Infants: Yeasts are beasts in early life
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
Flucytosine is not an option for candidiasis as monotherapy because resistance develops rapidly. Use of 5-FC for candidiasis is further limited by lack of a parenteral formulation in the United States, and it is not approved for use in infants. However, 5-FC is occasionally administered in combination with other antifungals for Candida meningoencephalitis [91]. In a cohort of 17 cases of Candida meningitis (including 11 infants), improvement was noted in 15 patients on combination therapy of amphotericin B deoxycholate and 5-FC [92]. An analysis of 27 ELBW infants with Candida meningitis revealed that time to clear infection was longer in infants given combination flucytosine and amphotericin B than those treated with amphotericin B alone [8]. Bone marrow suppression is the predominant toxicity.
Thyroid radionuclide imaging and therapy in thyroid cancer
Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner in Endocrine Surgery, 2017
The calculation of dosimetry to the bone marrow assumes all exposure derived from the blood activity bathing the bone marrow, and the gamma radiation from the rest of the body. The activity in the blood is sampled at the time of administration of the diagnostic tracer dose of I-131 at 24, 48, and 72 hours. By graphic or analytic methods, the area under the curve, the maximal uptake, and the administered activity yield the radiation dose to the blood, which is assumed to equal the dose to the bone marrow [41, 45]. The result is then used to calculate the activity of I-131 required to deliver a 200 rad (cGy) dose. Below this limit, one can avoid radiation-induced bone marrow suppression. The actual radiation dose absorbed by the bone marrow from the blood is believed to range from 30% to 60% of the dose to the blood [41], thus providing a margin of extra safety.
Albendazole
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Evidence of the efficacy of albendazole in cystic hydatid disease has accrued over many years, beginning with the original descriptions of successful treatment (Morris et al., 1983; Saimot et al., 1983; Gil-Grande et al., 1993; Nahmias et al., 1994). Nevertheless, guidelines for use of the drug for this condition are based on a number of small clinical studies, most of which are uncontrolled. In general, doses of 400 mg twice daily have been shown to be effective when continued for a period of 3 months or more (Gil-Grande et al., 1993). In most studies, treatment has been given in cycles of 28 days, with a 14-day break between cycles. The rationale for this dose regime arose from initial uncertainty of the safety of albendazole given continuously when the first studies were designed. This has remained the standard approach, although with increased experience there is less concern over continuous treatment, and several specialist centers now use continuous treatment without major problems (Teggi et al., 1993). The most common side effects encountered have been transient liver function abnormalities in up to 20% of cases, and alopecia (5%). The abnormalities in liver function tests may be due, in part or whole, to local reactions resulting from the death of the parasite (Teggi et al., 1995; Teggi et al., 1997). However, reports of significant hepatotoxicity suggest a direct drug effect as well (Morris and Smith, 1987). Rarely, bone marrow toxicity has been observed. Details of the clinical evidence has been reviewed in detail by Horton (1989); Horton (1997), and more recently by Junghans et al. (2008).
Improving long-term survival in diffuse intrinsic pontine glioma
Published in Expert Review of Neurotherapeutics, 2020
James Felker, Alberto Broniscer
Standard focal conformal fractionated radiation therapy (RT) remains the standard treatment of DIPG. The typical dose of RT is 30 fractions of 1.8 Gy for a total of 54 Gy [48]. Multiple attempts to hyperfractionate RT up to 66 to 75.6 Gy of radiation [49] failed to show an improvement in PFS or OS when compared to standard radiotherapy [50–52]. Conversely, attempts at hypofractionated RT to 5 Gy daily at a total of 25 Gy [53] narrowly failed to meet non-inferiority outcomes when compared to standard dose RT but did show improvement in the quality of life [54]. Several trials have tried to improve on the biologic effects of RT by adding radiation-sensitizer medications. A large review of 44 studies utilizing radiation-sensitizing agents showed a slight increase in median OS and PFS when compared to studies without radiosensitizers. It is difficult to directly compare these studies because of the heterogeneity of treatments and the lack of molecular information on most of the trials [49]. They also reported significant bone marrow toxicity in patients with concurrent treatments during RT [49]. Palliative re-irradiation after progression has been shown to be feasible, well tolerated in selected patients, as well as to improve symptoms and prolong survival by additional few months [55–57].
Safety of systemic therapy for noninfectious uveitis
Published in Expert Opinion on Drug Safety, 2019
Maria Soledad Ormaechea, Muhammad Hassan, Neil Onghanseng, Jung Hyun Park, Sarakshi Mahajan, Khalid Yusuf Al-Kirwi, Gunay Uludag, Muhammad Sohail Halim, Ariel Schlaen, Yasir J Sepah, Diana V Do, Quan Dong Nguyen
Chlorambucil has a similar side effect profile to cyclophosphamide with the exception that it does not cause bladder toxicity. However, the bone marrow toxicity is the most dose-limiting side effect [105]. Chlorambucil should be reserved for patients with severe ocular inflammations that are resistant to other immunosuppressive therapy or necessitate rapid inflammation control in the absence of other available treatments. In the SITE study, chlorambucil, similar to cyclophosphamide, was not associated with an increase in mortality, but was found to show a significant increase in cancer-related mortality [119]. The use of chlorambucil in pregnancy has been associated with significant urogenital malformation [129,130]. Therefore, it is labeled as Category D and its use should be avoided. In fact, it is recommended to discontinue therapy with chlorambucil at least 3 months before conception [131].
Treatment of Serpiginous Choroiditis with Chlorambucil: A Report of 17 Patients
Published in Ocular Immunology and Inflammation, 2018
Nazanin Ebrahimiadib, Bobeck S. Modjtahedi, Samaneh Davoudi, C. Stephen Foster
Bone marrow suppression is one of the dose dependent and predictable side-effects; however, due to high drug potency, this may become severe and protracted. Another potential side-effect, gonadal dysfunction, correlates to higher dosage and longer usage, whereas such a relationship does not exist for myelotoxic effects.24–26 Another potential adverse effect is the carcinogenic nature of the chlorambucil. Risk of hematopoietic cancer is low and correlates with duration of treatment and consumption of higher doses.23 The latent period of secondary malignancy has been reported to be 5.7 years ± 2.8 years after initiation of chlorambucil treatment.27 In a study evaluating the risk of malignancy secondary to chlorambucil with an average of 8 years follow-up after termination of chlorambucil, no lymphoma or skin cancer were reported. In this study, chlorambucil was used for treatment of severe ocular inflammatory conditions with a mean daily dose of 20 mg for a duration of 16 weeks.28 We used this drug with a limited total dose and duration of exposure and none of our patients developed malignancy. However, due to inadequate follow-up time, our series cannot support the conclusion of safety.
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