Private healthcare sector spine surgery: patient and surgeon profiles from a large open medical scheme in South Africa.

Background It is generally understood that the profile of spine surgery varies by setting, based on factors such as the age profile of the population, the economic context and access to healthcare. Relatively little is known about the profile of spine surgery in South Africa, although one previous report from the public healthcare sector suggested a high burden of trauma and infection-related surgery. To our knowledge, there has been no formal investigation in the private sector. A holistic understanding of spine surgery within our setting may be beneficial for applications such as resource allocation and informing the training needs of future specialists.   Objectives To provide insight into spinal surgery in the South African private healthcare sector by describing spine surgery characteristics within a large open medical scheme, including both patient and surgeon profiles.   Methods This retrospective review included adult inpatient spine surgeries funded by the largest open medical scheme in South Africa between 2008 and 2017. An anonymized dataset extracted from the scheme records included patient demographics, ICD-10 codes, procedure codes and surgeon specialization. Descriptive patient and surgery data were presented. Furthermore, the association between patient and surgery factors and surgeon specialization was investigated using univariate and multivariate analyses.   Results A total of 49,576 index spine surgeries were included. The largest proportion of surgeries involved members 40-59 years old (n=23,543, 48%), approximately half involved female members (n=25,293, 51%) and most were performed by neurosurgeons (n=35,439, 72%). At least 37,755 (76%) surgeries were for degenerative pathology, 2,100 (4%) for trauma and 242 (0.5%) for infection. Adjusted risk ratios (aRR) significantly associated with orthopaedic surgeon specialization included cervical spine region aRR = 0.49 (95% C.I. 0.39-0.61), trauma aRR = 1.50 (95% C.I. 1.20-1.88), deformity aRR = 1.77 (95% C.I. 1.33-2.35) and blood transfusion aRR = 1.46 (95% C.I. 1.12-1.91).   Conclusion Spine surgery in South Africa's largest open medical scheme was dominated by surgery for degenerative pathology in older adults and was performed largely by neurosurgeons. This constituted a stark contrast to a previous report from the public sector and highlighted a mismatch between exposure during public sector registrar training and private practice post-specialization. The findings support the need for private-public collaboration as well as the importance of spine fellowships for all specialists intending to practice spine surgery.

Incidence of spine surgery in the South African private healthcare sector: ten-year trends within a large open medical scheme.

PURPOSE: Studies from developed countries suggest a dramatic increase in the utilization of spine surgery in recent decades, however less is known about spine surgery rates in the developing world. The aim of this study was to investigate ten-year trends in the incidence of spine surgery within South Africa's largest open medical scheme. METHODS: This retrospective review included adult inpatient spine surgeries funded by the scheme between 2008 and 2017. The incidence of spine surgery was investigated by age group-overall and for degenerative pathologies, fusion and instrumentation. Surgeons per 100,000 members were determined. Trends were evaluated by linear regression and by crude 10-year change in incidence. RESULTS: A total of 49,575 spine surgeries were included. The incidence of surgery for lumbar degenerative pathology showed a significant upward trend among 60-79 year olds but declined among 40-59 year olds. The incidence of lumbar fusion and lumbar instrumentation declined significantly among 40-59 year olds with little change among 60-79 year olds. The ratio of orthopaedic spinal surgeons decreased from 10.2 to 6.3 per 100,000 members whereas the ratio of neurosurgeons decreased from 7.6 to 6.5 per 100,000. CONCLUSION: Spine surgery in the South African private healthcare sector bears some similarity to developed countries in that it is dominated by elective procedures for degenerative pathology. However, the findings did not reflect the marked increases in the utilization of spine surgery reported elsewhere. It is hypothesized that this may be partly related to differences in the supply of spinal surgery.

Development of active tuberculosis in patients treated with biological disease-modifying antirheumatic drugs.

BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) have been shown to be highly effective in the treatment of rheumatic conditions, but may increase the risk of infections. Development of tuberculosis (TB) while on bDMARD therapy is of particular concern in high TB burden settings such as Western Cape Province, South Africa. OBJECTIVES: To describe the diagnosis, management and outcome of patients who developed active TB while receiving a bDMARD. RESULTS: Ten patients who screened negative for TB prior to initiation of a bDMARD subsequently developed active TB. TB was diagnosed between 10 months and 9 years from bDMARD initiation, suggesting new infection, and included 6 cases of extrapulmonary TB. All patients required multiple tests to confirm the diagnosis of TB, and all were successfully treated. CONCLUSIONS: TB can occur in patients on bDMARD therapy despite initial screening, and may have unusual, extrapulmonary manifestations that pose a diagnostic challenge.

Vancomycin-resistant enterococcus bacteraemia in an endemic region: clinical features and genomic analysis: a 12-year cohort.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens with increasing prevalence worldwide. Hospitals in Jerusalem, Israel are known to have high rates of VRE carriage. However, the clonicity of this pathogen in endemic areas remains unclear. METHODS: The medical files of patients with VRE bacteraemia (N=182) hospitalized in the three major hospitals in Jerusalem between 2009 and 2020 were reviewed. These were compared with 100 patients with vancomycin-susceptible enterococcus (VSE) bacteraemia during the same period, and their clinical and demographic characters were analysed. Whole-genome sequencing (WGS) of the VRE isolates was performed, and the results were analysed considering the demographic, epidemiologic and clinical outcome data. RESULTS: Patients with VRE bacteraemia had higher rates of central line use, haematologic malignancy and immunosuppression compared with patients with VSE bacteraemia (63% vs 27%, P<0.001; 25% vs 13%, P=0.02; 24% vs 13%, P=0.04, respectively). Patients with VRE bacteraemia had significantly higher 7- and 30-day in-hospital mortality rates (31% vs 18%, P= 0.02; 57% vs 34%, P<0.001, respectively) and a longer mean hospital stay (39 vs 24 days, P=0.005) than patients with VSE bacteraemia. The WGS results of VRE isolates showed diversity rather than endemicity of a single clone. No clones were associated with specific ethnicity, geographical distribution or worse prognosis. CONCLUSIONS: WGS revealed the occurrence of small unrelated outbreaks rather than the expansion of large clusters in Jerusalem. VRE bacteraemia was found in sicker patients, and was associated with higher mortality and longer hospitalization compared with VSE bacteraemia.

Loss to follow-up among patients diagnosed with spinal tuberculosis at a tertiary hospital in Western Cape Province, South Africa: A retrospective cohort study.

BACKGROUND: Patients diagnosed with spinal tuberculosis (TB) at a major tertiary hospital in Western Cape Province, South Africa, are required to attend regular follow-up at the hospital's outpatient spine clinic and to remain on TB treatment for at least 9 months. This follow-up and lengthy treatment is intended to allow for specialist monitoring of TB treatment response and early identification of secondary complications, and to reduce the risk of recurrence. However, little is known about adherence to these recommendations. OBJECTIVES: The main objectives were to describe (i) loss to spine clinic follow-up (LTFU), and (ii) TB treatment duration among patients diagnosed with spinal TB at the hospital. Secondary objectives were to investigate (i) the association between LTFU and treatment duration, and (ii) factors associated with LTFU. METHODS: This retrospective cohort study included 173 adults diagnosed with spinal TB between 2012 and 2015 and investigated follow-up within 2 years from diagnosis. Clinical, demographic and appointment data were obtained from hospital records and a dataset provided by the provincial Department of Health. LTFU was presented as frequency (%) and as a survival analysis. TB treatment duration was reported as frequency <9 months or ≥9 months, and the association between LTFU and <9 months of treatment was investigated using relative risk (RR) with 95% confidence intervals (CIs). Univariate associations between explanatory variables and LTFU were investigated using simple logistic regression analysis. RESULTS: Patients had a median (interquartile range) age of 36 (29 - 48) years and included 98 females (57%) and 151 individuals (87%) residing <50 km from the hospital. Primary outcomes were that 129 patients (75%) were LTFU within 2 years of diagnosis and 45 (30%) completed <9 months of treatment. The RR of <9 months of treatment was 1.62 (95% CI 1.39 - 1.88) among those LTFU compared with those retained in follow-up. LTFU was not associated with any of the clinical or demographic variables investigated. CONCLUSIONS: Three-quarters of the patients did not complete follow-up at the tertiary hospital spine clinic, and almost one in three received <9 months of TB treatment. Remaining in spine clinic follow-up was significantly associated with receiving at least the minimum duration of TB treatment. However, LTFU could not be predicted from routine clinical and demographic information and is likely to be related to factors not accounted for in the current analysis.

Orthopaedic referrals using a smartphone app: uptake, response times and outcome

Background. It is well established that South Africa (SA) suffers an immense burden of violence and injuries. The responsibility of providing care for these injuries falls mainly on public health services, resulting in overloading of the health system. Prior to a recent intervention, the large burden had been exacerbated by limitations in the traditional referral system that highlighted the need for a better referral system. Vula's smartphone app was introduced at Tygerberg Hospital in August 2016. This study evaluated the uptake, response times and outcomes using this app.Objectives. The main objectives of the study were to describe: (i) the number of referrals; (ii) referral response times; (iii) referring facilities; and (iv) referral outcomes. Secondary objectives were to: (i) evaluate whether the referral outcome pathway was appropriate; and (ii) assess professional conduct and evidence of upskilling.Methods. This retrospective, descriptive study investigated Vula app referrals to the Division of Orthopaedic Surgery at Tygerberg Hospital between 1 August 2016 and 31 March 2017. Vula was advertised to key facilities in the hospital's referral network. All referrals to the division during the study period were systematically included in the analysis of operational outcomes, although some were excluded from the subsequent referral outcome analysis. Operational outcomes included the number of referrals, referring facilities and referral response times. Referral outcome analysis included the clinical diagnosis, referral pathway, whether the referral was used for upskilling and whether it was conducted in a professional manner.Results. A total of 2 275 referrals from 39 different facilities were received during the study period from 238 individual users; 50% of referrals received a response within 11 minutes, while a small percentage received no response. Clinical and demographic characteristics of 1 985 patients included in the referral outcome analysis indicated that the majority of trauma and emergency referrals involved males, with closed fractures being the most frequent clinical presentation. Although the most common referral outcome was immediate transfer, one-third of the patients were treated at the referring hospital with advice only.Conclusions. The large volume of orthopaedic referrals received through the Vula app suggests that Vula represents a successful alternative to traditional referral methods. Referrals managed by advice only could suggest that Vula facilitates some relief for the overburdened trauma services. Future research could further explore Vula's role in strengthening the public health system, including interventions for high-volume referral areas and upskilling of referring health workers

Child and adult spinal tuberculosis at tertiary hospitals in the Western Cape, South Africa: 4-year burden and trend.

The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6-4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.

Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D1, D2/D3, α1, α2, and 5HT2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D2/D3 receptor density, and 50% reduction in 5HT2A receptor density. α1 receptor density remained unaltered in hemi-PD and α2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D2/D3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D2/D3 receptor density.

The efficacy of HI-6 DMS in a sustained infusion against percutaneous VX poisoning in the guinea-pig.

Post-exposure nerve agent treatment usually includes administration of an oxime, which acts to restore function of the enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the oxime such as pralidoxime, atropine and diazepam. In addition to the autoinjector, it is likely that personnel exposed to nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities. As such, there is a need to understand the relationship between dose rate, plasma concentration, reactivation of AChE activity and efficacy, to provide supporting evidence for oxime infusions in nerve agent poisoning. Here, it has been demonstrated that intravenous infusion of HI-6, in combination with atropine, is efficacious against a percutaneous VX challenge in the conscious male Dunkin-Hartley guinea-pig. Inclusion of HI-6, in addition to atropine in the treatment, improved survival when compared to atropine alone. Additionally, erythrocyte AChE activity following poisoning was found to be dose dependent, with an increased dose rate of HI-6 (0.48mg/kg/min) resulting in increased AChE activity. As far as we are aware, this is the first study to correlate the pharmacokinetic profile of HI-6 with both its pharmacodynamic action of reactivating nerve agent inhibited AChE and with its efficacy against a persistent nerve agent exposure challenge in the same conscious animal.

Bioscavenger is effective as a delayed therapeutic intervention following percutaneous VX poisoning in the guinea-pig.

The prolonged systemic exposure that follows skin contamination with low volatility nerve agents, such as VX, requires treatment to be given over a long time due to the relatively short half-lives of the therapeutic compounds used. Bioscavengers, such as butyrylcholinesterase (BChE), have been shown to provide effective post-exposure protection against percutaneous nerve agent when given immediately on signs of poisoning and to reduce reliance on additional treatments. In order to assess the benefits of administration of bioscavenger at later times, its effectiveness was assessed when administration was delayed for 2h after the appearance of signs of poisoning in guinea-pigs challenged with VX (4×LD50). VX-challenged animals received atropine, HI-6 and avizafone on signs of poisoning and 2h later the same combination with or without bioscavenger. Five out of 6 animals which received BChE 2h after the appearance of signs of poisoning survived to the end of the study at 48h, compared with 6 out of 6 which received BChE immediately on signs. All the animals (n=6+6) that received only MedCM, without the addition of BChE, died within 10h of poisoning. The toxicokinetics of a sub-lethal challenge of percutaneous VX were determined in untreated animals. Blood VX concentration peaked at approximately 4h after percutaneous dosing with 0.4×LD50; VX was still detectable at 36h and had declined to levels below the lower limit of quantification (10pg/mL) by 48h in 7 of 8 animals, with the remaining animal having a concentration of 12pg/mL. These studies confirm the persistent systemic exposure to nerve agent following percutaneous poisoning and demonstrate that bioscavenger can be an effective component of treatment even if its administration is delayed.

Relationship between perceived exertion during exercise and subsequent recovery measurements.

The return towards resting homeostasis in the post-exercise period has the potential to represent the internal training load of the preceding exercise bout. However, the relative potential of metabolic and autonomic recovery measurements in this role has not previously been established. Therefore the aim of this study was to investigate which of 4 recovery measurements was most closely associated with Borg's Rating of Perceived Exertion (RPE), a measurement widely acknowledged as an integrated measurement of the homeostatic stress of an exercise bout. A heterogeneous group of trained and untrained participants (n = 36) completed a bout of exercise on the treadmill (3 km at 70% of maximal oxygen uptake) followed by 1 hour of controlled recovery. Expired respiratory gases and heart rate (HR) were measured throughout the exercise and recovery phases of the trial with recovery measurements used to calculate the magnitude of excess post-exercise oxygen consumption (EPOCMAG), the time constant of the EPOC curve (EPOCτ), 1 min heart rate recovery (HRR60s) and the time constant of the HR recovery curve (HRRτ) for each participant. RPE taken in the last minute of exercise was significantly associated with HRR60s (r=-0.69), EPOCτ (r=0.52) and HRRτ (r=0.43) but not with EPOCMAG. This finding suggests that, of the 4 recovery measurements under investigation, HRR60s shows modest potential to represent inter-individual variation in the homeostatic stress of a standardized exercise bout, in a group with a range of fitness levels.

Serving vegetables first: A strategy to increase vegetable consumption in elementary school cafeterias.

Vegetable consumption in the United States is low despite the wealth of evidence that vegetables play an important role in reducing risk of various chronic diseases. Because eating patterns developed in childhood continue through adulthood, we need to form healthy eating habits in children. The objective of this study was to determine if offering vegetables before other meal components would increase the overall consumption of vegetables at school lunch. We served kindergarten through fifth-grade students a small portion (26-33 g) of a raw vegetable (red and yellow bell peppers) while they waited in line to receive the rest of their lunch meal. They then had the options to take more of the bell peppers, a different vegetable, or no vegetable from the lunch line. We measured the amount of each vegetable consumed by each child. Serving vegetables first greatly increased the number of students eating vegetables. On intervention days most of the vegetables consumed came from the vegetables-first portions. Total vegetable intake per student eating lunch was low because most students chose to not eat vegetables, but the intervention significantly increased this value. Serving vegetables first is a viable strategy to increase vegetable consumption in elementary schools. Long-term implementation of this strategy may have an important impact on healthy eating habits, vegetable consumption, and the health consequences of vegetable intake.

Effects of competing news media frames of weight on antifat stigma, beliefs about weight and support for obesity-related public policies.

OBJECTIVES: In the popular news media, public health officials routinely emphasize the health risks of obesity and portray weight as under personal control. These messages may increase support for policies designed to reduce rates of obesity, but can also increase antifat stigma. Less often, the media cover 'Health at Every Size' or 'Fat Rights' perspectives that may have the opposite effects. We investigated how exposure to different 'fat frames' shifts attitudes about weight and support for obesity policies. METHODS: Across four experiments (n=2187), people read constructed news articles framing fatness as negative (unhealthy, controllable, acceptable to stigmatize) or positive (healthy, uncontrollable, unacceptable to stigmatize). RESULTS: Compared with people who read fat-positive frames, people who read fat-negative frames expressed more: belief in the health risks of being fat (d=0.95-1.22), belief weight is controllable (d=0.38-0.55), support for charging obese people more for health insurance (d=0.26-0.77), antifat prejudice (in three out of four experiments, d=0.28-0.39), willingness to discriminate against fat people (d=0.39-0.71) and less willingness to celebrate body size diversity (d=0.37-0.64). They were also less willing to say that women at the lower end of the obese range could be healthy at their weights. Effects on support for public policies, however, were generally small and/or nonsignificant. Compared with a control condition, exposure to fat-positive frames generally shifted attitudes more than fat-negative frames. In experiment 4, adding a message about the unacceptability of weight-based discrimination to unhealthy/controllable news articles only reduced antifat stigma on one of three measures compared with articles adding a discrimination-acceptable message. CONCLUSIONS: Exposure to different news frames of fat can shift beliefs about weight-related health risks and weight-based stigma. Shifting policy attitudes, however, is more challenging.

Impairment of 40-km time-trial performance but not peak power output with external iliac kinking: a case study in a world-class cyclist.

Iliac blood-flow restrictions causing painful and "powerless" legs are often attributed to overtraining and may develop for some time before being correctly diagnosed. In the current study, differences between actual performance parameters and performance parameters predicted from the Lamberts and Lambert Submaximal Cycle Test (LSCT) were studied in a world-class cyclist with bilateral kinking of the external iliac artery before and after surgery. Two performance-testing sessions, including a peak-power-output (PPO) test and a 40-km time trial (TT) were conducted before surgery, while 1 testing session was conducted after the surgery. Actual vs LSCT-predicted performance parameters in the world-class cyclists were compared with 82 symptom-free trained to elite male cyclists. No differences were found between actual and LSCT-predicted PPO before and after surgical intervention. However, there were differences between actual and LSCT-predicted 40-km TT time in the tests performed before the surgery (2:51and 2:55 min:s, respectively). These differences were no longer apparent in the postsurgery 40-km TT (2 s). This finding suggests that iliac blood-flow restrictions seem to mainly impair endurance performance rather than peak cycling performance. A standard PPO test without brachial ankle blood-pressure measurements might not be able to reflect iliac blood-flow restrictions. Differences between actual and LSCT-predicted 40-km TT time may assist in earlier referral to a cardiovascular specialist and result in earlier detection of iliac blood-flow restrictions.

The association between chewing and swallowing difficulties and nutritional status in older adults.

BACKGROUND: The aim of this study was to investigate the associations of chewing and swallowing dysfunctions to nutritional status in older adults. METHODS: This cross-sectional study comprised a convenience sample of 1065 community-dwelling older adults living in rural United States. Dietary assessment included the Block Full Length Food Frequency Questionnaire, 24-hour Food Intake Recall and Mini Nutritional Assessment. Classification of chewing and swallowing difficulties was determined by a criterion of outlined factors. RESULTS: In our sample, 113 (11%) had chewing difficulties, 51 (5%) had swallowing difficulties, and 11 (1%) had both. Compared to the Dietary Reference Intakes (DRIs), the study population was deficient in calories and several nutrients. Mean daily intake in individuals reporting chewing, swallowing, or difficulties with both were 1489 ± 360, 1461 ± 374 and 1374 ± 240 calories respectively. There was no statistically significant difference between the groups. Vitamin A, vitamin E and manganese were significantly lower in those with chewing difficulties while vitamin E and magnesium were significantly lower in individuals with swallowing difficulties (p < 0.05). CONCLUSIONS: These results emphasize the importance of chewing and swallowing difficulties in modulating nutritional outcomes in older adults. These co-morbidities should be monitored in this population and intake of nutrient dense foods should be increased in those at risk.

N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine.

CONTEXT: Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. OBJECTIVE: Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. MATERIALS AND METHODS: Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 µg.kg⁻¹), 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml⁻¹ Mucomyst™ at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. RESULTS: Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO2) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO2) significantly increased, and arterial blood pH and bicarbonate (HCO3⁻) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO3⁻ levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. DISCUSSION: NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving clinically relevant physiological indices affected by sulfur mustard exposure. CONCLUSION: Beneficial effects of nebulized NAC were apparent following inhaled sulfur mustard exposure. Further therapeutic benefit may result from a combination therapy approach.

Transradial approach in the catheterization laboratory: pros/cons and suggestions for successful implementation.

In the last decade the radial access use in the catheterization laboratory has sensibly grown up worldwide. From an initial sporadic use as alternative but challenging vascular approach, radial artery is today utilized by default for percutaneous procedures in many centers. The tangible interest in the transradial approach is also testified by increasing presence of specific sessions in the main interventional meetings and by continuous development of dedicated catheters and ancillary devices by manufacturers. In this review we describe the anatomical characteristics and the technical aspects related to transradial procedure underlying its pros/cons in opposition to femoral access. We also point up practical instructions trying to resolve the main concerns related to an extensive use of radial approach in catheterization laboratory, such as increased operator's discomfort, higher radiation exposure, safety and feasibility for complex high-risk procedures.

4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation.

BACKGROUND: Hyperpigmentary disorders like melasma, actinic and senile lentigines are a major cosmetic concern. Therefore, many topical products are available, containing various active ingredients aiming to reduce melanin production and distribution. The most prominent target for inhibitors of hyperpigmentation is tyrosinase, the key regulator of melanin production. Many inhibitors of tyrosinase are described in the literature; however, most of them lack clinical efficacy. METHODS: We were interested in evaluating the inhibition of skin pigmentation by well-known compounds with skin-whitening activity like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. We compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm skin model culture. For some compounds, the in vivo efficacy was tested in clinical studies. RESULTS: Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC(50)) in the millimolar range. Kojic acid is 10 times more potent with an IC(50) of approximately 500 µmol/L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC(50) of 21 µmol/L. In artificial skin models, arbutin was least active with an IC(50) for inhibition of melanin production > 5000 µmol/L. Kojic acid inhibited with an IC(50) > 400 µmol/L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC(50) below 40 µmol/L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC(50) of 13.5 µmol/L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily two age spots with a formula containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol. CONCLUSION: The present in vitro and in vivo data prove the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.

Myxoma virus induces apoptosis in cultured feline carcinoma cells.

There is growing interest in utilizing replicating oncolytic viruses as cancer therapeutics agents. The effectiveness of myxoma virus-induced oncolysis was evaluated in two feline cancer cell cultures. Although myxoma virus is a rabbit-specific pathogen, protein expression driven by myxoma virus and production of infectious viral particles were detected. Cell death occurred in primary feline cancer cells within 48 h of inoculation with myxoma virus. Future studies to determine if other feline neoplasms are susceptible to myxoma virus infection are warranted.