The Jamaican Haemophilia Registry: Describing the burden of disease.

INTRODUCTION: Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. AIM: The aim of this paper is to establish the current burden of disease in PWH in Jamaica. METHODS: PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health-related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. RESULTS: In all, 45 PWH were registered (mean age: 29, range: 0.17-69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels - mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores - mean Haemo-QoL-A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. CONCLUSIONS: There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.

[The way from cost approval to bariatric surgery : Analysis of resource utilization in a maximum care hospital]. / Vom Antrag auf Kostengutsprache bis zur bariatrischen Operation : Personelle Ressourcenanalyse an einem Zentrum der Maximalversorgung.

BACKGROUND: Morbid obesity is a medical and economic challenge. Patients who have the indications for bariatric surgery face a long way from the first visit until surgery and a high utilization of resources is required. OBJECTIVES: The present study aimed to evaluate labor costs and labor time required to supervise obese patients from their first visit until preparation of a bariatric report to ask for cost acceptance of bariatric surgery from their health insurance. In addition, the reasons for not receiving bariatric surgery after receiving cost acceptance from the health insurance were evaluated. MATERIAL AND METHODS: Patients who had indications for bariatric surgery according to the S3 guidelines between 2012 and 2013, were evaluated regarding labor costs and labor time of the process from the first visit until receiving cost acceptance from their health insurance. Furthermore, body mass index (BMI), age, sex, Edmonton Obesity Staging System (EOSS) stage and comorbidities were evaluated. Patients who had not received surgery up to December 2015 were contacted via telephone to ask for the reasons. RESULTS: In the present study 176 patients were evaluated (110 females, 62.5%). Until preparation of a bariatric report the patients required an average of 2.7 combined visits in the department of surgery with the department of nutrition, 1.7 visits in the department of psychosomatic medicine, 1.5 separate visits in the department of nutrition and 1.4 visits in the department of internal medicine. Average labor costs from the first visit until the bariatric survey were 404.90 ± 117.00 euros and 130 out of 176 bariatric reports were accepted by the health insurance (73.8%). For another 40 patients a second bariatric survey was made and 20 of these (50%) were accepted, which results in a total acceptance rate of 85.2% (150 out of 176). After a mean follow-up of 2.8 ± 1.1 years only 93 out of 176 patients had received bariatric surgery (53.8%). Of these 16 had received acceptance of surgery by their health insurance only after a second bariatric survey. CONCLUSION: A large amount of labor and financial resources are required for treatment of obese patients from first presentation up to bariatric surgery. The cost-benefit calculation of an obesity center needs to include that approximately one half of the patients do not receive surgery within more than 2.5 years.

Long-term in vivo degradation behavior and near-implant distribution of resorbed elements for magnesium alloys WZ21 and ZX50.

UNLABELLED: We report on the long-term effects of degrading magnesium implants on bone tissue in a growing rat skeleton using continuous in vivo micro-Computed Tomography, histological staining and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Two different magnesium alloys-one rapidly degrading (ZX50) and one slowly degrading (WZ21)-were used to evaluate the bone response and distribution of released Mg and Y ions in the femur of male Sprague-Dawley rats. Regardless of whether the alloy degrades rapidly or slowly, we found that bone recovers restitutio ad integrum after complete degradation of the magnesium implant. The degradation of the Mg alloys generates a significant increase in Mg concentration in the cortical bone near the remaining implant parts, but the Mg accumulation disappears after the implant degrades completely. The degradation of the Y-containing alloy WZ21 leads to Y enrichment in adjacent bone tissues and in newly formed bone inside the medullary space. Locally high Y concentrations suggest migration not only of Y ions but also of Y-containing intermetallic particles. However, after the full degradation of the implant the Y-enrichment disappears almost completely. Hydrogen gas formation and ion release during implant degradation did not harm bone regeneration in our samples. STATEMENT OF SIGNIFICANCE: Magnesium is generally considered to be one of the most attractive base materials for biodegradable implants, and many magnesium alloys have been optimized to adjust implant degradation. Delayed degradation, however, generates prolonged presence in the organism with the risk of foreign body reactions. While most studies so far have only ranged from several weeks up to 12months, the present study provides data for complete implant degradation and bone regeneration until 24months, for two magnesium alloys (ZX50, WZ21) with different degradation characteristics. µCT monitoring, histological staining and LA-ICP-MS illustrate the distribution of the elements in the neighboring bony tissues during implant degradation, and reveal in particular high concentrations of the rare-earth element Yttrium.

[Challenges in building a surgical obesity center]. / Herausforderungen beim Aufbau eines operativen Adipositaszentrums.

BACKGROUND: It is estimated that approximately 1 million adults in Germany suffer from grade III obesity. The aim of this article is to describe the challenges faced when constructing an operative obesity center. METHODS: The inflow of patients as well as personnel and infrastructure of the interdisciplinary Diabetes and Obesity Center in Heidelberg were analyzed. The distribution of continuous data was described by mean values and standard deviation and analyzed using variance analysis. RESULTS: The interdisciplinary Diabetes and Obesity Center in Heidelberg was founded in 2006 and offers conservative therapeutic treatment and all currently available operative procedures. For every operative intervention carried out an average of 1.7 expert reports and 0.3 counter expertises were necessary. The time period from the initial presentation of patients in the department of surgery to an operation was on average 12.8 months (standard deviation SD ± 4.5 months). The 47 patients for whom remuneration for treatment was initially refused had an average body mass index (BMI) of 49.2 kg/m(2) and of these 39 had at least the necessity for treatment of a comorbidity. Of the 45 patients for whom the reason for the refusal of treatment costs was given as a lack of conservative treatment, 30 had undertaken a medically supervised attempt at losing weight over at least 6 months. Additionally, 19 of these patients could document participation in a course at a rehabilitation center, a Xenical® or Reduktil® therapy or had undertaken the Optifast® program. For the 20 patients who supposedly lacked a psychosomatic evaluation, an adequate psychosomatic evaluation was carried out in all cases. CONCLUSIONS: The establishment of an operative obesity center can last for several years. A essential prerequisite for success seems to be the constructive and targeted cooperation with the health insurance companies.

Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation.

We have recently demonstrated that gonadal steroid hormones decrease formalin-induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti-inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones.

[The Treatment of the Complex Regional Pain Syndrome (CRPS 1 and CRPS 2) of the Upper Limb with Repeated Local Anaesthesia to the Stellate Ganglion.]. / Die Behandlung des komplexen regionalen Schmerzsyndroms der oberen Extremität mit wiederholter Lokalanästhesie des Ganglion stellatum.

Two female patients were referred to us with a complex regional pain syndrome (CRPS) of the upper limb. One patient developed a CRPS type 1 after a radius fracture, the other presented a CRPS type 2 after a wrist trauma with a nerve injury of N. ulnaris. Both patients had progressive pain in spite of medical treatment (NSAID, Gabapentine, Calcitonine), physiotherapy, occupational therapy and osteopathy. In addition to pain they also showed the typical autonomic symptoms like oedema, hyperhidrosis, disturbances of skin colour and temperature and a severely limited motility of wrist and fingers. The clinical symptoms of both types of CRPS are identical and not restricted to the peripheral nerve distribution. The sympathetic nerve system is not only involved in the pain mechanism with reflectory processes in the segment and with the sympathetic afferent coupling, it also takes part in the neuroplasticity and in the neurogenic inflammation. The logical therapeutic intervention is therefore to normalize the hyperactivity of the sympathetic nerve systems with local anaesthetics. This regulation is done with injections to the stellate ganglion if upper limbs are affected (affections of lower limbs are treated with injections to the lumbar sympathetic trunk). Repeated injections to the stellate ganglion caused immediate improvement of pain and other symptoms in both patients.

[Pathophysiology of pain and neural therapy]. / Pathophysiologie des Schmerzes und Neuraltherapie.

Neural therapy according to Huneke uses the injection of local anesthetics for diagnosis and treatment. Depending on the situation, a stimulus (and/or the interruption of pathological stress) is given into the areas of the reflector segment or into the so-called "interference fields". This can trigger and maintain a disease or pain symptoms outside of every segmental order. Neural therapy targets autoregulatory mechanisms of the autonomic nervous system (especially the sympathetic nervous system). The theoretical principles for this include knowledge of neurophysiology and modern physics.

[Operative management in the treatment of pancreatic cancer]. / Operatives Management bei der Therapie des Pankreaskarzinoms.

The carcinoma of the pancreas is one of the 10 leading causes of death in the Western countries. Because of the resistance of pancreatic cancer against radiation and/or chemotherapy surgery is still the only possibility for cure. However, about 80 % of patients with the diagnosis of pancreatic cancer are no more suitable for curative resection at the time of diagnosis because of local tumor infiltration or the presence of distant metastases. This is one reason for the unsatisfactory situation in terms of 5-year-survival rate of 3 to 24 %. In resectable tumors of the pancreas head the standard Whipple dominates still as the surgical method of choice. However, the pylorus preserving Whipple has been established as a surgical alternative to the classical Whipple. Other surgical procedures like extended or regional pancreatic resections, predominantly done by Japanese surgeons seem to fit the concept of radical resection. But compared to the classical Whipple or the pylorus preserving Whipple resection there is still no clear advantage in terms of long term survival. The prospective European multicenter study ESPAC-1 firstly demonstrated a survival advantage for adjuvant chemotherapy (5-FU and folic acid) but no gain for radiochemotherapy in the treatment of patients with R0 or R1 resected pancreatic cancer in terms of prolongation of mean survival (19.7 months vs. 14.0 months).

Testicular germ cell tumor with rhabdomyosarcoma successfully treated by disease-adapted chemotherapy including high-dose chemotherapy: case report and review of the literature.

Treatment and prognosis have not been well characterized in germ cell tumors (GCT) with a malignant nongerm cell component. Patients with a mediastinal tumor, neural or rhabdomyosarcomatous differentiation and distant metastases have the poorest prognosis. We report a rare case of mixed GCT composed of seminoma, teratoma and rhabdomyosarcoma with the rhabdomyosarcomatous component metastasized into the liver and bone marrow (BM) causing hypercalcemia. The patient was treated with differentiation-tailored chemotherapy (CHT) including a disease-adapted high-dose (HD) CHT regimen with purified autologous PBSCT (APBSCT) and pamidronate. To date, remission has lasted for 4 years. Tumor-adapted CHT including HD-CHT with APBSCT can induce long term remissions in high-risk patients with transformed GCT. A review of the literature is given.

Identification of fluorine sites at the surface of fluorinated gamma-alumina by two-dimensional MAS NMR.

By means of 27Al triple quantum Magic-Angle Spinning Nuclear Magnetic Resonance (3QMAS NMR) and 27Al[19F] WISE MAS NMR, we were able to detect three different Al-F sites on the surface of fluorinated gamma-alumina. Three 19F resonances at 9, 20, and 33 ppm (from C6F6) correlated to 27Al resonances in the octahedral range. While the positions of the maxima in the 27Al dimension were ill-defined due to the inherently low efficiency of the 27Al[19F] CPMAS process, the center of gravity of the lines shifted significantly upfield in that dimension with increasing wt.% F. Tentatively, these three resonances were assigned to (VI)Al(O(6-n)Fn) (n = 1, 2, 3) environments on the F/gamma-Al2O3 surface. At F contents above levels corresponding to the full fluorination of the gamma-Al2O3 surface, neoformation of an AlF3 x 3H2O phase was also evidenced with an 19F resonance at -8 ppm and with an 27Al resonance at -17 ppm.

A topically applied quaternary ammonium compound exhibits analgesic effects for orthopedic pain.

OBJECTIVE: To investigate the effectiveness of a topically applied emulsion of an analgesic ammonium solution for the temporary treatment of pain associated with arthritis, tendinitis and bursitis. DESIGN: 100 subjects in a single center, presenting with chronic pain associated with arthritis, tendinitis, or bursitis trialed against placebo in a double-blind cross-over protocol. MAIN OUTCOME MEASURES: Measures of treatment success include reduction in pain, improvement in clinical and/or mechanical evaluations, and evaluation of local and systemic adverse effects. Analysis was conducted at two weeks, after one week's clearance, and again after two weeks. RESULTS: For chronic neuralgia associated with arthritis, tendinitis, and bursitis, the test material had a positive effect at temporary pain reduction. Several subjects also recorded improvements in mechanical evaluations from baseline. Withdrawals due to systemic or local adverse reactions were minimal. CONCLUSION: A topical emulsion of a strong ammonium solution utilizing quaternary ammonium, enhanced with certain penetration enhancers, is effective for temporary relief of pain associated with arthritis, tendinitis, and bursitis.

Evidence that central dopamine receptors modulate sympathetic neuronal activity to the adrenal medulla to alter glucoregulatory mechanisms.

Previous reports suggest that analogs of dopamine (DA) can produce hyperglycemia in rats by interacting with DA receptors. Experiments reported here indicate the site of action and describe the metabolic sequalae associated with the hyperglycemic effect of apomorphine (APO), produced in conscious unrestrained rats. Apomorphine was more potent when administered by intracerebroventricular (i.c.v.) injection than when given subcutaneously (s.c.). Very small doses of the DA receptor antagonist pimozide, given intraventricularly, blocked the hyperglycemic effect of apomorphine administered subcutaneously. Sectioning of the spinal cord at thoracic vertebra T1-2 or sectioning the greater splanchnic nerve blocked apomorphine-induced hyperglycemia; whereas section of the superior colliculus or section at T5-6 had no effect. A dose of apomorphine or epinephrine (EPI) producing a similar degree of hyperglycemia elevated the concentration of EPI in serum to a similar degree, and the increase in EPI in serum preceded the increase in glucose in serum. Fasting animals for 2 or 18 hr had no significant effect on EPI- or apomorphine-induced hyperglycemia despite a reduction (91-93%) of the glycogen content of liver and skeletal muscle during the 18 hr fast. 5-Methoxyindole-2-carboxylic acid (MICA), an inhibitor of gluconeogenesis, blocked EPI- and apomorphine-induced hyperglycemia in rats fasted for 18 hr. However, 5-methoxyindole-2-carboxylic acid was ineffective in blocking hyperglycemia in animals fasted for 2 hr. Changes in insulin or glucagon in serum alone cannot account for the hyperglycemic action of apomorphine. These data demonstrate that apomorphine interacts with central DA receptors located in the hindbrain to activate sympathetic neuronal activity to the adrenal gland which subsequently releases epinephrine to alter homeostasis of glucose. Epinephrine may then, depending on the nutritional status, facilitate glycogenolytic or gluconeogenic processes to produce hyperglycemia.

Phenytoin and folic acid interaction: a preliminary report.

The effect of folic acid (1 mg/day orally) on phenytoin steady-state pharmacokinetics was studied in four male folate-deficient epileptic patients who were treated with only one anticonvulsant. Each patient served as his own control before and after starting folic acid replacement therapy. The Michaelis-Menten parameters, Vmax and Km, were calculated for each patient, and compliance with the single anticonvulsant drug (phenytoin) regimen was documented. Blood and urine samples were collected just before (day 1) and after 180 or 300 days of vitamin administration. Total and free phenytoin were measured in plasma; and phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), 5-(3,4-dihydroxyphenyl)-5-phenylhydantoin (DHD) were measured in 24-h urine. After the addition of folic acid, total phenytoin plasma concentration decreased 7.5-47.6% in three of the four patients, and the extent of this change correlated with Km (r2 = 0.99). Ratios of urinary metabolites to parent drug increased in those patients showing a decrease in plasma phenytoin caused by folic acid supplementation. This indicated that a folic acid-associated increase in phenytoin oxidative metabolism had occurred.

Phenytoin and folic acid: individualized drug-drug interaction.

The effect of folic acid supplementation on the disposition of phenytoin and the resultant loss of seizure control in a male folate-deficient epileptic is reported. Due to the increase in tonic-clonic seizures after the initiation of folic acid (1 mg, orally) the sodium phenytoin dosage was increased by 130 mg until control was achieved. Because of these dosage changes, the Vmax and Km were calculated before and after initiation of the folic acid. The Vmax remained relatively the same, but the Km decreased after folate supplementation.