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 Gordeev's needle is withdrawn and the catheter is pushed through to the portal vein.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 The mandrin is recovered from the catheter, heparin is administered into its canal, polyethylene plug is inserted and withdrawn through the abdominal wall outside with the aid of the blood-drawing needle.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.     

Surgical management of the diabetic foot

Diabetic foot is one of challenging diseases in vascular surgery. This is based on uncontrolled diabetes mellitus and its true character is the neuropathic gangrene due to microangiopathy. Diabetic foot, however, is sometimes accompanied by peripheral arterial occlusive disease, which true status is macroangiopathy. Therefore, the strategy for diabetic foot is as follows;the first step is the infection control by minor amputation and/or drainage, the second step is the assessment of the limb ischemia, and the final is the complete vascular reconstruction. To salvage these diabetic feet, it is important that doctors, who concern to diabetics, understand these strategies and also that they have a settled opinion for the diabetic foot.     

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.     

Effect of overall phenotypic selection on genetic change at individual loci.

The selective advantage of an allele Gi (relative to the mean of alleles at this locus) is given by (formula: see text) in which Ai is the average excess of the allele on the character, X; W(X) is the fitness function; F(X) is the frequency function; W is the mean fitness; and the prime denotes differentiation. With truncation selection si = AaF(C)/w in which F(C) is the ordinate at the culling level and w is the proportion saved; this does not depend on any assumption about the distribution of F(X). If the character is normally distributed, si = AiI/sigma2, in which I is the selection differential and sigma2 is the variance of the character distribution. Finally, if the logarithm of the fitness is proportional to the squared deviation from the optimum and the character is distributed normally, si = AiK(Xop--m), in which Xop is the optimum value of the character, m is the mean value, and K is a constant determined by the variances of the fitness function and the frequency function. Truncation is the most efficient form of directional selection in the sense of producing the maximum gene frequency change for a given effect of the gene on the character, but fitness functions can depart considerably from sharp truncation without greatly reducing the efficiency.     

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.     

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.     

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.     

Informed consent for digestive endoscopy

Informed consent is necessary in good clinical practice.It is based on the patient’s ability to understand the information about the proposed procedure,the potential consequences and complications,and alternative options.The information is written in understandable language and is fortified by verbal discussion between physician and patient.The aim is to explain the problem,answer all questions and to ensure that the patient understands the problems and is able to make a decision.The theory is clear but what happens in daily practice?     

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。     

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.     

Möglichkeiten der Handgelenkarthroskopie

The wrist is the most commonly involved joint in rheumatoid arthritis (RA). Because it becomes involved early in the disease course and because this involvement rapidly progresses, early and adequate treatment is necessary to prevent disease progression. Arthroscopic synovectomy is recommended for pain relief and functional recovery in early-stage RA and is also helpful in advanced RA. The technique is complicated, and the learning curve is steep, but its efficiency is high. Arthroscopic synovectomy of the wrist reduces pain and improves function in most cases. It also improves motion, which is an advantage to the open procedure, and patient acceptance of this procedure is high. Nevertheless, arthroscopic synovectomy may delay the need for complex surgery, such as wrist arthrodesis or total wrist arthroplasty in selected cases.     

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.     

Buerger's disease or thromboangiitis obliterans

The Buerger's disease or thromboangiitis obliterants (TAO) is a non atheromatous inflammatory disease which alters medium and small-sized arteries and veins. It can be found world-wide, but it is more frequent in Eastern Europe, Middle East, Asia and Southeast Asia. Young men and smokers are the most affected. The incidence of this disease is increasing among women. The cause of this disease is unknown yet. The most striking fact is the relationship between TAO and tobacco. The diagnostic is most often late in front of a digital leg ischemia. Complementary exams help to its diagnostic and management but none of them are specific out of the pathology. The affection is evolving towards distal gangrene with amputation in 5 to 10% of cases. Prostacyclin demonstrated its efficiency. Revascularization surgery is difficult but sometimes possible. Sympathectomy, medular stimulation must be suggested. The patient survival is not at stake and the prognosis is above all functional. The most important element in the treatment is stop smoking definitively.     

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.     

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.     

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     

Communication in the Heart: the Role of the Innate Immune System in Coordinating Cellular Responses to Ischemic Injury

Ischemic cardiac injury is the leading cause of heart failure and mortality in the USA and is a major expense to health-care systems. Once the heart is injured, a highly dynamic and coordinated immune response is initiated, which is dependent on both resident and recruited leukocytes. The goal of the inflammatory response is to remove ischemic and necrotic material and to promote infarct healing. If this system is perturbed, the myocardium heals poorly, leading to significant left ventricular dysfunction. Understanding how inflammatory cells coordinate and interact with each other is required prior to designing therapeutic interventions that target pathological processes at play and leave untouched those processes that are protective. This review will discuss the intercellular cross talk between cells of the innate immune system following myocardial ischemic injury and how that response is coordinated over time.     

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.     

II. Malignant potential of gastric polyps.

The malignant potential of gastric polyps is correlated to their features. The vast majority can be divided into two types: hyperplastic polyp and ademona. Hyperplastic polyp is composed of well-differentiated glands and rarely becomes malignant. It is small, smooth-surfaced, often multiple, and randomly distributed. Adenoma is composed of dysplastic glands and often becomes malignant. The small adenoma is flat-surfaced and slightly raised. The large adenoma is papillary and broad-based. Adenoma is usually single and located in the antrum. In either case, a separate independent carcinoma may be present in the same stomach.