Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report

Rationale:Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcomePatient concerns:A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks’ course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.Diagnosis:He was diagnosed with EFE but the condition responded poorly with the medications.Interventions:He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.Outcomes:At 3 months’ follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.Lessons:Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.     

Long-term treatment with interferon-α2b for severe pruritus in patients with polycythaemia vera

Summary. Pruritus is a major clinical problem in patients with polycythaemia vera (PV). Conventional symptomatic treatment is unsatisfactory. Recently, a favourable effect of interferon-α on pruritus in patients with PV has been reported. Also, interferon-α suppresses the increased haemopoiesis in PV. However, long-term treatment with interferon-α may be hampered by side-effects and the inconvenience of chronic subcutaneous injection therapy.
We conducted a long-term study (median follow-up 13 months) of the efficacy and tolerability of interferon-α in 15 patients (mean age 68 years) with PV and severe pruritus. Six patients were evaluable after 1 year. Pruritus significantly improved in 12/15 patients. Haematological control improved, as evidenced by a decreased number of phlebotomies from a mean of 4.3 in the year before the study to 1.8 while on interferon-α. Leucocyte and platelet numbers also decreased significantly. Five patients (33%) did not tolerate interferon-α. The effects of interferon-α could not be ascribed to an inhibitive effect on histamine production or to the disappearance of the abnormal erythroid progenitor clone, because erythropoietin-independent erythroid colony formation persisted during interferon-α treatment. We conclude that long-term interferon-α treatment is feasible and effectively relieves pruritus in patients with PV, but side-effects are an important concern. The optimal dose regimen that is well tolerated, relieves pruritus, and offers satisfactory haematological control at the same time remains to be established.     

Prognostic significance of coronary sinus filling time in patients with angina and normal coronaries at one year follow up

Background

Coronary sinus filling time (CSFT) has been proposed as a simple method for assessment of coronary microvascular function in patients with angina and normal coronaries. But its correlation with inducible ischemia and prognostic significance in predicting future cardiovascular events has not been studied. The present study assessed the prognostic significance of CSFT during one year of follow up.

Methods

We compared coronary sinus filling time of patients with angina and normal coronaries with that of control population. Control group was formed by those patients with supraventricular arrhythmia undergoing radiofrequency ablation and having normal coronaries. Baseline treadmill test (TMT) parameters like workload, duration and Duke Score were assessed. Patients were followed up for one year and a composite of cardiovascular mortality and non-fatal myocardial infarction was analyzed. Number of patients presenting to emergency or outpatient department with recurrent chest pain symptoms during one year follow up was considered for secondary outcome analysis. Coronary sinus filling time was analyzed with respect to cardiovascular events, repeat hospitalization for recurrent angina and TMT parameters.

Results

Total 72 patients and 16 controls were studied. Mean CSFT value in the study group was 5.31 ± 1.03 sec and in the control group was 4.16 ± 0.72 sec and the difference was significant (p value = 0.0001). No correlation was found between baseline and repeat TMT parameters with CSFT. There was no cardiovascular mortality or hospitalization for non-fatal MI during one year follow up. But patients with frequent emergency or outpatient department visits with chest pain had a high CSFT compared with asymptomatic patients (p value = 0.005).

Conclusion

Coronary sinus filling time may be used as a simple marker of microvascular dysfunction in patients with angina and normal coronaries. Patients with recurrent chest pain symptoms after one year follow up were found to have high CSFT compared to asymptomatic patients.     

Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony- stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment- related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.     

HIV Neuropathogenesis: a Tight Rope Walk of Innate Immunity

During the course of HIV-1 disease, virus neuroinvasion occurs as an early event, within weeks following infection. Intriguingly, subsequent central nervous system (CNS) complications manifest only decades after the initial virus exposure. Although CNS is commonly regarded as an immune-privileged site, emerging evidence indicates that innate immunity elicited by the CNS glial cells is a critical determinant for the establishment of protective immunity. Sustained expression of these protective immune responses, however, can be a double-edged sword. As protective immune mediators, cytokines have the ability to function in networks and co-operate with other host/viral mediators to tip the balance from a protective to toxic state in the CNS. Herein, we present an overview of some of the essential elements of the cerebral innate immunity in HIV neuropathogenesis including the key immune cell types of the CNS with their respective soluble immune mediators: (1) cooperative interaction of IFN-γ with the host/virus factor (platelet-derived host factor (PDGF)/viral Tat) in the induction of neurotoxic chemokine CXCL10 by macrophages, (2) response of astrocytes to viral infection, and (3) protective role of PDGF and MCP-1 in neuronal survival against HIV Tat toxicity. These components of the cerebral innate immunity do not act separately from each other but form a functional immunity network. The ultimate outcome of HIV infection in the CNS will thus be dependent on the regulation of the net balance of cell-specific protective versus detrimental responses.     

dic(4; 17)(p11;p11): A new recurrent chromosomal abnormality in chronic b-lymphoid disorders

We describe a new nonrandom rearrangement, dic(4;17)(p11;p11), which identified in three patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). All three cases had in common atypical morphological features with a significant component of prolymphocytes, an unusual clinical outcome, and were refractory to chemotherapy. To further define the cytogenetic breakpoints, we investigated the cases by whole chromosome painting and fluorescence in situ hybridization (FISH) with centromeric probes. FISH analysis detected the same cytogenetic rearrangement in all patients, suggesting that the dic(4;17)(p11;pll) is a recurrent translocation in SLL/CLL. Moreover, FISH analysis showed a monoallelic deletion of the TP53 gene in all cases, suggesting a correlation with the aggressive course of the disease and the clinical outcome observed in these patients. Genes Chromosom Cancer 17:185–190 (1996). © 1996 Wiley-Liss, Inc.     

An echocardiographic study of net atrioventricular compliance in juvenile and adult mitral stenosis

BACKGROUND: Left atrial compliance is an important determinant of symptoms in mitral stenosis. About one-third of patients with mitral stenosis have reduced left ventricular compliance. We measured the net atrioventricular compliance in rheumatic mitral stenosis patients noninvasively and analyzed if there were any clinical, electrocardiographic, roentgenographic or echocardiographic correlates of net atrioventricular compliance. METHODS AND RESULTS: Seventy-six patients with mitral stenosis were analyzed and as many normal subjects were taken as control group. Patients were divided into two groups--those 20 years and below were grouped as juvenile mitral stenosis and those above 20 years as adult mitral stenosis patients. The net atrioventricular compliance in patients with mitral stenosis was significantly impaired compared to normal population. Mean compliance in juvenile group was 4.66+/-2.18 ml/mmHg (range 2.17-9.6) and in adult group it was 4.79+/-1.99 ml/mmHg (range 2.04-8.9) (p = ns). There was no difference in net atrioventricular compliance between the juvenile and adult patients with mitral stenosis. Mitral valve area showed an independent positive correlation with net atrioventricular compliance. CONCLUSIONS: The net atrioventricular compliance was significantly reduced in patients with rheumatic mitral stenosis; however, there was essentially no difference in the net atrioventricular compliance between the juvenile and adult patients with mitral stenosis. The net atrioventricular compliance may not be responsible for the more severe symptoms observed in juvenile mitral stenosis.