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Showing papers by "St Bartholomew's Hospital published in 1996"


Journal ArticleDOI
TL;DR: Insulin-like growth factor I (IGF-I) mediates the majority of the growth-promoting effects of growth hormone (GH) after birth, and fetal tissues express IGF-I from fetal tissues.
Abstract: Insulin-like growth factor I (IGF-I) mediates the majority of the growth-promoting effects of growth hormone (GH) after birth.1 In the prenatal period, GH does not appear to have a major influence on fetal growth, whereas IGF-I does. Infants with congenital GH deficiency and defects in the GH-receptor gene have only mild retardation of growth at birth,2–4 whereas transgenic mice with a homozygous defect of the IGF-I gene (IGF-I knockout mice) have profound embryonic and postnatal growth retardation.5–7 Although there is no direct evidence that IGF-I has a prominent role in human fetal growth, fetal tissues express IGF-I from . . .

1,066 citations


Journal ArticleDOI
TL;DR: The effects of modulating HO during an acute complement–dependent inflammatory response are described, which resulted in a striking suppression, whereas inhibition of the enzyme led to a potentiation of the inflammatory response.
Abstract: Chronic inflammatory diseases place a heavy social and economic burden on the resources of many nations, but the number of safe and effective treatments is limited. To date, the major research effort has concentrated on those mediators responsible for the initiation and maintenance of the pathological process. In contrast, little attention has been focused on endogenous factors responsible for the resolution of the inflammation. Heme oxygenase ((HO); EC 1.14.99.3) is the rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO). Two isoforms of HO have been characterized, the constitutive isoform, HO-2, which is the major isoform present under physiological conditions, and the stress-induced isoform, HO-1, which has also been classified as heat-shock protein 32K (ref. 1). Increases in HO activity have been implicated in tissue protection against oxidative stress. In this communication, we describe the effects of modulating HO during an acute complement-dependent inflammatory response. Elevation of this enzyme resulted in a striking suppression, whereas inhibition of the enzyme led to a potentiation of the inflammatory response. Such novel enzyme modulation has application on the one hand to the treatment of inflammatory diseases and on the other hand to immnosuppressed states in which the impaired ability to mount an adequate inflammatory response may result in death from opportunistic infections.

793 citations


Journal ArticleDOI
TL;DR: The results of this study suggest that, even in iron-replete patients, those supplemented with i.v. iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO, compared with those patients receiving oral iron and no iron supplementation.

411 citations


Journal ArticleDOI
TL;DR: The overall hazard is sufficient to justify measures to restrict smoking in public places and workplaces, and to discourage people from smoking in their homes, but there is inconsistency between different estimates of the magnitude of risk.
Abstract: Environmental tobacco smoke is an important contaminant of indoor air. For a non- smoker living with a smoker the exposure is equivalent to about 1% of that from actively smoking 20 cigarettes a day (based on plasma cotinine).There is strong and consistent evidence that passive smoking increases the risk of lung cancer. It is estimated that there is an increase in risk of 24% (95% confidence interval 11—38%) compared to unexposed non-smokers, and several hundred lung cancer deaths per year in Britain are attributable to environmental tobacco smoke exposure. Passive smoking is associated with an increase in risk of chronic respiratory disease in adults of 25% (10—43%), and increases the risk of acute respiratory illness in children, by 50—100%. It is likely that passive smoking increases the risk of ischaemic heart disease, and that exposure in pregnancy lowers birthweight, but there is inconsistency between different estimates of the magnitude of risk.The overall hazard is sufficient to justify measures to restrict smoking in public places and workplaces, and to discourage people from smoking in their homes. Environmental tobacco smoke is probably the most important con- taminant of indoor air. It consists mainly of 'sidestream' smoke given off directly from the burning end of the cigarette; exhaled mainstream smoke is a minor component. The smoke differs in certain ways from active smoking: sidestream smoke is unfiltered (since it does not pass through the column of tobacco or the filter of the cigarette), and the nicotine is mainly in the gaseous phase in sidestream smoke and the paniculate phase in mainstream smoke. These differences notwithstanding, it is reasonable to expect in general that environmental tobacco smoke exposure, or passive smoking, would cause the same diseases as active smoking, but at a risk reduced approximately in proportion to the considerable dilution of the smoke. This expectation is secure in the case of smoking-relat ed cancers because of the evidence that carcinogens in general have no threshold. For other smoking related diseases there may plausibly be a threshold exposure level such that passive smoking constitutes too low a dose to convey any excess risk, or conceivably (though less plausibly) a near maximal response at low dose such that passive smoking conveys a risk of the same order of magnitude as active smoking.

329 citations


Journal ArticleDOI
TL;DR: An increasing volume of experimental research indicates that 5HT can act directly on the adrenal gland and possibly on the anterior pituitary as well, which has major implications for the interpretation of neuroendocrine studies of 5HT conducted in psychiatric conditions, such as depression.

319 citations



Journal ArticleDOI
TL;DR: Although most of the treated group V eyes could be salvaged with chemotherapy plus radiotherapy, the resultant visual acuity was often poor, and of the 12 surviving children, 5 have aVisual acuity better than l/60 in at least 1 eye.
Abstract: Objective: To determine the visual and anatomical results and survival after combined chemotherapy and whole eye radiotherapy for patients with bilateral Reese-Ellsworth group V retinoblastoma. Setting: A national referral center for retinoblastoma. Patients: Fourteen patients with bilateral Reese-Ellsworth group V retinoblastoma seen between March 1, 1989, and April 30, 1995, were treated. Interventions: Patients were treated with chemotherapy (using carboplatin, etoposide, and vincristine) and whole eye radiotherapy (40-44 Gy in 20-22 equivalent fractions). A medical record review was performed to determine outcomes. Main Outcome Measures: Survival, eye preservation rate, and visual acuity. Results: Two patients died, 1 from a primitive neuroectodermal tumor and the other from the meningeal spread of retinoblastoma. Four eyes were enucleated primarily because of severe disease at presentation. Of the remaining 20 eyes, 6 required enucleation. The disease recurred in 4 of those patients, and neovascular glaucoma developed in 2 patients. Of the 12 surviving children, 5 have a visual acuity better than 1/60 in at least 1 eye. Conclusion: Although most of the treated group V eyes could be salvaged with chemotherapy plus radiotherapy, the resultant visual acuity was often poor.

277 citations


Journal ArticleDOI
TL;DR: It is believed that the specificity 99mTc Infecton confers for bacterial infection and its ease of administration are the main advantages of this new agent.

265 citations


Journal ArticleDOI
TL;DR: While there are some diseases for which smoking shows a protective effect, the 'benefits' of these are negligible in relation to the illness and premature mortality caused by smoking.
Abstract: The detailed mortality and morbidity statistics on smoking tend to conceal the overall impact of the habit on health. About 3 million people die each year from smoking in economically developed countries, half of them before the age of 70. Cancers of eight sites are recognized as being caused by smoking--lung cancer almost entirely and the others (upper respiratory, bladder, pancreas, oesophagus, stomach, kidney, leukaemia) to a substantial extent. Six other potentially fatal diseases are also judged to be caused by smoking: respiratory heart disease, chronic obstructive lung disease, stroke, pneumonia, aortic aneurysm and ischaemic heart disease, the most common cause of death in economically developed countries. Non-fatal diseases, such as peripheral vascular disease, cataracts, hip fracture, and periodontal disease, which cause appreciable disability, cost and inconvenience are also caused by smoking. In pregnancy, smoking increases the risk of limb reduction defects, spontaneous abortion, ectopic pregnancy, and low birth weight. While there are some diseases for which smoking shows a protective effect, the 'benefits' of these are negligible in relation to the illness and premature mortality caused by smoking. About 20% of all deaths in developed countries are caused by smoking; an enormous human cost which can be completely avoided.

242 citations


Journal ArticleDOI
TL;DR: The inhibin‐A‐based four‐marker test is the most effective method of prenatal screening for Down's syndrome suitable for routine use and the extra cost required to carry out the inhibin-A test were less than about £3 per woman screened, so it would be financially cost‐effective.
Abstract: The value of measuring inhibin-A (a beta A dimer) with human chorionic gonadotrophin (total or the sub-units free a-hCG and free beta-hCG separately), alpha-fetoprotein (AFP), and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples from 77 Down's syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the sample, supplemented by data from 970 white women with unaffected pregnancies. Inhibin-A was elevated in the serum of women with Down's syndrome pregnancies with a median of 1.79 multiples of the median (MOM). Using the four serum markers AFP, uE3, total hCG, and inhibin-A, in addition to maternal age, 70 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, and total hCG with maternal age). If the estimate of gestational age were based on an ultrasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69-85 per cent] using the four serum markers including inhibin-A, compared with 67 per cent with the triple test or 79 per cent (95 per cent CI 71-87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound scan examination, the four-marker test would reduce the false-positive rate from 6-1 per cent using the triple test to 2-9 per cent. The results were virtually the same if free beta-hCG was used instead of total hCG. The inhibin-A-based four-marker test is the most effective method of prenatal screening for Down's syndrome suitable for routine use. If the extra cost required to carry out the inhibin-A test were less than about [symbol: see text]3 per woman screened, the four-marker test including inhibin-A would be financially cost-effective.

224 citations


Journal Article
TL;DR: It is suggested that the relationship between feeding pattern and BMI observed in the Adolescent and Middle-aged groups was caused by underestimation of 'habitual' energy intake from snacks and the omission of breakfast by females and those who were overweight.
Abstract: OBJECTIVE To assess the relationship between feeding pattern and body mass index in free-living humans. DESIGN AND SUBJECTS Feeding pattern was assessed from 220 7-day weighed dietary records. 187 records were obtained from three separate existing studies, and reanalysed. These studies contained data on three age groups in the British population; Elderly group (n = 88), Middle-aged group (n = 40), Working age group (n = 59). A separate study of 13-14 year olds living in Croydon was conducted from which 33 usable diet records were collected to produce a fourth, Adolescent group. RESULTS 'Nibbling' and greater energy intakes at breakfast were associated with a lower body mass index (BMI) in the Adolescent group. In the Middle-aged group, greater energy intakes at breakfast and lower energy intakes during the evening were associated with a lower BMI. However, when diet records which produced unreasonably low energy intakes were removed from the analysis, these relationships disappeared except for energy intakes at breakfast and BMI in the Adolescent group. CONCLUSION It is suggested that the relationship between feeding pattern and BMI observed in the Adolescent and Middle-aged groups was caused by underestimation of 'habitual' energy intake from snacks and the omission of breakfast by females and those who were overweight. The lack of relationship in the Working age group was attributed to the fact that more individuals in this group appeared to report valid diet records. Reported energy intake was directly related to BMI in the Working age group, but was not related to BMI in the other three age groups. It is concluded that feeding pattern is not a major factor in determining BMI in humans. Also, since snacks have a relatively high sugar and low fat composition compared with meals, it is suggested that biased under-reporting of snacks by the obese could produce spurious results from free-living studies which show that obesity is related to the proportion of energy from fat in the diet.

Journal ArticleDOI
TL;DR: The results of transsphenoidal pituitary surgery for acromegaly were analyzed to assess the longer‐term outcome for patients not offered further treatment when post‐operative levels of GH < 5 mU/l were achieved.
Abstract: OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew’s Hospital between 1985 and 1993. PATIENTS One hundred consecutive patients (53 male, mean age 46 years, range 18–68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5–8 years) after operation. MEASUREMENTS GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS Post-operatively, 42% of patients achieved a mean GH level of 100 mU/l achieved post-operative GH values < 5mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission postoperatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5–8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.

Journal ArticleDOI
30 Nov 1996-BMJ
TL;DR: CA 125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women and the risk in the year after a serum CA 125 concentration >/=100 U/ml is similar to the lifetime risk to women in high risk families.
Abstract: OBJECTIVE: To determine the risk of invasive epithelial ovarian cancer and fallopian tube cancer associated with a raised concentration of the tumour marker CA 125 in asymptomatic postmenopausal women. DESIGN: Serum CA 125 concentration was measured annually in study participants for one to four years. Participants with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. Follow up was by annual postal questionnaire. SETTING: General practice, occupational health departments, ovarian cancer screening unit in a teaching hospital. SUBJECTS: 22,000 volunteers, all postmenopausal women > or = 45 years of age; recruited between 1 June 1986 and 1 May 1990. INTERVENTION: Surgical investigation if the ultrasound examination was abnormal. MAIN OUTCOME MEASURES: Cumulative and relative risk of developing an index cancer (invasive epithelial cancer of the ovary or fallopian tube) after a specified CA 125 result. RESULTS: 49 index cancers developed in the study population during a mean follow up of 6.76 years. The overall cumulative risk of developing an index cancer was 0.0022 for the entire study population and was lower for women with a serum CA 125 concentration or = 30 U/ml (0.030) and > 100 U/ml (0.149). Compared with the entire study population the relative risk of developing an index cancer within one year and five years was increased 35.9-fold (95% confidence interval 18.3 to 70.4) and 14.3-fold (8.5 to 24.3) respectively after a serum CA 125 concentration > or = 30 U/ml and 204.8-fold (79.0 to 530.7) and 74.5-fold (31.1 to 178.3) respectively after a concentration > or = 100 U/ml. CONCLUSION: CA 125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women.

Journal ArticleDOI
TL;DR: Results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM, and suggest that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.
Abstract: To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-γ), T helper 2 (interleukin-4 and inter-leukin-10) lymphocytes and macrophages (tumour necrosis factor-α, interleukin-1 α and interleukin-1 Β) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-γ, tumour necrosis factor-α and interleukin-1 α than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p<0.05 for all). Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-α levels (p<0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 Β was not detectable in the serum of any control or test subject. To investigate whether high cytokine levels precede the onset of IDDM, we studied 28 non-diabetic identical co-twins of patients with IDDM, followed-up prospectively for up to 6 years after the diagnosis of the index. Levels of tumour necrosis factor-α and interleukin-1 α were elevated above the normal range more frequently in the eight twins who developed diabetes than in those 20 who did not (p<0.005). Analysis of T helper 1 and T helper 2 profiles of the twin groups did not reveal a clear difference between prediabetic twins and twins remaining non-diabetic. These results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM. This is associated with release of macrophage-derived cytokines, which is also a feature of the prediabetic period. The lack of evidence of a dominant T helper 1 profile of cytokine release before diabetes onset suggests that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.

Journal ArticleDOI
TL;DR: All 6 markers of haemostatic status were positively and statistically significantly associated with risk, providing further evidence for a hypercoagulable state in men at high risk for fatal coronary heart disease.
Abstract: The haemostatic system was examined in 2951 men aged 50 to 61 years, clinically free of cardiovascular disease, who were ranked according to a risk score for fatal coronary heart disease (CHD). Risk was judged from their serum cholesterol concentration, systolic blood pressure, body mass index and smoking habit. The status of the factor VII-tissue factor pathway was estimated from the plasma levels of factor VII coagulant activity, factor VII antigen and activated factor VII. Activation of factor IX was assessed from the plasma concentration of factor IX activation peptide. Activity within the common pathway was measured as the plasma concentrations of prothrombin fragment 1 + 2 and fibrinopeptide A. All 6 markers of haemostatic status were positively and statistically significantly associated with risk, providing further evidence for a hypercoagulable state in men at high risk for fatal CHD. Plasma fibrinogen and serum triglyceride concentrations were also graded positively with risk.

Journal ArticleDOI
TL;DR: The aim is to determine the value of serum screening for Down's syndrome at 8–14 weeks of pregnancy using seven potential serum markers (alpha‐fetoprotein, unconjugated oestriol, total human chorionic gonadotrophin, free α‐hCG, free P‐h CG, pregnancy associated plasma protein A (PAPP‐A), and dimeric inhibin A).

Journal ArticleDOI
TL;DR: The National Down Syndrome Cytogenetic Register is used to describe the cytogenetics and epidemiology of registered cases of Down Syndrome in England and Wales as mentioned in this paper, which includes 5737 cases registered between 1989 and 1993: 2169 prenatal and 3436 postnatal diagnoses, and 132 spontaneous abortions.
Abstract: Data from the National Down Syndrome Cytogenetic Register is used to describe the cytogenetics and epidemiology of registered cases. The register comprises notifications from cytogenetics laboratories in England and Wales. This report is of 5737 cases registered between 1989 and 1993: 2169 prenatal and 3436 postnatal diagnoses, and 132 spontaneous abortions. Eighty eight registrations were from multiple pregnancies. Ninety five percent had regular trisomy 21. In 4% there was a translocation, mostly Robertsonian t(14;21) or t(21;21). One percent were mosaics with one normal cell line. Mean maternal age was raised in free trisomy 21, but not in translocations. Where families had been investigated, about a third of translocations were inherited, six to seven times more often from the mother than the father. Associations between free trisomy 21 and structural chromosomal defects in the births were no more common than expected from newborn series. The overall sex ratio was raised (male to female: 1.23 to 1), and there was an excess of associated male sex chromosomal aneuploidy. However, in mosaics with one normal cell line the male to female ratio was 0.8 to 1, and in twins discordant for trisomy 21 there was also a female excess.

Journal ArticleDOI
TL;DR: Critical illness is associated with low circulating concentrations of insulin-like growth factor-I, insulin- like growth factors-II, and insulin- Like growth factor binding protein 3 and these low values are associated with induction of protease activity specifically directed against insulin-Like growth factorbinding protein 3.
Abstract: ObjectivesTo describe the sequential changes in the circulating concentrations of insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding proteins in critically ill patients. To determine whether critical illness is associated with induction of a specific

Journal ArticleDOI
TL;DR: The results show that TNF‐α mRNA expression is significantly elevated in pre‐eclamptic patients compared with the other two control groups, which is consistent with a major role for TNF­α in mediating endothelial disturbances, and suggest a key role in the development of pre-eclampsia.
Abstract: Pre-eclampsia is an endothelial disorder and TNF-α has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-α mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-α expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-α gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-α expression. Our results show that TNF-α mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-α may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-α in mediating endothelial disturbances, and suggest a key role for TNF-α in the development of pre-eclampsia.

Journal ArticleDOI
TL;DR: How important the doctor's role is in the provision of emotional support is shown by the results, which show patients who used information sources were more likely to have a higher locus of control over the course of their disease.
Abstract: For many cancer patients and their families the experience of cancer is an intensely stressful one. Emotional support is important for most cancer patients during their illness and can be gained from different people and services. This study evaluates patients' attitudes to different sources of support and rates their satisfaction with sources already used. A total of 431 patients completed a questionnaire covering the use of different sources, including individuals, support groups and information sources. The questionnaire also incorporated validated measurements of anxiety, depression and locus of control. The results revealed that the three most important sources of emotional support were senior registrars (73%) and family (73%), followed by consultants (63%). Patients would prefer doctor- and nurse-led support groups to patient only-led groups (26% vs 12%). Pamphlets, such as the BACUP booklets, proved the most important of the informational sources sought (50%). A total of 86% of patients were satisfied or very satisfied with the emotional support received. Patients who expressed dissatisfaction with their emotional support were significantly more likely to be anxious and depressed (P < 0.001). Patients who used information sources were more likely to have a higher locus of control over the course of their disease. These results show how important the doctor's role is in the provision of emotional support.

Journal ArticleDOI
TL;DR: It is essential to establish reliable standards to define GH deficiency in adults, as there is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels.
Abstract: The potential effects of growth hormone (GH) deficiency in adults and the importance of GH secretion in adult life have only been recognized and documented recently. It has been suggested that GH-deficient adults may have premature mortality, abnormalities in body composition and bone density with impaired physical performance and psychological well-being, which are sometimes improved by GH replacement. It is essential, therefore, to establish reliable standards to define GH deficiency in adults. Patients with possible GH deficiency often have primary pituitary or hypothalamic disorders or have undergone surgery or radiotherapy, and thus show evidence of a failure of one of the other pituitary hormones. Several biochemical approaches have been studied to define GH deficiency in the adult and no universal consensus has yet been reached. The most widely established criterion is the peak serum GH concentration achieved during a provocative test, usually the insulin tolerance test (ITT), or following other pharmacological stimuli (e.g. glucagon, arginine, clonidine or GH-releasing factor) but, alternatively, a more physiological stimulus (such as sleep, fasting or exercise) has been used. Spontaneous circulating levels of hormones of the GH axis [24-hour integrated GH concentration, serum insulin-like growth factor I (IGF-I) or IGF-binding protein-3] have been used in the diagnosis of childhood GH deficiency. They have been tested in adults as well but seem to have a more limited role. There are several factors complicating the evaluation of these results. Basal and stimulated GH and IGF-I levels decline with age and with obesity, levels tend to be higher in females and are dependent on nutritional and physical status. The ITT potentially has some risk attached, e.g. in the presence of ischaemic heart disease, but it has proved to be safe in general when used in specialized departments. Other tests are less reliable; releasing hormone tests only assess the readily releasable stores within the pituitary and not the physiological secretory status. The 'cut-off' point for the definition of subnormal responses ideally needs to be set for each provocative test, for each age group, for each degree of obesity and for both sexes. There is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels. The reproducibility of provocative tests can also be variable. An advantage of the hypoglycaemia and glucagon tests is that they allow simultaneous assessment of the adrenocorticotropic hormone reserve.

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TL;DR: A blinded trial in which 20 cases of chronic viral hepatitis were assessed by five histopathologists, using the Knodell and Scheuer scoring systems, concluded that, while both systems produced reasonable agreement, this was greater using the Scheuer system.

Journal ArticleDOI
TL;DR: A systematic genome linkage scan in eight triple A families obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity.
Abstract: The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes.

Journal ArticleDOI
TL;DR: Systolic blood pressure stress Responsivity increases with age in women but not in men, and in middle-aged men, exaggerated cardiovascular stress responsivity is associated with an unfavourable risk profile, but other data do not support the notion that stressresponsivity mediates age and gender differences in cardiovascular disease risk.
Abstract: Background Exaggerated cardiovascular and neuroendocrine responses to mental stress may enhance cardiovascular disease risk, Coronary heart disease and hypertension increase in prevalence with adva...

Journal ArticleDOI
TL;DR: In this article, the results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success.
Abstract: PURPOSEThe results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success.PATIENTS AND METHODSBiopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight.RESULTSThe biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-...

Journal ArticleDOI
TL;DR: The results suggest that human bronchial epithelial cells are capable of synthesizing RANTES and may therefore play an important role in the development of inflammation in allergic airways disease.
Abstract: Recent studies have demonstrated that RANTES, a member of the CC chemokine family affecting monocytes, T cells, basophils, and eosinophils, is expressed by several cell types. To investigate whether human bronchial epithelial cells can also express this chemokine, we investigated human bronchial epithelial cells for their ability to synthesize RANTES, both in vitro and in vivo. Additionally, we investigated the effect of treatment for 4 mo with inhaled corticosteroids on the expression of RANTES in these cells in vivo. Human bronchial epithelial cells cultured from surgical tissue expressed the mRNA for RANTES and synthesized RANTES, as demonstrated by polymerase chain reaction and immunocytochemical staining and enzyme-linked immunosorbent assay, respectively. Incubation of the cultures with 50 ng/ml of tumor necrosis factor-alpha (TNF-alpha) significantly increased the release of RANTES into culture medium after 18 to 48 h of incubation, an effect that was abolished by treatment of the cultures with anti-TNF-alpha antibody. RANTES was also expressed in the bronchial epithelium in vivo, as indicated by positive immunocytochemical staining of bronchial biopsy tissues obtained from mild asthmatic patients before and after treatment with 500 micrograms of inhaled beclomethasone dipropionate (BDP) twice daily or matched placebo for 4 mo. Quantitation, by color image analysis, of the percentage of epithelium staining for RANTES showed that treatment with BDP decreased the expression of RANTES in the bronchial epithelium from 17.12% to 4.22% (P < 0.05). The numbers of EG2-staining cells in the epithelium were also reduced, from 790.1/mm2 to 203.3/mm2 (geometric mean; P < 0.01), after BDP treatment. These results suggest that human bronchial epithelial cells are capable of synthesizing RANTES and may therefore play an important role in the development of inflammation in allergic airways disease. Furthermore, corticosteroids may prevent airway inflammation by downregulating the expression of proinflammatory cytokines in the bronchial epithelium.

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TL;DR: The association between IDDM and early consumption of cows' milk may be explained by the generation of a specific immune response to beta casein, and it is of interest that sequence homologies exist between Beta casein and several beta-cell molecules.

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TL;DR: It is concluded that, wherever possible, treatment days should not be missed, and it is important to compensate for them, preferably by one of the first of the above methods, in order to keep as close as possible to the original/standard prescription in terms of total dose, dose per fraction and overall time.

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TL;DR: It is predicted that this mutant GHR protein would not be anchored in the cell membrane and would be measurable in the circulation as GHBP, hence explaining the phenotype of severe GH resistance combined with elevated circulating GHBP.
Abstract: Laron syndrome (LS) is a severe autosomal recessive form of GH resistance resulting from molecular defects in the GH receptor (GHR). Affected individuals have extreme short stature and a typical facial phenotype. The point mutations in the GHR gene identified in this condition have until now been confined to the region encoding the extracellular domain of the receptor. We report here the first homozygous point mutation within the intracellular domain of the GHR in two LS cousins distinguishable from classical LS patients only by the presence of elevated GH-binding protein (GHBP) in their serum. A G to C transversion at the vital - 1 position in the splice donor site of exon 8 disrupts normal splicing, resulting in the complete skipping of exon 8, producing a mutant GHR protein lacking transmembrane and intracellular domains. We predict that this mutant protein would not be anchored in the cell membrane and would be measurable in the circulation as GHBP, hence explaining the phenotype of severe GH resistan...

Journal Article
TL;DR: The results suggest that, with maturity, progressive cell degeneration primarily by apoptosis results in clearance of certain cellular populations resulting in the typical keloid lesion, however, the persistence of fibroblast proliferation at the dermal/keloid interface propagates the fibrosis.
Abstract: Keloids are collagenous lesions acquired as a result of abnormal wound heating. In this study we have assessed the potential role of proliferation, apoptosis, and necrosis in keloids. Samples were immunolabeled for proliferating cell nuclear antigen or DNA strand breaks or stained with acridine orange. Proliferating cells were observed in the basal layer of the epidermis and fibroblasts in the dermis, the numbers of the latter being increased in comparison with normal skin. No proliferating cells were observed in the central region of the keloid. In normal skin, apoptotic cells were restricted to the basal layer of the epidermis. In keloid samples, numerous apoptotic cells were observed in the epidermis and dermis; the number and distribution of positive cells decreased more distal to the keloid lesion. Apoptotic endothelial cells of a small proportion of blood vessels in the dermis were also observed. Evidence of necrosis was also seen in the dermis. These results suggest that, with maturity, progressive cell degeneration primarily by apoptosis results in clearance of certain cellular populations resulting in the typical keloid lesion. However, the persistence of fibroblast proliferation at the dermal/keloid interface propagates the fibrosis.