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[Resistance and new antibiotic strategies. The problem with staphylococcus].

MRSA outside the hospital: From a major problem almost exclusively encountered in hospitalized patients, methicillin-resistant Staphylococcus aureus (MRSA) infection has become a cause of skin, soft tissue, and even systemic infections outside the hospital. In order to prevent further spread, patients carrying MRSA (recently hospitalized patients, drug abusers, debilitated subjects, etc) must be identified and the mode of acquisition of MRSA infection. (cross transmission between community and non-hospital care centers) must be recognized. Small colony variants: SCV produce non-pigmented colonies that are 10 times smaller than the usual S. aureus colonies and have particular metabolic and genetic properties. They can cause persistent, recurrent and drug-resistant infections. MRSA in France: Data obtained in a case-control study confirms the selection pressure as well as the important colonization pressure exerted by antibiotics on gentamicin-sensitive strains.

Colony Count, Microbial↗

The hair strand test - a new method for testing antifungal effects of antidandruff preparations.

Seborrheic dermatitis and its minimal variant, dandruff (pityriasis simplex capillitii), are among the most frequent diseases caused by Malassezia (M.) yeasts. Treatment studies have shown that antimycotics achieve clinical improvement, while recolonization leads to recurrent symptoms. Among the antimycotics used are azoles, hydroxypyridones, and various agents such as zinc pyrithione, tar, and selenium disulfide. However, comparative efficacy studies in vitro should not only consider the minimal inhibitory concentrations against Malassezia yeasts but also the bioavailability of the individual substances with regard to hair and scalp. By means of a new method, the hair strand test, hairs from ten volunteers were subjected to standardized 5-min incubation with different shampoo formulations. Thereafter they were rinsed with running water for 1 min and dried. Two hundred each of these hairs (length 1 cm) were given into a medium (olive oil on selective agar for pathogenic fungi) inoculated with M. sympodialis or M. globosa (5 x 10(3) CFU/microl), and the influence on growth was semiquantitatively determined over a period of up to 18 days. According to preliminary results, 1% climbazole proved to be particularly effective. The hair strand test, which can also be performed ex vivo, is a new method to find out whether antimycotic agents bind differently to the hair substance and, via a depot effect, may influence the growth of Malassezia yeasts and thus affect dandruff. This allows conclusions about the efficacy of antidandruff formulations.

Antifungal Agents↗

[Malignant brain glioma--a catamnestic study of 100 operated patients].

For 100 operated patients with malignant gliomas of the brain (63 malignant gliomas WHO grade IV--including 50 glioblastoma multiforme- and 37 astrocytomas WHO grade III-IV) the average survival time is 332 days. The survival rates show 6, 12 and 24 months after operation 55%, 32% and 12% of the patients alive. In addition to therapy there are some favourable prognostic factors: Young patients age at the onset of illness, localization in the non-dominant hemisphere, minor preoperative neurological deficit. On the other side unfavourable prognostic factors are: parietal localization (average survival time = 120 days), tumorous infiltration of the brain stem (average survival time = 143 days), preoperative clouding of consciousness (average survival time = 185 days). These factors influence survival time. The most important prognostic factor of therapy is the extent of operation: In case of macroscopical total resection of the tumor the mean survival time amounts to 554 days as compared to 202 days in subtotal tumor resection. The well known positive influence of postoperative radiation therapy is demonstrated by the high mean survival time of 456 days. In case of recurrent operation of the tumor (28 patients), the average survival time amounts to 443 days. In contrast to the literature our own analysis shows no prognostic value of histological variants in case of malignant glioma WHO grade IV. Two patients, whose histological slide preparations were neuropathologically graded a second time independent from the first view (1 anaplastic ependymoma WHO grade III and 1 glioblastoma multiforme WHO grade IV), are still alive more than 8 years after operation without any neurological deficit.

Adolescent↗

[Use of a precision technique in surgical treatment of pulmonary echinococcosis].

More that 15 variants of operative interventions in hydatid disease of the lungs have been suggested to date, but all have shortcomings and, in addition, do not exclude the possibility of a recurrence. The recent method of precision operation, when conducted, excludes completely a recurrence of the disease. In precision removal of hydatid cysts, the pulmonary tissue remains undamaged to maximum. The use of medical glue and carbon dioxide laser in the stages of the surgical intervention improves the operative techniques, reduces the number of operative and postoperative complications, and improves the results of treatment. The authors used the method in 24 patients and produced good results.

Adult↗

[The natural killer cell activity and count of large granule-containing lymphocytes in the blood of patients with malignant lymphomas].

The authors investigated the natural killer activity and number of large granule-containing lymphocytes (LGL) in donors, in the blood of patients with reactive lymphadenitis, lymphogranulomatosis and non-Hodgkin lymphomas. Patients with lymphomas and lymphogranulomatosis were subdivided in groups depending on the morphological variant and stage of the disease, length of remission. Results of the study allowed to establish disorders of the natural antitumour resistance in patients with malignant lymphomas, its dependence on histological verification, stage of the process, morphological variant. A positive correlation was obtained between natural killer activity and content of LGL in donors and in patients with malignant lymphomas during first admission, prolonged stable remission and recurrences.

Cells, Cultured↗

[The problem of cysto-sarcoma phyllodes (author's transl)].

Problems in the diagnosis and treatment of cysto-sarcoma phyllodes in thirteen women are discussed. This is a rare breast tumour which must be regarded as semi-malignant. Its malignancy consists of its tendency to recurrence and the development of distant metastases. Five patients had one or more recurrences and three patients had metastases which were fatal. Radiological and thermographic diagnosis of small tumours is unreliable. It is not possible to distinguish the benign from the malignant variants. Accurate classification depends on histological examination. The authors consider removal of the glandular tissue or simple mastectomy to be the best form of treatment.

Adolescent↗

Serous papillary carcinoma of the endometrium. A clinicopathologic study of 11 cases.

We review 11 cases of serous papillary endometrial carcinoma (SPEC) that are histologically identical to serous ovarian carcinoma. Six patients (55%) had extrauterine involvement at the time of presentation; five of these six died secondary to malignancy and one died of other causes. The remaining five patients presented with tumor confined to the uterine corpus and cervix. One of these developed a vaginal recurrence, one died of other causes without evidence of tumor, and three are alive without disease at 15 months, 18 months, and 13 years. SPEC is a biologically aggressive variant of endometrial carcinoma because it often presents at an advanced clinical stage with an associated high mortality rate.

Aged↗

Childhood acute lymphoblastic leukemia: genetic determinants of susceptibility and disease outcome.

The origin of acute lymphoblastic leukemia (ALL), the most common pediatric cancer, can be explained by a combination of genetic factors and environmental exposure. The environmental toxicants to which an individual is exposed are biotransformed and eliminated from the body after metabolic conversion mediated by Phase I and Phase II xenobiotic-metabolizing enzymes. Phase I enzymes catalyze hydroxylation, reduction and oxidation reactions of xenobiotics (carcinogens/drugs), often converting them into more active or toxic compounds. Phase II enzymes catalyze conjugation reactions (glucuronidation, acetylation, methylation), thereby converting the metabolites into non-reactive, water-soluble products that are eliminated from the organism. The genetic polymorphism underlying the variation in enzyme activity can modify susceptibility to diverse adult cancers, probably by influencing the activation and removal of toxicants or drugs. Here we present an overview of the role of genetic variants of certain Phase I and Phase II enzymes in the development of childhood ALL, a good model for such studies because of its short latency period. The genetic contribution to the development of ALL is examined by association studies that analyze the loci of Phase I enzymes (cytochrome P-450, myeloperoxidase) and Phase II enzymes (quinone-oxidoreductase, glutathione-S-transferase, N-acetyltransferase). The loci of the enzyme variants CYPlA1, CYP2E1, NQO1, GSTM1, GSTP1, NAT2 are associated with disease development, and evidence of gene-gene interactions has emerged as well. Despite the improvements in treatment, resistant cases of ALL remain a leading cause of cancer-related death in children. Although the underlying mechanism of drug resistance is not well understood, differences in the capacity of ALL patients to process drugs and environmental carcinogens could play a role by modifying the risk of recurrent malignancy, as well as the response to therapy. Therefore, polymorphic genes encoding carcinogen- and drug-metabolizing enzymes may not only increase the risk of ALL but also influence the risk of relapse in patients. We found that the prognosis of patients with CYPlA1 and NQO1 variants was worse than that of patients who lack these variants. We conclude that genotyping ALL patients for functional polymorphisms of candidate genes can become an important tool in predicting disease outcome.

Carcinogens↗

Stage II breast cancer is not simply a late stage I.

Conventional wisdom holds that stage II breast cancer (with positive axillary nodes) is a late stage I (with negative axillary nodes). The use of direct (e.g., 5-year) survival analysis, has led to the concept that these stages reflect a "delay" in diagnosis. Controlled clinical trials and demographic cancer registries, in which life table analysis of survival is used, provide data that require that this concept be reconsidered and perhaps discarded. Survival data published by NSABP B04 and the Connecticut Tumor Registry show that deaths in both stages start shortly after diagnosis but show different annual rates of dying. The anticipated "delay" (lead time bias) is not seen. These rates are permanently and consistently different. The local recurrence rates occurring in the two stages are different. The clinical response to tamoxifen citrate in postmenopausal women and chemotherapy in premenopausal women has been shown to be different between the two stages. Histopathologic examination of the primary tumor shows the two stages to be different with respect to size of tumor at time of diagnosis and the presence of lymphatic and vascular invasion. The conclusion must be reached that the two stages represent variants of breast cancer disease; stage II is not simply a late diagnosis of stage I.

Antineoplastic Agents↗

Treatment results of oral verrucous carcinoma and its biological behavior.

The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.

Adult↗

[Clinical significance of vascular endothelial growth factor in sera of patients with gynaecological malignant tumors].

BACKGROUND & OBJECTIVE: Experimental and clinical evidence links tumor growth, invasion, and metastatic potential with neoangiogenesis. This process is modulated by several angiogenic growth factors, such as vascular endothelial growth factor(VEGF). Few data are currently available on serum level in patients with gynaecological malignant tumors. This study was designed to determine the serum VEGF level in the patients with gynaecological malignant tumors and its significance as a tumor marker. MATERIAL & METHODS: Preoperative serum VEGF level were measured in 50 cervical cancer, 39 endometrial cancer, 89 ovarian cancer patients, and 80 normal healthy women; The serum VEGF levels were also measured in 3, 6, 9 months after operation and when recurrence in three curative resection patients with ovarian cancer; using commercially available enzymelinked immonosarbent assay (R & D systems Inc. Minneapolis, MN, USA). Statistical analysis was performed by using the SPSS9.0 software package. Using 5th and 95th percentage describe the variant degree. RESULTS: The median level of VEGF in sera of 80 healthy women was 218.50 ng/L(42.06-671.70 ng/L), while in 50 cervical cancer, 39 endometrial cancer, and 89 ovarian cancer patients were 272.00 ng/L(91.94-745.53 ng/L), 383.50 ng/L(105.67-776.50 ng/L), and 479.85 ng/L (99.47-1326.88 ng/L), respectively. The VEGF levels in endometrial cancer and ovarian cancer patients were significantly higher than that in healthy women (P < 0.0001). But in cervical cancer patients the VEGF level, was not significant diffent compare with health wanen. After operation, 3, 6, 9 months the VEGF levels in 3 ovarian cancer patients were significantly lower than that of preoperative but it ascended again when the disease was recurrent 14, 17 months later in two cases. The VEGF level was significantly higher in advanced ovarian cancer patients (stage III-IV) than that in the early stage (stage I-II) (P < 0.05). CONCLUSION: The serum level of the VEGF may be used as a new tumor marker of endometrial cancer and ovarian cancer, for diagnoses and monitoring the progress of the disease.

Adolescent↗

Papillary transitional cell carcinoma of the breast: a report of five cases with distinction from eccrine acrospiroma.

Papillary carcinomas of the female breast exhibit a spectrum of morphologic appearances and might be mistaken for benign intraductal papillary lesions or papillary adnexal neoplasms. We report herein five cases of papillary carcinoma in which the epithelium closely resembled transitional cells of the urinary bladder. Grossly, the tumors had a nodular or papillary appearance, white, tan, or red in color. The microscopic features were those of an intraductal papillary proliferation of solid layers of epithelial cells overlying fibrovascular cores. The proliferating cells assumed a whorled or streaming growth pattern, with flattening of superficial cells. One case showed microinvasion. Comparison with a similar number of cases of the solid variant of papillary carcinoma of the breast showed a greater range of nuclear pleomorphism, mitotic counts, and a more varied immunohistochemical profile in the papillary carcinomas with transitional cell features. Eight cases of eccrine acrospiroma occurring in the female breast also displayed a solid or solid papillary pattern, with flattened superficial cells. These occurred in a younger age group, were located in the dermis or subcutis, and usually had zones of clear cells visible at low magnification. No evidence of recurrent or metastatic disease was found in the four patients for whom follow-up was available; the length of follow-up ranged from 18 months to 11 years. The stimulus for the development of this unusual phenotype is unclear, but the transitional-like variant seems to behave in a fashion similar to that of other types of papillary carcinoma of the breast. Distinction of this malignant lesion from various benign lesions that occur in the same region is mandatory.

Acrospiroma↗

Recurrent genital herpes on the buttocks: "herpes disciformis".

We report a clinical variety of recurrent genital herpes on the buttocks of seven women ranging in age from thirty-four to eighty-one years. The lesions had recurred for one to nine years and had produced a characteristic cicatricial rounded area within the S2 to S3 dermatomes on one buttock. Herpes disciformis is believed to be an anatomical variant of the common genital herpes infection. We have only noted it in middle-aged or older women with no history of genital herpes.

Adult↗

Intrachiasmal craniopharyngioma: treatment with a cisternal catheter drainage and radiation.

A 54-year-old woman who presented with headaches and bitemporal visual field loss had an MRI that disclosed a cystic lesion within the optic chiasm. Craniotomy yielded an inconclusive biopsy; incisional decompression of the cyst provided only temporary improvement in vision. When vision declined 3 months later, an MRI showed recurrence of the cyst. The patient underwent a second craniotomy with biopsy that revealed an adamantinomatous craniopharyngioma. Because of the dangers of surgical removal, the cyst was left in place and connected by catheter to the prechiasmatic cisternal subarachnoid space. She received 54 Gy of three-dimensional conformal x-irradiation. At the time of her last follow-up examination 28 months postoperatively, the patient had marked improvement in her visual acuity and visual fields; an MRI demonstrated that the cyst remained decompressed. Cisternal catheter drainage represents a novel approach to the treatment of this rare variant of craniopharyngioma.

Biopsy↗

Pathological variants of basal cell carcinoma.

Although the pathological features of basal cell carcinoma are well known, there is no generally agreed classification of the subtypes of this tumour. Certain histological subtypes are associated with indistinct clinical margins, inadequate primary excisions and frequent recurrences, and these must be recognized and reported by pathologists so that the most appropriate therapy is given. The current classification of subtypes of basal cell carcinoma is discussed and reference made to the rarer forms of this tumour.

Biopsy, Needle↗

Recurrent and unusual infections unmasking a rare inborn error of immunity: a case report RAS-associated Autoimmune Lymphoproliferative Disease (RALD).

BACKGROUND: RAS-associated Autoimmune Lymphoproliferative Disease (RALD) is a rare, non-malignant lymphoproliferative disorder caused by somatic mutations in RAS genes that impair lymphocyte apoptosis. Patients often present with features of lymphoproliferation, autoimmune manifestations, and an increased risk of malignant transformation. CASE PRESENTATION: We report the case of a 3-year-old boy with splenic microabscesses and Burkholderia pseudomallei IgM serology positivity, who was treated as melioidosis. He had recurrent respiratory infections and chronic rhinorrhoea since the age of one year. Clinical examination revealed persistent lymphadenopathy and hepatosplenomegaly. Laboratory investigations demonstrated persistent absolute monocytosis and thrombocytopenia, while immunological evaluation showed elevated IgM levels and B-cell lymphocytosis. Whole exome sequencing identified a heterozygous pathogenic variant in NRAS, NM_002524.5:c.35G&#x2009;>&#x2009;C, NP_002515.1:p.Gly12Ala, establishing the diagnosis of RALD. The patient was subsequently started on antibiotic prophylaxis and immunoglobulin replacement therapy, and his family was counseled regarding the potential role of immunosuppressive therapy and hematopoietic stem cell transplantation (HSCT) in future management. CONCLUSIONS: This case highlights the coexistence of an unusual infection with a rare inborn error of immunity, expanding the recognized infectious spectrum of RALD. It underscores the importance of considering RALD in patients presenting with recurrent or atypical infections and persistent lymphoproliferative features. Early recognition and molecular genetic testing are essential for confirming the diagnosis and guiding individualized management.

Humans↗

Study of herpes simplex virus type 1 populations obtained from recurrences and primary infections.

The analysis of 23 clinical isolates of herpes simplex virus type 1 (HSV-1) showed that 15 of 15 isolates that had undergone a few passages in tissue culture (fresh isolates) and two of eight isolates that had never been passaged (new isolates) were composed of a mixed population with respect to plaque morphology in Vero cells. Cloning and characterization of 10 large plaque viruses (L variants) and nine small plaque viruses (S variants), obtained from seven different isolates, showed the following. BamHI DNA restriction patterns of the L and the S variants from a single isolate differed only with respect to the electrophoretic mobility of the fragments that contain reiteration of specific sequences; they did not differ regarding the presence or the absence of restriction endonuclease cleavage sites. The L and S variants differed with respect to the electrophoretic profiles of infected cell glycoproteins, thermosensitivity of growth and plaquing efficiency at 39 degrees C, and, at least in the case of the two couples of variants that we tested, pathogenicity for the mouse. The hypothesis that the L variants might arise from the S variant during in vivo replication is discussed.

Adult↗

Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.

OBJECTIVE: To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS. METHODS: Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes. RESULTS: Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found: 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants. CONCLUSION: The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.

Antigens, CD↗