Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report.

OBJECTIVE: Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer). The aim of our study was to establish the prevalence of malignancies in states of congenital IGF-I deficiency. SUBJECTS: We surveyed 222 patients with congenital IGF-I deficiency (Laron syndrome, GH gene deletion, GHRH receptor defects and IGF-I resistance) and 338 first and second-degree relatives. RESULTS: None of the IGF-I deficient patients had cancer, whereas 9-24% of the family members had a history of malignancy. CONCLUSIONS: Congenital IGF-I deficiency acts as a protecting factor for the development of cancer.

The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities.

The correlation between the molecular defects of the GH receptor (R), psychosocial development and brain abnormalities were evaluated in 10 patients with Laron syndrome (LS), in whom all data were available. The findings revealed that the intelligence quotient (IQ) and abnormalities in the brain of the patients with LS differ with various molecular defects of the GH-receptor. The most severe mental deficits and brain pathology occurred in patients with 3, 5, 6 exon deletion. Patients with point mutations in exons 2, 4 and 7 presented various degrees of medium to mild CNS abnormalities that correlated with the IQ. Notably, the patient with the E180 splice mutation in exon 6 had a normal IQ, which fits the report on normal IQ in a large Ecuadorian cohort with the same mutation. This is the first report to support a correlation between IQ, brain abnormalities and localization of the molecular defects in the GH-R gene. As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.

Hepatic haemangiomas: possible association with female sex hormones.

BACKGROUND AND AIMS: The association of hepatic haemangiomas with female sex hormones is not entirely clear. We prospectively evaluated the impact of female sex hormones on the natural history of liver haemangiomas. METHODS: We followed 94 women with 181 haemangiomas diagnosed by ultrasound for a period of1-17 years (mean 7.3 (5.5) years). The location, number, size, and ultrasonographic pattern of the lesions were evaluated. Patients were also evaluated by questionnaire for gynaecological and reproductive history. We compared the change in number and size of haemangiomas in patients who received or did not receive exogenous hormonal treatment. RESULTS: Age at first period was inversely associated with the size of haemangiomas (r = 0.181, p = 0.015) while age at menopause was positively correlated with the number of haemangiomas detected at first ultrasound (r = 0.542, p<0.0001). During follow up, no change in the ultrasonographic pattern or number of haemangiomas was observed. An increase in the size of the lesions was demonstrated in 5/22 (22.7%) hormone therapy exposed patients compared with 7/72 (9.7%) controls. Three variables (ultrasonographic pattern, number of haemangiomas, and hormone therapy) predicted whether or not a given haemangioma would increase in size. A hypoechoic pattern increased the risk of progression while a hyperechoic pattern decreases that risk (p = 0.003). The number of haemangiomas was inversely associated with the likelihood of progression (p = 0.006) and hormone therapy increased the risk of haemangioma enlargement (p = 0.05). CONCLUSIONS: Hepatic haemangiomas seem to be influenced by both endogenous and exogenous female sex hormones although significant enlargement occurs only in a minority of patients. Consequently, routine liver ultrasound follow up in women with hepatic haemangiomas receiving hormone therapy appears appropriate.

Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole.

BACKGROUND: The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. AIM: To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. METHODS: Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. RESULTS: One hundred and seventy-nine patients, mean age 45.8 +/- 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). CONCLUSIONS: Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.

Prevalence of Helicobacter pylori infection in health-care personnel of primary care and gastroenterology clinics.

BACKGROUND & AIMS: Helicobacter pylori (Hp) infection clusters within families, is usually acquired early in life, and is strongly associated with lower socioeconomic status during childhood. Transmission in adulthood is relatively rare, and reports on the prevalence of Hp infection among health personnel, especially endoscopists, are controversial. The present prospective study evaluated the prevalence of Hp infection in health-care workers in primary-care clinics and in gastroenterology units. METHODS: Health care personnel from gastrointestinal units (n = 191) and primary care-clinics (n = 98) of the Clalit Health Services (CHS) in Israel underwent the carbon 13 breath test (13C-UBT) and completed a 21-item demographic and socioeconomic questionnaire. The control group consisted of 4633 symptomatic patients with no evidence of previous Hp infection. RESULTS: The 13C-UBT was positive in 108 gastrointestinal unit personnel (73%) and 70 primary-care workers (71%); both rates were statistically higher significantly than the 53% positivity in the controls. Comparison of the 13C-UBT Hp-positive and Hp-negative health-care personnel yielded a significantly higher index of crowded living conditions in the Hp-positive group. In the gastrointestinal unit workers, Hp positivity was also associated with several years in practice, and in the primary-care workers, with Sephardic (Asian and African origin) versus Ashkenazi (Europe and American) origin. Profession (physician, nurse, technician, secretary, or maintenance worker), history of duodenal ulcer, smoking, marital status, and blood group did not have predictive value for Hp colonization. CONCLUSIONS: The prevalence of Hp infection in Israel is higher in health-care staff of primary-care clinics and gastrointestinal units than in the general population. This may be related to socioeconomic facts and professional hazard. Further studies are needed to clarify this issue.

Identification of two novel mutations in the human growth hormone receptor gene.

Deletions and mutations in the growth hormone receptor gene are the underlying etiology of Laron syndrome (LS). Most of the patients are distributed in and originating from the Mediterranean and Middle-Eastern countries. Thirty-nine mutations have been described so far. We hereby report 2 novel nonsense mutations, one in exon 2 found in three Jewish-Iraqi patients from Israel; and another in exon 6 found in an Italian girl. DNA sequencing of exon 2 revealed a G to A transition at nucleotide 83 in the fourth codon of the signal peptide (W-15X). In exon 6, a T to A transversion was found in amino acid 141 (L141X). Both mutations introduced a premature termination codon that led to a truncated non-functioning receptor. In addition we found in the Jewish-Iraqi patients, a mutation in exon 7 (R211H, previously described) and in the Italian family the polymorphism Gly168, in exon 6.

Evaluation of a novel continuous real time (13)C urea breath analyser for Helicobacter pylori.

AIM: To evaluate the sensitivity and specificity of a new (13)C urea breath test, Oridion BreathID, for the diagnosis of Helicobacter pylori. METHODS: A total of 97 consecutive symptomatic patients referred for upper endoscopy were included in the 'pre-therapy' part of the study. After endoscopy the patients were analysed for H. pylori by Oridion BreathID. BreathID continuously sampled the subject's breath for 20 min, and displayed the results on the BreathID screen in real time. Results of the BreathID were compared with the 'gold standard' (rapid urease test and histology). We also prospectively tested the validity of BreathID in comparison to isotope ratio mass spectrometry, in 40 patients referred to monitor the efficacy of H. pylori eradication treatment. RESULTS: Complete agreement was observed between the 'gold standard' and the Breath ID test in 96.9% (94 out of 97) of the patients. The sensitivity and specificity of BreathID were 97.8% and 96.1%, respectively. The correlation between BreathID and isotope ratio mass spectrometry breath test was 100%. CONCLUSIONS: The Oridion BreathID has comparable sensitivity and specificity to the claims of the currently available urea breath tests. Furthermore, BreathID has the potential advantages of ease of use with minimal medical staff requirement, and real time rapid results (20 min maximum) which may make the BreathID preferable to other urea breath test assays.