Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis

BACKGROUND: The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis. METHODS: To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs). RESULTS: By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic. CONCLUSIONS: Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease.     

Expression of Fas antigen in acute myeloid leukaemia is associated with therapeutic response to chemotherapy

Flow cytometric immunofluorescent analysis was used to assess Fas antigen (CD95) expression in blasts obtained from the bone marrow of 30 patients with acute myeloid leukaemia. The percentage of positive cells in each sample was highly variable. Fas antigen expression did not correlate with age, FAB subtype, white blood cell counts, or CD34 expression. Low expression of Fas was associated with a low complete remission rate after induction chemotherapy (62.5% in cases with < 20% positive cells v 92.9% in cases with > or = 20% positive cells, P < 0.01). The main cause for not achieving remission was resistant disease. Our results suggest that the quantitation of Fas expression can be predictive of treatment outcome in acute myeloid leukaemia.     

Intra-abdominal localization of acute leukaemia: report of six cases

Clinical findings leading to the diagnosis of acute leukaemia result from the consequences of both pancytopenia and tumoral manifestations. Although leukaemic infiltration of hematopoietic organs is common, the involvement of non-hematopoietic abdominal organs remains rare. The authors report a series of six cases, where intra-abdominal localization of acute lymphoblastic or myeloblastic leukaemia was detected at diagnosis or relapse. Chemotherapy may lead to remission or cure if the early abdominal complications are managed with care.     

Pyoderma gangrenosum associated with active chronic hepatitis: report of two cases

In two patients, active chronic hepatitis was complicated by the development of pyoderma gangrenosum. The favorable response of the pyodermatous lesions to azathioprine therapy suggests that this drug may be of value in treating this disorder in patients for whom corticosteroid therapy produces no benefit or is contraindicated because of side effects. Azathioprine, too, is a potentially toxic drug and may need to be discontinued. Possible causal relationships between pyoderma gangrenosum and active chronic hepatitis are discussed.     

Waldenstr?m's macroglobulinaemia terminating in acute myeloid leukaemia: report of a case and review of the literature

We report on a patient originally diagnosed as having monoclonal gammopathy of undetermined significance (MGUS) who progressed to develop Waldenstr?m's macroglobulinaemia (WM) after 3 years. Four years later he developed chronic myelomonocytic leukaemia (CMMoL) which terminated in acute myeloid leukaemia (AML) after another year. We also review published reports of similar cases.     

Obstructive jaundice associated with extrahepatic portal vein obstruction: report of two cases

We herein report two cases of obstructive jaundice with markedly dilated collateral veins either in or around the bile duct in the setting of extrahepatic portal vein obstruction (EHPO). In the first case, a proximal splenorenal shunt provided relief of biliary stenosis as well as eradication of esophageal varices due to a decompression of portal hypertension. This evidence proved that the markedly extended collateral veins in the hepatoduodenal ligament caused biliary stenosis by compressing the bile duct. In the second case, obstructive jaundice was probably caused by cholangitis and was relieved with biliary drainage. Portal decompressive surgery was not indicated because of the slight degree of esophageal varices. The relationship between cholangitis and EHPO in these patients calls for further investigation. In cases with EHPO manifesting obstructive jaundice associated with risky esophageal varices, portal decompressive surgery is recommended as the procedure of choice.     

Spondylolysis associated with Arnold-Chiari malformation and syringomyelia. A report of two cases

STUDY DESIGN: This is a report of two cases. OBJECTIVE: To document the occurrence and association of spondylolysis and Arnold-Chiari malformation Type I. SUMMARY OF BACKGROUND DATA: The association of spinal dysraphism has been reported with Arnold-Chiari Type II, but not with Arnold-Chiari Type I. METHODS: The senior author was involved in the care of these patients. All medical records, laboratory and radiologic investigations, and related literature were reviewed. RESULTS: The presence of cephalic and caudal neuropore maldevelopment may be present in various combinations. The presence of spondylolysis, with or without spina bifida occulta, associated with Arnold-Chiari malformation type I and syringohydromyelia, is demonstrated. CONCLUSIONS: In some patients, the presence of spondylolysis may represent a congenital anomaly and may be associated with cephalic neuropore maldevelopment, such as cerebromedullary malformation syndrome (i.e., Arnold-Chiari malformation Type I).     

Invagination of the vermiform appendix. A report of two cases associated with endometriosis

Two cases of invagination of the Vermiform appendix associated with endometriosis are presented. Classification, incidence, etiology, symptomatology, diagnosis and treatment are discussed. The literature is reviewed in brief, and it is concluded that the possibility of invagination of the Vermiform appendix should be considered in obsure abdominal cases with recurrent right lower quadrant pain.     

Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia

Gene transfer of the cytidine deaminase (CDD) cDNA has recently been shown to induce cellular resistance to cytarabine (AraC) in vitro. To investigate the role for CDD in acute myeloid leukaemia (AML) we analysed the CDD activity and CDD gene structure in blast material from well-defined patients with untreated and AraC refractory (RF) AML. Median CDD activity in previously untreated AML was significantly lower than in RF-AML blasts (P=0.015) and was significantly lower in patients with complete remission than with blast persistence following induction chemotherapy (P=0.043). Structural investigation of the CDD gene by Southern analyses and RT-PCR showed no detectable aberrations. Sequence analysis of the CDD cDNA from nine RF-AML patients showed inconsistent aberrations in three patients. Semiquantitative assessment of CDD mRNA expression revealed a significant correlation with CDD activity. In conclusion, concordant with another recent study our data suggest a correlation of pretherapeutic CDD activity with induction treatment response. Besides the previously described prognostic impact of mdrl expression, this result could be useful for the development of risk-adapted AML treatment strategies and warrants further studies of CDD activity in well-defined cohorts of AML patients and of the mechanisms involved in the regulation of CDD activity.     

Complete atlanto-axial dislocation associated with type II odontoid fracture: a report of two cases

Two cases of complete atlanto-axial dislocation with associated Type II odontoid fracture are reported. In one case, the instability associated with this injury was treated with primary odontoid fixation. In the second case, the patient had full cardiac arrest associated with this injury. Due to the extreme instability present with this fracture sub-type and the potential for neurological compromise, early recognition of this fracture pattern by the treating physician is imperative to prevent fatal spinal cord injury.     

A resolving sign of acute subdural hematoma: from report of two cases

A 7-year-old-boy (Case 1) and a 60-year-old-man (Case 2) presented with rare spontaneous resolution of acute subdural hematoma (ASDH). They were admitted with consciousness disturbance, drowsy in Case 1 and sleepy in Case 2. Initial CT showed ASDH associated with a low density band between the hematoma and the inner wall of the skull base, combined with right parietal contusion in Case 2. Repeat CT showed that the hematoma had resolved spontaneously after a few hours, and the patients regained clear consciousness next day in Case 1 within a few days in Case 2 without surgical treatment. The mechanism of spontaneous resolution of ASDH was thought to involve pulsatile flow of cerebrospinal fluid (CSF) through the tear in the arachnoid membrane, resulting in redistribution and dispersal of the hematoma, and retrograde flow into the subarachnoid space. The characteristic feature of the CT findings, the low density band between the hematoma and the inner wall of the skull bone, probably shows this process. Spontaneous resolution of ASDH requires that the brain compensatory function maintains the normal outflow of CSF, and controls the intracranial pressure by CSF buffering, blood outflow via the venous system, and brain elasticity. The low density band may be a useful finding to distinguish cases with good and bad prognosis.     

Agranulocytosis secondary to methimazole therapy: report of two cases

Seventy-three cases of thyrotoxicosis were treated at Lloyd Noland Hospital with methimazole, propylthiouracil or both. Two cases of agranulocytosis occurred (2.7%) secondary to methimazole. Both responded to hospitalization, reverse isolation, and antibiotic coverage with complete recovery of the peripheral blood picture. The toxicity of methimazole is noted. The need for careful monitoring of blood counts during therapy and immediate discontinuance of the drug at the first clinical sign of granulocytopenia is stressed.     

Colonoscopy-assisted colostomy--an alternative to laparotomy: report of two cases

PURPOSE: The objective of this study was to evaluate the feasibility of performing fecal diversion with the help of a colonoscope without a concomitant laparotomy. METHODS: Colostomies were performed on two patients who needed fecal diversion and who would benefit from avoiding the morbidity of laparotomy. A colonoscope was used in each case to guide the surgeon in selecting the appropriate bowel segment. RESULTS: No complications related to the colostomy were noted in either patient. CONCLUSIONS: The technique of colonoscopy-assisted colostomy that we have described offers an acceptable method of creating a stoma without the need for laparotomy.     

The expression of co-stimulatory molecules and their relationship to the prognosis of human acute myeloid leukaemia: poor prognosis of B7-2-positive leukaemia

We examined the expression of co-stimulatory molecules on leukaemic cells of 52 adult patients with acute myeloid leukaemia (AML) (34 men and 18 women) and analysed the relationship between these expressions and the patient's prognosis. B7-1 was not expressed in any of the 23 patients investigated, whereas B7-2 was expressed in 26/52 patients (50.0%). B7-2 was expressed in all AML patients with monocytic morphology (M4 or M5) and in 16/42 cases without monocytic morphology. CD54 was expressed in 28/ 37 patients examined (75.7%), and CD58 was expressed in all of the AML patients except one (M 7). The overall survival of the 26 B7-2-positive leukaemia patients (1-24 months, median survival 11.5 months) was significantly shorter than that of the 26 B7-2-negative leukaemia patients (1-71+ months, median 35.1 months) (P=0.0080). In addition, the B7-2-positive patients exhibited significantly shorter disease-free survival periods compared to the B7-2-negative patients (P=0.021). There was no significant difference in age, sex, haematological data and complete remission rate between the B7-2-positive and B7-2-negative patients. Our results indicated that B7-2 is one of the most crucial factors in the prognosis of adult acute leukaemia and can be expected to have an important role in tumour immunity.     

Intrathyroidal lymphoepithelial cyst. A report of two cases not associated with Hashimoto's thyroiditis

Two cases of intrathyroidal lymphoepithelial cyst are described. Both of them were solitary, one being found incidentally in a patient operated on for a multinodular goiter, the other being clinically obvious as a cold nodule. They exhibited features of cysts of branchial cleft origin, i.e. squamous cell lining epithelium and abundant lymphoid tissue with reactive germinal centers. The thyroid gland parenchyma showed a discrete lymphoid infiltration consistent with the diagnosis of focal lymphocytic thyroiditis. In the first case a single epidermoid solid cell nest was found. The histogenesis of intrathyroidal lymphoepithelial cysts remains unclear, but their origin from cystically degenerated ultimobranchial body remnants (solid cell nests) seems to be most probable. This assumption is supported by a similar immunohistochemical profile of solid cell nests and epithelial cells lining the cysts and also by the presence of one solid cell nest in the proximity to the cyst in one of our cases.     

Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukaemia

Seven relapsed and/or refractory acute promyelocytic leukaemia patients were treated by arsenic trioxide (As2O3). Four patients (4/7, 57%) achieved complete remission after one to three cycles of treatment and the most common acute side-effect was fluid retention (in six patients, 86%), including weight gains and pleuro-pericardial effusions. Evident polyneuropathy compatible with chronic arsenic toxicity was noted in two of the three patients who received As2O3 maintenance therapy and one of them had marked distal muscular atrophy. We suggest that As2O3 may be a useful salvage therapy for relapsed and refractory APL patients, but the acute or chronic arsenic toxicity should be carefully monitored.     

Leiomyoma of the bladder: report of two cases

We report 2 cases of leiomyoma of the urinary bladder. A 41-year-old female visited our hospital with the complaint of pollakisuria. A solid tumor of the urinary bladder was found by ultrasonography. A large shadow defect at the left-anterior wall was shown by drip infusion pyelography (DIP). Computed tomographic scan (CT) and magnetic resonance imaging (MRI) also revealed a large tumor. T1-weighted image revealed a homogeneous low intensity tumor and T2-weighted image disclosed heterogeneous low intensity tumor. Cystoscopy revealed a large submucosal tumor. Partial cystectomy was performed, and she has had neither recurrence nor metastasis for 36 months. A 32-year-old male was referred to our hospital with the complaint of macrohematuria. A solid tumor of the urinary bladder was found by ultrasonography. A shadow defect was not clearly detected by DIP. A large tumor was detected on the anterior wall by MRI. T1-weighted image showed a homogeneous low intensity tumor and T2-weighted image disclosed a high intensity tumor. Cystoscopy revealed a submucosal tumor on the anterior wall. Urine cytology did not suggest a malignancy. The biopsied specimens revealed only an inflammatory change in the mucosa. Partial cystectomy was carried out. He has had neither recurrence nor metastasis for 29 months. Histological diagnosis in both cases was leiomyoma of the urinary bladder.     

Vertebral osteomyelitis due to salmonellae: report of two cases and review

A static or kinetic visual disturbance affects subjects' ability to estimate the direction of the gravitational vertical. This kind of error is increased by a head roll inclination. In two experiments, we combined head orientation with a static (Experiment 1: tilted frame) versus kinetic (Experiment 2: rotating disk) visual disturbance. The results showed that with a static visual disturbance, the increase of errors in the inclined head condition was mainly the consequence of a postural head effect like an Aubert effect. On the contrary, with a kinetic visual disturbance, it appears that the disk effect increases with head inclination. However, individual errors observed with the head inclined in front of a stationary disk were systematically correlated with the errors triggered by the same head inclination in front of a rotating disk. These observations confirm that the head axis spatial reference plays an important role in orientation perception, whatever the head position and the kind of visual display.