and 30-day hypoglycaemia rate. RESULTS: The 2-hour PG excursions following breakfast (5.5 +/- 0.34 v. 7.2 +/- 0.34 mmol/l, p = 0.002) and dinner (2.4 +/- 0.27 v. 3.4 +/- 0.27 mmol/l, p = 0.018) were smaller with Mix25 than with 30/70. PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 (77.6 +/- 3.8 v. 89.5 +/- 4.3 mmol/h/ml, p = 0.001). PG AUC between lunch and dinner, dinner and bedtime, and bedtime and breakfast did not differ between treatments. Pre-meal and nocturnal PG were comparable. The postprandial insulin requirement for lunch meals was supplied equally by the two insulin treatments. The thirty-day hypoglycaemia rate was low (Mix25 0.049 +/- 0.018 v. 30/70 0.100 +/- 0.018 episodes/patient/30 days, p = 0.586) for both treatments. CONCLUSION: In patients with T2DM, Mix25 improved the 24-hour PG profile with lower postprandial PG excursions than with human insulin 30/70.

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.

Congenital lymphoedema in a child--an unusual diagnosis of ankle oedema seen at a peripheral hospital. A case report.

A patient with congenital lymphoedema--the clinical picture being that of Milroy's disease--is presented. The diagnosis, differential diagnosis and treatment are discussed and the modified autosomal dominant mode of inheritance with sex influence and variable expressivity is described.

Carbamazepine and its major metabolites in plasma: a summary of eight years of therapeutic drug monitoring.

For a period of 8 years, carbamazepine (CBZ) and its two major metabolites carbamazepine-10,11-epoxide (CBZE) and 10,11-dihydroxy-carbamazepine (CBZH) were monitored in plasma of black and white patients visiting outpatient epilepsy clinics. Mean CBZ, CBZE, and CBZH levels found in the black group (n = 451) were found to be significantly lower (p less than 0.0005) than in white patients (n = 2,225). The ratio of CBZE to CBZ levels was found to be significantly lower (p less than 0.0005) for blacks, with CBZ levels within the therapeutic range (5-10 micrograms/ml); the ratio of CBZH to CBZ levels was higher (p less than 0.0005), while there was no significant difference in the ratio of CBZH to CBZE between the two groups. This may indicate a difference in the monooxygenase enzyme activities, whereas the epoxide hydrase activity is probably the same for both groups. A poor linear correlation exists between CBZH and CBZ levels in both groups (for blacks, r = 0.614, n = 451; for whites, r = 0.338, n = 2,225); the correlation is better between CBZE and CBZ (for blacks, r = 0.745; for whites, r = 0.553) and good between CBZH and CBZE (for blacks, r = 0.752; for whites, r = 0.710). Abnormal ratios of CBZH to CBZE were found to be useful indicators of noncompliance in difficult cases presenting with therapeutic levels of CBZ.

The role of the doctor in the evaluation of children with learning problems in a developing country.

Twenty children in a Sub A class in Bophuthatswana were examined by a paediatrician. The examination was carried out during the second half of the school year and the results compared with the school results attained by the children at the end of the year. Although this was only a pilot study with a small group of children, positive results were obtained as far as the general neurological examination and a few other tests, such as asking the child to write his name and asking him to name a number written with the examiner's finger on his palm, and the general impression gained by the paediatrician who examined the children, were concerned.

[Beta-hemolytic streptococci as a cause of sore throat in the Pretoria area]. / Beta-hemolitiese streptokokke as oorsaak van seerkeel in Pretoria en omgewing.

A study was performed in Pretoria on 232 unselected patients who presented with the complaint of sore throat. A throat swab was positive for Lancefield group A beta-haemolytic streptococci in 33,2% of these patients. The incidence was significantly higher in Black patients (45,5%) than in White patients (23,2%) and 12,1% of healthy controls showed a positive culture. No seasonal variation was detected. Throat swabs kept overnight at room temperature were falsely negative for beta-haemolytic streptococci in 43,2% of cases. A correlation was found with certain clinical signs.