Iron burden and endocrine complications in transfusion-dependent thalassemia patients In Sarawak, Malaysia: a retrospective study.

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

Predicting bone scan positivity in non-metastatic castration-resistant prostate cancer.

BACKGROUND: To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort. METHODS: Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations. RESULTS: A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ⩾ 50 ng ml(-1), respectively (P-trend <0.001). Men with PSADT ⩾ 15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan. CONCLUSIONS: PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans.

A calcium prerinse required to form calcium fluoride in plaque from a sodium fluoride rinse.

The purpose of this study is to determine whether a calcium (Ca) prerinse used before a 228 µg/g (ppm) fluoride (F) rinse would induce the formation of 'calcium fluoride-like' (CaF2-like) deposits in human dental plaque. Sixty minutes after the use of the Ca prerinse/F rinse, plaque samples were collected from 10 volunteers, homogenized, and split into 2 aliquots. The plaque mass from one aliquot was then extracted with a 'plaque-like' solution that extracted all the CaF2-like deposits. The total F in both aliquots was then determined and compared. The results demonstrated that, as in previous studies, the Ca prerinse induced large increases in plaque fluid and total plaque F. However, unlike previous results without the Ca prerinse, 30% of the plaque F deposits were CaF2 or CaF2-like. Given that maintaining an elevated F concentration in the vicinity of a developing lesion may play an important role in the cariostatic effect of this ion, and the potential advantages of CaF2-like deposits as an F source, these results suggest that a Ca prerinse may increase the cariostatic effect of topical agents.

Remineralization of demineralized enamel via calcium phosphate nanocomposite.

Secondary caries remains the main problem limiting the longevity of composite restorations. The objective of this study was to investigate the remineralization of demineralized human enamel in vitro via a nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP). NACP were synthesized by a spray-drying technique and incorporated into a dental resin. First, caries-like subsurface enamel lesions were created via an acidic solution. Then, NACP nanocomposite or a commercial fluoride-releasing control composite was placed on the demineralized enamel, along with control enamel without a composite. These specimens were then treated with a cyclic demineralization/remineralization regimen for 30 days. Quantitative microradiography showed typical enamel subsurface demineralization before cyclic demineralization/remineralization treatment, and significant remineralization in enamel under the NACP nanocomposite after the demineralization/remineralization treatment. The NACP nanocomposite had the highest enamel remineralization (mean ± SD; n = 6) of 21.8 ± 3.7%, significantly higher than the 5.7 ± 6.9% for fluoride-releasing composite (p < 0.05). The enamel group without composite had further demineralization of -26.1 ± 16.2%. In conclusion, a novel NACP nanocomposite was effective in remineralizing enamel lesions in vitro. Its enamel remineralization was 4-fold that of a fluoride-releasing composite control. Combined with the good mechanical and acid-neutralization properties reported earlier, the new NACP nanocomposite is promising for remineralization of demineralized tooth structures.

An Octacalcium Phosphate Forming Cement.

The osteoconductive and possibly osteoinductive characteristics of OCP increased the interest in preparation of bone graft materials that contain OCP in its composition. Calcium phosphate cements (CPCs) were prepared using a mixture of α-tricalcium phosphate (α-TCP) and dicalcium phosphate anhydrous (DCPA), with α-TCP / DCPA molar ratio of 1/1 and distilled water or 0.5 mol / L phosphate aqueous solution (pH = 6.1 ± 0.1) as the cement liquid. Hardening time was (30 ± 1) min for the CPC mixed with water and (5 ± 1) min for the CPC mixed with phosphate solution. Diametral tensile strength (DTS), porosity (P), and phase composition (powder x-ray diffraction) were determined after the hardened specimens had been immersed in a physiological-like solution (PLS) for 1 d, 3 d, and 7 d. In CPC specimens prepared with water, calcium hydroxyapatite (HA) was formed and DTS and P were (9.03 ± 0.48) MPa and (37.05 ± 0.20) vol % after 1 d, respectively, and (9.15 ± 0.45) MPa and (37.24 ± 0.63) vol % after 3 d, respectively. In CPC specimens prepared with phosphate solution OCP and HA were formed and DTS and P were (4.38 ± 0.49) MPa and (41.44 ± 1.25) vol % after 1 d, respectively,(4.38 ± 0.29) MPa and (42.52 ± 2.15) vol % after 3 d, respectively, and (4.30 ± 0.60) MPa and (41.38 ± 1.65) vol % after 7 d, respectively. For each group DTS and P did not change with PLS immersion time. DTS was significantly higher and P was significantly lower for CPCs prepared with water. HA formation slightly increased with immersion time from 40 mass % after 1 d to 50 mass % after 3 d in CPCs prepared with water. OCP + HA formation increased with immersion time from 30 mass % after 1 d to 35 mass % after 3 d and to 45 mass % after 7 d in CPCs prepared with 0.5 mol / L phosphate solution.

Novel CaF(2) nanocomposite with high strength and fluoride ion release.

Secondary caries and restoration fracture remain common problems in dentistry. This study tested the hypothesis that combining nano-CaF(2) and glass fillers would yield nanocomposites with high mechanical properties and F release. Novel CaF(2) nanoparticles (56-nm) were synthesized via spray-drying and incorporated into resin. F release increased with increasing the nano-CaF(2) content, or with decreasing pH (p < 0.05). F-release rates at 70-84 days were 1.13 microg/(cm(2) x day) and 0.50 microg/(cm(2) x day) for nanocomposites containing 30% and 20% nano-CaF(2), respectively. They matched the 0.65 microg/(cm(2) x day) of resin-modified glass ionomer (p > 0.1). The nanocomposites had flexural strengths of 70-120 MPa, after 84-day immersion at pH 4, pH 5.5, and pH 7. These strengths were nearly three-fold that of resin-modified glass ionomer, and matched/exceeded a composite with little F release. In summary, novel CaF(2) nanoparticles produced high F release at low filler levels, thereby making room in resin for reinforcement glass. This yielded nanocomposites with high F-release and stress-bearing properties, which may help reduce secondary caries and restoration fracture.

No calcium-fluoride-like deposits detected in plaque shortly after a sodium fluoride mouthrinse.

Plaque 'calcium-fluoride-like' (CaF(2)-like) and fluoride deposits held by biological/bacterial calcium fluoride (Ca-F) bonds appear to be the source of cariostatic concentrations of fluoride in plaque fluid. The aim of this study was to quantify the amounts of plaque fluoride held in these reservoirs after a sodium fluoride rinse. 30 and 60 min after a 228 microg/g fluoride rinse, plaque samples were collected from 11 volunteers. Each sample was homogenized, split into 2 aliquots (aliquots 1 and 2), centrifuged, and the recovered plaque fluid combined and analyzed using microelectrodes. The plaque mass from aliquot 1 was retained. The plaque mass from aliquot 2 was extracted several times with a solution having the same fluoride, calcium and pH as the plaque fluid in order to extract the plaque CaF(2)-like deposits. The total fluoride in both aliquots was then determined. In a second experiment, the extraction completeness was examined by applying the above procedure to in vitro precipitates containing known amounts of CaF(2)-like deposits. Nearly identical fluoride concentrations were found in both plaque aliquots. The extraction of the CaF(2)-like precipitates formed in vitro removed more than 80% of these deposits. The results suggest that either CaF(2)-like deposits were not formed in plaque or, if these deposits had been formed, they were rapidly lost. The inability to form persistent amounts of CaF(2)-like deposits in plaque may account for the relatively rapid loss of plaque fluid fluoride after the use of conventional fluoride dentifrices or rinses.

Strong nanocomposites with Ca, PO(4), and F release for caries inhibition.

This article reviews recent studies on: (1) the synthesis of novel calcium phosphate and calcium fluoride nanoparticles and their incorporation into dental resins to develop nanocomposites; (2) the effects of key microstructural parameters on Ca, PO(4), and F ion release from nanocomposites, including the effects of nanofiller volume fraction, particle size, and silanization; and (3) mechanical properties of nanocomposites, including water-aging effects, flexural strength, fracture toughness, and three-body wear. This article demonstrates that a major advantage of using the new nanoparticles is that high levels of Ca, PO(4), and F release can be achieved at low filler levels in the resin, because of the high surface areas of the nanoparticles. This leaves room in the resin for substantial reinforcement fillers. The combination of releasing nanofillers with stable and strong reinforcing fillers is promising to yield a nanocomposite with both stress-bearing and caries-inhibiting capabilities, a combination not yet available in current materials.

Next generation calcium phosphate-based biomaterials.

It has been close to a century since calcium phosphate materials were first used as bone graft substitutes. Numerous studies conducted in the last two decades have produced a wealth of information on the chemistry, in vitro properties, and biological characteristics of granular calcium phosphates and calcium phosphate cement biomaterials. An in depth analysis of several key areas of calcium phosphate cement properties is presented with the aim of developing strategies that could lead to break-through improvements in the functional efficacies of these materials.

Calcium Fluoride Precipitation and Deposition From 12 mmol/L Fluoride Solutions With Different Calcium Addition Rates.

The effects of different Ca-addition rates on calcium fluoride (CaF2) precipitation and deposition were investigated in 12 mmol/L sodium fluoride solutions to which 0.1 mol/L calcium chloride solution was continuously added at average rates of (5, 7.5, 10, 12.5, 15 or 20) mmol L(-1) min(-1). The changes in ionic fluoride and calcium concentrations, as well as turbidity, were continuously recorded by F and Ca electrodes, and a fiber optic based spectrophotometer, respectively. The F(-) concentration decreased and turbidity increased with time indicating precipitation of CaF2. For the systems with Ca-addition rates of (5, 7.5, 10, 12.5, 15, and 20) mmol L(-1) min(-1), the 1 min CaF2 depositions in the model substrate (cellulose filter paper, pores 0.2 µm) expressed as mean ± SD of deposited F per substrate surface area were (3.78 ± 0.31, 11.45 ± 0.89, 9.31 ± 0.68, 8.20 ± 0.56, 6.63 ± 0.43, and 2.09 ± 0.28) µg/cm(2), respectively (n = 10 for each group). The 1-min F depositions did not show positive correlation to Ca-addition rates. The lowest 1-min F deposition was obtained in the systems with the highest Ca-addition rate of 20 mmol L(-1) min(-1) for which CaF2 precipitation rate reached the maximum value of 0.31 mmol L(-1) s(-1) almost immediately after beginning of reaction (6 s). The largest 1-min F depositions were obtained from the systems with Ca addition rates of (7.5 to 12.5) mmol L(-1) min(-1) in which CaF2 precipitation rates continuously increased reaching the maximum values of (0.13 to 0.20) mmol L(-1) s(-1) after (18 to 29) s, respectively. The 1-min F depositions were greatly enhanced in comparison with the control F solutions that did not have continuous Ca-addition. This indicates that continuous Ca addition that controls the rate of CaF2 formation could be a critical factor for larger F depositions from F solutions. The efficacy of conventional F mouthrinses could be improved with addition of a substance that continuously releases Ca.

Calcium pre-rinse greatly increases overnight salivary fluoride after a 228 ppm fluoride rinse.

BACKGROUND: Large increases in salivary fluoride were reported 1 h after a calcium pre-rinse/NaF rinse. AIMS: This study examined the persistence of these increases. METHODS: 12 subjects rinsed in the evening with water, with a 228 microg/g (ppm) F rinse or with 150 mmol/l calcium lactate followed by a 228 microg/g F rinse. In a second experiment these same patients rinsed with a 912 microg/g F rinse. Saliva samples were obtained the morning after rinsing, centrifuged and the supernatants analyzed. RESULTS: The Ca pre-rinse/228 microg/g F rinse induced an increase in overnight salivary F over the 912 microg/g F rinse (approximately 2.5 times) and a statistically significant increase over the 228 mug/g F rinse (approximately 5.5 times). CONCLUSIONS: The results suggest that a Ca pretreatment may increase the cariostatic effect of topical F agents.

Ca pre-rinse greatly increases plaque and plaque fluid F.

Previous studies demonstrated that a Ca pre-treatment greatly increases salivary F from a subsequent NaF rinse. This study examines if these increases are found in plaque and plaque fluid F. Thirteen individuals accumulated plaque before rinsing with: (1) 12 mmol/L NaF (228 microg/g F), (2) 150 mmol/L Ca rinse, or (3) the Ca rinse followed by the F rinse. One hr later, plaque samples were collected, the plaque fluid was recovered, and the plaque residues were extracted 5 times with pH 6.8 or pH 4.8 buffers, and then by acid. The F in each extract after the Ca rinse/F rinse greatly exceeded the corresponding F from the NaF rinse. Consequently, the Ca rinse/F rinse increased the total plaque F and the plaque fluid F by 12x and 5x, compared with the NaF rinse alone. These and the previous salivary results suggest that a Ca pre-treatment may increase the cariostatic effects of topical F agents.

Effects of calcium phosphate nanoparticles on Ca-PO4 composite.

Nano-particles of dicalcium phosphate anhydrous (DCPA) were synthesized for the first time. The objectives of this study were to incorporate DCPA nano-particles into resin for Ca-PO(4) release to combat dental caries, and to investigate the filler level effects. Nano-DCPA and nano-silica-fused silicon nitride whiskers at a 1:1 ratio were used at filler mass fractions of 0-75%. The flexural strengths in MPa (mean +/- SD; n = 6) of DCPA-whisker composites ranged from (106 +/- 39) at 0% fillers to (114 +/- 23) at 75% fillers, similar to (112 +/- 22) of a non-releasing composite (TPH) (p > 0.1). The composite with 75% fillers in a NaCl solution (133 mmol/L, pH = 7.4, 37 degrees C) yielded a Ca concentration of (0.65 +/- 0.02) mmol/L and PO(4) of (2.29 +/- 0.07) mmol/L. Relationships were established between ion-release and DCPA volume fraction V(DCPA): Ca = 4.46 V(DCPA)(1.6,) and = 66.9 V(DCPA)(2.6). Nano-DCPA-whisker PO(4) composites had high strength and released high levels of Ca-PO(4) requisite for remineralization. These new nano-composites could provide the needed combination of stress-bearing and caries-inhibiting capabilities.

Salivary fluoride from fluoride dentifrices or rinses after use of a calcium pre-rinse or calcium dentifrice.

The low concentration of available calcium (Ca) in oral fluids limits the formation of Ca-mediated fluoride deposits that maintain oral fluoride (F) after a topical F treatment. The purpose of this study was to examine if a high concentration of Ca would increase salivary F when used before a F rinse or dentifrice. We found that a Ca pre-rinse (150 mmol/l Ca lactate) or Ca dentifrice (0.084 g Ca glycerolphosphate per gram dentifrice) used immediately before a 60 s 228-ppm F rinse (12 mmol/l NaF) produced a 4.6x or 3.6x increase (p < 0.05) respectively in the 1 h salivary F concentrations over the F rinse alone. Reducing the post-Ca F rinse to 10 s still produced a significant 2.2x increase in salivary F compared to the 60 s F rinse alone. Used with a conventional 1,100 ppm F (i.e. 1,100 microg F per gram) NaF dentifrice (Crest), the above Ca pre-rinse increased 1 h salivary F levels by 2.3x over the F dentifrice alone. However, a F rinse given before a Ca rinse produced no increase in 1 h salivary F concentrations. Although the persistence of these increases requires further study, these results suggest that a moderately high concentration of Ca given shortly before a F rinse or F dentifrice may increase the cariostatic effect of the F product.

Nano DCPA-whisker composites with high strength and Ca and PO(4) release.

The main challenges facing composite restorations are secondary caries and bulk fracture. The objective of this study was to develop nano DCPA (dicalcium phosphate anhydrous)-whisker composites with high strength and Ca and PO(4) ion release to combat caries. Flexural strength for the nano DCPA-whisker composites at a nano DCPA:whisker mass ratio of 1:2 ranged from (148 +/- 9) MPa to (167 +/- 23) MPa, significantly higher than the (103 +/- 32) MPa of an inlay/onlay commercial control composite without Ca-PO(4) release. The nano DCPA-whisker composite released PO(4) to a concentration of (1.95 +/- 0.13) mmol/L and Ca of (0.68 +/- 0.05) mmol/L. Compared with previous conventional Ca- and PO(4)-releasing composites, the nano DCPA-whisker composites had strengths two-fold higher, and released comparable or higher levels of Ca and PO(4). In conclusion, combining nano-DCPA with whiskers yielded novel composites that released high levels of Ca and PO(4) requisite for remineralization. These high-strength composites may provide a unique combination of stress-bearing and caries-inhibiting capabilities.

Effect of a calcium prerinse on salivary fluoride after a 228-ppm fluoride rinse.

The objective of this study was to determine if a concentrated calcium prerinse given before a fluoride rinse would cause an increase in the post rinse sali vary fluoride (F). A panel of 5 subjects used a 30, 150 or 300 mmol/l calcium lactate prerinse followed by a 1-min NaF rinse. All calcium prerinses significantly increased the 1-hour saliva F relative to the NaF control without a prerinse. The maximum increase was produced by the 150 mmol/l calcium lactate prerinse and was about ninefold higher than the NaF control.

A water setting tetracalcium phosphate-dicalcium phosphate dihydrate cement.

The development of a calcium phosphate cement, comprising tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD), that hardens in 14 min with water as the liquid or 6 min with a 0.25 mol/L sodium phosphate solution as the liquid, without using hydroxyapatite (HA) seeds as setting accelerator, is reported. It was postulated that reduction in porosity would increase cement strength. Thus, the effects of applied pressure during the initial stages of the cement setting reaction on cement strength and porosity were studied. The cement powder comprised an equimolar mixture of TTCP and DCPD (median particle sizes 17 and 1.7 microm, respectively). Compressive strengths (CS) of samples prepared with distilled water were 47.6 +/- 2.4 MPa, 50.7 +/- 4.2 MPa, and 52.9 +/- 4.7 MPa at applied pressures of 5 MPa, 15 MPa, and 25 MPa, respectively. When phosphate solution was used, the CS values obtained were 41.5 +/- 2.3 MPa, 37.9 +/- 1.7 MPa, and 38.1 +/- 2.3 MPa at the same pressure levels. Statistical analysis of the results showed that pressure produced an improvement in CS when water was used as liquid but not when the phosphate solution was used. Compared to previously reported TTCP-DCPD cements, the greater CS values and shorter setting times together with a simplified formulation should make the present TTCP-DCPD cement a useful material as a bone substitute for clinical applications.

Reduction in dentin permeability using mildly supersaturated calcium phosphate solutions.

Treatments that obturate dentin tubules have been used for reducing dentin hypersensitivity. The objective of this study was to determine the effects of multiple treatments with a mildly supersaturated calcium phosphate solution on the hydraulic conductance (Lp) of partially occluded dentin discs in vitro. The treatment solution contained 6.5 mmoll(-1) each of calcium and phosphate, 0.25 mmoll(-1) fluoride, 30 mmoll(-1) KCl, and 50 mmoll(-1) HEPES buffer (pH adjusted to 7.0). The mean baseline Lp (in microlcm(-2)min(-1) H(2)O cm(-1)) was 0.108+/-0.041 (mean +/- S.D.; n=9, microlcm(-2)min(-1) H(2)O cm(-1) = 10.20 microlcm(-2)min(-1)KPa(-1)) and after five consecutive treatments, the mean relative Lp, presented as percentage of baseline, were 71+/-11, 58+/-10, 46+/-18, 40+/-14, and 25+/-10, respectively. The Lp values of the baseline and treatment groups were significantly (P<0.05) different. Consecutive treatments appeared effective in further reducing Lp of dentin discs.

Remineralization effect of a low-concentration fluoride rinse in an intraoral model.

A previous study showed that a sodium hexafluorosilicate-calcium chloride-based two-solution fluoride (F) rinse containing 6 mmol/l of F was more effective than a 12 mmol/l F sodium fluoride rinse in depositing F on tooth surfaces and increasing oral F levels. The present study compared the remineralization effects of these two rinses in an intraoral de- and remineralization model. The results showed that the 6 mmol/l F two-solution rinse produced greater remineralization in increasing lesion mineral contents and reducing lesion depths. The results demonstrated that the effectiveness of an F regimen depends less on the F dose and more on the ability of the treatment to utilize F efficiently for remineralization.