The empty sella

The data from 55 patients with empty sellae seen during the past five years are examined. The clinical and radiological features most helpful in defining and classifying each case are identified. The most frequent and most serious complications and the warning signs useful in diagnosis are discussed. The indications for and the results of surgical treatment are reviewed.     

Myelokathexis: a rare form of chronic benign granulocytopenia

A case of childhood chronic neutropenia due to myelokathexis is reported. This extremely rare condition (the fourth case in the literature) has been diagnosed from the characteristic bone marrow abnormalities in the neutrophils.     

Dynamics of serum anti-Müllerian hormone levels during the luteal phase of controlled ovarian hyperstimulation

BACKGROUND: To investigate the dynamics of serum anti-Müllerian hormone (AMH) levels during the luteal phase of controlled ovarian hyperstimulation (COH) and its possible association with follicle development. METHODS: We prospectively studied 34 women undergoing COH with GnRH agonist and FSH. On the day of hCG (dhCG), serum AMH, estradiol (E2), progesterone and hCG levels were measured, and ovarian follicles were sorted into three size classes: <12, 12-15 and 16-22 mm. Hormonal measurements were repeated 4 days (hCG + 4) and 7 days (hCG + 7) after hCG. RESULTS: From dhCG to hCG + 4, we observed a decline in serum AMH levels (-64 +/- 3%; P < 0.0001), which paralleled that of E2 levels. From hCG + 4 to hCG + 7, an increase in AMH levels occurred (82 +/- 28%; P < 0.02), whose magnitude was correlated with the number of < 12 mm follicles (r = 0.68; P < 0.0001) but not with other follicle size classes nor with the remaining hormone levels. CONCLUSIONS: After hCG, AMH levels initially decline, presumably as an effect of follicle luteinization, then increase during the mid-luteal phase. Although the mechanisms implicated in the mid-luteal AMH increase are unclear, its positive association with small follicle count, but not with luteal progesterone and E2 levels, supports the hypothesis that AMH levels might reflect luteal follicle development.     

Citrus huanglongbing in São Paulo State, Brazil: PCR detection of the 'Candidatus' Liberibacter species associated with the disease

Symptoms of huanglongbing (HLB), one of the most serious diseases of citrus in Asia and Africa, have been noticed in March 2004 in the Araraquara region of S?o Paulo State, Brazil. HLB has not been reported previously from America. The causal HLB bacteria, Candidatus Liberibacter africanus in Africa and Candidatus Liberibacter asiaticus in Asia, can be detected in symptomatic citrus leaves by PCR amplification of their 16S rDNA with previously described primers. When this technique was applied to 43 symptomatic leaf samples from the Araraquara region, all PCR reactions were negative. This suggested that a new pathogen, not detected by the above primers, could be involved in HLB in the State of S?o Paulo. Indeed, by using universal primers for amplification of bacterial 16S rDNA, a new liberibacter species, Candidatus Liberibacter americanus, has recently been identified. Specific primers for PCR amplification of the 16S rDNA of Ca. L. americanus have been selected. Using these primers, the new liberibacter could be detected in 214 symptomatic leaf samples tested. The leaves of two additional samples were infected with Candidatus Liberibacter asiaticus, and two further samples contained both Ca. L. americanus and Ca. L. asiaticus. The samples came from 47 farms in 35 municipalities. The psyllid vector of Ca. L. asiaticus, Diaphorina citri, is established in South, Central, and North America (Florida and Texas). Ca. L. americanus could be detected by PCR in several batches of D. citri psyllids collected on symptomatic sweet orange trees infected with Ca. L. americanus, strongly suggesting that D. citri is the vector of Ca. L. americanus. The results reported here confirm the presence of HLB in the State of S?o Paulo. Ca. L. americanus is the most widely distributed pathogen.     

Induction of the hypoxia-inducible factor system by low levels of heat shock protein 90 inhibitors

The heterodimeric hypoxia-inducible factor-1 (HIF-1) is involved in key steps of tumor progression and therapy resistance and thus represents an attractive antitumor target. Because heat shock protein 90 (HSP90) plays an important role in HIF-1alpha protein stabilization and because HSP90 inhibitors are currently being tested in clinical phase I trials for anticancer treatment, we investigated their role as anti-HIF-1alpha agents. Surprisingly, low-dose (5-30 nmol/L) treatment of HeLa cells with three different HSP90 inhibitors (17-AAG, 17-DMAG, and geldanamycin) increased HIF-1-dependent reporter gene activity, whereas higher doses (1-3 micromol/L) resulted in a reduction of hypoxia-induced HIF-1 activity. In line with these data, low-dose treatment with HSP90 inhibitors increased and high-dose treatment reduced hypoxic HIF-1alpha protein levels, respectively. HIF-1alpha protein stabilized by HSP90 inhibitors localized to the nucleus. As a result of HSP90-modulated HIF-1 activity, the levels of the tumor-relevant HIF-1 downstream targets carbonic anhydrase IX, prolyl-4-hydroxylase domain protein 3, and vascular endothelial growth factor were increased or decreased after low-dose or high-dose treatment, respectively. Bimodal effects of 17-AAG on vessel formation were also seen in the chick chorioallantoic membrane angiogenesis assay. In summary, these results suggest that dosage will be a critical factor in the treatment of tumor patients with HSP90 inhibitors.     

Hair dye use and risk of lymphoid neoplasms and soft tissue sarcomas

We analyzed the relation between hair dye use and the risk of Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) and soft tissue sarcomas (STS) in a hospital-based case-control study conducted between 1985 and 1997 in northern Italy. Cases included 158 patients with histologically confirmed incident HD, 446 with NHL, 141 with MM, 221 with STS and controls included 1,295 patients with acute nonneoplastic conditions. Compared to never use of any type of hair dyes, the odds ratio (OR) for ever use was 0.68 (95% confidence interval, CI, 0.40-1.18) for HD, 1.03 (95% CI 0.73-1.44) for NHL, 1.17 (95% CI 0.70-1.97) for MM and 0.73 (95% CI 0.45-1.17) for STS. The OR were close to unity for permanent and semipermanent dyes analyzed separately or when the analysis was restricted to women. Our study indicates that there is no appreciable association between ever use of any type of hair dyes and the risk of HD, NHL, MM or STS.     

Cancer immunotherapy based on killing of Salmonella-infected tumor cells

A major obstacle for the development of effective immunotherapy is the ability of tumors to escape the immune system. The possibility to kill tumor cells because they are recognized as infected rather than as malignant could help overcome immune escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumors and killing of infected tumor cells. Attenuated but still invasive, Salmonella typhimurium can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-Salmonella-specific T cells. However, to fully appreciate the anticancer therapeutic properties of S. typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium before intratumoral Salmonella injection. Tumor infection when coupled to anti-Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome on larger tumors. Invasive Salmonella also exert an indirect toxic effect on tumor cells through the recruitment of inflammatory cells and the cross-presentation of tumor antigens, which allow induction of tumor-specific immune response. This is effective in retarding the growth of untreated established distant tumors and in protecting the mice from subsequent tumor challenges.     

Family history of cancer and the risk of prostate cancer and benign prostatic hyperplasia

We analysed the relation between family history of cancer in first-degree relatives and risk of prostate cancer (PC) and benign prostatic hyperplasia (BPH) using data from a multicentric case-control study conducted in Italy from 1991 to 2002 on 1,294 cases of incident, histologically confirmed PC, 1,369 cases of BPH and 1,451 men admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (OR) of PC and BPH, adjusted for age and other confounders. Men with a family history of PC had an OR of PC of 4.0 (95% confidence interval [CI] 2.5-6.5), and the risk was higher when the proband was younger, when 2 or more relatives were affected or when the affected relative was a brother. The risk of PC was also increased in men with a family history of cancer of the ovary (OR = 6.2, 95% CI 1.2-32), bladder (OR = 3.5, 95% CI 1.6-7.4) and kidney (OR = 3.1, 95% CI 1.1-8.5). An involvement of breast/ovarian cancer predisposition genes in a small proportion of PCs was suggested by the cluster of these cancers in female relatives of a few PC cases. The risk of BPH was increased in men with a family history of bladder cancer (OR = 2.2, 95% CI 1.0-5.0) but not PC (OR = 1.2, 95% CI 0.7-2.2). Our study adds further information on the association of family history of cancer and risk of PC and is, to our knowledge, the first comprehensive epidemiologic information on family history of cancer and risk of BPH.