Surgery for Rathke cleft cysts: technical considerations and outcomes

OBJECT: The aim of this study was to identify the optimal surgical goals and techniques for managing symptomatic Rathke cleft cysts (RCCs). METHODS: The authors conducted a retrospective study of 62 consecutive patients who had undergone surgery for RCCs. Postoperative follow up was a mean of 28 months. Fifty-six patients underwent transsphenoidal cyst decompression and biopsy procedures, and six underwent cyst wall resection. Postoperatively, symptoms improved in 91% of patients with headaches and 92% of patients with visual deficits. Decompression and biopsy were associated with a 10% incidence of new anterior pituitary hormone deficiencies and a 6% incidence of new permanent diabetes insipidus; the incidence of new hormone deficiencies was significantly higher in the few patients who had undergone cyst wall resection. The incidence of relapse, defined as cyst regrowth with either recurrent symptoms or chiasmal compression, was 16%. Resection of the cyst wall was associated with a trend toward a decreased risk of relapse. Sellar packing, sellar floor reconstruction, and irrigation with absolute ethanol did not affect the likelihood of relapse. Squamous metaplasia and inflammation increased the risk of relapse. Residual cyst demonstrated on postoperative magnetic resonance imaging was associated with an increased risk of subsequent asymptomatic cyst regrowth. Seven patients (11%) underwent repeated operation with symptomatic improvement and minimal morbidity; only one patient relapsed following a second surgery. CONCLUSIONS: Decompression and biopsy procedures in the treatment of RCCs lead to improvement in signs and symptoms, with low morbidity rates. Repeated operations will be required in as many as 16% of patients but are also associated with symptomatic improvement, low morbidity, and durable remission. Decompression and biopsy may represent the optimal surgical management of RCC.     

Hereditary medullary thyroid carcinoma in patients greater than 50 years old

BACKGROUND: Despite near complete penetrance and frequent early evaluation of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia 2 (MEN 2) variants, a significant minority of patients are evaluated later in life. METHODS: With the aim of characterizing the expression of hereditary MTC in an older cohort, MEN 2 patients from our institutional database who were evaluated after age 50 years were identified, and clinical data were reviewed. RESULTS: Thirty-nine patients (36 MEN 2A, 3 FMTC, and no MEN 2B) who were evaluated after age 50 years were identified; they represented 9% of all MEN 2 patients who were enrolled in our program. Most of the patients (79%) had abnormal screening examinations, and the AJCC staging was significantly higher in this cohort compared with younger patients. Overall, 43% of the patients had normal calcitonin levels after operation. There were 3 observed MTC-related deaths, all from distant metastases; the overall survival rate was 86% at 5 years and 74% at 10 years. The distribution of RET mutations in this cohort was similar to younger patients. CONCLUSIONS: These results suggest the presence of modifiers of MTC expression. Despite the tendency of older patients with hereditary MTC to have advanced stage disease at evaluation, they have high rates of biochemical cure, and the overall survival is excellent.     

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study

Introduction

Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T→C polymorphism.

Methods

Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses.

Results

We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A ₂/A ₂ genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A ₁/A ₁ (wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions.

Conclusion

We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene-environment interactions.     

Immune function of astrocytes

Astrocytes are the major glial cell within the central nervous system (CNS) and have a number of important physiological properties related to CNS homeostasis. The aspect of astrocyte biology addressed in this review article is the astrocyte as an immunocompetent cell within the brain. The capacity of astrocytes to express class II major histocompatibility complex (MHC) antigens and costimulatory molecules (B7 and CD40) that are critical for antigen presentation and T-cell activation are discussed. The functional role of astrocytes as immune effector cells and how this may influence aspects of inflammation and immune reactivity within the brain follows, emphasizing the involvement of astrocytes in promoting Th2 responses. The ability of astrocytes to produce a wide array of chemokines and cytokines is discussed, with an emphasis on the immunological properties of these mediators. The significance of astrocytic antigen presentation and chemokine/cytokine production to neurological diseases with an immunological component is described.     

Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma

OBJECT: In this paper the authors describe the indications for and the results and complications of repeated transsphenoidal surgery (RTSS) to treat recurrent or residual pituitary adenoma. METHODS: A retrospective review was conducted of 96 consecutive patients who underwent RTSS to treat recurrent or residual pituitary adenoma. Ninety-six patients underwent RTSS: 42 to treat a recurrent or residual pituitary mass and 54 to treat a recurrent or persistent hormone hypersecretion. There was no case of perioperative death and there was a 1% incidence of major complications. Postoperative endocrinological deficiencies were uncommon unless planned total hypophysectomy was performed to treat Cushing disease. Clinical remission occurred in 93% of patients undergoing RTSS to treat a tumor mass, and 15% of patients initially experienced remission only to face a relapse after a mean of 32 months. Endocrinological remission occurred in 57% of patients undergoing RTSS to treat hormone hypersecretion; most of these patients had Cushing disease. Thirty-five percent of patients with an initial endocrinological remission experienced a relapse of their symptoms after a mean of 31 months (thus, 37% of patients achieved sustained endocrinological remission). We failed to identify factors that accurately predicted initial symptom remission or delayed relapse following RTSS. Ten patients in our series eventually underwent a third transsphenoidal surgery without major complications. CONCLUSIONS: Repeated transsphenoidal surgery is a more effective treatment for recurrent or residual mass than it is for hormone hypersecretion and has acceptable rates of morbidity and mortality. If hypophysectomy is not performed, endocrinological deficiencies are unlikely following RTSS.     

异常黑胆质性哮喘与ECP、IgE及FEV1的关系研究

目的探讨异常黑胆质性哮喘与嗜酸细胞阳离子蛋白（ECP）、血清总免疫球蛋白E（T-IgE）、血清特异性免疫球蛋白E（S-IgE）、第1秒用力呼气流量（FEV1）之间的关系。方法对76例支气管哮喘患者按维医体液论进行辨证分型，异常黑胆质性哮喘组30例，非异常黑胆质性哮喘组46例，并与正常对照组89例进行对照，分别测定各组血清ECP、T-IgE、S-IgE、FEV1水平。结果血清ECP、T-IgE、S-IgE变化在3组间有显著差异（P〈0．01），异常黑胆质性哮喘组明显高于正常对照组（P〈0．01），异常黑胆质性哮喘组明显高于非异常黑胆质性哮喘组（P〈0．01），非异常黑胆质性哮喘组明显高于正常对照组（P〈0．01），FEV1水平变化在3组间有显著性差异（P〈0.01），异常黑胆质性哮喘组明显低于非异常黑胆质性哮喘组和对照组（P〈0．01），非异常黑胆质性哮喘组也低于正常对照组（P〈0．01）。结论异常黑胆质性哮喘的气道炎症程度更明显，阻塞情况更严重。     

Evidence for cytochrome P450 2A6 and 3A4 as major catalysts for N'- nitrosonornicotine alpha-hydroxylation by human liver microsomes

The tobacco specific carcinogen N'-nitrosonornicotine (NNN), is believed to be a causative agent for esophageal cancer in smokers. NNN requires metabolic activation to exert its carcinogenic potential. Metabolism occurs through cytochrome P450 (P450) catalyzed 2'- and 5'- hydroxylation, which generates unstable metabolites that decompose to 4- hydroxy-1-(3-pyridyl)-1-butanone ('keto alcohol') and 4-hydroxy-4-(3- pyridyl)butanal, respectively. The latter cyclyzes to 5-(3-pyridyl)-2- hydroxytetrahydrofuran ('lactol'). 2'-Hydroxylation of NNN is believed to be the pathway critical for esophogeal NNN carcinogenesis in the rat. The ability of human liver microsomes and expressed human P450s to metabolize [5-(3)H]NNN to keto alcohol and lactol was determined by reverse phase HPLC with radioflow detection. At low NNN concentrations, 11 human liver microsomes metabolized NNN primarily by 5'-hydroxylation to lactol. This reaction was strongly correlated (r = 0.92) with coumarin 7-hydroxylation, suggesting that NNN 5'-hydroxylation is catalyzed mainly by P450 2A6. 2'-Hydroxylation of NNN by human liver microsomes correlated with 6beta-hydroxylation of testosterone, a P450 3A4-specific activity (r = 0.94). The relative rates of 2'- and 5'- hydroxylation by human P450s 2A6, 2E1, 2D6 and 3A4 expressed in Sf9 cells by the baculovirus-insect cell expression system, and human P450 3A4 produced by stable expression in Chinese hamster ovary cells, were determined. Human P450 2A6 metabolized 1 microM NNN exclusively by 5'- hydroxylation. The rate of lactol formation was 317 pmol/min per nmol P450. Human P450s 2E1 and 2D6 also metabolized NNN only to lactol, but at much lower rates, 0.4 and 0.8 pmol/min per nmol of P450 respectively. In contrast, the metabolism of NNN by expressed human P450 3A4 was specific for keto alcohol formation. The Km for 5'- hydroxylation by baculovirus-expressed P450 2A6 was 2.1 microM, and k(cat) was 953 pmol/min per nmol of P450. The Km for lactol formation by human liver microsomes containing high levels of P450 2A6, was 5 microM . Human liver microsomes exhibited a Km of 312 microM for keto alcohol formation. Coumarin, 8-methoxypsoralen (P450 2A6 inhibitors), and anti-2A6 monoclonal antibody were strong inhibitors of NNN-derived lactol formation in human liver microsomes. Troleandomycin, an inhibitor of P450 3A4, effectively inhibited the metabolism of NNN to keto alcohol by human liver microsomes. These results are consistent with P450 2A6 mediated 5'-hydroxylation and P450 3A4 mediated 2'- hydroxylation of NNN in human liver microsomes.      

Malnutrition, cell-mediated immune deficiency and acute upper respiratory infections in rural Bangladeshi children

A community-based longitudinal study conducted in rural Bangladesh investigated the association between nutritional status, cell-mediated immune status and acute upper respiratory infections (URI). A total of 696 children aged 0–59 months was followed prospectively for 1 y yielding 183 865 child-days' observation. Trained field workers visited each child every 4th d and collected morbidity data on symptoms suggesting URI (cough, fever, nasal discharge) for the preceding 3 d by recall. On the day of visit they examined each child reporting cough and/or fever to record the temperature, presence of nasal discharge, rate of respiration and presence of chest indrawing. Anthropometry for all children was conducted monthly. Cell-mediated immune competence was assessed by a multiple antigen skin test at baseline and thereafter every 3 months. The incidence of URI was 5. 3 episodes per child-year observed. Approximately three-quarters of the study children were below -2 Z-score weight for age and height for age, and a quarter below -2 Z-score weight for height. During different test periods 9–21 % of the study children did not respond to any of the test antigens. In a regression model children < -2 Z-score for weight for height had 16% [odds ratio (OR) 1. 16, 95% confidence interval (CI) 1. 03–1. 31, p = 0. 01] higher risk of developing URI. Anergic children had 20% higher risk (OR 1. 20, CI 1. 05–1. 38, p = 0. 009) of URI than immunocompetent children. The study demonstrated that wasting and depressed cell-mediated immunity (CMI), but not stunting, were associated with the incidence of URI among rural Bangladeshi children.