Effects of FK-506 on the Course of Murine Salmonellosis

Abstract

Bacterial infections are a major threat to immuno-compromised patients. Therefore, the effect of immunosuppression with cyclosporin A and FK-506 on the course of murine salmonellosis was tested. Treatment of mice with both substances reduced the amount of circulating CD4⁺ T-cells and CD8⁺ T-cells in uninfected and infected mice. The substances effectively suppressed the proliferation of spleen cells of treated mice upon activation with concanavalin A (ConA) and upon activation by mouse peritoneal macrophages infected with live salmo-nellae, but left the response to lipopolysaccharide (LPS) unaltered. In particular, treatment of mice with non-toxic doses led to an increase in Salmonella typhimurium counts in the organs of primarily infected mice from day 14 onward, but not in the early phase of infection. In mice treated during secondary infection with S. typhimurium the bacterial counts in the organs were increased from day 3 of infection onward. We conclude that both substances aggravate murine salmonellosis, most likely by inhibition of T-cell function. Patients receiving FK-506 might also be, therefore, at risk of salmonella infection.     

Early Detection and Successful Treatment of Drug-Induced Pneumonitis with Corticosteroids

A 69-year-old patient with non-small cell lung cancer developed pneumonitis with the use of the chemotherapeutic drugs gemcitabine, paclitaxel, and vinorelbine. He developed progressively worsening dyspnea, fevers, chills, and night sweats three weeks after initiation of chemotherapy treatment with no improvement with antibiotics. Bronchoscopic lung biopsy and endotracheal cultures were negative. Four weeks after the onset of symptoms, chest computed tomography scan showed a ground glass appearance of the lung parenchyma bilaterally consistent with pneumonitis. Gemcitabine is a nucleoside analog with activity against solid tumors, including breast and non-small cell lung cancers. Pneumonitis is a rare and potentially deadly complication of gemcitabine. Early treatment with corticosteroids leads to a complete resolution of this patients pneumonitis. Gemcitabine was discontinued and his chemotherapeutic regimen was changed to include paclitaxel, vinorelbine, and topotecan with no recurrence of pneumonitis. Pneumonitis should be included in the differential diagnosis of dyspnea in patients undergoing gemcitabine-based chemotherapy.     

Successful Treatment of chronic Esophageal Candidosis with oral Ketoconazole

Summary: Oral treatment with 200 mg ketoconazole once daily for 1 month cured a patient with severe relapsing esophageal candidosis. The drug was well tolerated.
Zusammenfassung: Ein Patient mit schwerey, rezidivierender Oesophaguskandidose wurde durch die einmal täigljche orale Verabreichung von 200 mg Ketoconazol über einen Monat geheilt. Das Arzneimittel wurde gut vertragen.     

Successful Treatment of Advanced Ovarian Cancer with Thermochemotherapy and Adjuvant Immune Therapy

We report on a 4-year progression-free survival of a 54-year-old female first diagnosed in December 2007 with advanced bilateral ovarian cancer FIGO IIIc, disseminated peritoneal carcinosis and malignant diaphragm invasion. Treatment started in January 2008 with 6 cycles of Taxol 175 mg/m²/carboplatin AUC 5 in 3-week intervals. Twenty-four hours following each chemotherapy session, fever-range long-duration whole-body hyperthermia (WBH) was performed at the temperature plateau of 40°C body core temperature for 6 h. Three months after completion of chemotherapy, 4 more long-duration WBH procedures were performed in monthly intervals. Importantly, long-duration WBH was paralleled with intradermal vaccination of autologous dendritic cells. No other treatment was given to the patient. Four years following the first diagnosis, the patient is still in complete remission with no evidence of disease.Key Words: Ovarian cancer, Thermo-chemotherapy, Adjuvant immune therapy, Whole-body hyperthermia, Dendritic cell therapy     

Successful Treatment of Esophageal Cancer with Airway Invasion with Induction Chemotherapy and Concurrent Chemoradiotherapy

Esophageal cancer with airway invasion with or without fistula presents a challenging therapeutic dilemma with no standard therapy. Recent studies in Japan have focused on the use of definitive chemoradiotherapy. However, this approach is associated with significant treatment-related morbidity and mortality. We present a case report of a patient with thoracic esophageal squamous cell carcinoma with bronchial invasion who was treated to a clinical complete response with induction chemotherapy followed by consolidation with concurrent chemoradiotherapy. The patient also underwent restaging with a positron emission tomography scan after induction chemotherapy. Such a staged approach may reduce the morbidity of upfront radiation. The use of an interim positron emission tomography scan may also identify early treatment failure.     

Successful Treatment of an Angiosarcoma of the Nose with Radiation Therapy

Angiosarcoma is a rare, aggressive malignancy of endothelial cells lining blood vessels. It poses therapeutic challenges since there is no standard established treatment. It is typically treated with resection and wide-field postoperative radiation therapy. Chemotherapy and radiation therapy have also been reported as initial therapies. Regardless of the treatment rendered, the risk of local regional failure and distant relapse remains high for this disease. We present the case of a patient who developed a well-differentiated angiosarcoma of the nose with bilateral malar extension. No commonly associated risk factors such as lymphedema, prior radiotherapy or chronic venous ulceration were present. Given her age, pre-existing renal condition and preference not to receive chemotherapy, systemic therapy was not utilized. Surgery was also refused by the patient due to the projected cosmetic deficit. The patient was ultimately treated with definitive radiotherapy, utilizing electrons to the central face, differential thickness bolus, an intraoral stent, eye shields, an aquaplast mask for immobilization and a wax-coated lead shield over the face in order to limit penumbra of the radiation beam. Right and left anterior 6-MV photons were used to tangentially treat the bilateral malar region in order to extend the field edges. At the time of this report, the patient remains disease free at nearly 2.0 years after radiotherapy. To the best of our knowledge, this represents only the second case in the literature reporting radiotherapy as a single modality treatment that resulted in complete remission of an angiosarcoma of the face.Key Words: Angiosarcoma, Endothelial cells, Radiation therapy, Single modality treatment     

Successful Nilotinib Treatment in a Child with Chronic Myeloid Leukemia

A 16-year-old female was diagnosed incedentally with chronic myeloid leukemia (CML) in the chronic phase. She showed complete remission after 3 months of nilotinib treatment. CML is a rare malignant neoplasm in pediatric age. It is characterized by a Philadelphia chromosome, which comes from a genetic translocation between chromosomes 9 and 22. This translocation results in an abnormal fusion called BCR-ABL oncogene which encodes a chimeric BCR-ABL protein. This protein is the underlying cause of CML. Nilotinib is a newly licensed drug for CML in adults. Structurally, it is similar to imatinib (the older tyrosine kinase inhibitor), but it is much more potent in inhibiting BCR-ABL due to its much increased affinity for its binding site. Specific guidelines for CML treatment in children have yet to be determined. In our patient, nilotinib was used as an off-label drug because it is not licensed for children. According to the pharmacokinetic response to drugs, children cannot be considered small adults irrespective of their weight. Off-label drug use based on evidence that it is the best treatment available is an important tool in the hands of expert treating physicians.Key Words: Chronic myeloid leukemia, Nilotinib, Off-label drug use, Tyrosine kinase inhibitor     

Immunoblastic Lymphadenopahy in a Five-month-old Girl: Successful Treatment with Immunosuppressants

A five-month-old girl developed high fever, erythema, hepatosplenomegalyand generalized lymphadenopathy. Laboratory examinations revealedelevated peripheral leukocyte counts, C-reactive protein, lactatedehydrogenase and serum ferritin level. Pathologic examinationof the lymph nodes revealed immunoblastic lymphadenopathy (IBL)on the basis of the complete effacement of the normal architecture,replacement by a diffuse infiltrate composed of immunoblasts,plasmacytoid cells and small lymphocytes, and an abortive proliferationof blood vessels. B-cells and T-cells were nearly equally mixedthroughout the lymph nodes. No rearrangements of the Bcell immunoglobulinand T-cell receptor genes were detected. The patient was initiallytreated with -interferon with dramatic efficacy. After relapse,however, the disease was well controlled with cyclosporin A(CyA) and subsequently with combination regimens of CyA, deoxyspagarinand azathioprine with fair success. An alternating regimen of6-mercaptopurine, cyclophosphamide and methotrexate was theninstituted which continued the complete remission for 12 months.The effects of immunosuppressants in the treatment of IBL meritinvestigation.     

Case Study in Refractory Non-Hodgkin's Lymphoma: Successful Treatment with Plerixafor

The present case study describes our experience in treating a young woman diagnosed with a relapsing case of diffuse large cell lymphoma, who was heavily pre-treated with chemotherapy and radiotherapy. Our only chance to improve her survival was by using high-dose chemotherapy, followed by peripheral stem cell rescue. Unfortunately, in this patient, collecting sufficient stem cells for bone marrow transplantation proved to be very difficult since she had already been heavily treated with chemotherapy and radiotherapy. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used treatments for stem cell mobilization. However, 5-30% of patients do not respond to these agents. Plerixafor is a new hematopoietic stem cell-mobilizing drug that antagonizes the binding of chemokine stromal cell-derived factor-1α to CXC chemokine receptor 4. It is indicated in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma [Kessans et al.: Pharmacotherapy 2010;30:485-492; Jantunen: Expert Opin Biol Ther 2011;11:1241-1248]. Based on our findings, we consider plerixafor to be a very efficient and practical solution to mobilize and collect stem cells among all patients in such a situation, enabling us to proceed to autologous bone marrow transplantation and peripheral stem cell rescue in order to improve the patients' overall survival.     

Successful Treatment of Solitary Bone Metastasis of Non-Small Cell Lung Cancer with Bevacizumab and Hyperthermia

Non-small cell lung cancer (NSCLC) represents 85 % of all malignant lung cancers. In metastatic disease the principle goal of palliative therapy is to prolong survival with least toxicity and best patients’ quality of life. Bevacizumab (BEV) has been approved as first line treatment in combination with platinum based chemotherapy and maintenance therapy in NSCLC. BEV can be added safely to several chemotherapeutic agents, however there is no data on coadministration with thermotherapy. Even in localized disease no robust evidence exists about the beneficial effect of loco-regional thermotherapy on overall survival, but it might be used successfully in symptom palliation. In this article a successful co-administration of BEV and hyperthermia is reported in a patient with monolocalized bone metastasis from previously operated NSCLC. This case suggests that electrohyperthermia can probably be incorporated in palliative therapy added not only to radiotherapy or chemotherapy but also to anti-angiogenic BEV treatment.     

The Early Successful Treatment of Glioblastoma Patients with Modified boron Neutron Capture Therapy

We very effectively treated two patients with recurrent glioblastoma with modified boron neutron capture therapy (BNCT). In this paper, we describe the effectiveness of this treatment, and discuss the ways in which we modified the treatment. A 61-year-old man had a first operation for a right temporal glioblastoma, followed by full-dose chemo-radiotherapy. One year after the operation a partial removal was performed for the recurrent tumor at the same site. Fifty days after the second surgery, the patient received BNCT. We used an epithermal neutron beam as the neutron source, and used both sodium borocapate and boronophenylalanine as boron compounds with the craniotomy. Forty-eight hours after the BNCT, the follow-up MRI was applied to estimate the early effect of this treatment, which showed a 70% reduction in the contrast enhanced lesion, compared with the pretreatment MRI. In addition, the lesion/normal brain ratio of thallium-SPECT had improved markedly. No serial sequelae appeared after this treatment, and the patient remains healthy 6 months after the treatment. A 29-year-old young lady had a right temporal brain tumor, which was partially resected and followed by stereotactic radiosurgery for the residual mass. Seven months after the radiosurgery, a second operation was performed, which revealed the glioblastoma as diagnosis. We applied BNCT uneventfully for this patient with epithermal beam and two kinds of boron compounds as described above. For the treatment of the patient irradiation was applied without craniotomy with marked reduction of tumor volume immediately after the treatment.     

Indeterminate Cell Histiocytosis in a Pediatric Patient: Successful Treatment with Thalidomide

The 15-year-old male patient presented several 2–6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.     

Successful Treatment of an Aspergillus fumigatus Infection with Voriconazole Via a Nasogastric Tube

Abstract

Extended-spectrum beta-lactamase (ESBL) production by Enterobacteriaceae is an emerging problem. This 3-year prospective study was undertaken to determine the prevalence of such enzymes among the clinically significant isolates of the Enterobacteriaceae family gathered from patients, and to evaluate the different techniques for their detection as well as their clinical significance. Members of the Enterobacteriaceae family isolated from blood, inhibited by the third-generation cephalosporins with minimum inhibitory concentrations (MICs) of ≤2 μg/ml and MIC ≤8 μg/ml and isolates from other sources inhibited by MIC ≤8 μg/ml were also investigated for ESBL production by VITEK2 and E test. Their clinical significance in septicemic patients was analyzed. Out of 3,215 isolates, 1018 (31.7%) were ESBL-producers by both VITEK2 and E test. Of these, 428 (42%) were Klebsiella pneumoniae and 376 (37.0%) were Escherichia coli with overall prevalence rates of 13.3% and 11.7%, respectively. There were a total of 184 septicemic patients infected by ESBL-producing Enter-obacteriaceae out of which 134 (73%) needed modification of therapy; most (58%) of these patients were initially on third-generation cephalosporin therapy. A total of 58 (31.5%) patients were infected by ESBL-producing blood isolates which were inhibited by cefotaxime/ceftriaxone at MICs ≤8 μg/ml (within the susceptibility range). Resistance to both aminoglycosides and quinolones were significantly higher among ESBL-producing isolates compared to non-producers (P<0.05). This study highlights a high prevalence of ESBL-producing Enterobacteriaceae in a major tertiary teaching hospital in our country and demonstrates that almost a third of the ESBL-producing Enter-obacteriaceae blood isolates would have been released as susceptible by routine susceptibility testing; a finding inimical to optimal therapeutic success.     

Successful Treatment of Rhinocerebral Mucormycosis with Liposomal Amphotericin B and Surgery in Two Diabetic Patients with Renal Dysfunction

Abstract

The zygomycetes are a class of fungi that can cause a variety of infections in humans. Rhinocerebral mucormycosis is a rare disease and usually affects diabetic or immunosuppressed patients. The disease progresses rapidly and is usually fatal despite aggressive surgical and medical therapy. We report the management of two cases of rhino-sinusal and orbital mucormycosis in diabetic patients on treatment with corticosteroids, and mild renal impairment, successfully treated with a combination of aggressive surgical debridement and liposomal amphotericin B.