Permanent Remission Research Articles

Transsphenoidal interventions peculiarities at pituitary adenoma, secreting ACTH

Technical peculiarities of transsphenoidal interventions based on experience of 121 procedures at 107 patients with pituitary adenoma, secreting ACTH, are described. Unilateral transnasal paraseptal transsphenoidal approach was preferable. Permanent clinical remission was achieved at 83 (77,6%) patients.

Index of Suspicion in the Nursery

A 5-week-old previously well female born at 41 weeks gestational age presents to the pediatric emergency department in the winter with a 2-day history of poor feeding. Her mother is concerned that the baby is more tired than usual, “is not getting enough to eat,” and is having difficulty latching on to the breast. The mother explains that 2 weeks ago, the infant developed a dry cough and began having emesis after each feeding. She describes the emesis as nonbilious and nonbloody and approximately 1 ounce. An outside pediatrician prescribed a cough and cold medication and told the mother that the emesis was “normal baby spit-up.” Three days ago, the infant developed projectile vomiting immediately following each feeding. Today, the mother reports that the infant is breathing much harder and deeper than usual, with continued and more frequent coughs. She describes the cough as paroxysmal, although she experiences no color changes. The mother is concerned that her baby does not look like herself and is difficult to arouse. A review of systems reveals that the baby has not taken any human milk today, although her urine output has remained the same, with heavy, wet diapers. Her 2-year-old sister, who attends child care, has a cough and upper respiratory tract infection. The infant has no diarrhea, and her bowel movements are normal. There were no complications during the pregnancy. Her birthweight was 2,722 g, and she has been gaining weight appropriately, although the mother describes her as “scrawny” at birth. Physical examination of the infant in the emergency department shows a temperature …

Use of the Leksell Gamma Knife in the Treatment of Prolactinoma Patients

The current treatment of choice for prolactinomas is pharmacologic therapy with dopamine agonists (DA). However, these drugs must be taken long-term or even life-long, and they are unsuccessful in adenoma patients who are resistant to or intolerant of DA. Other options in such patients include surgical treatment or radiosurgery with the Leksell gamma knife (LGK). This non-randomized trial was designed to examine the effectiveness of LGK irradiation in treating prolactinoma patients who were resistant to or intolerant of DA. A secondary aim was to investigate the effect of LGK in improving the effects of DA on the size of adenomas, shortening the length of administration of DA, and normalizing prolactin levels permanently. The study population was comprised of 35 patients with prolactin secreting pituitary adenomas (27 females and 8 males), with an average age of 40.3 years (range: 18-71). Nine of the 35 patients (25.7%) had microprolactinomas and 26 of the 35 (74.3%) had macroprolactinomas. The mean ± SD follow-up period was 75.5 ± 34.4 months. Twenty-five patients (71.4%) received only pharmacologic therapy with DA before LGK and 10 patients (28.6%) underwent pituitary adenoma surgery in addition to DA therapy. LGK irradiation was indicated because of drug intolerance (31.4%), partial or complete DA resistance (45.7%), and attempts to shorten the period of treatment with DA or reduce the dosage (22.9%). Pituitary function was monitored regularly by measuring hormone levels at 6-month intervals. The median central radiation dose was 70 Gy (range: 40-80 Gy) and the median minimal peripheral dose was 34 Gy (range: 20-49 Gy). Normoprolactinemia was achieved in 80% (28/35) of the study patients. This included 37.1% (13/35 patients) who discontinued DA treatment and 42.9% (15/35 patients) who continued DA treatment after irradiation. After discontinuation of DA in the study subjects, the median time for hormonal normalization was 96 months. None of the patients achieving normoprolactinemia with LGK experienced any disease relapse. Only 1 patient (2.5%) experienced further growth of the adenoma after LGK irradiation. These findings suggest that LGK may achieve normoprolactinemia in 80.0% of the patients with pituitary adenomas who fail pharmacological therapy due to resistance to, or intolerance of, DAs and insufficient response to DA before radiation. The absence of relapse after normalization with LGK contrasts with DA therapy which produces a permanent remission in less than 50% of patients after discontinuation.

Administering toxins with antithyroids. Does this prevent recidivism of Graves disease?

There are three possibilities in the treatment of Graves-Basedow disease: antithyroids drugs, sub-total thyroidectomy and I131. In the USA there is a clear preference for definitive therapy with I131 once the thyrotoxicosis has been controlled. In Europe and Japan, however, the preference is for trying a conservative treatment, in the hope of inducing a permanent remission without recourse to radical methods. The most usual conservative pattern involves starting with high doses of antithyroids which are progressively reduced over the course of one year. The high rate of recurrence obtained with this method has fired the imagination of the endocrinologists in the search for other patterns that would provide more satisfactory results. One of these alternative patterns consists of combining thyroxine with antithyroids drugs. In this paper the characteristics of this combined pattern are reviewed. Following the justification, the clinical and experimental foundations on which it is based are outlined. Thirdly, details are given of clinical experiences taken from the medical literature and, finally, our own clinical experience is described after a five years follow up. It is concluded that: 1. The combined treatment delays the appearance of recurrence but does not reduce its frequency. 2. The addition of thyroxine alone following a course of combined treatment is not justified and 3. Prospective studies are needed in which hyperthyroid patients are grouped according to the variables that can affect recurrence.

Systemic minocycline as a therapeutic option in predominantly oral mucous membrane pemphigoid: a cautionary report

The aim of this study was to evaluate the therapeutic benefit of minocycline in mucous membrane pemphigoid (MMP) predominantly involving the oral cavity. A descriptive, open clinical study with no control group, including 9 patients, was developed. The diagnosis was confirmed by histopathological examination and direct and salt-split-skin indirect immunofluorescence analysis. Target antigens were sought by immunoblotting. Patients received minocycline (200mg/day) for a variable period. All patients were followed up for at least 2 years after initial diagnosis. Therapeutic response was assessed by clinical improvement in three categories: major response, minor response and no response. A major response was observed in 3 patients (33%), a minor response in 4 (44%) and 2 (22%) patients showed no improvement. Two of the 3 patients with a major response showed no immunoblot reactivity; 80% of patients with circulating autoantibodies (autoAb) against BP180 had a minor or no response. Permanent remission of signs with no relapse was only obtained in one patient. 5 patients (55%) stopped the drug because of adverse effects, such as vertigo and gastralgia. The results revealed temporary clinical benefits in MMP predominantly involving the oral cavity with minocycline, although frequently side effects led to drug withdrawal.

Seasons of Survivorship Revisited

Several decades ago the chance of a cancer survivor enjoying long-term survival was limited. At that time the terms cancer survivor and cancer survivorship were new. A cancer survivor was defined as a person from the moment of diagnosis onward for as long as they live. Cancer survivorship was also described in several "seasons" including; acute survivorship (the experience of diagnosis and treatment), extended survivorship (a time for "watchful waiting"), and then permanent survivorship (long-term remission). Today, acute cancer survivorship is still a time of intense emotion and medical activity surrounding the diagnosis, staging, and actual treatment. We then propose that after the intense initial therapy is completed the survivors enter a "season" that can be called "transitional cancer survivorship" reflecting the transition from active treatment to careful observation and the emotional, social, and medical adaptations that occur. Next, there are a growing number of cancer survivors who are (1) alive and "living with cancer" but requiring ongoing treatment for recurrent, active, and often advanced disease; (2) in a complete remission that requires ongoing therapy; or (3) in a complete remission and with a favorable prognosis. Collectively, this is a diverse group in "extended survivorship" and some later go on to obtain a permanent remission although others experience disease progression. Finally, there are millions of long-term or "permanent survivors." This group is also very heterogeneous and is comprised of 4 subgroups including (1) survivors who are "cancer-free but not free of cancer," (2) survivors who are cancer-free but continue to have significant "fall-out" from cancer and its treatment including psychosocial, medical, financial, or legal sequelae, (3) survivors who go on to develop second cancers which may be unrelated to the first cancer or its treatment, or may be more likely due to genetic or environmental factors, and also (4) survivors who later develop cancers that are secondary to the initial treatment.

What are the rules when treatment with 6-MP/AZA is started?

The most important rule is assurance that the patient realizes that Crohn’s disease (CD) is a lifetime pathological process and that the gastroenterologist has explained the specific indications for using 6-mercaptopurine/azathioprine (6-MP/AZA) for their particular case, that 6-MP/AZA may result in a prolonged and possibly permanent remission, and that the risks of adverse reactions in using the drug, although infrequent, are mostly reversible and understood. While ulcerative colitis (UC) is theoretically curable by colectomy, 6-MP/AZA are effective just as much as in CD and the possibility of postoperative complications such as pouchitis, risk of mucosal cancer, impotence, or permanent ileostomy warrant a fair trial of immunosuppressives. Since the metabolism of the drug varies, the initial dose is low (I start at 50 mg/d) but an increase may be anticipated pending inadequate response, and stopped or decreased pending a fall in the white blood cell count (WBC) or platelets or development of abnormal liver function tests. The patient must be compliant with having blood drawn for complete blood count (CBC) weekly usually for the first 3 weeks and subsequently no matter how much the interval is increased. This is managed in my own center by request that reports be faxed by the laboratory and then the patients call for directions on the dose and the interval. Compliance is better achieved by monitoring the results of the blood work, and the phone call from the patient to receive directions, than by the results of serological tests that also require the patients’ cooperation and motivation but a longer lag period. While measurement of the enzyme thiopurine methyltransferase (TPMT) is of value, its measurement is rarely essential since its complete absence (potentially leading to bone marrow depression) occurs in only 1 out of 300 patients. Meanwhile, the CBC is monitored very carefully in all. Most patients are still on steroids at the time when 6-MP/AZA are introduced, which serves to increase the WBC, and the use of granulocyte stimulating factor offers further protection, although rarely needed. Whenever fever occurs, regardless of cause, 6-MP/AZA should be temporarily stopped and the CBC measured. Since early on it has been my own conviction that the initial dose of 6-MP/AZA should not be based on the patient’s weight; both experience and the pursuit of measuring levels of serological metabolites have supported these early observations. While the standard of dose introduction at 1.5 mg/kg for 6-MP and 2.5 mg/kg of AZA date back to the early placebo-controlled crossover trial conducted via the private offices of Korelitz and Present, and the National Cooperative Crohn’s Disease Study conducted at 14 centers, it soon became clear that efficacy in some patients tolerating only one-half a tablet of 6-MP every 2–3 weeks fared equally well as another patient requiring 5–6 tablets daily. This is best explained serologically by the preferential shunting via a metabolic pathway to the effective moiety 6TG rather than 6MMP, which is far less if at all effective and proportionally leads to hepatic toxicity. Therefore, in those cases when efficacy is clinically not achieved, measurement of 6TG and 6PPT may lead to increasing the dose of 6-MP/6TG much sooner. Until now this goal has been accomplished without serological measurements by reintroducing steroids (or raising the dose back to original levels), always accompanied by raising the dose of 6-MP/AZA by 25–50 mg/day at the same time. The reintroduction or raising the dose of steroids should be brief, not permitting either steroid-dependence or steroidresistance to occur. Despite the fact that 6-MP/AZA has proven to be the most effective drug for maintenance in moderate to severe UC and CD to date, its disadvantage has been the delayed time to effectiveness (3–12 months), requiring corticosteroids or infliximab to buy time until doses are raised and efficacy becomes evident. What then can be done to try to enable 6-MP/AZA to work faster? Administering the drug intravenously has not yet been shown to accomplish this purpose. There is some evidence that the use of 5-aminosalicylic acid (5-ASA) products will speed up the action of 6-MP/AZA, presumably by switching more of its metabolites to 6TG, but practically speaking almost all patients started on immunosuppressives are already taking 5-ASA products without any evident clinical counterpart. There is currently some hope that continuous use of Allopurinol, which until now has been recognized as risking severe leukopenia in those who require the drug along with the 6-MP/AZA will From the Lenox Hill Hospital, New York University School of Medicine, New York, USA. Copyright © 2008 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20705 Published online in Wiley InterScience (www.interscience.wiley.com).

Therapieergebnisse beim Morbus Hodgkin

The results of therapy in 239 patients (161 men, 78 women, median age 33 [13-80] years) who had been treated for Hodgkin's disease between 1972 and 1986 were evaluated retrospectively. The proportion of complete remissions depended on the stage of the disease and was 90% (35 out of 39 patients) for stage IA, 90% (9 out of 10) for stage IB, 84% (40 out of 48) for stage IIA, 88% (22 out of 25) for stage IIB and 86% (37 out of 43) for stage IIIA. At five and ten years, survival rates among patients in stages IA to IIB were 76 and 69%, respectively, and for patients in stage IIIA 81 and 52%, respectively. For patients who enjoyed complete remissions the probability of surviving for 5 or 10 years without recurrence was 62% or 54%, respectively, for stages IA to IIB, and 75 or 43%, respectively, for stage IIIA. There were no statistically significant differences between stages I, II and IIIA as regards remission rate, survival time or recurrence-free survival time. During these stages the patient's age proved to be the only prognostic factor of any statistical significance. For stages IIIB and for IVA and IVB the proportion of complete remissions achieved by combined chemotherapy with COPP was 62%. At 5 and 10 years the proportion of these patients in permanent remission was 63 and 53%, respectively, while survival rates in the entire series were 46% and 40%, respectively. A genuine cure--in the sense of at least 10 years' survival without recurrence after the first complete remission--can be expected in one third of patients in stages IIIB to IVB.

Resultados de los tratamientos biológicos en las enfermedades autoinmunitarias

The use of the biological therapies has revolutionized in the last years the handling of numerous autoimmune processes. It has taken to numerous physicians and investigators to try to apply these therapies in other diseases (lupus, Sjögren, vasculitis, etc). From the introduction of corticosteroids and immunosupressives, vasculitis were no more a mortal diseases, and it was possible to obtain high rates of remission. Nevertheless, they are delayed, they are not sustained, and require of the use of maintained drugs. Against this background, the new biological drugs have to surpass the challenge to induce an earlier and permanent remission that diminishes irreversible organ damage, to reduce (or to eliminate) the exposition to steroids and immunesupressives and to improve the patient function. This article reviews data present until now in literature with respect to the utility of biological drugs in systemic vasculitis.

Special considerations for a first seizure in childhood and adolescence

Children with a first unprovoked seizure almost always present with a convulsive seizure. The differential diagnosis includes many paroxysmal events, especially convulsive syncope but even with a good history; there is often uncertainty that cannot be eliminated by investigations. In general, an EEG and MRI are indicated with other investigations determined on a case-by-case basis. Epilepsy syndrome identification may be very valuable. Current literature allows at least partial answers to parents' six most common questions: Will it happen again? How long do I have to wait for a recurrence? Could my child die during a recurrence? Could there be brain damage with a recurrence? If medication treatment is delayed will there be any long-term change in the chance of a permanent remission? Now that my child has had a seizure, how should his/her activities be restricted?

Treatment of Vasospasm Secondary to Subarachnoid Hemorrhage Using Intra-Arterial Nimodipine in Low Dosage

There are currently no consensus criteria to define the dosage of intra-arterial Nimodipine to be used to obtain permanent remission of vasospasm secondary to subarachnoid haemorrhage. The purpose of this paper is to establish a mathematical relation between the number of vessels affected by this kind of vasospasm and the Nimodipine dose that must be used for intra- arterial angioplasty to obtain permanent remission of the vasospasm.

Exendin-4 Improves Reversal of Diabetes in NOD Mice Treated with Anti-CD3 Monoclonal Antibody by Enhancing Recovery of β-Cells

Immune modulators can arrest loss of insulin secretion in type 1 diabetes mellitus (T1DM), but they have not caused permanent disease remission or restored normal insulin secretion. We tested whether exendin-4, a glucagon-like peptide-1 receptor agonist, would enhance remission of T1DM in NOD mice treated with anti-CD3 monoclonal antibody (mAb) and studied the effects of exendin-4 treatment on cellular and metabolic responses of beta-cells. Diabetic NOD mice treated with anti-CD3 mAb and exendin-4 had a higher rate of remission (44%) than mice treated with anti-CD3 mAb alone (37%) or exendin-4 (0%) or insulin or IgG alone (0%) (P < 0.01). The effect of exendin-4 on reversal of diabetes after anti-CD3 mAb was greatest in mice with a glucose level of less than 350 mg/dl at diagnosis (63 vs. 39%, P < 0.05). Exendin-4 did not affect beta-cell area, replication, or apoptosis or reduce the frequency of diabetogenic or regulatory T cells or modulate the antigenicity of islet cells. Reversal of T1DM with anti-CD3 mAb was associated with recovery of insulin in glucose transporter-2(+)/insulin(-) islet cells that were identified at diagnosis. Glucose tolerance and insulin responses improved in mice treated with combination therapy, and exendin-4 increased insulin content and insulin release from beta-cells. We conclude that treatment with glucagon-like peptide-1 receptor agonist enhances remission of T1DM in NOD mice treated with anti-CD3 mAb by enhancing the recovery of the residual islets. This combinatorial approach may be useful in treatment of patients with new-onset T1DM.

Surgical Management of Graves` Hyperthyroidism in Saudi Arabia: A Retrospective Hospital Study

The aim of the study was to determine surgical indication and complication of subtotal thyroidectomy in patients being treated for Graves' disease at King Khalid University Hospital Riyadh Saudi Arabia in the period between January 1996 and December 2005. Twenty-five out of 194 adult patients with Graves' disease had thyroidectomy for hyperthyroidism during the 10-year period representing 13% comprising 11 males and 14 females. Mean age at presentation for all the patients was 28±12 years. Males had higher serum T4 77.7±20.7 than females 49.8±21.9 pmol L-1; p<0.05. Serum T3 levels were similar in both groups 31.9±15.2 for males and 29.4±15.7 pmol L-1 for females, p = NS. Failure of antithyroid and/or radioiodine along with severe ophthalmopathy (52%), patient preference (12%) and large goiter alone (8%) were major indications for thyroidectomy in this group. Permanent remission occurred in 15 patients (60%) following the surgery. Hypothyroidism and relapse were observed in 16 (64%) and 4 (16%) of patients, respectively. One patient (4%) each experienced permanent recurrent laryngeal nerve palsy and hypoparathyroidism. It was concluded that more males than females with severe hyperthyroidism had thyroidectomy and that failure of antithyroid/radioiodine treatment and severe ophthalmopathy were the commonest indications for surgery in patients in patients with Graves' disease while post surgical permanent hypoparathyroidism and recurrent laryngeal nerve palsy were uncommon.

Zerebelläres Syndrom bei Langerhans-Zell-Histiozytose

We report a 24-year-old patient with a progressive cerebellar syndrome and history of Langerhans' cell histiocytosis. Neurological symptoms started 5 years after completion of combined radio- and chemotherapy which had led to complete and permanent remission of the primary disease. The clinical and neuroradiological findings obtained mirror progressive neurodegenerative alterations of the cerebellum that represent one of the three classic CNS manifestations of Langerhans' cell histiocytosis.

Statin Therapy Does not Seem to Benefit Giant Cell Arteritis

Since statins interfere with a variety of immune-inflammatory pathways shared by atherosclerosis and giant cell arteritis (GCA), they might be potentially useful as adjunctive therapy to glucocorticosteroids in GCA. Our aim was to examine whether concomitant use of statins had any potential benefit in GCA. Retrospective follow-up study of an unselected population of 121 patients with GCA. A comparative analysis between patients with and without statin therapy was performed. At the time of the GCA diagnosis, 30 patients (25%) had already been receiving statins and continued taking them during the corticosteroid treatment. No statistically significant reduction in the incidence of severe ischemic complications (including visual manifestations, jaw claudication, cerebrovascular accidents, ischemic heart disease, and limb claudication due to large artery stenosis) was observed in this group compared with the remaining patients. When we analyzed follow-up data, we found no significant differences between groups in terms of frequency of relapses, incidence of aortitis, and percentage of patients recovered from GCA. The duration of therapy and corticosteroids requirements among patients in permanent remission was similar in both groups. We did not observe a significant benefit derived from the use of statins at low to moderate doses in the incidence of severe ischemia or the disease outcome.

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p<0.001); a titer equal to (or) more than 46.5 UI/L could identify patients who had never achieved long-term remission with a sensitivity of 52% and a specificity of 78%. Also fall rate of TRAb at 6 months of follow up and after therapy withdrawal were useful to predict the final outcome (p<0.001). At 6 months of follow up the time of therapy withdrawal, a decrease of TRAb lower than 52.3% or even its increase could identify patients who had never achieved permanent remission with a sensitivity of 55% and a specificity of 79.1%. No single parameter among TRAb, satisfactory identified a sub-set of patients who achieved long remission. Accordingly to our data, the best result in predicting long term remission is probably given by the presence of at least one of the two features evaluated at 6 months (TRAb titer and/or percentage of TRAb fall rate), with a sensitivity of 63% and specificity of 88%. TRAb titers evaluated both at the onset of hyperthyroidism that at 6 months of therapy or their rate of fall at 6 months and at ATD withdrawal are predictors of outcome. However, the presence of at least one, between titers of TRAb or their rate of fall at six months, resulted to be the best predictor of remission with the higher sensitivity and specificity.

Donor CD34+ Cell Chimerism at Day 28 and Chronic Graft-Versus-Host Disease (GvHD) but Not High-Risk Cytogenetics Influence Outcome of Allogeneic Hematopoetic Cell Transplantation (HCT) Following Reduced Intensity Conditioning (RIC) in Patients with AML and MDS.

HCT after RIC is used increasingly to treat older or infirm patients with AML or MDS. In the current analysis we looked for risk factors influencing outcome including cytogenetics, kinetics of donor CD34+ and T-cell chimerism (CC).Patients and methods: From July 1998 - December 2005, 119 consecutive patients [66 m/53 f; median age 60 (range 21–74) years] with AML (n=99; 83%) and high-risk MDS (n=20; 17%) were treated within the OSHO AML studies before HCT. Seventy (59%) of the patients had intermediate-risk cytogenetics and 44 (37%) high-risk cytogenetics. Patients were either in CR1 (n= 66; 55%), CR2 (n=18; 15%), >CR2 (n=28; 24%), or were untreated (n=7; 6%) at transplant. HCT was performed from matched related (n= 33; 28%) and matched unrelated (n= 86; 72%) donors after RIC (200cGy TBI + fludarabine 30 mg/m2/day on 3 consecutive days) and followed by immunosuppression with cyclosporine and mycophenolate mofetil. Marrow donor chimerism was determined in T-, and CD34+−cells at days (d) 28, 56, 84, and thereafter at 3 month intervals using either XY chromosome FISH in gender mismatched, or PCR based analysis of polymorphic micro satellite regions in gender matched HCT.Results: Engraftment was documented in 112 (94%) of the 119 patients. Survival (OS), disease free survival (DFS), relapse incidence (RI), and non-relapse mortality (NRM) of engrafted patients was 40%, 38%, 46%, and 30% at 3 years respectively. In multivariate analysis, only >90% donor CD34+ CC at d 28, chronic GvHD, and CR1, but not cytogenetic risk factors were associated with an improved OS and DFS. Patients with >90% donor CD34+ CC at d 28 (group I) had an OS of 50% compared to 9% in patients with donor CD34+ CC <90% (group II) (p=0.002). Accordingly, RI in group I was 35% compared to 85% in group II (p<0.0001). Again, donor CD34+ CC at d 28 but neither donor T-cell chimerism nor high-risk cytogenetics correlated with relapse. Relapse occurred in 41/109 (38%) patients at a median of 121 d. All patients (n=19) with haematological relapse within 100 days post transplant died despite reduction/withdrawal of immunosuppression. Of the 22 patients with later relapse, six went into permanent complete remission by reduction/withdrawal of immunosuppression. A decrease of CD34+ chimerism was detected in a further six patients and all responded to a decrease in immunosuppression. The incidence of acute (grades ≥ I) and chronic (limited and extensive) GvHD was 50%, and 55% respectively. OS was 10%, 46%, and 62% for patients with no GvHD (A), acute GvHD only (B), and chronic GvHD (C) (p=0.0001). DFS for A, B, C was 20%, 38%, and 55% respectively ((p=0.0001). RI was highest for A (72%) compared to B (49%) and C (25%) (p<0.0001).Conclusions: HCT after RIC offers long-term OS and DFS in AML/MDS even in patients with high-risk cytogenetics. CR1, donor CD34+ CC >90% at d 28 and chronic GvHD correlate with an improved outcome and decreased relapse incidence. Careful monitoring of donor CD34+ CC can identify patients at risk for relapse, thereby allowing early immunmodulation.

New therapies for systemic lupus erythematosus: has the future arrived?

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by defects in many parts of the immune cascade. Current therapies can be criticized for being too wide-ranging in their actions, but newer biological therapies described in this article might, in the future, enhance efficacy and reduce toxicity by targeting specific aspects of B-cell, T-cell and cytokine function. Some evidence for these newer agents is encouraging but unwanted and unexpected effects have been encountered suggesting their usefulness might be questioned. While minimizing unwanted effects and maximizing the effectiveness of treatment is the current aim of therapy, permanent remission or cure must be the gold standard aim in the future. The extent to which we are approaching this exciting objective is reviewed in this article.

Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders

To elucidate an effective therapeutic strategy for ‘ESES syndrome’, epilepsy with electrical status epilepticus during slow sleep (ESES) and its related epileptic disorders, we studied the effect of treatment on the EEG pattern of continuous spike-waves during slow wave sleep (CSWS) in 15 afflicted patients. Basically performed in the following order, the employed therapies included (1) high-dose valproate (VPA) therapy (serum level >100 μg/ml); (2) a combination therapy of VPA and ethosuximide (ESM); (3) short cycles of high-dose diazepam (oral or intrarectal DZP, 0.5–1 mg/kg per day for 6–7 days); and (4) intramuscular synthetic ACTH-Z therapy (0.01–0.04 mg/kg per day for 11–43 days). Regarding the initial EEG effect, a remission of CSWS was achieved by high-dose VPA therapy in 7 of 15 trials (47%), by the combination therapy of VPA and ESM in 3/7 trials (43%), by short cycles of high-dose DZP in 2/4 trials (50%), and by ACTH-Z therapy in 2/5 trials (40%). A permanent remission of ESES syndrome was achieved by high-dose VPA therapy and/or combination therapy of VPA and ESM in 10 patients (67%). The effects of short cycles of high-dose DZP and ACTH-Z therapy were at best temporary. Our strategy for the treatment of ESES syndrome is therefore considered valid.

Therapie und Prävention der Hyperthyreose

A decreased serum TSH level can be observed in more than 10% of the German population. Although treatment is not mandatory in each of these cases patients with an unrecognized autonomous thyroid dysfunction have a substantial risk of developing thyrotoxicosis when exposed to large amounts of iodine. Thionamid drugs in combination with potassium perchlorate are given for preventive and therapeutic reasons until definitive thyroidectomy or radioiodine therapy is performed. In younger patients Graves' disease is the main cause of hyperthyroidism. Medical treatment with antithyroid drugs is established to render patients euthyroid. Having decreased the dose as far as possible, drug therapy is continued for 12-18 months to achieve a maximum rate of permanent remission. Ongoing clinical research aims to characterize clinical or laboratory predictors associated with a high risk of relapse after medication is stopped. Selenium supplementation is proposed to be a new therapeutic approach for autoimmune thyroid disease. It is already used quite liberally although data of powerful randomized trials are not available.