Chronic headache and pituitary tumors

Pituitary tumors come to clinical attention due to endocrine dysfunction, distortion of local structures surrounding the pituitary fossa, or as an incidental finding during neuroimaging for headache. Explanations for pituitary tumor-associated headache include stretching of the dura mater and invasion of pain-producing structures within the cavernous sinus. However, small functional pituitary lesions may present with severe headache without cavernous sinus invasion or suprasellar extension. Prolactinomas and growth hormone-secreting tumors have a high prevalence of rare headache phenotypes with or without autonomic features, suggesting that biochemical abnormalities within the hypothalamo-pituitary axis may play a role in headache. Somatostatin analogues may be highly effective at aborting headache associated with functionally active pituitary lesions, particularly in the case of acromegaly. A proposed mechanism for this is inhibition of nociceptive peptides. This article summarizes the clinical features, pathophysiology, and potential treatment approaches to pituitary tumor-associated headache.     

Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period.

Although botulinum toxin A (BTX) has been licensed in Canada for treatment of various movement disorders since 1990, few clinical studies regarding its long-term efficacy and side effects have been reported. We conducted a retrospective analysis of 235 patients who received BTX from our movement disorders clinic over a 10-year period (January 1990 to December 1999). A total of 2,616 treatment cycles (multiple injections) were administered to 235 patients with cervical dystonia (CD), hemifacial spasm (HS), blepharospasm (BP), and other movement disorders. Substantial benefit at 5 years was seen in most patients (90% in BP, 88% in HS, 63% in CD, 100% in jaw closing and lower limb dystonia, and 56% in writer's cramp). Benefit was maintained for up to 10 years in CD, HS, and BP data, with a 75.8% benefit reported. Twenty-eight percent of patients discontinued treatment during the follow-up period due to a variety of reasons. Of these, 9.1% of patients developed primary resistance, and 7.5% of patients secondary resistance. Adverse effects, mostly minor, developed in 27% of patients at any one time, occurring over 4.5% of treatment cycles. These were most frequently reported in blepharospasm (22 of 36 patients in 40 cycles), followed by hemifacial spasm (21 of 70 patients in 46 cycles), and cervical dystonia (17 of 106 in 28 cycles). Only 1.3% of patients discontinued therapy due intolerable adverse effects. The results show that BTX is a safe and effective treatment of various types of movement disorders, and most side effects are well tolerated. Discontinuation for any reason was also low after 5 years. Efficacy was maintained after long periods of treatment with high degree of patient satisfaction.     

Budesonide enema active haemorrhagic proctitis—a controlled trial against hydrocortisone foam enema

Background: The aim was to compare budesonide enema, 2 mg/100 mL (Entocort) and hydrocortisone acetate foam enema, 125 mg (Colifoam) in patients with active haemorrhagic proctitis. Methods: The trial was a controlled, randomized, investigator-blind study with two parallel groups. Endoscopy, histology and diary cards were used to assessed the response to therapy. Safety was assessed by laboratory tests and adverse event recording. Results: Seventy-two patients were included. Investigations were made before treatment and after 2 and 4 weeks. Both treatment groups showed statistically significant improvement in endoscopic scores but significant differences between the groups were not found. In the hydrocortisone group, plasma cortisol was significantly lowered after 4 weeks compared with budesonide. Bowel habits and quality of life variables did not differ between the treatments. The recorded adverse events were mild or moderate and may have been due to the proctitis. Conclusions: These results suggest that budesonide enema is as effective as hydrocortisone foam enema, but without the potential for side-effects associated with suppression of plasma cortisol.     

Child and Adolescent Psychiatric Screening Inventory-Retrospect (CAPSI-R): a questionnaire for adults concerning child and adolescent mental disorders.

This study examines the properties of the Child and Adolescent Psychiatric Screening Inventory-Retrospect, CAPSI-R, a self-report 146-item questionnaire for adults concerning earlier child psychiatric symptoms, comprising both DSM-IV categories and functional impairment. The instrument was mailed to 359 former child psychiatric patients born between 1951 and 1977 (164 of whom responded) and to a matched control group (193 of whom responded). There was good internal consistency (Cronbach's alpha ranged between 0.62-0.93, and between 0.76-0.93 after elimination of one item). The lifetime prevalence of a mental disorder was 87.8% in the former patients' without considering impairment and 76.8% when impairment was considered. The corresponding figures for the control group were 49.7% and 10.4%, respectively. When the former patients' CAPSI-R diagnoses (with incorporation of the impairment criterion) were validated against the DSM-IV diagnoses based on information in their medical records, generally, an acceptable sensitivity and specificity were obtained. The overall kappa between CAPSI-R diagnoses and those from medical records was 0.79. The CAPSI-R shows promise for further evaluation and may be useful in recognising child and adolescent mental disorders in adults.     

CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn's disease

Caspase activation and recruitment domain 15 (CARD15) and Toll-like receptor 4 (TLR4) are respectively intracellular and membrane-bound receptors for bacterial cell wall components [respectively muramyl dipeptide (MDP) and lipopolysaccharide (LPS)]. Polymorphisms in CARD15 and TLR4 have been linked with Crohn's disease (CD). Adherent-invasive Escherichia coli (AIEC) strains with particular adhesion and invasion characteristics have been specifically associated with CD ileal mucosa. The aim of this study was to investigate the functional impact of these polymorphisms on monocytes in patients with CD, in response to MDP, LPS and AIEC strain LF82. Monocytes were isolated from 40 patients with CD using magnetic cell sorting, stimulated with LPS or MDP or infected with AIEC. IL-1beta, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor alpha induction was assessed using quantitative real time-polymerase chain reaction, Cytometric Bead Array and ELISA. Bacterial intracellular survival and replication was assessed using a gentamicin protection assay. Results were linked with the presence of CARD15 and TLR4 polymorphisms. Monocytes of patients with CARD15 polymorphisms showed an early reduced cytokine response (IL-1beta, IL-6 and IL-10) to infection with AIEC, which was restored after 20 h. A gene-dose effect was seen, comparing wild-types, heterozygotes and homozygotes. We found no differences in intracellular survival and replication of AIEC. Heterozygous carriage of TLR4 polymorphisms did not influence monocyte response. In conclusion, patients with CD carrying CARD15 polymorphisms show a disturbed early inflammatory monocyte response after infection with AIEC strain LF82. For the first time, a functional defect was detected in single heterozygous carriers. These findings reflect the potential role of a genetically altered host response to disease-related bacteria in the pathogenesis of CD.     

No relationship observed between human p53 codon-72 genotype and HPV-associated cervical cancer in a population group with a low arginine-72 allele frequency

Infection with high-risk human papillomavirus (HR-HPV) is a necessary but not a sufficient event in the development of cervical cancer, as most infections regress without intervention. Thus, genetic host factors and cellular immune responses could be potential modifiers for the risk of developing cervical cancer. In particular, p53 is considered as the most critical tumour suppressor gene and is involved in regulating cell division. The polymorphism on p53, which encodes either a proline or an arginine amino acid residue at codon 72, has been reported as a possible risk factor for cervical disease. This polymorphism has been shown to differentially affect the efficiency of degradation of p53 protein mediated by HR-HPV E6 oncoprotein. Women with histologically proven cancer of the cervix (n = 111) and hospital-based controls (n = 143) were included in this study. The patients and controls were from the Western Cape Province in South Africa. Genotyping of the p53 polymorphism was conducted using polymerase chain reaction and restriction fragment-length polymorphism method. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups. In this study, we observed no association between the distribution of p53 polymorphism and susceptibility to cervical cancer in the Western Cape Province populations (P = 0.466). However, the frequency of the Pro/Pro residue at codon 72 was increased in the South African population when compared to Caucasians, Indians and Portuguese population groups. Notably, as the distribution of the Pro/Pro at codon 72 of p53 gene was significantly different (P < 0.05) between the control groups of South Africa and other population groups. This result suggests that ethnic disparity may influence the levels of p53 produced.     

Does vitamin D supplementation in infancy reduce the risk of pre-eclampsia?

Vitamin D has been suggested to affect the balance between T helper (Th1) and (Th2) type cytokines by favouring Th2 domination. We investigated the association between infant vitamin D supplementation and later pre-eclampsia, a disorder suggested to be dominated by Th1 response. We used data on 2969 women born in the Northern Finland Birth Cohort 1966 of whom 68 (2.3%) had pre-eclampsia in their first pregnancy. Risk of pre-eclampsia was halved (OR 0.49, 95% confidence interval (CI) 0.26-0.92) in participants who had received vitamin D supplementation regularly during the first year of life and this association was not affected by adjustment for own birth order, birth weight, gestational age, social class in 1966 and hospitalizations or pregnancy-induced hypertension of their mothers. Together with earlier observations on a reduced risk of type 1 diabetes after vitamin D supplementation, these data suggest that vitamin D intake in infancy may affect long-term programming of the immune response pattern.