Pneumonitis in elderly patient with ANCA-positive glomerulonephritis during treatment with cyclophosphamide

A 78 year-old woman with extracapillary glomerulonephritis was treated with cyclophosphamide and corticosteroids. Three months after starting the therapy, the patient had an episode with breathlessness, cough and sputum without fever. X-ray showed bilateral interstitial infiltrates. She was initially treated with empirical antibiotics without achieving clinical or radiological changes. After ruling out an infectious cause, activity of the underlying disease, and other causes of fibrosis, treatment with cyclophosphamide was stopped. Following this, there was an immediate improvement of her clinical and radiological states. The administration of cyclophosphamide was considered directly related to the cause of her symptoms.     

Conservatively treated glassy cell carcinoma of the cervix

Background

Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment.

Case presentation

We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms.

Conclusion

This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause. It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms.     

Empty sella following spontaneous resolution of a pituitary macroadenoma

BACKGROUND/AIM: Empty sella is a radiological finding characterized by the presence of arachnoid herniation into the sella, resulting in compression of the pituitary against the sella wall. The objective of this case presentation is to discuss secondary empty sella in a patient with spontaneous resolution of a pituitary macroadenoma. METHODS: A case of empty sella syndrome is presented. Static and dynamic testing was performed. Etiology, pituitary function, and imaging are discussed. RESULTS: A 69-year-old African-American woman was referred by her primary care physician for evaluation and treatment of 'hypothyroidisim'. Thyroid tests were performed because of muscle and joint tenderness and revealed low free thyroxine and normal thyroid-stimulating hormone levels. The diagnosis of secondary hypothyroidism was made, and magnetic resonance imaging (MRI) of the pituitary revealed an empty sella turcica. In retrospect, the patient had presented 11 years earlier with tinnitus, and an MRI of her auditory canals demonstrated an 'incidental' 1.5-cm pituitary tumor. No endocrine evaluation was done at that time, and neurosurgical follow-up of the pituitary tumor by serial MRIs demonstrated the genesis into empty sella. CONCLUSIONS: In our patient the natural history of her pituitary tumor was that it involuted and resulted in an empty sella. Although oftentimes speculated as a cause of empty sella, tumor involution has rarely been shown to be causative. In this instance, empty sella was associated with hypopituitarism. This case illustrates the importance of endocrine evaluation of patients with this radiological finding.     

杨树桑黄饮片水提物对免疫低下小鼠的免疫功能的影响

探究桑黄饮片水提物对环磷酰胺所致免疫低下小鼠的免疫功能的影响。本研究以桑黄饮片为原料,采用超声和沸水提取方法得到桑黄饮片水提物,注射环磷酰胺造成小鼠免疫功能低下,通过测定脾脏和胸腺指数、血清免疫球蛋白和细胞因子、脾淋巴细胞增殖、碳粒廓清等实验,对免疫低下小鼠的免疫功能进行研究评价。结果表明,灌胃桑黄饮片水提物的小鼠与模型组相比,免疫器官指数、血清中免疫球蛋白含量、细胞因子水平、脾淋巴细胞增殖程度、巨噬细胞的吞噬速率和吞噬指数、小鼠耳肿胀度均有提高,脾脏苏木精-伊红(HE)染色也表明桑黄饮片水提物可以改善环磷酰胺导致的脾脏组织病理状态。本研究表明桑黄饮片水提物对环磷酰胺所致的免疫抑制小鼠具有良好的免疫保护作用,为桑黄饮片扩大临床应用提供实验依据。     

Conjugal disharmony: a hitherto unrecognised cause of strokes.

Two women of reproductive age suffered strokes. Neither was taking oral contraceptives, and investigations showed no other causal factors. The radiological findings were characteristic of traumatic internal carotid artery occlusion, but neither patient gave a history of trauma. Only after further inquiry into the patients'' social circumstances did it emerge that each had survived an attempt at strangulation by her husband. Such a cause of stroke in young women should be considered when other causes of carotid artery occlusion cannot be identified.     

Primary malignant melanoma of the duodenum without visible melanin pigment: a mimicker of lymphoma or carcinoma

ABSTRACT: Primary malignant melanoma of the duodenum is an unusual oncologic entity. Patients usually present the similar clinical symptoms like other common tumors in this site. And there are no specific radiological features either. The cases with only little melanin pigment or without notable melanin pigment are very misleading, especially in small biopsies or frozen sections. Definite diagnosis depends on both careful histologic examination and the use of proper immunohistochemical stains. Moreover, detailed history and thorough investigation should be made to exclude the preexistence or coexistence of a primary lesion elsewhere. Herein we report the case of a 60-year-old male patient with primary malignant melanoma of the duodenum, which was misdiagnosed as lymphoma or undifferentiated carcinoma in frozen consultation. The patient had achieved disease-free survival for more than 46 months without any evidence of recurrence after surgery. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1221457317710561.     

Urothelial cell changes due to busulfan and cyclophosphamide treatment in bone marrow transplantation

Since the administration of cyclophosphamide and busulfan can cause hemorrhagic cystitis and changes in urothelial cells, an investigation was carried out to see whether patients undergoing bone marrow transplantation (BMT) who were treated with these drugs showed such urothelial changes and whether exfoliative urinary cytology can contribute to the early diagnosis and monitoring of such changes. Morphologic and morphometric analyses were performed on cytocentrifuged, Papanicolaou-stained preparations of 700 samples from 107 patients. Various degrees of urothelial cell changes were found in 30.8% of the cases. These changes consisted mainly of a considerable increase in the size of the nucleus and of a cytoplasm that was often bizarrely shaped. Even the structures of the nucleus and the cytoplasm changed. The results of this study showed that exfoliative urinary cytology permits an early diagnosis and monitoring of urothelial cell changes related to the administration of busulfan and cyclophosphamide in connection with BMT.     

Familial adult onset X-linked hypophosphataemic osteomalacia (report of a family; clinical and experimental studies)

From four patients (a great-grandmother, grandmother, her daughter and her grandson) suffering from a very severe form of familial X-linked hypophosphataemic osteomalacia (XLH), belonging to a 23-number-kindred of five generations, the youngest patient a 24-year-old man with an adult onset XLH was treated with phosphate and calcitriol for two years. Phosphate was given in increasing doses (500-6000 mg elemental phosphate) by mouth for a relatively short-term period and calcitriol in high doses per os combined with intermittent intravenous administration. Long-term treatment consisted of daily three grams of phosphate and 1.25 micrograms calcitriol by mouth combined with daily 2 micrograms calcitriol intravenously for one week every month. Dramatic clinical improvement occurred accompanied with definite radiological and scintigraphical changes. Serum phosphate increased from 0.525 +/- 0.478 mmol/l to 1.054 +/- 0.041 mmol/l (p < 0.001) in response to 3000 mg phosphate. A close correlation (r = 0.69) was found between serum phosphate and urinary phosphate excretions (p < 0.001) and an inverse correlation (r = -0.31) was found between serum phosphate and tubular reabsorption of phosphate (p < 0.01). Serum and urinary calcium values, parathormone as well as renal functions did not change. Administration of high doses of phosphate seemed to be an effective and probably safe form of treatment in XLH provided that development of hyperparathyroidism is prevented by the coadministration of high doses of calcitriol.     

臭牡丹根伍用小剂量环磷酰胺治疗慢性肾炎16例

目的：探讨臭牡丹根伍用小剂量环磷酰胺治疗慢性肾炎的疗效。方法：本文采用臭牡丹根伍用小剂量环磷酰胺（cyclophos-phamide,CTX）治疗慢性肾炎16例,其小剂量CTX用量为200 mg/日,采用静脉滴注的连续给药方式,其总有效率为93.75%,且BUN、Scr明显下降,复发率为6.25%,无明显的毒副作用。结果：臭牡丹根伍用小剂量环磷酰胺治疗慢性肾炎疗法疗效显著,肾功能改善明显,复发率低,且该单味中药来源广泛,使用方便。结论：臭牡丹根伍用小剂量环磷酰胺治疗慢性肾炎,不失为一种治疗慢性肾炎值得推广的方法。     

Stimulation of the brachial plexus by a dislocated ICD lead: a rare complication

A 64-year-old female with a history of myocardial infarction in 2003 with an ejection fraction of 23% underwent an ICD implantation in July 2008 without complications (figure 1). In 1945 her right leg was amputated as a result of a war injury and in 2007 she was treated for a right-sided mamma carcinoma with a sentinel node procedure and curative radiotherapy. One month after the implantation of the ICD the patient had complaints of contractions of the biceps of her left arm resulting in continuous bending of her left arm with a frequency of 40 beats/min.     

Tinea corporis due to Trichophyton rubrum in a Woman and Tinea capitis in her 15-Day-Old Baby: Molecular Evidence of Vertical Transmission

We report a case of a 40-year-old Caucasian woman who came under our observation with a 7-year history of a chronic erythematous scaly dermatitis, diagnosed as psoriasis, involving gluteal area and thighs, and treated with topical steroids without benefit. During pregnancy, a progressive worsening of her condition and an extension of cutaneous lesions were observed. Her newborn, a 15-day-old girl, presented a similar scaly and squamous lesion on her scalp. Mycological examination was positive for Trichophyton rubrum in both cases, and random amplified polymorphic DNA analysis confirmed the isogenicity of the two isolates. We performed a diagnosis of T. rubrum tinea corporis and tinea capitis. The case we describe illustrates an unusual clinical presentation of tinea corporis with remarkable extension of cutaneous lesions due to the diagnostic delay and the continuous use of local steroids, together with a rare tinea capitis in the newborn. Our experience highlights the possibility of mother-child transmission and the importance of an early diagnosis.     

Chemotherapy in pancreatic cancer: results of a controlled,prospective, randomised,multicentre trial.

Forty patients with inoperable pancreatic cancer were included in a prospective, randomised, controlled trial of multiple chemotherapy. The survival of 19 untreated control patients was compared with that of 21 patients who received an initiation course of intravenous fluorouracil, cyclophosphamide, methotrexate, and vincristine given over five days followed by intravenous fluorouracil and mitomycin given over three or five days at six-week intervals thereafter. Median survival in treated patients was 44 weeks, which was significantly longer than the nine weeks seen in controls. In patients without metastases median survival was 48 weeks in the treated group and 12 weeks in controls. In patients with metastases it was 30 weeks in treated patients and seven weeks in controls. The treatment was well tolerated and seemed to confer a significant prolongation of survival, comparing favourably with previous reports of chemotherapy with or without radiotherapy. If the results are confirmed this regimen may be useful in district general hospital practice.     

Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation.

A girl with autosomal dominant hypophosphatemic rickets, presented with clinical, radiological and laboratory signs of rickets at the age of 11 months. She showed a good response to the treatment with low doses of oral phosphate and calcitriol. Surprisingly, she lost her renal phosphate wasting at the age of 8 years, indicating that the disturbed phosphate metabolism can be compensated by hormonal or other factors.     

Atypical vertebral hemangioma: an aggressive form of a benign disease. Case Report and Literature Review

Vertebral hemangiomas are an incidental and relatively common radiological finding and a benign tumor of vascular origin. VH are the most common spine tumors with an estimated incidence of 1.9-27% in the general population. Rarely, vertebral hemangiomas can exhibit extraosseous expansion with resulting compression of the spinal cord. Such lesions are termed aggressive or atypical vertebral hemangiomas (AVH) and account for less than 1% of spinal hemangiomas. A 68-year-old female was referred with progressive walking difficulty and sensory disturbances in her lower extremities. MRI imaging of the thoracic spine revealed a T1- and T2-weighted hyperintense lesion involving the T10 vertebra. Additionally, there was extraosseous extension of the tumor into the spinal canal, located both anterior and posterior to the spinal cord, causing severe spinal cord compression. A combined endovascular and surgical approach (arterial coil embolization and en bloc resection) for treatment was decided. Although vertebral hemangiomas are an incidental and relatively common radiological finding, the findings of our case were consistent with an aggressive hemangioma with atypical MRI and clinical prognostic characteristics. In summary, the present case highlights the need for multidisciplinary approach and in-depth knowledge of this rare pathologic entity.     

Development of an <Emphasis Type="Italic">in vitro</Emphasis> assay for the investigation of metabolism-induced drug hepatotoxicity

In a number of adverse drug reactions leading to hepatotoxicity drug metabolism is thought to be involved by generation of reactive metabolites from nontoxic drugs. In this study, an in vitro assay was developed for measurement of the impact of metabolic activation of compound on the cytotoxicity toward a human hepatic cell line. HepG2 cells were treated for 6 h with compound in the presence or absence of rat liver S9-mix, and the viability was measured using the MTT test. The cytotoxicity of cyclophosphamide was substantially increased by S9-mix in the presence of NADPH. Three NADPH sources were tested: NADPH (1 mmol/L) or NADPH regenerating system with either NADP⁺/glucose 6-phosphate (G6P) or NADP⁺/isocitrate. All three NADPH sources increased the cytotoxicity of cyclophosphamide to a similar extent. Eight test compounds known to cause hepatotoxicity were tested. For these, only the cytotoxicity of diclofenac was increased by S9 enzymes when an NADPH regenerating system was used. The increased toxicity was NADPH dependent. Reactive drug metabolites of diclofenac, formed by NADPH-dependent metabolism, were identified by LC-MS. Furthermore, an increase in toxicity, not related to enzymatic activity but to G6P, was observed for diclofenac and minocycline. Tacrine and amodiaquine displayed decreased toxicity with S9-mix, and carbamazepine, phenytoin, bromfenac and troglitazone were nontoxic at all tested concentrations, with or without S9-mix. The results show that this method, with measurement of the cytotoxicity of a compound in the presence of an extracellular metabolizing system, may be useful in the study of cytotoxicity of drug metabolites.     

Induction of specific-locus and dominant-lethal mutations by cyclophosphamide and combined cyclophosphamide-radiation treatment in male mice

Cyclophosphamide is the most widely used antineoplastic agent. It is also used to condition patients for bone-marrow transplantations. Because of the general interest of this compound we initiated a systematic study of the induction of dominant-lethal and specific-locus mutations in male mice. In addition, we investigated the induction of specific-locus mutations by the combined treatment of cyclophosphamide and ionizing radiation.A dose of 40 mg/kg bw of cyclophosphamide caused dominant-lethal mutations in male mice only in the 1st and 2nd week after treatment. A dose of 120 mg/kg induced dominant-lethal mutations in the mating intervals 1–21 days posttreatment. No dominant lethal mutations were observed after the 3rd week. The same differential spermatogenic response was observed for the induction of specific-locus mutations. Cyclophosphamide induced recessive mutations exclusively in spermatozoa and spermatids. No mutations were recovered from treated spermatocytes and spermatogonia. In contrast to cyclophosphamide, radiation induces specific-locus mutations in all germ-cell stages.The pretreatment with cyclophosphamide 24 h before radiation enhanced the frequency of specific-locus mutations in spermatogonia. The distribution of the observed mutations among the 7 loci and their viability supports the hypothesis that these mutations were induced by radiation rather than by cyclophosphamide. The compound causes an immediate inhibition of DNA and RNA synthesis in spermatogonia. The inhibition very likely interferes with the repair process. The disturbance of the repair process is probably the cause of the synergistic effect for the induction of specific-locus mutations in spermatogonia of mice after pretreatment with cyclophosphamide 24 h before irradiation.     

Complete gallbladder torsion diagnosed with sequential computed tomography scans: a case report

ABSTRACT: INTRODUCTION: Torsion of the gallbladder is an extremely rare cause of acute abdomen, which commonly affects thin elderly women. A prompt surgical approach is necessary to avoid fatal complications associated with gangrene and perforation of the gallbladder. However, it is difficult to make a preoperative diagnosis using ordinary imaging modalities. CASE PRESENTATION: An 84-year-old Japanese woman was admitted to our hospital due to left lower abdominal pain. Her pain shifted suddenly to the right upper abdomen a half day after admission. Although her enlarged and wall-thickened gallbladder had been already seen at admission, it rotated approximately 180 degrees and deviated to the midline of her abdomen on the second computed tomography scan, which helped us to make a correct diagnosis of gallbladder torsion. The patient underwent an emergency operation (detorsion and cholecystectomy) and recovered without any complications. The gallbladder had necrosis due to torsion. CONCLUSION: Sequential diagnostic imaging might be helpful to make a preoperative diagnosis of gallbladder torsion when the gallbladder is enlarged and wall thickened but the patient does not present with typical clinical symptoms.     

Clinical trial with long-term therapy of generalized plasmacytoma]

The authors report on findings in long-term therapy made by means of a combination of cyclophosphamide as attack dosis (partially also with polychemotherapy--COP, COPP-scheme) and double plasmapheresis. Since 1967 33 patients have been treated in this way. A group (6 patients) only received cyclophosphamide in a attack therapy of 15...25 mg/5g per body weight; a second group of 14 patients received the same dosis in combination with a double plasmapheresis. The third group of 13 patients in an advanced stage of the illness was treated polychemotherapeutically according to various schemes (COP-cyclophosphamide, vincristine, prednisone; COPP with Natulan) likewise in combination with double plasmapheresis. The observations made for 4 years in the two groups first mentioned showed favourable results in the second group with an average survival time of 35 months. In the third group only experiences of two years can be reported and thus a final answer cannot be given. However, it can already be stated that a clinical success requires the cytostatic therapy to be continued for a long time in combination with plasmapheresis.     

Short term administration of costimulatory blockade and cyclophosphamide induces remission of systemic lupus erythematosus nephritis in NZB/W F1 mice by a mechanism downstream of renal immune complex deposition

NZB/W F(1) mice with established nephritis were treated with a single dose of cyclophosphamide with or without a 2-wk course of murine CTLA4Ig, either alone or in combination with anti-CD154. Sixty to 80% of treated mice entered remission, and remission could be reinduced following relapse. A decrease in the frequency of anti-DNA-producing B cells and activated T cells was observed in treated mice, but this effect lasted only 3-6 wk, while remissions were sustained for up to 20 wk. Light microscopy of the kidneys of mice in remission revealed less glomerular inflammation, less tubular damage, and less infiltration of inflammatory cells. By immunofluorescence, however, IgG and C3 staining of glomeruli was no different in treated mice vs controls. Since chemokines and their receptors play an important role in inflammatory cell infiltration of affected organs in autoimmune diseases, we examined chemokine expression in the kidneys. Decreases in the expression of inflammatory cytokines and chemokines were evident in mice in the early stages of remission, but these differences were no longer present in late remission. Increased expression of CXCL13 was detected in the inflammatory infiltrates of the control NZB/NZW mice. Strikingly, we could not detect any CXCL13 in the kidneys of the treated group even in late remission. These findings suggest that costimulatory blockade together with cyclophosphamide influence the activation state of renal CD11c-positive cells and therefore lead to less B and T cell infiltration and nephritis.     

Aspects of early arthritis. Definition of disease states in early arthritis: remission versus minimal disease activity

With regard to rheumatoid arthritis, remission as currently used in the literature can have two meanings: either a state with persistent absence of clinical and radiological signs of disease activity without being treated for a specific time period, or it may point to a disease state with minimal disease activity during antirheumatic treatment. A risk factor for the first is absence of autoantibodies, with the anti-CCP-antibodies as best predictors, whereas risk factors for achieving a drug-induced state of minimal disease activity are not well defined. These definitions of remission refer to different disease states; therefore, we propose that the term remission is reserved for patients that are not treated with antirheumatic drugs.