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PubMed2005

Intracranial tuberculomas developing while on therapy for pulmonary tuberculosis.

We describe the case of a south Asian man who developed symptomatic intracranial tuberculomas while on therapy for pulmonary tuberculosis. The development or progression of intracranial tuberculomas during the course of appropriate antituberculous therapy has been recognised previously. We review the epidemiology, pathophysiology, diagnosis, and treatment of this paradoxical phenomenon. Although the aetiology of this reaction is unknown, it may be related to an enhanced immune response during the course of therapy. Routine brain imaging for all patients diagnosed with tuberculosis is not recommended; however, in patients presenting with new neurological findings, neuroimaging is clearly warranted. Stereotactic brain biopsy should be done whenever the diagnosis of an intracranial tuberculoma is in doubt. When intracranial tuberculomas become symptomatic, antituberculous therapy generally does not need to be changed. Corticosteroids are indicated in all symptomatic cases.

Adult↗
PubMed1991

Antigen-specific therapy of experimental allergic encephalomyelitis by soluble class II major histocompatibility complex-peptide complexes.

Experimental allergic encephalomyelitis is a T-cell-mediated, major histocompatibility complex (MHC) class II gene-linked autoimmune demyelinating disease of the central nervous system. To develop therapies that will specifically inactivate only the autoantigen-reactive T cells, mice were treated with soluble MHC class II molecules that had been complexed with encephalitogenic peptides. Intravenous injections of 300 micrograms of complexes consisting of encephalitogenic peptide 91-103 of myelin basic protein plus I-As protein on day 0, 4, and 7 were effective in preventing experimental allergic encephalomyelitis. Similarly, administration of 45 micrograms of I-As protein complexed to peptide 139-151 from proteolipoprotein on day 1, 4, and 7 prevented mortality and significantly reduced paralysis induced by immunization with the encephalitogenic proteolipoprotein peptide. Histological examination of sections of animal brains revealed that treatment with I-As protein plus myelin basic protein 91-103 peptide prevents the development of inflammatory lesions characteristic of experimental allergic encephalomyelitis. Thus, treatment with MHC-self-peptide complexes could serve as a highly specific therapeutic modality in treating autoimmune disease when the putative autoantigen and the MHC restricting elements are known.

Animals↗
PubMed2006

Clinical applications of newer radionuclide therapies.

When radio-iodine was first used in the treatment of metastasized thyroid carcinoma in 1943, its success in terms of tumour response, quality of life improvement and survival was considered a 'miracle', as in those days metastatic cancer was generally fatal. Inspired by this, many efforts have been made to apply radioisotope therapy to other tumours. Radionuclide therapy uses radioactive isotopes labelled with specific targeting agents that aim to deliver the irradiation of the isotope to the tumour, while sparing normal tissues. Its unique modality allows to systemically target radiosensitive tumours throughout the body. Another important principle is its so-called 'cross-fire' action, whereby, owing to the larger reach of the radiation in relation to the cell diameter, a tumour cell receives lethal hits also from isotopes in the neighbourhood that are not directly associated with this cell. The treatment is therefore less hampered by inhomogeneous distribution and metabolism than for example chemo- or immunotherapy. The European Association of Nuclear Medicine has issued guidelines on so-called 'established' therapies (www.eanm.org), i.e. hyperthyroidism, thyroid carcinoma, refractory synovitis, bone metastases, mIBG therapy, 32P therapy and Lipiodol therapy. Newer therapies include radio-peptide therapy, radio-immunotherapy of lymphoma and microsphere therapy for liver cancer. The aim of a recently held workshop at the ECCO13 conference 2005 and this review is to inform the oncology community about these new developing therapies.

Forecasting↗
PubMed1999

Evidence-based medicine: empiric antibiotic therapy in community-acquired pneumonia.

A number of national society guidelines exist for empiric management of community-acquired pneumonia but these are, to a large extent, not evidence-based, but based on clinical experience, in vitro data, pragmatism and common sense. Many randomized controlled trials of antibiotic therapy in community-acquired pneumonia have been conducted, but most of these have been powered to demonstrate equivalent efficacy of new treatments in comparison with conventional antimicrobial therapy. Development of new antibiotics has been driven by the emergence of penicillin-resistant Streptococcus pneumoniae, but so far there is no hard evidence that beta-lactam therapy fails in community-acquired pneumonia, at least with the higher doses of penicillins that are commonly used in hospital practice. Nonetheless, newer antibiotics have been deployed including macrolides and quinolones, and have demonstrated equivalent (and in some cases, marginally improved) efficacy to older antibiotic treatments in randomized control trials. A number of studies have shown that it is possible to stratify patients according to severity of illness, to in-patient or out-patient management protocols. These have been validated and refined.

Anti-Bacterial Agents↗
PubMed2001

Using liquid ventilation to treat patients with acute respiratory distress syndrome: a guide to a breath of fresh liquid.

Research with liquid ventilation indicates that this technology may benefit patients with acute lung diseases such as ARDS. In addition to improving gas exchange, this novel therapy may enhance the delivery of antibiotics and other drugs and thus hasten the recovery from other serious diseases. Additional research on using perflubron in combination with other developing therapies is under way. Clearly, liquid ventilation is not a cure for ARDS. However, it may be helpful in the supportive management of patients with ARDS. As the phase 3 clinical trials are completed, liquid ventilation may become a part of treatment in the intensive care unit. Understanding how liquid ventilation works and knowing what to look for in patients treated with PLV will help ensure better outcomes for patients when this therapy becomes part of clinical practice.

Humans↗
PubMed2002

[Sturge-Weber syndrome: medical management of choroidal hemangiomas].

PURPOSE: To investigate the outcome of irradiation of complicated choroidal hemangiomas in Sturge-Weber syndrome. PATIENTS AND METHODS: The charts of 6 patients (7 eyes) with Sturge-Weber syndrome and choroidal hemangiomas were reviewed. An exudative retinal detachment was the indication for treatment in all cases. The mean age of the 6 patients was 13 years (range, 4 to 20 years). The minimum follow-up time was 1 year. Patients were checked for initial and final best-corrected visual acuity, fundus examination, fluorescein angiography, and tumor thickness on B-scan ultrasonography. The patients were treated with radiotherapy. A total dose of 20 Grays was applied to 7 eyes: 2 with a circumscribed choroidal hemangioma underwent proton therapy and 5 with diffuse hemangioma were treated by external beam irradiation. RESULTS: Complete resolution of the subretinal fluid was achieved in all cases with the tumor height decreased. Visual acuity improved to 1 line or more in 5 eyes and remained stable in 2 eyes. Two cases that underwent proton therapy developed radiation retinopathy. CONCLUSION: External beam radiation is an effective and safe option in the management of choroidal hemangiomas complicated by retinal detachment. Based on our experience, proton therapy should be reserved for sporadic circumscribed choroidal hemangioma.

Adolescent↗
PubMed1994

Recombinant activated factor VII (rFVIIa) therapy for intracranial hemorrhage in hemophilia A patients with inhibitors.

We report the use of recombinant VIIa (rFVIIa) in the treatment of five ICHs in two factor VIII-deficient patients with inhibitors. In four of five ICHs, rFVIIa was the only factor replacement used at doses of 60-135 micrograms/kg every 2-4 hr for 12-14 days. Hemostasis at the primary site of bleeding was achieved in all cases, and all patients survived with no permanent neurologic deficits. However, the patient who received the highest dose of rFVIIa during the first 4 days of therapy developed clinical symptoms consistent with a cerebral vascular accident of the brainstem characterized by acute onset of truncal ataxia and upward-gaze nystagmus on day 8 of rFVIIa therapy. While receiving rFVIIa therapy for treatment of these five ICHs, four treatment courses were complicated by bleeding at sites other than the primary site, including two episodes of localized oozing at central line insertion sites, two episodes of hemarthrosis, and two episodes of epistaxis. Antifibrinolytic therapy with tranexamic acid was effective in two of these episodes. Laboratory evaluation revealed shortening of the PT, variable shortening without normalization of the APTT, peak factor VII activity levels 7-30-fold higher than normal baseline values, and normal antithrombin III (ATIII) and alpha 2-antiplasmin levels. In four of five ICHs, there was a 20-40% decrease in fibrinogen levels from baseline. The decrease in fibrinogen was accompanied by an increase in fibrin degradation products in 3/5 episodes and a 15-35% decrease in plasminogen activity levels in 2/5 episodes. Tissue factor pathway inhibitor (TFPI) levels remained stable and in the normal range. Although rFVIIa is an effective new therapy for the treatment of ICH in hemophilia patients with inhibitors, its optimal use with respect to safety and efficacy requires further clinical study.

Cerebral Hemorrhage↗
PubMed2002

Pre-transplant positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose (FDG) predicts outcome in patients treated with high-dose chemotherapy and autologous stem cell transplantation for non-Hodgkin's lymphoma.

We investigated the predictive value of sequential FDG PET before and after high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in 24 patients suffering from non-Hodgkin's lymphoma (NHL). FDG PET was performed at baseline, after three cycles of induction therapy, before and after HDT with ASCT. Response assessment from sequential PET scans using standardized uptake values (SUV) was available in 22 patients at the time of transplantation. Partial metabolic response (PMR) was defined as a >25% decrease of SUV between successive PET scans [corrected]. Six of seven patients who did not achieve a PMR after complete induction therapy developed lymphoma progression, while 10 of 15 patients with complete metabolic response (CMR) or PMR remained in continuous remission. Four of seven patients with less than PMR after induction therapy died vs two of 15 patients with CMR/PMR. Median progression-free and overall survival of patients with less than PMR after HDT and ASCT was 9 and 29 months, respectively. In contrast, neither conventional re-staging nor the International Prognostic Index were predictive. These data suggest that sequential quantitative PET imaging does enlarge the concept of chemosensitivity used to select patients with high-risk NHL for HDT and ASCT or to route them to alternative treatments.

Adult↗
PubMed1987

Neck tumour with syncope due to paroxysmal sympathetic withdrawal.

A patient with recurrent squamous carcinoma metastatic to the neck after radical neck dissection and high dose radiation therapy developed paroxysmal hypotensive episodes that were severe, spontaneous and characterised by suppressed sympathetic but not enhanced parasympathetic activity. Intravenous pressors were successful in treating acute episodes but neither drug therapy nor surgical neck exploration reliably prevented syncopal attacks. Glossopharyngeal and/or vagal nerve infiltration by tumour with episodic activation of the afferent limb of the baroreflex arc producing vasodilatation primarily due to sympathetic withdrawal is the likely mechanism of life threatening syncope in this patient.

Adrenergic Fibers↗
PubMed2005

Translational crossroads for biomarkers.

A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute-supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.

Antineoplastic Agents↗
PubMed2005

Steroid-resistant inflammation in a rat model of chronic obstructive pulmonary disease is associated with a lack of nuclear factor-kappaB pathway activation.

RATIONALE: Emphysema is one component of chronic obstructive pulmonary disease (COPD), a respiratory disease currently increasing in prevalence worldwide. The mainstay therapy adopted to treat patients with COPD is glucocorticoids; unfortunately, this treatment has limited impact on disease symptoms or underlying airway inflammation. OBJECTIVE: There is an urgent need to develop therapies that modify both the underlying inflammation, thought to be involved in disease progression, and the structural changes in the emphysematous lung. METHODS: We have characterized an elastase-driven model of experimental emphysema in the rat that demonstrates COPD-like airway inflammation and determined the impact of a clinically relevant glucocorticoid. MEASUREMENTS AND MAIN RESULTS: We observed an increase in lung neutrophils, lymphomononuclear cells, mucus production, and inflammatory cytokines. Also present were increases in average air space area, which are associated with emphysema-like changes in lung function, such as increased residual volume and decreased flow; these increases in area were maintained for up to 10 weeks. In addition, we observed that elastase-induced airway neutrophilia is steroid resistant. Interestingly, the inflammation observed after elastase administration was found to be temporally associated with a lack of nuclear factor-kappaB pathway activation. This apparent nuclear factor-kappaB-independent inflammation may explain why treatment with a glucocorticoid was ineffective in this preclinical model and could suggest parallels in the steroid-resistant human disease. CONCLUSION: We believe that this model, in addition to its suitability for testing therapies that may modify existing emphysema, could be useful in the search for new therapies to reduce the steroid-resistant airway inflammation evident in COPD.

Algorithms↗
PubMed1991

[Juvenile parkinsonism. 18 cases].

The accepted Juvenile Parkinson denomination includes patients who present the characteristic symptoms before 40 years old. We are reporting 18 such patients, between 15 and 34 years old, who had a follow-up between 9 to 17 years. Based on our observations and a revision of the literature, and after considering inheritance, clinical, evolutive and therapeutic outlook we were able to reach a conclusion as to the essential features of this particular form of parkinsonism. Apparently the impairment to L-Dopa therapy developed more slowly in these patients than in presenile forms and it would be related more with the duration of the illness than with that of L-Dopa therapy.

Adolescent↗
PubMed2001

Case report. Recurrence of increased intracranial pressure with antiretroviral therapy in an AIDS patient with cryptococcal meningitis.

We present the case of an AIDS patient with cryptococcal meningitis who, after an excellent clinical and mycological response to antifungal therapy, developed an exacerbation of signs and symptoms, including elevated intracranial pressure and an increase in cerebrospinal fluid cryptococcal antigen and white blood cells, following the initiation of highly active antiretroviral therapy (HAART). Cultures yielded no growth and the patient responded to repeated lumbar punctures without changing or intensifying antifungal therapy. To our knowledge, this is the first report of symptomatic elevated intracranial pressure occurring during HAART-related immune recovery in a patient with cryptococcal meningitis. Exacerbation of symptoms does not necessarily reflect mycological failure that requires a change in antifungal therapy, but may relate to acutely increased intracranial pressure that will respond to simple measures, such as repeated lumbar punctures.

AIDS-Related Opportunistic Infections↗
PubMed1991

Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states.

Adult↗
PubMed1994

[Lichenoid eruption induced by gold salts. An autonomous eruption].

INTRODUCTION: We report a severe lichenoid drug eruption due to gold salts which relapsed 8 months after the cessation of chrysotherapy. CASE REPORT: A 56 year old man, 3 months after the beginning of a gold sodium propanol sulfonate therapy, developed a polymorphous eruption with violin papules on the trunk, eczematous lesions on the limbs and erosive stomatitis. Gold salts were definitively withdrawn. We saw the patient four months after gold therapy cessation: the eruption remained and diagnosis of severe drug cutaneo-mucous lichenoid eruption was done. We saw thereafter the patient again, 8 months after gold therapy cessation: the eruption had relapsed, more intense. DISCUSSION: We suggest that lichenoid eruption, first caused by gold salts, has become autonomous.

Antirheumatic Agents↗
PubMed2005

Conservative treatment of high grade superficial bladder tumours.

AIM OF THE STUDY: To review our previous experience in the treatment of high grade superficial bladder tumour. MATERIAL AND METHODS: Data from 71 consecutive patients (12 women and 59 men) with high grade (G3) superficial (Ta-T1) bladder tumour were considered. After endoscopic treatment 31 patients received intravesical immunotherapy with Bacillus Calmette Guerin (BCG), 14 patients were treated with a combined scheme of intravesical chemotherapy and immunotherapy and respectively 3 patients and one patient with intravesical chemotherapy with mitomycin (MMC) or epirubicin (EPI) alone. A group of 16 patients received no further treatment after TUR and other 6 patients was treated with systemic chemotherapy or radiotherapy. Patients were followed up with urine cytology and cystoscopy every three months, renal sonography every six months and intravenous pyelography every 2 years or in the case of positive cytology associated with negative cystoscopy. RESULTS: Out of 16 patients treated with TUR alone 11 recurred (69%) BCG was initiated in 31 patients and 12 out of them suffered recurrences (42%), whereas 7 out of 14 patients who had combined epirubicin/BCG therapy developed recurrences (50%). Out of 19 patients who recurred after treatment with BCG alone or combined with epirubicin, five underwent immediate cystectomy and other five delayed cystectomy after a second course of intravesical therapy. In the latter group higher pathological stages were observed. We were not able to identify any factor predictive of recurrence after BCG treatment: sex (M 16/40 vs F 3/5 p = 0.35), stage (Ta 1/6 vs T1 18/39 p = 0.11), associated carcinoma in situ (CIS) (No CIS 1/8 vs CIS 18/37 p = 0.11), multifocal (single 13/31 vs multiple 6/14 p = 1.00), age (66.8 +/- 7.8 vs 62.9 +/- 11.9 years p = 0.19) and number of previous recurrences (0.42 +/- 0.90 vs 1.31 +/- 2.16 p = 0.06). Under chemotherapy (MMC or EPI) all 4 treated patients suffered recurrences (100%). Out of all recurrent patients after conservative treatment of an high grade superficial bladder tumours, seven presented tumours with a low grade histology (downgrading). In all but one of these patients an high grade tumour recurred within 30 months. CONCLUSIONS: The adoption of a correct strategy of intravesical metaphylaxis with BCG allows to spare cistectomy in up to 60% of the patients with high grade superficial bladder carcinoma and the optimisation of treatment protocols will lead to even more effective results. However this tumour still demands the highest level of attention in the follow up and in the case of recurrence primary conservative treatment with BCG should be promptly converted to radical surgical treatment considering that the development of less invasive surgical procedures has reduced the impact on the patient's quality of life

Adjuvants, Immunologic↗
PubMed1994

Abdominal abscesses complicating peritonitis in continuous ambulatory peritoneal dialysis patients.

Ten patients with end-stage renal disease maintained on continuous ambulatory peritoneal dialysis therapy developed abdominal abscesses between 1982 and 1992. During this period, 537 patients cared for in our continuous ambulatory peritoneal dialysis unit developed 1,345 episodes of peritonitis. All abdominal abscesses were attributed to concomitant or antecedent peritonitis, suggesting that abscesses developed in 0.7% of peritonitis episodes. Abdominal pain, tenderness, fever, and nausea and vomiting were the most common presenting symptoms and signs. Radiographic findings that were helpful in establishing the diagnosis included abnormalities on computed tomography (CT) scanning, ultrasound, and Indium scanning. Seven patients developed intraperitoneal abscesses, two developed abdominal wall abscesses, and one developed both abdominal wall and intraperitoneal abscesses. Drainage of the abscesses was performed in all cases either surgically or percutaneously. Two patients died. The remaining eight patients have been maintained on hemodialysis therapy. The present data suggest that abdominal abscesses are uncommon complications of continuous ambulatory peritoneal dialysis-associated peritonitis. Prompt diagnosis by clinical criteria and radiographic techniques is important to permit appropriate drainage of the abscess cavity.

Abscess↗
PubMed2004

Normal expression of DNA repair proteins, hMre11, Rad50 and Rad51 but protracted formation of Rad50 containing foci in X-irradiated skin fibroblasts from radiosensitive cancer patients.

About 5% of oncology patients treated by radiation therapy develop acute or late radiotoxic effects whose molecular mechanisms remain poorly understood. In this study, we evaluated the potential role of DNA repair proteins in the hypersensitivity of cancer patients to radiation therapy. The expression levels and focal nuclear distribution of DNA repair proteins, hMre11, Rad50 and Rad51 were investigated in skin fibroblasts strains derived from cancer patients with adverse early skin reaction to radiotherapy using Western blot and foci immunofluorescence techniques, respectively. Cells from cancer patients with normal reaction to radiotherapy as well as cells from apparently healthy subjects served as controls. Cellular radiosensitivity after in vitro irradiation was assessed by the clonogenic survival assay. The clonogenic survival assay and Western blot analysis of the DNA repair proteins did not reveal any abnormalities in cellular radiosensitivity in vitro and in protein expression levels or their migration patterns in the fibroblasts derived from cancer patients with hypersensitive reaction to radiotherapy. In contrast, in vitro irradiated cells from radiosensitive patients exhibited a significantly higher number of nuclei with focally concentrated Rad50 protein than in both control groups. The observed alteration of the distribution of radiation-induced Rad50 foci in cells derived from cancer patients with acute side reactions to radiotherapy might contribute to their radiation therapy outcome. These data suggest the usefulness of the Rad50 foci analysis for predicting clinical response of cancer patients to radiotherapy.

Acid Anhydride Hydrolases↗