Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases.

AIMS: Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects. PATIENTS AND METHODS: We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure. RESULTS: Patients were followed up for a mean of 19.5 months (12 to 34). Infection was eradicated in 96 patients with a single procedure and all four recurrences were successfully managed with repeat surgery. Adverse events were uncommon, with three fractures, six wound leaks and three unrelated deaths. Outcome was not dependant on C-M host class, microbial culture, wound leakage or presence of nonunion. CONCLUSION: This single-stage protocol, facilitated by the absorbable local antibiotic, is effective in the treatment of chronic osteomyelitis. It offers a more patient-friendly treatment compared with other published treatment options. Cite this article: Bone Joint J 2016;98-B:1289-96.

Gene reprogramming in exercise-induced cardiac hypertrophy in swine: A transcriptional genomics approach.

Cardiac hypertrophy of the left ventricle (LV) in response to dynamic exercise-training (EX) is a beneficial adaptation to increased workload, and is thought to result from genetic reprogramming. We aimed to determine which transcription factors (TFs) are involved in this genetic reprogramming of the LV in swine induced by exercise-training. Swine underwent 3-6 weeks of dynamic EX, resulting in a 16% increase of LV weight/body weight ratio compared to sedentary animals (P=0.03). Hemodynamic analysis showed an increased stroke volume index (stroke volume/body weight +35%; P=0.02). Microarray-analysis of LV tissue identified 339 upregulated and 408 downregulated genes (false discovery rate<0.05). Of the human homologues of the differentially expressed genes, promoter regions were searched for TF consensus binding sites (TFBSs). For upregulated and downregulated genes, 17 and 24 TFBSs were overrepresented by >1.5-fold (P<0.01), respectively. In DNA-binding assays, using LV nuclear protein extracts and protein/DNA array, signal intensity changes >2-fold were observed for 23 TF-specific DNA probes. Matching results in TFBS and protein/DNA array analyses were obtained for transcription factors YY1 (Yin Yang 1), PAX6 (paired box 6) and GR (glucocorticoid receptor). Notably, PAX6 and GR show lower signals in TFBS and protein/DNA array analyses upon exercise-training, whereas we previously showed higher signals for these factors in the remodeled LV of swine post-myocardial infarction (MI). In conclusion, we have identified transcription factors that may drive the genetic reprogramming underlying exercise-training induced LV hypertrophy in swine. PAX6 and GR are among the transcription factors that are oppositely regulated in LV hypertrophy after exercise-training and MI. These proteins may be at the base of the differences between pathological and physiological hypertrophy.

A population-based study of tuberculosis epidemiology and innovative service delivery in Canada.

OBJECTIVE: To compare and interpret tuberculosis (TB) incidence rates in a Canadian population across two decennials (1989-1998 and 1999-2008) as a benchmark for World Health Organization targets and the long-term goal of TB elimination. The population under study was served by two urban clinics in the first decennial and two urban and one provincial clinic in the second. METHODS: TB rates among Status Indians, Canadian-born 'others' and the foreign-born were estimated using provincial and national databases. Program performance was measured in on-reserve Status Indians in each decennial. RESULTS: In each decennial, the incidence rate in Status Indians and the foreign-born was greater than that in the Canadian-born 'others'; respectively 27.7 and 33.0 times in Status Indians, and 8.0 and 20.9 times in the foreign-born. Between decennials, the rate fell by 56% in Status Indians, 58% in Canadian-born 'others', and 18% in the foreign-born. On-reserve Status Indians had higher rates than off-reserve Status Indians, and the three-clinic model out-performed the two-clinic model among those on-reserve. Rates in the foreign-born varied by World Bank region, and were highest among those from Africa and Asia. CONCLUSION: Status Indians and the foreign-born are at increased risk of TB in Canada. Significant progress towards TB elimination has been made in Status Indians but not in the foreign-born.

A novel mechanism: Erxian Decoction, a Chinese medicine formula, for relieving menopausal syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Many clinical and experimental reports demonstrated that Erxian Decoction (EXD) was effective in relieving menopausal syndrome. AIM OF THE STUDY: The mechanisms of action of EXD were explored on the endocrine and antioxidant regimen. MATERIALS AND METHODS: Menopause causes a decline in both endocrine function and activities of antioxidant enzymes. In this study, 12-month-old female Sprague-Dawley-rats (SD-rats) with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD were assessed by the determination of their serum estradiol level and ovarian mRNA levels of aromatase, which is a key enzyme for biosynthesis of estradiol. Meanwhile, superoxide dismutase-1 (SOD), catalase (CAT) and glutathione peroxidase (GPx-1) in the liver were also determined to assess the effect of EXD on the antioxidant regimen. RESULTS: Results revealed a significant elevation in serum estradiol level and the mRNA level of ovarian aromatase and liver CAT in the EXD-treated menopausal rat model. CONCLUSIONS: The results obtained from mRNA and estradiol level of the present investigation revealed that the EXD relieves the menopausal syndrome involved an increase of endocrine and antioxidant function through, at least, the activation of aromatase and CAT detoxifying pathways.

Genetic diversity and variation of saponin contents in Panax notoginseng roots from a single farm.

Radix notoginseng, the root of Panax notoginseng (Burk.) F. H. Chen, has been widely used in traditional Chinese medicine. Its main components, saponins, have been reported to have many pharmacological activities. To test the general assumption that herbs of a single species planted and harvested from a single location are uniform in chemical and genetic makeup, chemical analysis and DNA fingerprinting were carried out. High-performance TLC together with HPLC analysis were used to analyze 17 randomly sampled 3-year-old roots from a single farm for the presence of six saponins. Five roots showed distinct chemical profiles with changed ratios of ginsenosides Rd/Rg1, Re/Rg1, or Rb1/Rg1. The same samples, together with some 1- and 2-year-old samples, were also subjected to fluorescent amplified fragment length polymorphism (AFLP) analysis, and their internal transcribed spacer 2 (ITS 2) regions were sequenced. Fluorescent AFLP analysis was found to be much more polymorphic than the ITS 2 sequence and showed clear evidence of genetic diversity within the tested population. In conclusion, genetic diversity and variation of saponin contents between individual P. notoginseng roots have been detected. We suggest that genetic diversity affects the contents of the six saponins. The saponin contents variation and genetic diversity were also found among P. notoginseng root samples collected from China and Singapore markets. Since variable saponin contents may affect therapeutic efficacy, combining the use of genetic profiling with chemical profiling will help ensure greater uniformity in the quality of P. notoginseng roots. The genetic and chemical diversity within a population also provides the opportunity for breeding new cultivars with more desirable chemical constituents.

Long-term therapy with paricalcitol for secondary hyperparathyroidism in hemodialysis patients.

PURPOSE: The efficacy of the vitamin D analog paricalcitol has mainly been shown in short-term studies. There are limited data regarding long-term treatment with this agent. This purpose of this study was to determine long-term effects of paricalcitol therapy on parathyroid hormone (PTH) suppression and serum levels of calcium, phosphorus and calcium-phosphorus product (Ca x P). PATIENTS AND METHODS: Patients who received paricalcitol for > or = 3 months had the following data collected: demographics, drug dosage, serum PTH, corrected serum calcium concentration, serum phosphorus concentrations and serum Ca x P values. RESULTS: Sixteen patients received paricalcitol for a mean of 18 months. The mean +/- SD dose of paricalcitol was 0.13 +/- 0.12 mcg/kg. The mean +/- SD pre-paricalcitol serum PTH concentration was 705 +/- 423 pg/mL. PTH concentration did not change significantly over the duration of treatment (mean +/- SD: 821 +/- 480 pg/mL). The number of patients who had at least one corrected serum calcium concentration > or = 11.5 mg/dL, one serum phosphorus concentration > or = 6.5 mg/dL, or one Ca x P level > or = 70 were 75%, 94% and 82%, respectively. Hypercalcemia and elevated Ca x P value resulted in a mean of 17% of doses being withheld during therapy. CONCLUSION: During the study, PTH was not adequately suppressed by paricalcitol. This was primarily attributed to withholding paricalcitol doses due to elevated serum calcium and Ca x P levels.

Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4 quality of life instrument into traditional Chinese.

The need for a culturally sensitive instrument to assess quality of life (QOL) of patients in international oncology clinical trials has been well documented. This study was designed to evaluate the psychometric properties of the traditional Chinese translation (TCHI) of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4. The FACT-BMT consists of the FACT-General and treatment-specific concerns of bone marrow transplantation. The Chinese translation follows the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology. Bilingual teams from the United States and Hong Kong reviewed the translation to develop a provisional TCHI FACT-BMT, which was then pre-tested by interviewing 20 native Chinese-speaking BMT patients in Hong Kong. The pre-test results indicated good content coverage and overall comprehensibility. A refined translation, taking into account patient comments, was validated by 134 BMT patients in Hong Kong. The results indicated the high internal consistency of the TCHI FACT-BMT scales, with Cronbach's alpha coefficients ranging from 0.71 (emotional well-being) to 0.92 (FACT-BMT total). The FACT-BMT also demonstrated good construct validity when correlated with SF-36 Health Survey scales. The QOL of Chinese BMT patients can now be evaluated using a well-validated international QOL instrument in their own language.

Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2.

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.

Studying how different terminal groups change the motion of H2NSO2C6H4CONH(EG)3R when bound to the active site of human carbonic anhydrase II.

Molecular dynamics simulations have been used to explore the motions of series of ligands containing coupled benzenesulfonamide and oligoethylene glycol moieties (H2NSO2C6H4CONH(CH2-CH2OCH2CH2OCH2CH2)R+; R+ = NH3+, NHCOCH2NH3+, NHCOCH(CH2Ph)NH3+) bound at the active site of human carbonic anhydrase II (HCAII; E.C. 4.2.1.1). These complexes have been examined previously by X-ray crystallography; the locations of the terminal groups of these ligands were not defined in the crystal structures. These stimulations, carried out in the presence of water, provide dynamic information about the motion of the bound ligand that supplements the quasistatic information from crystallography. Our results suggested that the Gly and Phe groups of these ligands interacted weakly with the protein adjacent to the active site. Quantitative estimates of energies of binding did not correlate usefully with observed free energies of binding, but in the absence of information about entropies, it is not possible to tell if the lack of correlation between calculated energies and observed free energies represents inaccuracies in the energies, or a compensation between enthalpies and entropies. When the terminal Phe group was placed near a previously identified hydrophobic patch in the active site (Phe20 and Pro202) the average conformation of the ligand inferred from this simulation was inconsistent with that from the crystal structure; this result illustrates the problems of misleading local minima in these types of simulations.

Pharmacy practice and education in the People's Republic of China.

OBJECTIVE: To describe the pharmacy profession and the education programs available to train pharmacists in the People's Republic of China (PRC). The practice of pharmacy in the hospital setting and the current development of clinical services are also described. BACKGROUND: There are two streams of medical practices in the PRC: traditional Chinese medicine and Western medicine. Hospital and community pharmacies are responsible for the dispensing of medicinals used for both streams of medical practices. Forty-two colleges of pharmacy offer pharmacy education, half of which provide a Western medicine approach and the other half traditional Chinese medicine. Both types of colleges offer a four-year curriculum with options for specialization. Opportunities for graduate study are also available. Most of the graduates work in hospital pharmacies. Hospital pharmacies participate in the bulk manufacture of drugs and parenteral fluids. A bulk dispensing system is used by some hospitals; individual patient doses are dispensed in others. Recently, the need to develop clinical pharmacy services in PRC was recognized and training courses were begun. Curricula with specialization in clinical pharmacy are being considered by colleges of pharmacy. CONCLUSIONS: It is anticipated that through increased awareness of the potential contribution of pharmacists in the PRC healthcare system, more opportunities for educating pharmacists will be made available to satisfy the vast need of the country. Development of clinical pharmacy services also will be expected to improve the quality of care provided.

Inhibition of reverse transcriptase activity by extracts of cultured blue-green algae (cyanophyta).

Lipophilic and hydrophilic extracts of over 900 strains of cultured blue-green algae (cyanophyta) were examined in vitro for their ability to inhibit the reverse transcriptases (RT) of avian myeloblastosis virus (AMV) and human immunodeficiency virus, type 1 (HIV-1). Eighteen (2.0%) aqueous extracts showed activity against AMV and HIV RTs. The maximal level of RT inhibition achieved by some of the active extracts was equivalent to that measured for 3'-azido-2',3'-di-deoxythymidine (AZT) at 668 ng/ml. Examination of partially purified fractions prepared by C18 column chromatography demonstrated that the RT inhibition observed could not be attributed entirely to the degradation of transcript DNA, template RNA, or enzyme protein in the reaction mixture. Thus, these results indicate that cultured blue-green algae may represent a novel source of compounds that inhibit RT activity, including that of HIV-1.

Women's perspectives on chronic illness: ethnicity, ideology and restructuring of life.

This inquiry into the lives of women living with a chronic illness brings to attention the complex processes that frame the existential meanings of illness. Data from immigrant Chinese and Anglo-Canadian women with diabetes are used to show that illness is constructed in a complex social, political and economic nexus. When the circumstances of women's lives are examined, styles of managing illness that could be attributed to ethnicity, become recognizable as pragmatic ways of dealing with the harsh realities of material existence. It is argued that the trends toward individualizing social problems, and shifting the responsibility for caretaking from the state to the individual, obfuscate the social context of illness, and exclude the socially disadvantaged from adequate health care.

Short-term and long-term renal response to nifedipine monotherapy.

Twenty-six essential hypertensive patients were entered into a protocol to assess the blood pressure and renal effects of the dihydropyridine calcium antagonist, nifedipine (30 to 120 mg/d given in divided dosage) administered for twelve weeks. Nifedipine monotherapy effectively lowered blood pressure. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were increased following short-term therapy (four weeks); however, there was no net change in GFR or ERPF (compared to placebo) following long-term therapy (12 weeks). Renal vascular resistance was reduced. The filtration fraction and urinary albumin excretion was unchanged throughout the 12-week protocol. We conclude that nifedipine monotherapy does not adversely effect renal function. Tolerance occurs to the initial renal vasodilator response; hyperfiltration and hyperperfusion do not persist.

Effect of nifedipine on renal function in patients with essential hypertension.

Twenty-six essential hypertensive patients were entered into a protocol to assess the blood pressure and renal effects of the dihydropyridine calcium antagonist nifedipine (30-120 mg/day given in divided doses) administered for 4 weeks. Nifedipine monotherapy effectively lowered blood pressure in 73% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 13.3 and 19.6%, respectively. The filtration fraction and urinary albumin excretion remained unchanged. Renal vascular resistance was markedly reduced (25.2%). Changes observed in renal function were independent of the patients' initial glomerular filtration rate. Furthermore, there was no correlation between the systemic and renal effects of nifedipine monotherapy. Patients with a poor systemic blood pressure response exhibited increases in both glomerular filtration rate (+13%) and effective renal plasma flow (+20%), changes comparable with increases in glomerular filtration rate (+13%) and effective renal plasma flow (+19%) observed in patients achieving a goal blood pressure response (diastolic blood pressure less than or equal to 90 mm Hg, or a greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or both). These results suggest that nifedipine monotherapy has the potential to improve renal function abnormalities encountered in the essential hypertensive state independently of its effect on systemic blood pressure.

Amlodipine therapy corrects renal abnormalities encountered in the hypertensive state.

Calcium antagonists may increase glomerular filtration rate and renal plasma flow by antagonizing the intrarenal effects of angiotensin II and/or norepinephrine. We prospectively studied the effects of amlodipine, a once-a-day dihydropyridine calcium channel antagonist, in 19 patients with essential hypertension. Studies were performed after 4 weeks of placebo and 6 weeks of amlodipine therapy, and included the assessment of systolic and diastolic BP, renal clearances of inulin and p-aminohippurate, and determination of body fluid composition. Systolic and diastolic BPs were reduced following 6 weeks of amlodipine monotherapy. In spite of significant decreases in mean arterial pressure, there were increases in inulin clearance (+ 13%), and p-aminohippurate clearance (+ 19%). Filtration fraction was not changed. Renal vascular resistance was decreased (-25%). Total blood volume, extracellular fluid volume, and total body water and body weight were not changed. We conclude that amlodipine therapy has the potential to reverse renal abnormalities encountered in the hypertensive state.