Human pharmacokinetics of molsidomine

Molsidomine is well absorbed by the gastro-intestinal tract and is taken up by the liver during the first passage. Its bioavailability is 60 per cent. Digestive or sublingual absorption is rapid: maximal plasma concentrations are obtained 0.5 to 1.0 hours after administration. Molsidomine is minimally bound by plasma proteins and is distributed in a volume of 1 litre/kg. The excretion is essentially extrarenal: less than 2 per cent of the administered dose is excreted in the form of unchanged molsidomine. Molsidomine is metabolized in the liver to two pharmacologically active metabolites which spontaneously and rapidly breakdown into inactive metabolites which are excreted by the kidneys. The plasma half-life of molsidomine is 1 to 2 hours: it is not modified in patients with renal failure, but it is prolonged in patients with hepatic failure. The kinetics are linear and independent of the route of administration and the dose. There is a correlation between the plasma concentration and the pharmacological effect: the minimal effective concentration is about 5 ng/ml. At the usual dose of 2 mg three times a day, there is no accumulation of the drug.     

Improvement of the method of collection of blood flowing from the adrenal glands in the experiment on dogs

Blood from the adrenal gland can flow in two directions--into the caudal vena cava and by anastomoses into the portal vein. A method of multiple blood procuring from these vessels in dogs for the purpose of studying the adrenal gland function is suggested. Polyethylene catheters, 0.9 mm in diameter and 35--40 mm in length glued to capron plates, mandrins, Gordeev's needles and blood-drawing needles are necessary. Transperitoneal surgical approach to the caudal and mesenteric veins is to be provided. Purse-string suture is applied on the wall of the mesenteric vein. The catheter is washed with heparin, the mandrin is introduced into it and it is inserted into the Gordeev's needle. A puncture is made in the centre of the purse-string suture with this needle, which is introduced into the vein together with the catheter. Gordeev's needle is withdrawn and the catheter is pushed through to the portal vein. The purse-string suture is tightened, and the capron plate is fixed in the wall of the vein. The mandrin is recovered from the catheter, heparin is administered into its canal, polyethylene plug is inserted and withdrawn through the abdominal wall outside with the aid of the blood-drawing needle. The catheter is introduced into the caudal vena cava in the same way. Blood samples can be obtained on the 14th postoperative day.     

Limited venous access and pacemaker insertion in a haemodialysis patient: case report

The population of haemodialysis patients is increasing as is their age. There is a higher risk of cardiac comorbidities in these patients. Pacing is increasingly common in this group. We present a case highlighting the difficult issues and exemplifies the need for careful planning preprocedure. Haemodialysis patients often have difficult and limited vascular access. Insertion of pacing leads is associated with subclavian vein stenosis. If this is on the side of an AV fistula there is significant risk of losing the fistula with obvious consequences to the patient. Careful consideration of site and route of access needs to be made prior to pacing. The need for involvement of renal and vascular teams before starting the procedure is essential as it is paramount that the best route of access for pacing wires is selected.     

Preparation of Poly Aluminum-Ferric Chloride (PAFC) Coagulant by Extracting Aluminum and Iron Ions from High Iron Content Coal Gangue

Poly aluminum-ferric Chloride (PAFC) is a new type of high efficiency coagulant. In this study, high iron type gangue is used as a main raw material. It is calcined at 675 °C for 1 h and 3% CaF₂ is added to the calcined powder and reacted with 20% hydrochloric acid at 93 °C for 4 h. The leaching ratio of aluminum ions is 90% and that of iron ions is 91%. After Fe²⁺ ions are oxidized in the filtrate, CaCO₃ is used to adjust the pH of the filtrate to 0.7. The microwave power is adjusted to 80 W and the filtrate is radiated for 5 min. After being aged for 24 h, PAFC product is obtained. The prepared PAFC is used to treat mine water and compared with the results of PAC and PAF, the turbidity removal ratio of PAFC is 99.6%, which is greater than 96.4% of PAC and 93.7% of PAF. PAFC is a mixture with different degrees of polymerization. It demonstrates that extracting aluminum and iron ions from high iron content gangue to prepare PAFC by microwave is efficient and feasible.     

肝纤维化血清学诊断的研究

肝纤维化是多种慢性肝病的共同病理过程,可导致肝硬化及相关并发症的发生,而肝纤维化具有可逆性。因此,肝纤维化诊断对慢性肝病的防治及预后评估具有重要意义。肝活检一直是诊断肝纤维化的金标准,但有其局限性,近来研究发现血清学指标与肝纤维化之间有良好的相关性,且简便易行,有望替代肝活检,本文就血清学检查在肝纤维化诊断中的研究作一概述。     

The harmful, nontherapeutic use of animals in research is morally wrong

It is argued that using animals in research is morally wrong when the research is nontherapeutic and harmful to the animals. This article discusses methods of moral reasoning and discusses how arguments on this and other bioethical issues might be defended and critiqued. A basic method of moral argument analysis is presented and used to show that common objections to the view that "animal research is morally wrong" fail: ie, common arguments for the view that "animal research is morally permissible" are demonstrably unsound or in need of defense. It is argued that the best explanations why harmful, nontherapeutic research on human beings is wrong, ie, what it is about humans that makes such experimentation wrong, apply to many animals as well. Thus, harmful and nontherapeutic animal experimentation is wrong for reasons similar to the reasons that harmful and nontherapeutic human experimentation is wrong.     

Asthma in the elderly

Asthma is common in the elderly population and the differences between younger and older asthmatics should be appreciated (Table 2). Asthma is frequently overlooked in the geriatric population. Objective measures of pulmonary function can aid in a prompt diagnosis and lead to effective treatment and improved quality of life. Because smoking is an important risk factor for asthma-like symptoms of wheezing, cough, and sputum production, asthma is frequently confused with COPD. When airflow obstruction is found, attempts to demonstrate reversibility can uncover an asthmatic component to the disease. In patients who have asthma symptoms and no airflow obstruction, methacholine testing is helpful. When a normal methacholine challenge is present, a diagnosis of asthma can be excluded and the physician can pursue other diagnostic considerations such as heart failure, chronic aspiration syndrome, pulmonary embolic disease, and carcinoma of the lung. The onset of wheezing, shortness of breath, and cough in an elderly patient is likely to cause concern. Although the adage "all that wheezes is not asthma" is true at any age, it is especially true in the elderly. Diagnosis based on objective measures is essential.     

Influence of Factors in the Photopolymerization Process on Dental Composites Microhardness

The aim of the present paper is to investigate the influence of factors in photopolymerization process that govern microhardness of three types of dental composites—universal (UC), bulk-fill (BC), and flowable (FC). Cylindrical specimens with different thicknesses are made and light cured. The significance of light intensity, irradiation time, and layer thickness on Vickers microhardness is evaluated by experimental design, analysis of variance, and regression analysis. It is found that the main factor influencing the microhardness on the top surface of the three composites is light intensity. The second factor is layer thickness for the UC and FC, while for BC, it is curing time. The third factor is curing time for the first two composites and layer thickness for bulk-fill. The significance of factors’ influence on the microhardness of the bottom surface is the same for the UC and FC, but different for BC. The main factor for the first two composites is layer thickness, followed by curing time and light intensity. For bulk-fill, curing time is main factor, light intensity is second, and layer thickness is last. Different significance of factors influencing the microhardness on top and bottom surfaces of investigated composites is revealed for the first time in the present study.     

Local care and medical treatment for ischemic diabetic ulcers

Optimal medical treatment of ischemic diabetic ulcers is multifactorial. Infection is very common and it is necessary to distinguish between limb or life threatening infections and non-limb-threatening infections. The major pathogen associated with non-limb-threatening infection is staphylococcus aureus; oral antibiotics such as amoxicillin/clavulanate or clindamycin can be used. For severe infection, empiric antibiotic therapy is broader-spectrum covering staphylococci, streptococci, gram-negative bacilli and enterococci; intravenous administration is the rule. Duration of antibiotic therapy depends on severity and depth of infection, and on requirement of surgical debridment. Granulocyte colony-stimulating factor is a growth factor stimulating proliferation and function of neutrophils. As an adjunctive therapy for limb-threatening infections, it is associated with a lower rate of amputation. Increasing arterial perfusion if the patient is unsuitable for reconstructive surgery or angioplasty is desirable. Iloprost is an analogue of epoprostenol with effects on platelet aggregability and vasodilatation. It improves ulcer healing, decreases pain, slightly diminishes the rate of amputation. Systemic hyperbaric oxygen therapy can perhaps improve clinical outcome but additional research is needed to define the specific indications and benefits of this treatment modality. Local care is not rationalized and depends on local habits. Debridment is required. Non necrotic wounds can be covered by modern dressing (hydrophilic dressing, alginates, hydrocolloid). Necrotic wounds are dryed until surgical revascularization, or excised if they are limited and superficial. Pinch grafts are very useful for arterial ulcers. The place of topical growth factor like PDGF (platelet derived growth factor) and of living skin equivalents (dermagraft, apligraf) is not defined in ischaemic diabetic ulcers. Treatment of edema is necessary, because it retards or complicates healing. Inelastic bandages can be useful with good tolerance if ischemia is not critical. Pneumatic foot compression is under evaluation. Electric stimulation could be an adjuncting treatment, but with a problem of compliance. Reducing plantar pressure is always necessary.     

Retroperitoneal cystic lymphangioma]

The lymphangioma is a rare disease, more frequently reported in children and just occasionally in the adult patient. The lymphangioma is considered a benign neoplasm of embryonic origin of the lymphatic vessels. Its habitual location is in the cervical and axillary area; it is rarely found in the abdominal cavity and exceptionally in the retroperitonio. In this latter location, the lesion habitually is asymptomatic. The clinical diagnosis of the retroperitoneal cystic lymphangioma is not often due to its rarity and the absence of clinical expression. The size of the lesion is more important than its location to the symptomatology development. The findings of the abdominal ultrasonography and computerized tomography of the abdomen usually show a cystic lesion and its location. The treatment is surgical and it consists of the resection of the cyst or group of cysts once the liquid accumulation in its interior may be responsible for the development of some important complications of this disease. The cure is obtained when the lesion is completely resected also with the resection of eventual adhesive structures. The relapse may take place when the resection is incomplete. A case of retroperitoneal lymphangioma in a female adult patient as incidental finding of abdominal ultra-sonography is described. It is discussed the clinical picture, the radiologic diagnosis, the treatment and the prognostic of this unusual disease.     

Benign ulceration of the gecum presenting with massive hemorrhage

Massive gastrointestinal hemorrhage secondary to benign cecal ulceration is a rare occurrence. The diagnosis of bleeding from this benign condition is rerely entertained and is often a finding on a pathologic examination. A case of massive hemorrhage from a cecal ulcer is presented, and the literature is reviewed. The role of angiographic demonstration of the lesion, if angiography is readily available, is emphasized, but surgery is the definitive therapy.     

Post-infarct left ventricular free wall rupture-not always a lethal complication of acute myocardial infarction

Post-myocardial infarction cardiac rupture is an important complication and cause of death in the period following myocardial infarction. It is rarely diagnosed before death. However, early diagnosis is crucial as successful treatment is possible with surgery. A successful outcome is sometimes compromised by difficult anatomy or an extensive infarct. Presentation, diagnosis and treatment of cardiac rupture is reviewed in this article, and is illustrated by five cases of cardiac rupture.     

Inhibition of hepatic tryptophan-2,3-dioxygenase: Superior potency of melatonin over serotonin

ABSTRACT: In view of the biogenic amine deficiency hypothesis of depression and the contentious claim that hepatic tryptophan-2,3-dioxygenase (TDO) is the major peripheral determinant of brain tryptophan, brain serotonin (5-HT), and ultimately melatonin, the regulation of TDO by melatonin and 5-HT is investigated and discussed. It is concluded that TDO activity is regulated differentially by melatonin and 5-HT. Melatonin is a competitive inhibitor of TDO and 5-HT is predominantly an allosteric inhibitor. In the presence of 5-HT the effects of melatonin are nullified. However melatonin alone is a more potent inhibitor of TDO. Melatonin is also shown to be a reversible negative effector of TDO.     

Diagnosis and therapeutic problems of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) leads to a progressive destruction of the intra- and extrahepatic bile ducts. The cause is unknown but genetic and immunological mechanisms may play a role. The median survival time from diagnosis to death is about 12 years. MRCP is almost equal to ERCP for diagnosing PSC and shows the typical localised or multifocal strictures and interfering segments of ectatic bile ducts. Liver histology can be helpful in making the diagnosis but is often unspecific and there is a large sampling variability. The treatment of PSC is disappointing. The combination of ursodeoxycholic acid with endoscopic dilatation is probably the best treatment. Patients with cirrhosis and/or recurrent cholangitis should be evaluated for liver transplantation as the outcome after liver transplantation is good, especially if there is no cholangio-carcinoma present and if the Child-Pugh score is not too high. There is also a need to treat the complication of PSC such as osteoporosis, cholangitis and the development of cholangiocarcinoma.     

Primary pulmonary lymphoma.

Three distinct entities are now covered by the definition of primary pulmonary clonal lymphoid proliferation. The aim of this review is to describe the pathophysiological, diagnostic, prognostic and therapeutic aspects of these three entities. Low-grade pulmonary B-cell lymphoma is the most frequent form of primary pulmonary clonal lymphoid proliferation. It arises from mucosa-associated lymphoid tissue. It is usually indolent and appears in the form of a chronic alveolar opacity. The prognosis is excellent, but treatment is controversial (simple monitoring, surgery or single-agent chemotherapy). High-grade pulmonary B-cell lymphoma is far rarer and usually occurs in individuals with an underlying disorder (e.g. immunodeficiency). The prognosis is poor and therapeutic options depend on the underlying disorder. The inclusion of lymphomatoid granulomatosis in the definition of primary pulmonary lymphomas is controversial. The clonal nature of the proliferation is very rarely demonstrated and extrapulmonary involvement is frequent (upper airways, skin, kidneys, central nervous system, etc.). The prognosis is extremely variable, with some authors reporting complete remission with steroids and cyclophosphamide and others reporting failure of combination chemotherapy.     

Bronchiolitis obliterans and airways obstruction associated with graft-versus-host disease

Bronchiolitis obliterans is a nonspecific pathologic lesion seen after fume inhalation and infections, which is associated with connective tissue disorders and is a complication of organ transplantation. Bronchiolitis obliterans with organizing pneumonia is also associated with the connective tissue disorders but is usually idiopathic and has better prognosis with corticosteroid therapy. Bone marrow-related obliterative bronchiolitis is limited to patients who develop chronic graft-versus-host disease. Symptoms begin with cough in 3 to 6 months and progress to dyspnea and severe airflow obstruction. The roentgenogram is normal or shows hyperinflation. Prognosis is poor and most patients develop disabling irreversible airflow obstruction. Bronchiolitis obliterans is the most important clinical complication in heart-lung transplant recipients. It is not preceded by typical features of chronic graft-versus-host disease, but has the same clinical course of dyspnea, airflow obstruction, and poor response to therapy. Bronchiolitis obliterans in transplant recipients may represent a form of allograft rejection.     

Leiomyosarcoma of the inferior vena cava

A case of leiomyosarcoma of the inferior vena cava in a 74 year old woman is reported. The clinical and pathological features are described and the outcome and response to treatment analysed. This is a very rare form of malignant disease (less than 100 published cases) which mainly affects elderly women. The diagnosis is often made at a late stage because the symptomatology is not specific and because the tumour is so rare. Treatment is mainly surgical and is only possible in the infrarenal part of the inferior vena cava. It is very difficult or impossible to operate on the upper part of the vessel. The prognostic is poor. There are no reports of survival after 5 years.     

Antipsychotic drugs and diabetes—an application of the Austin Bradford Hill criteria

There is concern that antipsychotic drugs cause diabetes. Although there has been an explosion in the quantity of literature about this subject, it remains confusing and inconsistent. To assess whether the association between antipsychotic drugs and diabetes is causative, we applied the Austin Bradford Hill criteria to the available evidence. In support of a causative relationship, there is temporality for some cases of diabetes, and there is a biologically plausible explanation. The causative link between antipsychotic drugs and diabetes is coherent with our understanding of diabetes and there are other analogies. However the strength of association is weak, there is lack of consistency or specificity, and there is little evidence to support a biological gradient. We should therefore conclude that the evidence surrounding a causative link between antipsychotic drugs and diabetes is inconclusive. Moreover, the risk is probably low and the attributable risk of developing diabetes is greater for traditional risk factors such as family history, ethnicity, obesity and ageing than it is for receiving an antipsychotic drug. Consequently, the majority of patients receiving second-generation antipsychotics will not develop diabetes as a result of their medication.Electronic Supplementary Material Supplementary material is available for this article at     

Radioactive iodine therapy for Graves' disease in childhood and adolescence

While the diagnosis of Graves' disease in childhood and adolescence is relatively straightforward, its treatment remains controversial. The first choice therapy is the use of anti-thyroid drugs, although side effects are more frequent than in adults and remission is low. Surgery is not usually indicated as initial treatment. Instead, it is generally recommended after recidive of the disease or due to side effects of medical treatment. The use of radioiodine therapy is increasing in this age group, especially in North America, and control of the hyperthyroidism is achieved in 3 to 6 months in 90% of the cases. There is no evidence that radioiodine therapy is associated with a higher risk of thyroid cancer, and the occurrence of side effects is lower than surgery. Based on the positive results obtained with this therapy, patients with poor responsiveness to medical treatment should be considered for early radioiodine therapy.     

Percutaneous transluminal angioplasty of the peripheral arteries.

Balloon angioplasty is being used with increasing frequency in the management of patients with peripheral vascular disease. Balloon angioplasty is useful alone and as an adjunct to conventional surgery. Angioplasty is relatively inexpensive, is performed under local anesthesia, and is associated with few complications. Technical success depends on the morphologic characteristics of a lesion and on the skill and experience of the operator. Long-term patency is more likely with larger vessels and short-segment stenosis. Careful selection of patients is vital and depends on cooperation between the vascular consultant and radiologist. PCTA is most often used at the extremes of clinical severity. Most complications are minor and do not require surgical treatment. The main disadvantage is the high incidence of restenosis. Angioplasty can be repeated easily, however, and its use does not preclude later surgery.