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.

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.

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.

Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies.

BACKGROUND: Breast cancer patients are at increased risk of osteoporosis. Contributing factors include age and/or chemotherapy. The selective estrogen modulator, raloxifene (RAL), effective in the prevention of breast cancer and approved for the treatment and prevention of osteoporosis, may prove beneficial in current breast cancer treatment modules. The purpose of this study was to evaluate RAL in combination with 5-fluorouracil (5-FU) and trimetrexate (TMX) to determine the most effective sequence in which to administer these cell cycle specific agents while taking into consideration the cellular mechanism of action. The goal was to maintain cytotoxicity to breast cancer cells and capitalize on the selective estrogen receptor modulatory effects of RAL. MATERIALS AND METHODS: MCF-7 cells were exposed to (i) TMX, 5-FU or RAL alone, or (ii) RAL 24 h prior to 5-FU followed 2 h later by TMX, or (iii) 5-FU 2 h prior to TMX followed 24 h later by RAL. The cell viability was determined using the Quick Cell Proliferation Assay. RESULTS: The growth rate of MCF- 7 cells exposed to early RAL was 68.25 +/- 4.11% that of the control, however, late RAL exposure produced a growth of 34.75 +/- 4.79% that of the control. Late RAL maintained the cytotoxicity of the regimen. The findings were further supported by cell flow cytometry and Western blot analysis data. CONCLUSION: RAL given prior to 5-FU/TMX significantly compromised cytotoxicity to breast cancer cells.

Sequential combination chemotherapy in human breast cancer: a basis for increased antineoplastic activity and bone marrow protection.

These studies were designed to develop procedures that would capitalize on the growth inhibitory effects of tamoxifen (Tam) and methotrexate (MTX) in breast cancer, while protecting bone marrow with a priming dose of 5-fluorouracil (5-FU). High-dose MTX (10 microM) cytotoxicity is maintained in MCF-7 breast cancer cells but reduced in human bone marrow by a priming and nontoxic dose of 5-FU (10 microM). MTX cytotoxicity is decreased in MCF-7 breast cancer cells when the selective estrogen receptor modulator (SERM) Tam (10 microM) is administered 24 hours prior to 5-FU (10 microM) followed two hours later by MTX (early Tam) resulting in a growth rate of 57.42 +/- 4.38% of the control rate. However, when breast cancer cells are exposed to Tam 24 hours after 5-FU + MTX (late Tam), the interaction between MTX and Tam is not antagonistic, the percentage of the control is 29.47 +/- 4.54%. Bone marrow exposure to these drug combinations exhibits a protective effect to the MTX cytotoxicity, with the early Tam combination yielding 59.45 +/- 16.38% of the control for MTX alone. These studies suggest that a) Tam in combination with a priming dose of 5-FU protects bone marrow from MTX cytotoxicity, b) the interactions between Tam and MTX are sequence-dependent, c) Tam decreases the effect of MTX when Tam administration precedes MTX.

Carboxyl group orientation in K-palmitate/water using 13C double resonance spectroscopy.

13C-NMR is used to probe the motion and orientation of the carboxyl group in a 70% potassium palmitate/30% water mixture. An increase in delta sigma with increasing temperature corresponds to a change of orientation of the carboxyl group. Comparison with 2H-NMR and lineshape simulations show that near 57 degrees C the molecules exchange between two orientations at a rate between 10-500 Hz.

Behaviour of a glycosphingolipid with unsaturated fatty acid in phosphatidylcholine bilayers.

N-(Oleoyl)galactosylceramide with perdeuterated acyl chain was prepared by partial synthesis, and studied by wide line 2H-NMR in phospholipid liposomes. Spectra were obtained for low glycolipid concentrations in bilayers of dimyristoyl-, distearoyl-, and 1-palmitoyl-2-oleoylphosphatidylcholines. In an attempt to isolate the effects of glycosphingolipid fatty acid cis unsaturation on glycolipid behaviour in membranes, spectral findings related to the above species were compared to literature NMR data for pure 1-palmitoyl-2-oleoylphosphatidylcholine bilayers in which the oleoyl chain of the phospholipid had been deuterated, and to analogously deuterated glycerol based lipids in Acholeplasma laidlawii membranes. The results for N-(oleoyl-d33)galactosylceramide proved to be qualitatively and quantitatively very similar to published data dealing with glycerol based lipids at comparable temperatures. In addition, the results were strikingly similar for glycolipids dispersed in saturated and unsaturated phospholipid host matrices. It would appear that the primary effects of cis 9,10 fatty acid unsaturation in glycosphingolipids (at low concentration in fluid phospholipid membranes) are the same as those of fatty acid cis unsaturation in glycerolipids. It further appears that the overall dynamic behaviour of N-(oleoyl)galactosylceramide in fluid phospholipid membranes is very similar to that of glycerolipids with comparable acyl chains.

The temperature dependence of molecular order and the influence of cholesterol in Acholeplasma laidlawii membranes.

2H nuclear magnetic resonance (NMR) of Acholesplasma laidlawii membranes grown on a medium supplemented with perdeuterated palmitic acid shows that at 42 degrees C or above, the membrane lipids are entirely in a fluid state, exhibiting the characteristic 'plateau' in the variation of deuterium quadrupolar splitting with chain position. Between 42 and 34 degrees C there is a well-defined gel-to-fluid phase transition encompassing the growth temperature of 37 degrees C, and at lower temperatures the membranes are in a highly ordered gel state. The 2H-NMR spectra of the gel phase membranes are similar to those of multilamellar dispersions of chain perdeuterated dipalmitoyl phosphatidylcholine (Davis, J.H. (1979) Biophys. J. 27, 339) as are the temperature dependences of the spectra and their moments. The incorporation of large amounts of cholesterol into the membrane removes the gel to fluid phase transition. Between 20 and 42 degrees C, the position dependence of the orientational order of the hydrocarbon chains of the membranes is similar to that of the fluid phase of the membranes without cholesterol, i.e., they exhibit the plateau in the deuterium quadrupolar splittings. However, the cholesterol-containing membranes have a higher average order, with the increases in order being greater for positions near the carbonyl group of the acyl chains. Below 20 degrees C the 2H spectra of the membranes containing cholesterol change dramatically in a fashion suggestive of complex motional and/or phase behaviour.

Bilayer rigidity of the erythrocyte membrane2H-NMR of a perdeuterated palmitic acid probe.

Perdeuterated palmitic acid was intercalated into the human erythrocyte membrane and its motion studied by dueterium nuclear magnetic resonance (2H-NMR). From analysis of temperature dependent changes in the 2H-NMR spectra and from an analysis of derived moments we conclude that the acyl chains of the erythrocyte lipids do not exhibit a detectable phase transition.

2H-NMR investigation of DMPC/glycophorin bilayers.

Deuterium nuclear magnetic resonance spectroscopy was used to investigate the phase equilibria, and the temperature and concentration dependences of the phospholipid hydrocarbon chain order, of mixtures of glycophorin in dimyristoylphosphatidyl-choline. In the fluid phase it is found that the protein has only a slight effect on the first moment of the 2H spectrum, which for perdeuterated chains is a direct measure of the average chain orientational order. However, analysis of the rate of change of the first moment with respect to protein concentration, at different temperatures within the fluid phase, shows that at a molar protein concentration of about 0.0295 +/- 0.01, the lipid chain order (or M1) is essentially independent of temperature. At this concentration the chain order is determined by the lipid's interaction with the protein and one can conclude that about 34 (+/- 12) lipids are required to solvate the protein. At higher lipid concentrations these lipids are freely exchanging, on the NMR time scale, with the other lipids in the bilayer. At glycophorin concentrations below about 1 mol% there is a two-phase coexistence region at temperatures below the pure lipid's chain melting transition. The boundary between the fluid phase and this two-phase region curves downwards (is concave downwards), whereas the boundary between the two-phase region and the gel phase, while naturally occurring at lower temperatures than the upper boundary, is concave upwards. As a consequence the protein partitions preferentially into the fluid phase. This behaviour is similar to that observed in a number of other protein/lipid and peptide/lipid mixtures where it was suggested that those systems may have been close to a critical mixing point and some characteristics of a continuous phase change were noted. Indeed, at glycophorin concentrations near and above 1 mol% there are indications that the phase behaviour becomes more complex, suggesting the presence of significant protein/protein interactions and that this system may be close to a critical point.

Studies on the interaction of human erythrocyte band 3 with membrane lipids using deuterium nuclear magnetic resonance and differential scanning calorimetry.

Human erythrocyte band 3, reconstituted into large unilamellar phospholipid vesicles, has been used as a model system for studying the interactions between membrane lipids and large transmembrane glycoproteins. Both 2H-nuclear magnetic resonance (2H-NMR) and differential scanning calorimetric techniques have been used to probe dimyristoylphosphatidylcholine-band 3 interactions over the temperature range 4-32 degrees C. Analysis of 2H-NMR spectra allowed the assignment of liquid crystal, gel phase and two-phase regions for several protein/lipid mole fractions in the range (1-20) X 10(-4). Sample size was limited by the amount of available glycoprotein and this precluded exact determination of the phase boundaries for this system. The sharp discontinuity in the spectral first moment, M1, seen at the phase transition of the pure phospholipid is progressively diminished by addition of protein, and at the highest protein concentration the first moment varies smoothly between the two phases. For T greater than 26 degrees C or less than 16 degrees C, the moments are relatively insensitive to protein concentration, while between 20 and 26 degrees C the moments increase with protein concentration up to the boundary of the two-phase region. Beyond this boundary, they remain constant or decrease slightly with increasing amount of protein. A preliminary phase diagram for band 3 in this lipid system is presented, based on 2H-NMR data. Differential scanning calorimetry (DSC) showed that addition of glycoprotein dramatically alters the scan shape and tends to extend the coexistence of two phases to higher temperatures.

Orientation of alpha-helical peptides in a lipid bilayer.

Samples of pure lipid (dipalmitoylphosphatidylcholine) and lipid containing short alpha-helical peptides were oriented and examined by X-ray diffraction, together with unoriented samples of pure peptide. X-ray reflections from the bilayer and the alpha-helices showed that the peptides had oriented in the bilayer with their helical axes perpendicular to the surface.

Human erythrocyte membranes are fluid down to -5 degrees C.

This first observation of the deuterium nuclear magnetic resonance (2H-NMR) spectrum of phospholipid molecules incorporated into intact human erythrocyte ghosts shows that the liquid crystalline phase is stable down to a temperature of -5 degrees C. The quality of the 3H-NMR spectra indicate that it is now possible to carry out clinical studies of erythrocyte membranes using the techniques employed in this study.

Phase behaviour of amphotericin B multilamellar vesicles.

Because side effect profiles and key physical properties of liposomal amphotericin B reflect the molecular nature of the hydrated preparations, effort has been directed toward understanding this nature. We describe here an examination by differential scanning calorimetry in the region of the main transition of the phase behaviour of amphotericin B multilamellar liposomes used investigationally for patient treatment. Liposomes were composed of 7:3 dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (7:3 DMPC/DMPG) containing up to 33 mol% drug. Preparations in which pure DMPC or pure 1-oleoyl-2-stearoylphosphatidylcholine (OSPC) was substituted for 7:3 DMPC/DMPG were subjected to the same measurements for comparison. The DSC-derived partial phase diagrams were similar to those previously recorded using EPR spectroscopy for unsonicated liposomes of 7:3 DMPC/DMPG containing amphotericin B, and for mixtures with different pure saturated and unsaturated phosphatidylcholines (Grant, C.W.M., et al. (1989) Biochim. Biophys. Acta 984, 11-20). Fluidization onset temperatures for liposome host matrices were relatively unaffected by drug compared to the temperatures of completion. This effect was particularly marked for the unsaturated phospholipid matrix. Partial phase diagrams were interpreted as demonstrating that amphotericin B has a tendency to separate into a rigid phase within the membrane. This is consistent with molecular modelling considerations which suggest that amphotericin B may exist as oligomers in a phospholipid matrix. Drug-induced alterations of DSC melting profiles for the phospholipid bilayers studied were less extensive than those reported for partially sonicated preparations of 7:3 DMPC/DMPG (Janoff, A.S., et al. (1989) Proc. Natl. Acad. Sci. USA 85, 6122-6126). Melting profiles obtained did not change upon further sample incubation, suggesting that the hydrated preparation represented a thermodynamically stable form.

High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis.

PURPOSE: To determine whether consolidation therapy with high-dose melphalan, etoposide, and total-body irradiation (TBI) with autologous stem-cell support would improve the prognosis for patients with newly diagnosed metastatic Ewing's sarcoma (ES). PATIENTS AND METHODS: Thirty-two eligible patients with newly diagnosed ES metastatic to bone and/or bone marrow were enrolled onto this study. Treatment was initially comprised of five cycles of induction chemotherapy (cyclophosphamide, doxorubicin, and vincristine alternating with ifosfamide and etoposide) and local control. Peripheral-blood stem-cell collection was performed after the second cycle of chemotherapy, with delay if the bone marrow was persistently involved. If patients had a good response to initial therapy, they proceeded to consolidation therapy with melphalan, etoposide, TBI, and stem-cell support. RESULTS: Of the 32 eligible patients, 23 proceeded to high-dose therapy consolidation. Of the nine patients who did not proceed to consolidation, four were secondary to progressive disease and two were secondary to toxicity. Three patients died from toxicity during the high-dose phase of the therapy. The majority of the patients who underwent high-dose consolidation therapy experienced relapse and died with progressive disease. Two-year event-free survival (EFS) for all eligible patients is 20%. The 2-year post-stem-cell reconstitution EFS for the subset of 23 patients who received consolidation therapy is 24%. Analysis of peripheral-blood stem-cell collections by molecular techniques for minimal residual disease showed contamination of at least some samples by tumor cells in all three patients with available data. CONCLUSION: Consolidation with high-dose melphalan, etoposide, TBI, and autologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.

Deuterium Magnetic Resonance Studies of Senescence-Related Changes in the Physical Properties of Rose Petal Membrane Lipids.

The physical properties of membrane lipids in senescing rose (Rosa hybrida L., cv Mercedes) petals were studied by deuterium nuclear magnetic resonance (2H-NMR) and fluorescence depolarization. All of the 2H-NMR spectra arising from deuterated dimyristoylphosphatidylcholine mixed with whole-lipid extracts from membranes of petals of different ages had a shape that is characteristic of liquid-crystalline lipid at 30[deg]C. Arrhenius plots of the moments of the 2H spectra and fluorescence depolarization values measured from 1,6-diphenyl hexatriene-labeled rose petal membrane lipid samples indicated that membrane lipid order increased with decreasing temperature as well as with increasing age of the petals. The latter trend is explained by previously observed increases in fatty acid saturation and increases in the sterol-to-phospholipid ratio that occur in rose petals during senescence. The 2H-NMR spectra obtained at 0[deg]C also contained quadrupolar splitting lines from lipid in the gel phase, confirming the occurrence of this phase in membranes from this tissue.

Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery.

OBJECTIVE: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. METHODS: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 microA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 micrograms/.kg-1 x min-1, intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. RESULTS: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control = 100%, n = 12; SC 30 micrograms = 50%, n = 6; SC 60 micrograms = 0%, n = 6; p < 0.05). SC resulted in a reduction in thrombus weight (p < 0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U.kg-1). SC (60 micrograms.kg-1 x min-1, intravenously, n = 6) or saline (n = 6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p < 0.05). CONCLUSIONS: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor.

Relationship between Russian roulette deaths and risk-taking behavior: a controlled study.

A review of medical examiner records yielded data on 19 men and one woman who died playing Russian roulette. The men differed significantly from 95 male suicide victims who died of gunshot wounds to the head on several variables including age, race, ethnicity, religion, citizenship, marital status, living situation, health, and the likelihood of the death being witnessed. The Russian roulette victims were significantly less likely to die in the bedroom, die in the morning, leave a suicide note, and be depressed but were significantly more likely to have alcohol or drugs in their body fluids and to have a previous history of drug and alcohol abuse.

The very sudden cardiac death syndrome -- a conceptual model for pathologists.

Sudden unexpected death usually involves one of two mechanisms, fast heart stoppage or slow heart stoppage with respiratory arrest. These physiological derangements arise from diverse causes that are sometimes purely functional without structural correlates. The autopsy is considered to be only an investigative tool to be employed and is interpreted in the light of the terminal event, social and medical history, and environmental circumstances.

Complications of cardiac resuscitation.

In a prospective study of the complications of cardiac resuscitation, 705 cases were autopsied to identify the cause of death and the pathologic findings attributable to cardiac resuscitation. Thoracic complications were observed in 42.7 percent of the cases. A total of 31.6 percent had rib fractures, 21.1 percent had sternal fractures, and 18.3 percent were reported as having anterior mediastinal hemorrhage; 20.4 percent of the cases had an upper airway complication. Abdominal visceral complications were noted in 30.8 percent of the cases, and pulmonary complications occurred in 13 percent of the resuscitation population. Life-threatening complications, such as heart and great vessel injuries, occurred in less than .5 percent of the cases.