Sustained trilineage recovery and disappearance of abnormal chromosome clone in a patient with myelodysplastic syndrome following combination therapy with cytokines (granulocyte colony-stimulating factor and erythropoietin) and high-dose methylprednisolone

We report a case of hypoplastic myelodyplastic syndrome (MDS) (refractory anemia (RA)) in which sustained trilineage haematological response and persistent disappearance of an abnormal chromosome clone were achieved after treatment with combination therapy of cytokines (granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo)) and methylprednisolone (mPSL) pulse dose. The patient's haematological recovery was rapid and maintained even after cessation of the therapy. In addition, the predominant chromosome clone 13q− in bone marrow cells disappeared in the fourth week. The patient's improved bone marrow haemopoiesis and disappearance of the abnormal chromosome has continued to the present, 13 months after treatment. The occurrence of both trilineage response and abnormal chromosome disappearance in MDS patients treated with cytokine(s) or steroids in rare. Combination therapy might therefore be advantageous in MDS.     

Desmopressin in mild hemophilia A: indications,limitations, efficacy,and safety

Replacement therapy with blood products has long been the only available therapeutic option for patients with bleeding disorders. Plasma-derived cryoprecipitate and factor (F) VIII concentrates, which have been used for hemophilia A patients, involve the risk of transmitting blood-borne diseases. Both plasma-derived and recombinant FVIII concentrates are expensive, and there is a global shortage. The synthetic vasopressin analogue desmopressin acetate (1-deamino-[8-D-arginine]-vasopressin, DDAVP) increases plasma concentrations of coagulation FVIII and von Willebrand factor (vWF) two fold to six fold through endogenous release. The drug is an attractive therapeutic alternative because it carries no risk of transmission of infectious diseases. Desmopressin is today a widely used hemostatic agent not only in patients with mild hemophilia A or von Willebrand disease (vWD) but also in those with congenital or acquired platelet dysfunction. There is a long clinical experience with the drug because it has been used for prevention of bleedings in connection with invasive procedures and for treatment of bleedings since the mid-1970s. Not all hemophilia A patients can be treated. The clinical usefulness depends on the postdesmopressin plasma concentration of FVIII, which in turn depends on the patient's basal FVIII level. Therefore, a test dose is recommended in candidate patients. In general, only the mildest hemophilia A patients respond sufficiently. Optimal hemostatic effect is achieved with a dosage of 0.3 microg/kg given intravenously. An intranasal desmopressin spray is suitable for the home treatment.     

Critical role of microenvironmental factors in angiogenesis

Therapeutic angiogenesis, which entails the induction of new blood vessels by the delivery of angiogenic growth factors, is a highly attractive approach to the treatment of ischemic diseases. However, it is becoming increasingly clear that this is not easily achieved, as the effects of angiogenic growth factors can differ markedly depending on the timing of their expression, on the shape of the concentration gradients they form in vivo, and the interactions between endothelial cells and pericytes they induce. In fact, the same dose of vascular endothelial growth factor can induce stable, nonleaky, pericyte-covered normal capillaries or aberrant vascular structures that develop into hemangiomas. This difference in outcome can be due solely to the spatial characteristics of the delivery method. If delivery allows a homogeneous spatial distribution of VEGF in the microenvironment around each producing cell, angiogenesis can be therapeutic, whereas if the total dose is the average of diverse spatial levels, aberrant angiogenesis cannot be avoided. To achieve therapeutic angiogenesis, a means of regulating the microenvironmental levels of angiogenic factors will be critical to the generation of effective new treatment strategies.     

Use of lithium as an adjunct to radioiodine therapy of thyroid carcinoma.

The effect of lithium on iodine kinetics after oral 131I-iodide was studied in an athyreotic patient with follicular thyroid carcinoma. Lithium decreased the disappearance rate of 131I from the whole body and from a tumor mass in the patient's thigh from control values of 0.126/day, respectively, while having only a minimal effect on the rate of 131I disappearance from blood. The increased tumor 131I retention would be expected to increase the therapeutic:toxic ratio of 131I. However, a subsequent therapeutic dose of 131I-iodide given with lithium was accompanied by an unanticipated increase in blood 131I and, therefore, in whole body radiation, resulting in significant bone marrow depression. Although lithium may be a useful adjunct in 131I therapy of functional thyroid carcinoma, it must be used cautiously in future studies.     

Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis.

Sulphasalazine is widely used in the maintenance treatment of ulcerative colitis but the optimum dose is not known. In the present study, 170 patients were allotted at random to three treatment groups, in which the daily dose was 1, 2 and 4 g respectively, and the trial period of treatment lasted for six months. A daily dose of 2 g was found to be much more efficacious than 1 g. A daily dose of 4 g was more efficacious than 2 g but at the price of fairly frequent symptomatic side-effects. Haematological abnormalities were observed at all dosage levels, but they occurred chiefly among the patients on 4 g daily. Both symptomatic and the haematological side-effects were usually associated with high concentrations of serum sulphapyridine and these high levels occurred chiefly among the slow acetylators. It is concluded that, for general use, a daily dose of 2 g sulphasalazine is satisfactory for the maintenance treatment of ulcerative colitis. If a patient does not do well on 2 g daily, it is worth trying a larger dose but in this case the patient's condition should be monitored by blood film, haemoglobin, MCV, and reticulocyte count.     

Therapy control in cardiology: serum level monitoring

Treatment of cardiac patients with drugs of low therapeutic ratio (i.e. cardiac glycosides, antiarrhythmics) must be individualized to avoid undertreatment or intoxication with their often deleterious consequences. However, in most cases the dose-response effect cannot be predicted, especially in those instances in which the desired effect is hard to measure (e.g. intermittent arrhythmias). Very often a potentially useful drug is not effective because the applied dose is either too low or administered at incorrect intervals. An effective medication can also be incorrectly assumed to be intolerable when the dose administered is too high relative to the patient's impaired renal or liver function. Fixed application schedules will not be successful in the majority of cases due to the following large interpatient variables: absorption, distribution, elimination, biotransformation, protein and tissue binding, and effect on the target organ. If drug efficacy cannot be proven by clinical observation the determination of blood levels of substances with a narrow therapeutic ratio cen be helpful. However, an interpretation should only be made by considering the clinical condition of the patient and the inherent kinetic variables of the drug.     

Diagnostic and treatment goals in elderly patients

Improved quality of life and greater independence are becoming increasingly important as treatment goals in elderly patients, while merely extending life expectancy is only rarely the primary treatment goal. In elderly patients in particular, the patient's wishes are extremely important when deciding on the treatment goals. If patients are no longer able to express their wishes, the treating physician must establish what their presumed wishes are. Relatives and carers are particularly important in determining a patient's presumed wishes. A standardized geriatric assessment and interventions conducted on the basis of this assessment can give patients greater independence in everyday activities (e.g., walking, personal hygiene, eating) and can avoid them having to go into a nursing home or at least delay this move. In addition, the patient's prognosis is improved, which is manifested inter alia in a longer life-span. A basic geriatric assessment should therefore be conducted in all elderly patients. Standardized testing methods are used to examine the following areas: everyday activities, mobility/risk of falling, and cognition. Patients with the relevant risk combinations should also be screened for malnutrition. Comorbidities are a decisive factor influencing the prognosis in tumor patients. The comorbidities should be recorded using a structured method, e.g., the Charlson Comorbidity Index, and taken into account when deciding on treatment.     

Home Treatment of Haemophilia and Christmas Disease: Five Years'' Experience

Summary. The Oxford home treatment programme began in 1971. The material used was human factor VIII concentrate made by the Lister Institute's Plasma Fractionation Laboratory at Oxford Haemophilia Centre. The first group of patients admitted to the programme were those making heaviest demands on the Centre for ‘on demand’ treatment. No problems were encountered by these patients, and other patients have been admitted to the programme each year since. By the end of 1975, 56 haemophilic patients and seven Christmas disease patients were receiving regular home treatment. The haemophilic patients on home treatment have on average increased their factor VIII requirements while on home treatment by 31 % to 1945 u of factor VIII per month, although some of the patients who were making very heavy demands for treatment are now using less than before starting home treatment. Since the introduction of home treatment programme, 68% of the treatment received by the 56 haemophilic patients in the scheme was given at home thus saving the patients the cost and discomfort of travelling to the Centre to receive treatment, and saving the staff of the Centre the work of giving the treatment. Including factor VIII used to cover surgical procedures and doses received at other hospitals, the patients received on average 1893 u of factor VIH per month after commencing home treatment. The standard home treatment dose received by the haemophilic patients during 1975 was 250 International Units of factor VIII which proved satisfactory in resolving the majority of bleeds. The lesions treated at home required on average 1.16 doses per bleed (290 u of factor VIII). The Christmas disease patients receive human factor IX concentrate made by the Plasma Fractionation Laboratory in Oxford and follow a regime of weekly or fortnightly prophylactic infusions of 800–1600 u of factor IX, depending on the weight of the patient. Prophylactic infusions account for 40% of the home treatment doses received by the Christmas disease patients.     

The Origins of the Drug-Free Therapeutic Community

In this paper an attempt is made to trace the origins of the drug-free therapeutic community. Virtually all such programmes in North America may be traced to Synanon, which in turn may readily be traced back through Alcoholics Anonymous to the so-called Oxford Group. At this point the line of evolution becomes less evident. But an examination of various aspects of the background and career of Dr. Frank Buchman, founder of the Oxford Group, suggests a strong link with the Protestant Reformation and, through it, with the forms and practices of primitive Christianity as embodied in the Dead Sea Scrolls. It is suggested that the present-day therapeutic community is only the most recent reincarnation of a particular type of religious organization which dates from at least the Intertestamentary Period.     

Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis

OBJECTIVE: In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy. METHODS: Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients. RESULTS: Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs 49.6 nmol/l (s.d. 12.5) in untreated controls (P=0.55). Mean EMTX was 215.56 nmol/l (s.d. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P=0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P=0.9). CONCLUSIONS: We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.     

Epsilon-Aminocaproic Acid Therapy for Dental Extractions in Haemophilia and Christmas Disease: A Double Blind Controlled Trial

Summary . The results are reported of a pilot study and two separate double blind controlled trials of the effectiveness of epsilon-aminocaproic acid (EACA) in dental extractions in patients with haemophilia and Christmas disease. In the major trial 31 patients were studied; 23 at Oxford and eight at Cardiff. All patients received either EACA (6 g four times daily for 10 days at Oxford or for 7 days at Cardiff) or a placebo, in conjunction with a single preoperative dose of therapeutic materials expected to raise the plasma factor-VIII or factor-IX level to 50%. Post-operative therapeutic materials were withheld unless intraoral bleeding occurred. Despite the fact that plasma factor-VIII or factor-IX levels were, on average, lower, the number of teeth extracted larger, the amount of therapeutic concentrates less and the postinfusion plasma factor-VIII or factor-IX levels lower in the EACA group at Oxford, the incidence of postoperative intraoral bleeding was lower and the requirements for postoperative therapeutic materials less in the group treated with EACA. Side-effects were not a major problem. The number of patients studied at Cardiff was too few for statistical analysis but the results were similar to those at Oxford. The total conservation of therapeutic materials at Oxford in comparison to the amount utilized before EACA was used is estimated on the basis of these results to be approximately 12 000 factor-VIII or factor-IX units/patient, or approximately 190 units/kg/patient, equivalent, for each patient, to the amount derived from approximately 120 blood donations. These results show that EACA in conjunction with preoperative therapeutic concentrates sufficient to raise the plasma factor-VIII or factor-IX level to 50% can be useful for all patients with haemophilia and Christmas disease undergoing tooth extraction. In some patients EACA therapy is contraindicated and for these patients adequate cover with therapeutic materials must be provided during the postoperative period.     

Use of Protein-A column and porcine factor VIII

Extracorporeal immunoadsorption of factor VIII (FVIII) antibodies using Sepharose matrix columns coupled with staphylococcal Protein-A was reported two decades ago. The efficiency of this technique for removing FVIII antibodies of the IgG subtypes was clearly demonstrated. The recent widespread use of a variety of apheresis techniques for the management of a multitude of haematological and oncological conditions has made this technology more accessible and affordable. For the treatment of patients with FVIII inhibitors, the use of porcine FVIII makes it possible to control haemostasis with a therapeutic product for which in vitro testing can help predict the in vivo efficacy. By lowering the level of FVIII inhibitors, immunoadsorption can make the use of pFVIII concentrate possible in situations otherwise untreatable with FVIII preparations. Moreover, lowering the level of FVIII inhibitors by immunoadsorption allows adequate haemostasis to be achieved with much lower doses of FVIII leading to significant saving. Our preliminary data suggest that immunoadsorption combined with the use of pFVIII should be considered early in the treatment plan for controlling haemostasis in patients with FVIII inhibitors.     

In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation

BACKGROUND/AIMS: Artificial liver support represents a potentially useful option for the treatment of severe liver failure. A sufficient 'dose' might be crucial for such treatments to provide a survival benefit. The aim of this study was to compare in vivo efficiency and resulting delivered treatment dose of two commercially available devices that use different therapeutic principles: albumin dialysis (AD, MARS) and fractionated plasma separation (FPS, Prometheus). METHODS: Eight patients with acute-on-chronic liver failure were treated alternately with AD and FPS. Thirty-two treatments at identical blood and dialysate flow rates were evaluated. Clearance and reduction ratio (a measure of delivered treatment dose) were compared for bilirubin subfractions, ammonia and urea. RESULTS: FPS achieved significantly higher clearance for all measured protein-bound and water-soluble markers. This resulted in significantly higher reduction ratios for FPS compared to AD. Unconjugated bilirubin, a marker for strongly albumin-bound toxins, was influenced only by FPS. CONCLUSIONS: FPS provided a higher delivered treatment dose than a matching treatment with AD. Reduction ratios of bilirubin and urea should be reported in clinical studies on liver dialysis, since delivered dose is likely to be linked to the clinical effectiveness of extracorporeal liver support therapies.     

Control of cholesterolemia in Spain, 2000. A tool for cardiovascular prevention

The document "Cholesterolemia Control in Spain, 2000: A Tool for Cardiovascular Disease Prevention" reviews the current evidence on cardiovascular disease prevention and the therapeutic advances achieved in recent years, in order to aid risk-based clinical decision-making. Cardiovascular diseases rank as the first cause of death in Spain. Their demographic, health and social impact is increasing and it is likely to continue to do so in the next decades. Appropriate treatment for high blood cholesterol and other major risk factors is crucial in cardiovascular disease prevention. Individual risk stratification is essential to determine follow-up periodicity and treatment. Priorities for the control of cholesterolemia and the consequent cardiovascular risk are based on risk stratification. In primary prevention, the therapeutic objective in high risk patients has been established as LDL-cholesterol < 130 mg/dl. In secondary prevention, drug treatment is indicated when LDL-cholesterol > or = 130 mg/dl and the therapeutic objective is LDL-cholesterol < 100 mg/dl. Statins are first line drugs for treatment of high blood cholesterol. In moderate-severe hypertriglyceridemia or low HDL-cholesterol, fibrates are preferred. In acute coronary syndrome, hypolipemiant treatment, should be started as soon as possible, when indicated. Secondary prevention programmes that continually provide good clinical and risk factor control should be provided to coronary heart disease patients.     

Hypertension, changes in high-density lipoproteins and antihypertensive therapy

The risk for development of coronary heart disease (CHD) is related to a number of factors. Among these, both hypertension and various lipid abnormalities have been shown to play an important role. A clear inverse relation between high-density lipoprotein (HDL) cholesterol and CHD has been observed in numerous observational and short studies. Pharmacologic treatment of hypertension has been shown to reduce dramatically some of the sequelae of high blood pressure--renal failure, cerebrovascular accidents and congestive heart failure. However, a consistent reduction in associated CHD has not been demonstrated, and the dissociation between reducing blood pressure and reduction in CHD has not been definitively explained. One of the suggested explanations relates to alterations in blood lipid levels that may be induced by certain antihypertensive agents. Changes in HDL cholesterol levels or other lipid alterations due to antihypertensive therapy could modify the beneficial effects achieved by the direct reduction of blood pressure. If so, antihypertensive agents could be subclassified as atherogenic or antiatherogenic depending on the associated changes in lipid levels. Therefore, the antihypertensive agents of choice for patients whose cholesterol levels are a concern would be those that reduce the CHD risk factor of hypertension without compromising the risk factor associated with a patient's lipid profile.     

糖皮质激素联合ACEI治疗糖尿病合并原发性肾病综合征的效果探究

目的分析糖皮质激素联合ACEI治疗糖尿病合并肾病综合征的效果。方法选择该院2019年1月—2020年1月糖尿病合并肾病综合征患者共80例,数字表随机分两组,每组40例。对照组的患者给予常规药物治疗,观察组在该基础上增加糖皮质激素联合ACEI治疗。比较两组机体肿胀消失时间、尿蛋白转阴时间、血糖达标时间、治疗前后患者收缩压监测水平、舒张压监测水平、血糖水平和肾功能指标、总有效率、并发症。结果观察组机体肿胀消失时间、尿蛋白转阴时间、血糖达标时间短于对照组,治疗后患者收缩压监测水平、舒张压监测水平、血糖水平和肾功能指标低于对照组,总有效率高于对照组,并发症少于对照组,差异有统计学意义(P<0.05)。结论糖皮质激素联合ACEI治疗对于糖尿病合并肾病综合征的治疗效果确切,可有效改善临床症状,并降低血糖和血压水平,促进患者肾功能的改善,减少并发症的发生。     

Does early intervention with inhaled corticosteroids alter the natural history of mild persistent asthma?

In most patients, both adults and children, who have a new diagnosis of asthma and whose symptoms are mild but persistent, treatment with inhaled corticosteroids (ICS) should be recommended as soon as the diagnosis is made. This is a cost-effective and safe treatment. Patients should be cautioned that their asthma will not be cured with short-term treatment and that their symptoms may recur and their lung function may decline again if treatment is discontinued. If patients are reluctant to use ICS daily for long periods of time, it would be reasonable to delay the onset of treatment with ICS. They could subsequently be managed with intermittent therapy with either ICS or in combination with other medications, such as long-acting beta-agonists. Initial therapy with leukotriene receptor antagonist is not likely to be as effective as initial therapy with ICS. Since treatment adjustments based on eosinophil counts in sputum can reliably predict short-term responses to corticosteroids and help identify the appropriate add-on therapy, it may be useful to use this measurement, when available, to guide intermittent therapy.     

Role of Ambulatory Blood Pressure Monitoring in Hypertension and Diabetes

The prevalence of hypertension and diabetes are both rising in the USA and around the globe. The treatment of hypertension in the ambulatory setting begins with proper blood pressure measurement, and often the involvement of home blood pressure monitoring. If the diagnosis of hypertension is confirmed, then education on lifestyle modifications is the foundation to reaching blood pressure goals. If it is unclear, then ambulatory blood pressure monitoring should be performed to properly evaluate daily trends in blood pressure. The National Institute for Health and Clinical excellence (NICE) recommends 24-hour ambulatory blood pressure evaluation in all newly diagnosed patients with hypertension. The much-anticipated JNC 2013, while not likely to endorse this approach, will likely recommend an office goal systolic blood pressure of less than 140 mmHg in patients with diabetes as do the most recent American Diabetes Association clinical practice guidelines. All new guidelines are derived from a critical evidence based evaluation of the available data.     

A pilot study of the possibility and the feasibility of haemoglobin dosing with red blood cells transfusion

Background and Objectives Red blood cell concentrates (RBCs) are the major blood component transfused. Although the haemoglobin content is variable, the transfusion dose is prescribed as units of red cell concentrates. Thus, by chance, large volume patients may receive a low haemoglobin dose and low volume patients may be transfused with haemoglobin‐rich RBCs. The aim of this study was to evaluate whether the haemoglobin increment (grams per litre) in the patient can be predicted from the haemoglobin dose (in grams) transfused, with and without correction for estimated blood volume. If this is true, it may be possible to achieve the predicted transfusion outcome by selecting RBCs for each patient. Materials and Methods Haemodynamically stable patients scheduled for day treatment with transfusion of RBCs were recorded. A total of 52 transfusions episodes, 27 for women and 25 for men, were recorded. Blood volumes were estimated, haemoglobin content in the RBCs was measured before transfusion, and pre‐ and post‐transfusion haemoglobin concentrations were obtained. Results The haemoglobin content of the RBCs prepared for transfusion showed a wide range, varying from 38·7 g/unit to 69·0 g/unit. There were statistically significant correlations between haemoglobin concentration in the RBCs and haemoglobin increment in patients. Conclusion Post‐transfusion increment in circulating haemoglobin can be predicted from the haemoglobin content of transfused cells, but knowledge of the patient’s blood volume improves the accuracy of prediction. It may be feasible to select the high haemoglobin content RBC for patients with largest blood volume and vice versa.