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A promising approach to improving outcomes in patients with cryptococcal meningitis is to use adjunctive passive immunotherapy with a monoclonal antibody (MAb) directed against the capsular polysaccharide of Cryptococcus neoformans. This is the first application of MAb therapy for the treatment of a fungal disease in humans. We determined the safety and maximum tolerated dose of the murine anticryptococcal MAb 18B7 in a phase I dose-escalation study. The subjects were human immunodeficiency virus-infected patients who had been successfully treated for cryptococcal meningitis. Six dosing cohorts received MAb 18B7 at 0.01 to 2 mg/kg of body weight as a single infusion. Three patients each received 0.01, 0.05, 0.2, and 0.5 mg of MAb 18B7 per kg without significant adverse events. Four of the subjects who received the 1-mg/kg dose had mild study drug-associated toxicity, including transient nausea, vomiting, back pain, and urticarial rash. Two of the subjects who received 2 mg/kg developed drug-associated mild to moderate nausea, vomiting, chills, and myalgias. One of the subjects who received 2 mg/kg developed intracranial hypertension 10 weeks after MAb 18B7 administration. Serum cryptococcal antigen titers in the cohorts receiving doses of 1 and 2 mg/kg declined by a median of twofold at 1 week and a median of threefold at 2 weeks postinfusion, but the titers subsequently returned toward the baseline values by week 12. The half-life of MAb 18B7 in serum was approximately 53 h, while the MAb was undetectable in the cerebrospinal fluid of all patients. These data support the continued investigation of MAb 18B7 at a maximum single dose of 1.0 mg/kg.
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PMID:Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. 1572 88

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.
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PMID:Intravenous immunoglobulin: adverse effects and safe administration. 1639 92

Intravenous immunoglobulin (IVIg) is administered both for the treatment of immunodeficiencies and for an expanding list of autoimmune diseases. Most adverse effects are mild and transient including headaches, flushing, fever, chills, fatigue, nausea, diarrhea, blood pressure changes and tachycardia. IgA deficiency-related anaphylactic reactions are largely preventable. Late adverse events are rare and include acute renal failure and thromboembolic events. Acute renal failure, usually oliguric and transient, occurs generally in insufficiently hydrated patients and with sucrose-stabilized products due to osmotic injury. Thromboembolic complications occur due to hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic events, immobilization, diabetes mellitus, hypertension, dyslipidemia or those receiving high-dose IVIg in a rapid infusion rate or excessive dose. Slow infusion rate and good hydration may prevent renal failure, thromboembolic events and aseptic meningitis. In our experience in more than 200 patients receiving IVIg for different autoimmune diseases and near 10000 infusions for relapsing-remitting multiple sclerosis patients, the occurrence of adverse effects was 24-36% after high dose IVIg, most were headaches and all were mild adverse events. We conclude that IVIg is a safe therapy when given in a slow infusion rate in well-hydrated patients, better avoiding patients with known risk factors.
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PMID:Safety of intravenous immunoglobulin (IVIG) therapy. 1731 19

A 60-year-old woman presented to our clinic with a complaint of a dermatitis that had recurred 2 or 3 times a month for the past 5 years. No trigger episode or obvious pattern of recurrence was noted. She reported some itching or burning as a prodromal symptom. Recurrence has been at multiple sites, in a dermatome pattern, including areas around the arm, face, back, abdomen, knees, and ears. Each occurrence is at a different anatomic site (and she only has lesions at this 1 site during each occurrence. For example, after formation and resolution at 1 site (ie, the right medial forearm) the patient will then have a later recurrence at another site (ie, the upper left part of the back). The patient has no complaints of fevers, chills, or adenopathy. Medical history includes type 2 diabetes and hypertension. Results of a basic laboratory screening at the time were all within normal limits. No other contributory history was noted. On examination, the medial arm just proximal to the elbow had clusters of vesicles (Figure). Viral culture performed on the lesion confirmed our suspicion of the presence of herpes simplex virus (HSV). The patient was started on valacyclovir and asked to return if no improvement was noted. To date the patient has not returned to the clinic.
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PMID:One hundred twenty recurrences of herpes simplex virus in an immunocompetent patient. 1761 75

An 88-year-old Caucasian man of Italian ancestry came into our clinic with multiple, painful purple-red "growths" on his left foot that he'd had for several years. The patient had no systemic complaints (no fever, chills, weight loss, night sweats). He had a history of hypertension, a cardiac valve replacement, and chronic back pain (secondary to a motor vehicle accident). He was taking warfarin and nadolol. The patient had multiple, 0.1- to 0.5-cm purple-red papules and nodules on the dorsal and plantar surfaces of the left foot, with associated moderate lower extremity edema and mottled dyspigmentation. We did a punch biopsy, which showed a nodular neoplasm composed of moderately plump, spindle-shaped cells in short interweaving fascicles and numerous extravasated erythrocytes in the spaces ("vascular slits") between the spindle-shaped cells. What is your diagnosis, and how would you manage this condition?
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PMID:Purple-red papules on foot. 1854 22

Nausea and vomiting during the infusion of cryopreserved peripheral blood stem cells (PBSC) are common. The aim of this study was to explore the effect of lollipop with strawberry aroma on the infusion-related nausea and vomiting of cryopreserved autologous PBSCs. We compared 2 groups of adult patients receiving lollipop with strawberry aroma during cryopreserved PBSC infusions or not to assess the incidences of nausea and vomiting occurring during infusions. All patients received granisetron 3 mg i.v. twice a day, and lorazepam 1 mg every 4 hours orally for prophylaxis of the nausea and vomiting during conditioning phase and infusion day. Before infusion, all patients were premedicated with pheniramine maleate 45.5 mg i.v. and paracetamol 500 mg orally. The patients had no evidence of nausea or vomiting prior to cryopreserved PBSC infusions. The patients with ongoing nausea or vomiting owing to conditioning regimens and/or receiving additional antiemetics were excluded from the study. One hundred fifty-eight patients who consecutively underwent autologous stem cell transplantation for malignancy were included in the study. The first 110 patients (median age: 42.5, range: 17-75) were observed for the infusion related adverse effects only. The consecutive 48 patients (median age: 48, range: 18-80) were given a lollipop with strawberry aroma during cryopreserved PBSC infusions and observed for the infusion-related adverse effects. The 2 groups were comparable with respect to age, sex, diagnosis, stem cell collection methods, conditioning regimens administered, total mononuclear cell dose infused, number of total nucleated cells (TNCs) infused, number of CD34+ cells infused, number of bags infused, total volume infused, amount of dimethylsulfoxide (DMSO), and infusion rate. Patients who received a lollipop with a strawberry aroma during infusions had significantly less nausea (6.3%, n = 3 versus 21.8%, n = 24, P = .02) and vomiting (2%, n = 1 versus 13.6%, n = 15, P = .04) than the ones who did not (observation only group). Other infusion-related adverse events were as follows; hypoxia, cough, dyspnea, abdominal cramping, tachycardia, hiccup, fever, chills, chest pain, hypotension, hypertension, agitation, sore throat, and arrhythmia. Incidences of each of these adverse events were <5% in both groups and were comparable. The use of a lollipop with a strawberry aroma during infusion of cryopreserved autologous PBSCs may be promising in reduction of infusion-related nausea and vomiting, with an easy administration at a very cheap cost.
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PMID:The lollipop with strawberry aroma may be promising in reduction of infusion-related nausea and vomiting during the infusion of cryopreserved peripheral blood stem cells. 1904 Oct 66

Metoprolol succinate is a widely used medication for the management of hypertension, heart failure, and angina. We report the case of a 36-year-old woman who developed erythema multiforme after administration of a low dose of this drug. She also presented with pruritic burning pain throughout her body accompanied by chills. While erythema multiforme has been reported with carvedilol, this is the first observation of metoprolol succinate causing this and physicians should be aware of this potential, yet rare, side-effect.
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PMID:Metoprolol succinate therapy associated with erythema multiforme. 1913 Apr 21

An endotoxin-like reaction is a host response to an agent that induces the release of endogenous pyrogens, including cytokines. The typical reaction that is associated with gentamicin is fever and chills, rigor, shivering, tachycardia with hypertension or hypotension, respiratory symptoms and muscle cramps. We report a case of a 92-year-old patient who developed an endotoxin-like reaction in the post-operative recovery unit following 200 mg of gentamicin. The reported side effect is not included in the drug sheet or in the British National Formulary. No similar incidents were reported in the UK. We discuss the clinical picture of this rare event, along with a review of the literature and recommendations.
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PMID:Endotoxin-like reaction following once-daily gentamicin. 1938 87

Mrs. M.S. is a 67-year-old African American woman with a history of rheumatoid arthritis and psoriatic arthritis who presented to the emergency room with complaint of new-onset rash, chills, and fatigue after she started taking ramipril (5 mg orally every day) for her hypertension. The rash involved entire upper chest, both arms, palms, and soles and was characterized as exfoliating with scattered small pustules of 1-2 mm in size. Patient was admitted with a differential diagnosis of exfoliative dermatitis versus adverse drug reaction for which her ramipril was stopped. After admission, the patient spiked a temperature of 102 degrees F with chills, the entire workup for which was negative, including blood cultures, chest x-ray, and urine analysis. She underwent skin biopsy to find the cause of her rash. With her given clinical characteristics, she was presumed to have generalized pustular psoriasis (GPP), which was later confirmed by biopsy results. She was treated with methylprednisolone to which she responded dramatically with much improvement in her rash and her fever subsided. The flare of GPP was considered to be secondary to ramipril. After reviewing the published literature, there are no published cases of ramipril-induced GPP. Captopril, a different angiotensin converting enzyme (ACE) inhibitor, is known to cause flare of GPP. We presented this case as apart from being the first reported case of ramipril-induced GPP; clinicians and dermatologist should also be aware of this potentially serious complication of psoriasis when they start ramipril in patients with psoriasis.
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PMID:Ramipril-induced generalized pustular psoriasis: case report and literature review. 1953 36

Infection is the second most common cause of mortality in patients with end stage re-nal disease (ESRD). Following strict aseptic precautions during a hemodialysis (HD) session could reduce dialysis-related infection, thereby reducing mortality and morbidity rates. This retrospective study was undertaken to identify the prevalence of dialysis-related bacteremia, sepsis, and catheter infections during HD at Bahrain Specialist Hospital, Bahrain, after following rigid infection control procedures. All HD sessions performed between January 2004 and December 2007 were included. Strict aseptic precautions were observed for every patient in our dialysis unit. The patients' demographic characteristics as well as presence of hypertension (HTN), diabetes mellitus (DM) and use of immunosuppressive drugs were recorded. Results of culture of dialysis catheter tip were collected for all catheters removed or changed during the study period. Catheter surface culture yielding more than 15 colonies and catheter lumen culture yielding more than 1000 CFU/mL were considered positive. All episodes of rigors, chills, bacteremia, and sepsis were recorded. Overall, a total of 1084 HD sessions performed on 46 patients were studied. The mean age of the study patients was 55.2 years (SE 2.5). Fifty four percent were male, 50% had DM, 85% had HTN and 11% were immunosuppressed. With implementation of strict aseptic precautions no catheter-related infection, bacteremia or sepsis was found. Culture of 50 dialysis catheters showed Diptheroid in three patients, MRSE in two patients and MSSE, Enterobacter, and Klebsiella in one patient each. None of the study patients had signs or symptoms of infection or bacteremia. Our study further indicates that following strict aseptic precautions during HD sessions can reduce, if not eliminate, infection as a major cause of mortality and morbidity.
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PMID:Infection-free hemodialysis: can it be achieved? 1958 20


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