Zygomycosis: An emerging fungal infection with new options for management

Zygomycosis occurs primarily in immunosuppressed patients and those with diabetes mellitus. Diabetes remains the most common risk factor; however, zygomycosis has increased among transplant recipients and patients with hematologic malignancy. Treatment or prophylaxis with voriconazole seems to be associated with the development of zygomycosis among severely immunosuppressed patients in these latter risk groups. Rhino-orbital-cerebral zygomycosis is the most common manifestation in patients with diabetes mellitus, but transplant recipients and patients with hematologic malignancy are more likely to develop pulmonary infection. Zygomycosis remains difficult to treat and requires a multifaceted approach involving elimination of predisposing factors, surgical debridement, and antifungal therapy. Lipid formulations of amphotericin B are the treatments of choice. The use of posaconazole has been successful in salvage trials but should not be used as first-line therapy until an effective intravenous formulation is available.     

EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda

It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting Prakriti types: Vata, Pitta, and Kapha. EGLN1 was one among 251 differentially expressed genes between the Prakriti types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLN1 gene. Furthermore, the TT genotype of rs479200, which was more frequent in Kapha types and correlated with higher expression of EGLN1, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in Pitta and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in Pitta and positively correlated with altitude globally (P < 0.001), including in India. Thus, EGLN1 polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema.     

Inter-DRG resource dynamics in a prospective payment system: a stochastic kernel approach

This paper empirically investigates the resource distribution dynamics across Diagnosis Related Groups (DRGs) of elective surgery patients, in a continuing Prospective Payment System (PPS). Existing econometric literature has mainly focussed on the impact of PPS on average Length of Stay (LOS) concluding that the average LOS has declined post PPS. There is little literature on the distribution of this decline across DRGs, in a PPS. The present paper helps fill this gap. It models the evolution over time of the empirical distribution of LOS across DRGs. The empirical distributions are estimated using a non parametric “stochastic kernel approach” based on Markov Chain theory. The results for inlier episodes suggest that resource redistribution will increase capacity and expected number of admissions for DRGs having increasing waiting times. In addition, adjustments in relative cost weights are perceived as price signals by hospitals leading to a change in their casemix. The results for high outlier patients reveal that improved quality of care is one of the factors causing reduction in high outlier episodes.

Voriconazole-induced photosensitivity

Voriconazole is a broad-spectrum triazole antifungal agent indicated for invasive aspergillosis, refractory Candida infections, and other emerging invasive fungal infections. Adverse cutaneous reactions associated with voriconazole therapy occur in fewer than 10% of treated patients and range from mild erythematous eruptions to life-threatening reactions such as the Stevens-Johnson syndrome and toxic epidermal necrolysis. Photosensitivity reactions are an uncommon but characteristic dermatitis in voriconazole recipients, particularly following chronic administration. We report a case of voriconazole-induced phototoxicity in a 50-year-old male with Candida parapsilosis endocarditis that reversed on discontinuation of the drug.     

Role of Centchroman in Regression of Mastalgia and Fibroadenoma

Objectives Centchroman (Ormeloxifene) is a novel non-steroidal, selective antiestrogen. Because of its selective antiestrogen action, centchroman has been used for treatment of mastalgia and fibroadenoma. Materials and Methods Benign breast disease patients up to 35 years of age attending our surgery outpatient department from August 2003 to September 2004 and fulfilling the inclusion criterion were included in this study. They were started on centchroman 30 mg on alternate days for a period of 3 months and were followed up for 6 months. Results were recorded as per clinical examination, visual analog scale (VAS) for pain, and ultrasonography for breast lump size. Results A total of 60 patients were included in this pilot study, 42 (70%) of whom had mastalgia with or without nodularity, and 18 (30%) had fibroadenoma. Noncyclical pain was recorded in 38 patients (90%), and cyclical pain was recorded in only 4 (10%) patients. A VAS score of 10 was recorded by 33 (80%) patients (severe pain), and the remaining 9 patients (20%) had VAS scores from 7 to 10. Fibroadenoma size ranged from 1.5 to 5 cm., single or multiple in one or both breasts. There was a good response in the mastalgia group, with a decrease in the VAS scoring from 10 to 3 in 90 % of the patients in the first week. Almost all of the patients were painless at the end of one month, with complete disappearance of the nodularity. In the fibroadenoma group there was a mixed response, with complete disappearence in 40%, partial regression in 20%, and no response at all in the remaining 40%. There were very few side effects. Conclusions Centchroman is a safe nonsteroidal drug for the treatment of mastalgia and fibroadenoma. It has shown good results in mastalgia and is a safe drug as compared to the drugs of choice used at present (danazole and bromocriptine). Further randomized studies are in progress and are needed to determine its definitive role in this patient group. Presented at the BSI Prize Session, International Surgical Week “ISW2005,” 41st World Congress of Surgery of ISS/SIC, 21–25 August 2005, Durban, South Africa     

Changing epidemiology of rare mould infections: implications for therapy

There has been an increase in rare mould infections in recent decades. These infections have been reported primarily in severely immunocompromised patients. The emergence of these organisms is multifactorial and can be related to more intense immunosuppression, the prolonged survival of patients who have what were previously fatal diseases, and the selective pressure of broad spectrum antifungal agents used for prophylaxis or therapy. Among these rare mould infections, the Zygomycetes are the most commonly encountered, and in some institutions the increase in these organisms appears to be associated with the use of voriconazole. Aspergillus terreus, a species that is resistant to amphotericin B, and less frequently, A. ustus and A. lentulus, have been noted increasingly as causes of invasive aspergillosis in tertiary care centres in the US. Several species of Scedosporium with innate resistance to many antifungal agents have emerged as major causes of disseminated mould infections that are frequently very difficult to treat. Among patients who have haematological malignancies, are neutropenic or have received a haematopoietic stem cell transplant, infections due to Fusarium species respond poorly to many antifungal agents. Dematiaceous, or brown-black, fungi, most often associated with chronic localised infections, are now increasingly reported as a cause of disseminated infection in immunosuppressed hosts.Concomitant with the increased number of infections with these rare moulds, several new mould-active antifungal agents have been developed. The new expanded spectrum azole, voriconazole, has changed our approach to moulds such as S.apiospermum, Fusarium species and A. terreus that are amphotericin B resistant. Posaconazole, the most recently approved expanded spectrum azole, is the first drug in the azole class to show activity against the Zygomycetes and has proven extremely useful for step-down therapy after initial treatment with amphotericin B. It is not known whether posaconazole is effective as primary therapy for zygomycosis; the use of this agent for that purpose awaits clinical trials with the recently developed intravenous formulation of posaconazole.     

Incremental value of live/real time three-dimensional transthoracic echocardiography in the assessment of left ventricular thrombi

This is a case series on three adult patients who contain left ventricular (LV) thrombus and the incremental benefits of live/real time three-dimensional transthoracic echocardiography (3DTTE) in comparison to two-dimensional transthoracic echocardiography (2DTTE) in evaluating LV thrombi. These cases illustrate that 3DTTE is of additional benefit by demonstrating the following: (1) cropping of a single 3DTTE apical dataset may be enough to provide comprehensive assessment of the LV in a timely manner even without breath holding in a not fully cooperative patient (2) it identifies the exact point of attachment of the thrombus to the left ventricular wall, (3) helps to delineate the absence or presence of focal echolucent areas within thrombi indicative of the presence and extent of clot lysis, which may have potential therapeutic and prognostic implications, and (4) provides more accurate assessment of thrombus mobility which has prognostic indications.