Absence of Helicobacter pylori in oral mucosal lesions

A prospective study was conducted in 26 patients with benign oral ulcers and oral carcinoma and 26 age and sex matched controls to determine the prevalence of Helicobacter pylori in oral mucosal biopsies. Oral mucosal biopsies were subjected to rapid urease test, campylobacter like organism (CLO) test, histopathological examination and bacteriological culture for demonstration of H pylori. Urease test was positive for H pylori in 3 (11.4%) out of 26 cases and CLO test in 2 (14%) out of 14 cases. On histology, H pylori was identified in 4 (15.38%) out of 26 cases. The spiral organism was universally absent in culture of both patients and controls. These pilot data negate the casual association of H pylori in oral mucosal lesions.     

Adjuvant treatment with cyclosporin A increases the toxicity of chemotherapy for remission induction in acute non-lymphocytic leukemia

P-glycoprotein (Pgp)-related multidrug resistance (MDR) is frequently observed in acute non-lymphocytic leukemia (ANLL) and is associated with a poor response to standard chemotherapy. Cyclosporin A (CsA) is an effective downmodulator of Pgp-related MDR in vitro and has already been tested for that purpose in vivo also. Since Pgp is expressed in several normal cells and tissues, the modulation of Pgp can also modify total body exposure to antileukemic drugs and can alter and increase the toxicity of the antileukemic treatment. We report here the results of a study where 46 consecutive adult patients with ANLL were assigned to receive the same standard chemotherapy regimen of arabinosyl cytosine and idarubicin (IDA) for remission induction or consolidation, without or with CsA. Twenty-eight patients received 36 courses of chemotherapy without CsA and 18 patients received 32 courses of chemotherapy with CsA. CsA dose was 10-12.5 mg/kg/day and was given as a continuous i.v. infusion for 72 h. Whole blood CsA steady-state concentration ranged between 0.61 and 1.14 microM. The IDA area-under-the-curve was about twice as high in the cases that received CsA than in the other cases. CsA had no detectable effects on renal function and fluid balance, but significantly increased systemic blood diastolic pressure and conjugated bilirubine concentration. Furthermore, CsA-treated patients had greater, and more severe, oral and intestinal mucosal toxicity, with more severe adverse events, including more cases of gram-negative bacteremia, and with a delayed hemopoietic recovery. In conclusion, this study showed that an attempt at an effective downmodulation of Pgp-mediated MDR would substantially increase the hemopoietic and mucosal toxicity of antileukemic treatment and that the increase is accounted for, at least in part, by an increase of total body exposure to IDA.     

Disseminated intravascular coagulation (D.I.C.) and fibrinolysis in patients with acute leukemia (author's transl)

Biological symptoms of D.I.C. were investigated in 43 patients with acute leukemia. Ten of them were found to be positive either at the onset or at the relapse of the disease and in some cases D.I.C. was triggered by chemotherapy. Among the ten positive cases 3 patients had an acute promyelocytic leukemia, 4 had an acute lymphoblastic leukemia, 2 a myeloblastic and 1 a monoblastic leukemia. D.I.C. was found either in patients with an hypercellular form of the disease or in patients with a normal or low white cell count. Symptoms of D.I.C. in acute leukemia must be systematically sought at the onset and during treatment by chemotherapy and treated with heparin and platelet transfusions as it is now admitted for acute promyelocytic leukemia.     

Acute leukemia during reproductive life: its course, complications and sequelae for fertility

Acute leukemia is less common during the reproductive years than in children or in post-menopausal women. Effective chemotherapy exists for adult lymphocytic leukemia, and the median survival is 18 to 20 months. Acute myelogenous leukemia still has a less favorable prognosis, with a medial survival of 12 months despite effective chemotherapeutic agents. The occurrence of acute leukemia in pregnancy does not change the overall prognosis, which depends primarily on the cytopathologic types. If leukemia occurs during the first trimester, therapeutic abortion is advised since the rate of spontaneous abortion after chemotherapy is high in the first trimester and fetal malformations are common. Acute leukemia can be treated in the second and third trimesters with little effect on the pregnancy or fetus. In patients cured of acute leukemia, the potential for subsequent pregnancies exists with little likelihood of increases in fetal malformations.     

Adult T cell leukemia/lymphoma effectively treated with chronic oral etoposide

A 52-year-old man, who complained of tarry stool and systemic lymphadenopathy, was admitted to our hospital on July 2, 1992. Biopsy showed diffuse large cell lymphoma. Leukocytosis with atypical lymphocytes was not shown in the peripheral blood, but there was an elevated serum LDH level. The man was found to have both HTLV-I antibody and the monoclonal integration of proviral DNA in malignant lymph node cells obtained at biopsy. The diagnosis was lymphoma-type adult T-cell leukemia (ATLL). The chemotherapy regimens of MI-FP, CHOP and modified DHAP were used for the treatment, but were not effective. So, he was treated with etoposide 75 mg orally for 25 days (chronic oral etoposide therapy) and achieved partial remission. This chemotherapy induced myelosuppression with neutropenia, but there was no documented infection. Chronic oral etoposide therapy is an effective regimen for patients with relapse or refractory lymphoma.     

Beta-carotene concentration in buccal mucosal cells with and without dysplastic oral leukoplakia after long-term beta-carotene supplementation in male smokers

OBJECTIVE: To measure the beta-carotene concentration in buccal mucosal cells in smoking men who had received long-term beta-carotene (BC) supplementation in a controlled trial. To assess the association of cellular BC on the prevalence of dysplasia in oral leukoplakia. DESIGN: An end-of-trial examination of a part of subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study. SUBJECTS AND METHODS: 343 men who for 5-7 years had received BC (20 mg/d) or alpha-tocopherol (AT) (50 mg/d), or both of these or placebo. BC concentration of buccal mucosal cells was compared in the subjects with BC supplementation (n = 173) to that of those without it (n = 170). Oral mucosae were examined clinically and lesions showing leukoplakia histopathologically. RESULTS: Mean (s.d.) BC concentration in buccal mucosal cells was 7.7 (10.3)mg/kg protein in the subjects who received BC compared to 1.1 (1.7) mg/kg protein in those who did not. The BC concentration in the cells of supplemented subjects correlated with their serum BC levels (P < 0.001). AT supplementation had no effect on BC concentration nor was daily amount of smoking statistically significantly associated with the BC concentration in buccal cells. Altogether 17 subjects showed oral leukoplakia, 7 had dysplasia. In these 7 subjects, the BC concentration in buccal mucosal cells did not differ statistically significantly compared to subjects with only hyperkeratosis (n = 10) (F-test, P = 0.74). CONCLUSIONS: After long-term BC supplementation, BC concentration in oral mucosal cells was 7-fold greater than without supplementation. There was no evidence to support an association between cellular BC concentration and precancerous lesions among the few subjects having them in their oral mucosae.     

Acute necrotizing gastritis associated with adult T-cell leukemia in the course of chemotherapy

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.     

Gonadal function after chemotherapy for acute lymphoblastic leukemia

Object of this study was to verify long term effects on gonadal function in pre- and pubertal patients affected by acute lymphoblastic leukemia (ALL). The population examined was represented by 15 patients, 10 males and 5 females, who came to our Unit after a period of time ranging from 4.5 to 6.2 years. All the patients underwent combined chemotherapy without alkylating agents, such as cyclophosfamide and citosine arabinoside, and intrathecally radiotherapy for a mean period of two years. All the patients were off-therapy and without symptoms of relapse except for one case. The examination of the male and female gonadal function was done on the basis of hormonal assay, ultrasonographic examinations, Tanner's determination of the pubertal development, monitoring of the ovulation and seminal fluid evaluation. The clinical results obtained showed an absence of negative effects both on the gonadal function and on pubertal development. Combined chemotherapy for ALL during pre- and pubertal stage without alkylating agents does not alter the normal gonadal function during the following ten years. Prospective studies will establish the risk of partial follicular atresia and the incidence of premature gonadal failure.     

Clinical diagnosis and management of hormonally responsive oral pregnancy tumor (pyogenic granuloma)

OBJECTIVE: To present a review of our experience and that of the medical literature in the diagnosis and management of oral pregnancy tumor (pyogenic granuloma), the natural History of the disease, its hormonal etiology, histopathologic features and management strategies. STUDY DESIGN: Medical literature review. RESULTS: This common, benign, hyperplastic oral mucosal lesion is much less familiar to gynecologists and obstetricians than to dentists. CONCLUSION: For practitioners engaged in primary care obstetrics and gynecology, routine oral examination and proper identification of pyogenic granuloma are important to avoid misdiagnosis and overtreatment.     

Cytarabine-induced pericarditis

We report two cases of cytarabine (Ara-C) induced pericarditis. The first patient was a 61-year-old man with de novo acute myelogenous leukemia (AML) with trilineage myelodysplasia (M2). Fever and pericardial effusion developed after treatment with low-dose Ara-C and etoposide (VP16) during the patient's second leukemic relapse. The second patient was a 65-year-old man with myelodysplastic syndrome (MDS) transformed into AML (M2). He achieved a complete remission after treatment with low-dose Ara-C and VP16. However, during consolidation chemotherapy consisting of oral cytarabine ocfosfate and VP16, fever and pericardial effusion developed. In both cases, pericardiocentesis revealed exudative effusion with many neutrophils. Neither bacterial nor fungal infection was demonstrated. Chest symptoms and fever were resolved by methylprednisolone pulse therapy and pericardial drainage. Both patients were given a diagnosis of pericarditis caused by allergic reaction to Ara-C. We also report on 6 other patients with Ara-C syndrome who have been encountered by our hospital.     

Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles

DNA vaccines are usually given by intramuscular injection or by gene gun delivery of DNA-coated particles into the epidermis. Induction of mucosal immunity by targeting DNA vaccines to mucosal surfaces may offer advantages, and an oral vaccine could be effective for controlling infections of the gut mucosa. In a murine model, we obtained protective immune responses after oral immunization with a rotavirus VP6 DNA vaccine encapsulated in poly(lactide-coglycolide) (PLG) microparticles. One dose of vaccine given to BALB/c mice elicited both rotavirus-specific serum antibodies and intestinal immunoglobulin A (IgA). After challenge at 12 weeks postimmunization with homologous rotavirus, fecal rotavirus antigen was significantly reduced compared with controls. Earlier and higher fecal rotavirus-specific IgA responses were noted during the peak period of viral shedding, suggesting that protection was due to specific mucosal immune responses. The results that we obtained with PLG-encapsulated rotavirus VP6 DNA are the first to demonstrate protection against an infectious agent elicited after oral administration of a DNA vaccine.     

Lipoprotein Lp(a) excess and coronary heart disease

A pharmacokinetic study of all-trans retinoic acid (ATRA) was performed in 8 patients with various types of leukemia and MDS. After oral administration at a dose of 30 mg/m2, the mean peak plasma concentration was 430 ng/ml and was reached at 150 min. In one patient who failed to respond a very low plasma ATRA level was seen. Though the plasma ATRA exposure decreased significantly with daily drug administration, an intermittent schedule of ATRA administration would yield higher plasma drug concentrations. We treated 2 patients with refractory acute promyelocytic leukemia (APL) in a pilot study of ATRA followed by intensive chemotherapy (APL-ATRA protocol). Two patients successfully achieved complete remission with ATRA after failing under conventional chemotherapy. Based on the pharmacokinetic study of ATRA, an intermittent schedule of ATRA in addition to chemotherapy suggests an effective regimen for children with APL. Phase II trials to evaluate the role of intermittent schedules of ATRA are planned in Children's Cancer and Leukemia Study Group.     

The SPINRPHEX club

A 3-year-old Japanese domestic cat with a diagnosis of lymphocytic leukemia showed severe generalized seizures in the course of chemotherapy after leukemic condition was improved clinically. Computed tomography (CT) and magnetic resonance (MR) imaging of the brain were carried out. Both contrast procedures disclosed enhancements at the falx cerebri and the margin of cerebral cortex. Among these procedures contrast MR imaging demonstrated the lesion most clearly. Cytological examination of cerebrospinal fluid obtained by spinal puncture showed the infiltration of malignant cells and the diagnosis of meningeal syndrome associated with lymphocytic leukemia was defined. Intrathecal administration of cytosine arabinoside partially improved the neurologic dysfunction. Autopsy and histopathological examination confirmed the infiltration of leukemic cells in the areas of meningeal lesion demonstrated with contrast CT and MR imaging. Thus these imaging techniques, especially contrast MR imaging, are useful tools for rapid and precise diagnosis of meningeal syndrome.     

Comparison of two oral evacuants (Citromag and Golytely) for bowel preparation before barium enema

Oral regimens for bowel preparation before barium enema examination are routinely used because of their convenience and simplicity, rather than the traditional method of colonic wash-out. We performed a prospective study comparing the side-effects and efficacy of two commonly used oral bowel evacuants (Citromag and Golytely) for bowel preparation before barium enema examination in 102 patients. The side-effects associated with the agents were assessed by analysing a questionnaire completed by the patients. There was no significant difference in the side-effects between the two agents although more patients taking Golytely (45.5%) deemed its taste unacceptable than those taking Citromag (25.9%). The results of the bowel preparation were assessed by two independent radiologists giving scores on the amount of faecal residue and the quality of mucosal coating. The amount of faecal residue was less in the Golytely group (p < 0.05). The quality of mucosal coating by barium was also better in the Golytely group than the Citromag group (p < 0.05).     

Granulocytic sarcoma with mediastinal involvement

BACKGROUND: Granulocytic sarcoma is more frequent in adults; it can be a tumoral localization of acute non-lymphoblastic leukemia. This report describes an infantile case revealing an acute myeloid leukemia. CASE REPORT: A 14 month-old girl was admitted because of enlarged bilateral cervical lymph nodes. They had increased in volume over the past month and were accompanied by fever and anorexia. The liver and spleen were moderately enlarged. Hematologic data were: Hb = 7.5 g%; leucocytes = 14,900/mm3; platelets = 614,000/mm3. There were no abnormal cells. X-rays and MRI showed a mediastinal mass. Bone scintigraphy was normal but the myelogram showed a few atypical cells that were also seen in a biopsy of the cervical lymph node. Electron microscopic examination of these cells showed that they were myeloid in origin. This was confirmed by immunohistochemistry. The cytogenetic examination showed many chromosomal abnormalities in the lymph node and myelogram. The child is now recovered after nine months of chemotherapy. CONCLUSION: Diagnosis of acute myeloblastic leukemia in children is difficult when it is revealed by granulocytic sarcoma without major infiltration of bone marrow. The clinical presentation as a mediastinal mass is rare. The cytogenetic study was determinant for diagnosis.     

Impact of exogenous growth factors on proliferation and chemosensitivity of minimal residual acute myeloid leukemia

The biological heterogeneity of AML makes growth factor augmentation of cell cycle-dependent chemotherapy unlikely to be successful for all patients. Patients whose leukemic cells empirically demonstrate cytokine-induced chemosensitization in vitro might benefit from the concurrent administration of growth factors during consolidation chemotherapy. We have explored the growth factor-dependence and response of primary bone marrow samples from patients with AML at diagnosis, remission, and relapse to determine whether minimal residual leukemia remains growth factor-responsive. Most cases of AML studied at all phases of treatment were growth factor-responsive. Growth factor response of occult remission clonogenic leukemic precursors (CFU-L) was usually concordant with their response at diagnosis. Occult CFU-L were markedly resistant to cytosine arabinoside (median LD99% 20 microM); preincubation with IL-3 or GM-CSF did not significantly improve their ara-C sensitivity. While occult remission CFU-L appear to remain growth factor-responsive, it appears unlikely that growth factor augmentation of consolidation chemotherapy will overcome the important problem of drug resistance of residual leukemia.     

The effect of ethanol upon early development in mice and rats. XXIV. The effect of acute ethanol intoxication upon implantation in mice

The primary mode of human immunodeficiency virus (HIV) transmission worldwide is by exposure to the virus at vaginal, rectal, and oral mucosal surfaces. To understand HIV/simian immunodeficiency virus (SIV) transmission events at mucosal portals of entry, we used the SIV-macaque model to determine if mucosal surfaces function as barriers and select for particular viral genotypes. Rhesus macaques were inoculated intravaginally, intracolonically, intrarectally, or orally with the complex primary viral isolate SIV/DeltaB670. Peripheral blood mononuclear cells, collected within the first two weeks postinoculation, were cloned and sequenced from all infected macaques. In the majority of the animals analyzed, multiple genotypes were identified, independent of the route of infection. These findings suggest that the mucosal barrier may play a minor role in the genotypic selection observed during sexual transmission of HIV and emphasize the need to evaluate the viral diversity present within the mucosal secretions of chronically infected individuals.     

Candida infections in patients with acute leukemia: ineffectiveness of nystatin prophylaxis and relationship between oropharyngeal and systemic candidiasis

Ninety-three hospitalizations of 70 patients, who underwent induction chemotherapy for acute leukemia to determine the effectiveness of oral nystatin in preventing oropharyngeal and systemic candidiasis were reviewed. Sixty-two percent of patients who received prophylactic nystatin and 58% of patients who did not receive nystatin developed oropharyngeal candidiasis; 11% of patients who received prophylaxis and 21% of those who did not receive prophylaxis developed systemic candidiasis. The use of oral nystatin did not significantly diminish the risk of developing either type of Candida infection. Oropharyngeal candidiasis occurred more commonly in patients who had severe and prolonged leukopenia, had received more parenteral antibiotics, and had developed chemotherapy-induced mucositis. Systemic candidiasis developed almost exclusively in patients who had prior oropharyngeal candidiasis. Guidelines for the empiric use of amphotericin B in these patients are provided.     

The influence of uptake from the gastrointestinal tract and first-pass effect on oral bioavailability of (Z)-alkyloxyimino penicillins

We have investigated the contribution of uptake from the gastrointestinal tract and first-pass effect to the poor oral bioavailability of a series of (Z)-alkyloxyimino penicillins in mice. Investigative studies in gut sacs and perfused small intestine demonstrated that these penicillins were able to pass across the mucosal epithelium although to a lesser extent than amoxycillin and cyclacillin, both of which exhibit excellent oral bioavailability in man and animals. In the jejunal gut sacs the mucosal to serosal flux for BRL 44154 was approximately half that of amoxycillin and four times less than that of cyclacillin, and for all, uptake was pH dependent. The serosal to mucosal fluxes were however similar for these compounds and significantly lower than mucosal to serosal fluxes, suggesting involvement of carrier mechanisms in uptake from the mucosal surface. The order of results for the alkyloxyimino penicillins paralleled that observed for oral bioavailability in the mouse. For the alkyloxyimino penicillins, between 5.5 and 9.9% was taken up from the perfused intestine, values which were significantly less than those for amoxycillin (13.2%) and cyclacillin (33.3%). However, uptake was concentration-dependent for BRL 44154 as it was for amoxycillin, thus confirming the possible use of carrier mechanisms in absorption. These observations suggest that the poor peripheral blood concentrations of the alkyloxyimino penicillins achieved after oral dosing were not a consequence of the inability of the compounds to cross the mucosal epithelium. The biliary clearance of the alkyloxyimino penicillins was, however, considerably greater than for amoxycillin and cyclacillin, a finding which may well have been a contributory factor to the comparatively low peripheral concentrations of BRL 44154 and its analogues achieved after oral administration.