bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Pathogens as Potential Biocontrol Agents of Hydrilla
Authors: Shabana Y. M. , Cuda J. P. , Charudattan R.
Published: November 2003

During a 1‐year survey for micro‐organisms associated with hydrilla, approximately 2200 microbes were recovered from hydrilla, surrounding water and sediment collected from 10 man‐made ponds and three natural lakes in Florida, USA. A representative selection of fungi (651), bacteria (330) and actinomycetes (38) from this collection was screened against hydrilla in bioassays. Severity of damage (DS) was determined on a scale of 0 to 4, where 0 = healthy, 1 = 1–25% damage, 2 = 26–50% damage, 3 = 51–75% damage, and 4 = 76–100% damage (100% = complete kill). Of the 1019 isolates that were examined in this manner, none of the actinomycetes were pathogenic on hydrilla, however two strains of bacteria (0.6% of the bacteria tested), and 42 isolates of fungi (6.5% of the fungi tested) were effective at DS level 4 (DS4) on hydrilla 3 weeks postinoculation. Fungi and bacteria capable of killing hydrilla are considered to have potential as biocontrol agents or as sources of novel herbicidal metabolites. These includedAcremoniumsp.,Botrytissp.,Curvulariasp.,Cylindrocarponsp.,Fusarium culmorumandF. moniliforme. The biocontrol potential ofF. culmorumhas been established in several tests. For maximum bioherbicidal activity of this fungus against hydrilla, its inoculum should be applied at a rate of 5 × 105 conidia/ml at 20–25°C water temperature.
Incidence of Viruses Infecting Winter Oilseed Rape (Brassica napus ssp. oleifera) in Iran
Authors: Shahraeen N. , Farzadfar Sh. , Lesemann D.‐E.
Published: November 2003

Oilseed rape (Brassica napus ssp. oleifera) is an important crop in Iran. Of 581 oilseed rape samples tested by DAS‐ELISA and immunoelectron microscopy during a preliminary survey from 1999 to 2001, 14.45% were infected with Beet western yellows virus (BWYV, Luteovirus), 12.9% with Cauliflower mosaic virus (CaMV, Caulimovirus) and 9.3% with Turnip mosaic virus (TuMV, Potyvirus). Cucumber mosaic virus (4.6%) and Tomato spotted wilt virus (0.51%) also occurred, but to a lesser extent. The occurrence of BWYV, TuMV and CaMV in oilseed rape crops could have important consequences for rape seed production in Iran and infected plants could also serve as sources of virus for other susceptible vegetable crops.
Natural Spread of Plum Pox Virus in Ankara, Turkey
Authors: Eli̇büyük İ. Ö.
Published: November 2003

Plum pox virus (PPV) has a limited distribution in Turkey, so is not a serious problem for stone fruit production. However, it is widespread in apricot, plum and peach trees in the Ankara region where its natural spread was studied between 1995 and 2002 in 10 home gardens planted with apricot, plum and peach trees. The presence of the virus was determined by visual observation of symptoms in leaves and fruits and by double antibody sandwich enzyme‐linked immunosorbent assay (DAS‐ELISA); strains were identified by double antibody sandwich indirect enzyme‐linked immunosorbent assay (DASI‐ELISA) and immunocapture reverse transcription‐polymerase chain reaction (IC‐RT‐PCR) tests. Within 8 years, PPV incidence in the gardens near to, and 0.5 km from an infection source was 85.7–100 and 25–29.4%, respectively. This difference in incidence was attributed to the distance from the infection source. All PPV isolates were identified as PPV‐M. It was found that sharka disease was introduced to the healthy gardens by mealy plum aphids (Hyalopterus pruni), the only vector of PPV found in Ankara. This is the first report of PPV spread in Turkey.
Germinability of Cochliobolus sativus Conidia Exposed to Solar Radiation
Authors: Arabi M. I. E. , Jawhar M.
Published: November 2003

Under field conditions, conidia of Cochliobolus sativus, the causal agent of barley spot blotch, were exposed to direct solar radiation or placed in a ventilated enclosure in darkness for 0.5–12 h. In addition, conidia were either exposed or not exposed to UV light (254 nm) from 1 to 75 min in the laboratory. Conidia were placed after exposure on water agar in closed Petri dishes and allowed to germinate for 24 h. Germinability of conidia was reduced up to 99% after 12 h of exposure to solar irradiance (GS) (690–900 w/m2). Germinability of conidia that were not exposed to sunlight (GNS) did not decrease significantly during experiment time. Similar results were obtained when the variable (GNS−GS)/GNS was applied. Temperature accounted for limited variation in germinability, whereas solar radiation accounted for most of the variation. Germinability of conidia in the laboratory was reduced up to approximately 100% by doses of UV‐C of approximately 14.4 kJ/m2. Germinability of conidia in the field was reduced up to approximately 100% by doses of UV‐B of approximately 39.9 kJ/m2. The information obtained from this study will contribute to the development of a forecast system that incorporates the probability of incoming aerial spores.
Genetic Structure of a Plasmopara viticola Population in an Isolated Italian Mountain Vineyard
Authors: Gobbin D. , Pertot I. , Gessler C.
Published: November 2003

In this paper we investigated the genetic population structure of Plasmopara viticola, the causal organism of downy mildew on grapevines (Vitis spp.). We selected an isolated and newly established mountain vineyard, where the disease was observed for the first time. As soon as disease symptoms appeared, they were collected (three samplings) and they were genetically analysed by means of four microsatellite markers. Our study revealed that a human‐mediated allochthon oosporic import, rather than naturally immigrating secondary propagules, presumably provided the starting inoculum that initiated the very mild epidemic. Fifteen genotypes initiated the disease during three of the at least seven infection periods. Genotypes participating in the epidemic showed a very variable and strain‐specific aptitude in generating secondary lesions. Only two genotypes multiplied asexually and generated some tens of secondary lesions, probably because of the unfavourable climatic conditions of the mountain region. The mountain P. viticola population appeared with a poor gene pool, genetically separated and isolated‐by‐distance from the valley natural stocks as well as recently established by a founder effect event.
Studies of Rosellinia necatrix Perithecia Found in Nature on Avocado Roots
Authors: Pérez‐Jiménez R. M. , Zea‐Bonilla T. , López‐Herrera C. J.
Published: November 2003

Ascomata of Rosellinia necatrix were found on roots of a dead avocado tree, documenting the occurence of the sexual stage in a commercial field in southern Spain, and a description of the teleomorph was done. Additionally, the Dematophora state was obtained by inoculating avocado plants with germinating ascospores from these perithecia, connecting the anamorph and teleomorph phases of this species and confirming the infection capacity of the mycelium from these ascospores.
Comparisons of the resistance to Japanese theileriosis among Santa Gertrudis × Japanese Shorthorn F1, Japanese Shorthorn and their reciprocal crosses
Authors: HIGUCHI Mikito , HANADA Hirofumi , NAGAMINE Yoshitaka , AWATA Takashi
Published: November 2003

To improve the resistance of Japanese Shorthorn (JS) calves to the hemoprotozoan parasite Theileria sergenti (Ts), Santa Gertrudis (SG) × JS F1 and its reciprocal backcross (F1 × JS and JS × F1) calves were produced. All the calves were born from February to April and kept on pasture with their dams from May to October. Blood samples were collected biweekly until 18 weeks of grazing and two indices of resistance to the parasite, percentage of parasitized erythrocytes (PE) and hematocrit value (Ht) were monitored. There was a weak negative correlation between daily gain (DG) on pasture and the average PE (P < 0.1), and was a significantly positive correlation between DG on pasture and the average Ht (P < 0.01) in the experimental period. Although maximum PE observed at six or eight weeks of grazing period was not significantly different among the four mating types, SG × JS F1 calves exhibited a significantly larger decrease in PE compared to purebred JS after the peak PE. F1 calves also showed maximum Ht through the grazing period. There were no apparent differences in the two indices among the two reciprocal backcrosses and purebred JS. These results indicated that Ts infection and subsequent decrease in Ht affected the DG of calves in the grassland. The present study also demonstrated that the introduction of the SG gene into JS was effective at the F1 level in regard to the resistance to theileriosis, and that in the backcrosses an improvement in resistance could not be expected.
Changes in concentrations of plasma metabolites and insulin‐like growth factor‐1 after feeding in Japanese Black and Japanese Shorthorn cattle
Authors: SUDA Yoshihito , SHINOHARA Hisashi , YOSHIOKA Ken‐ichi , NAKAGAWA Kazuki , CHIBA Takashi , YUSA Fumihiro , NIHEI Akira , NISHIDA Akira , YAMAGISHI Toshihiro
Published: November 2003

The aim was to characterize the changes of plasma component concentrations after feeding in Japanese Black (B) and Japanese Shorthorn (S) cattle. Eight females, five B and three S, with a mean bodyweight (standard deviation) of 282.0 (20.3) kg  were  selected  and  supplied  with  only  water  for  28 h  after  feeding.  Blood  was  taken  from  the  jugular  vein  at 4‐h intervals for 32 h after feeding. Metabolite (cholesterol, CL; glucose, GLU; nonesterified fatty acid, NEFA; triacylglycerol, TG; total protein, TP) and insulin‐like growth factor‐1 (IGF‐1) concentrations in plasma were measured. In both breeds GLU tended to decrease linearly with a similar slope. Differences between the initial mean NEFA at 4 h after feeding (Start) and that at 24 h after the start (End) were significant in both breeds, but S increased significantly more than B at and after 8 h from the Start. The TG in S tended to change more than in B, and CL and IGF‐1 in both breeds changed continuously at similar levels. The TP in B tended to decrease more slowly and be lower than S. The change in NEFA, especially, suggests that nutritional status sensitively reflects genetic background.
Outbreaks of serogroup X meningococcal meningitis in Niger 1995–2000
Authors: Djibo S. , Nicolas P. , Alonso J.‐M. , Djibo A. , Couret D. , Riou J.‐Y. , Chippaux J.‐P.
Published: November 2003

In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero‐subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (±6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.
Malaria parasitaemia in relation to HIV status and vitamin A supplementation among pre‐school children
Authors: Villamor Eduardo , Fataki Maulidi R. , Mbise Roger L. , Fawzi Wafaie W.
Published: November 2003

Objectives  To ascertain whether malaria parasitaemia in children is associated with HIV status. To examine the effect of vitamin A supplementation on malaria parasitaemia in children.

Methods  We studied the cross‐sectional associations between HIV status and malaria parasitaemia among 546 children 6–60 months of age who participated in a double‐blind, randomized clinical trial of vitamin A supplementation. Prevalence ratios and 95% confidence intervals (CI) were estimated for the presence of malaria parasites at baseline by HIV status in uni‐ and multivariate models that adjusted for sociodemographic and environmental variables. Among children with malaria, correlates of high parasite loads were identified. Next, we examined the effect of vitamin A supplementation on the risk of malaria parasitaemia and high parasite density at 4–8 months of the first dose in a subset of children.

Results  The prevalence of malaria parasitaemia was 11.4% among HIV‐infected children, compared with 27.6% among uninfected. After adjusting for season, anaemia, use of bednets, maternal education and indicators of socioeconomic status, we found some evidence for lower prevalence of parasitaemia among HIV positive compared with HIV‐negative children (prevalence ratio = 0.56; 95% CI = 0.29, 1.09; P = 0.09). Other important correlates of malaria parasitaemia at baseline included low level of maternal education, poor quality of water supply, and the presence of animals at home. Vitamin A supplementation did not have a significant effect on malaria parasitaemia at 4–8 months of follow‐up, overall or within levels of potential effect modifiers.

Conclusion  HIV infection appears to be negatively correlated with malaria parasitaemia in this group of children. Investing in women's education is likely to decrease the prevalence of malaria parasitaemia in children. Vitamin A supplementation does not seem to have an effect on malaria parasitaemia in this population; possible benefits against clinical episodes and severe malaria deserve further examination.
Interactions between Schistosoma haematobium and Schistosoma mansoni in humans in north Cameroon
Authors: Cunin P. , Tchuem Tchuenté L.‐A. , Poste B. , Djibrilla K. , Martin P. M. V.
Published: November 2003

Objectives  To analyse the relationships between the frequency of ectopic localizations of Schistosoma haematobium and S. mansoni eggs.

Methods  Studies were conducted in 11 villages in north Cameroon, around Bessoum, a village where an epidemic of bloody diarrhoea caused by S. mansoni occurred in 1997.

Results  The results revealed infection prevalence rates of 70.5% for S. haematobium and 30.8% for S. mansoni. Interestingly, S. mansoni eggs were found in 14.5% of the urine samples and S. haematobium eggs in 3% of the stool samples. These ectopic eliminations of schistosome eggs resulted from sexual interactions between the two species of schistosomes, and from a spill‐over of high infection loads. The clinical study showed that the morbidity was lower in individuals with mixed infections and high loads of S. haematobium than in those with S. mansoni infections only, suggesting a possible lowering effect of S. haematobium infection on S. mansoni morbidity.

Discussion  The results obtained in human populations are discussed in relation to the known schistosome interspecific interactions in animal models.
The use of formal and informal curative services in the management of paediatric fevers in four districts in Kenya
Authors: Amin Abdinasir A. , Marsh Vicki , Noor Abdisalan M. , Ochola Sam A. , Snow Robert W.
Published: November 2003

Objective  To assess the sources, costs, timing and types of treatment for fevers among children under 5 years of age in four ecologically distinct districts of Kenya.

Methods  Structured questionnaires were administered to caretakers of one randomly selected child aged <5 years per homestead to establish whether the child had had a fever within the last 14 days and the types, sources, costs, and timing of treatment. Drug charts of common proprietary anti‐malarial and antipyretic drugs in Kenya were used as visual aids.

Results  A total of 2655 fevers were reported among 6287 (42.2%) children with significant differences between the four districts (P < 0.01). A substantial number of fevers remained untreated (28.1%) across all districts and more fevers were treated in Greater Kisii than any other district (P < 0.01). The median delay to any treatment was 2 days [inter‐quartile range (IQR): 2, 4]. The informal retail sector had no transport costs associated with it and charged less for drugs than all the other sectors. Most antimalarial treated fevers occurred in the formal public sector (52.6%). Only 2.3% of fevers were treated within 24 h of onset with a sulphur‐pyrimethamine drug, the nationally recommended first‐line drug for the management of uncomplicated malaria.

Conclusions  The Abuja target of ensuring that 60% of childhood fevers are treated with appropriate antimalarial drugs within 24 h of onset by 2010 is largely unmet and a major investment in improving prompt access to antimalarial drugs will be required to achieve this.
Inadvertent exposure of pregnant women to ivermectin and albendazole during mass drug administration for lymphatic filariasis
Authors: Gyapong John O. , Chinbuah Margaret A. , Gyapong Margaret
Published: November 2003

The current strategy for the interruption of transmission of lymphatic filariasis in areas where the disease is co‐endemic with onchocerciasis is repeated annual mass treatment of endemic communities with ivermectin and albendazole. These drugs are not recommended for use in pregnancy. Pregnant women are excluded on the basis of their last menses. This exclusion criterion based on recall carries some inherent errors, leading sometimes to inadvertent exposure of foetuses to these drugs. This study set out to document the extent of inadvertent exposure of pregnant women to albendazole and ivermectin and assess the relative risk of congenital malformations because of inadvertent treatment with these drugs in early pregnancy. The study was conducted in the Ahanta West District of Ghana. Local pregnancy revelation norms were studied, followed by a household survey of women aged 15–45 years to assess drug administration coverage. All infants born within 42 weeks of the mass drug treatment were examined to document any congenital malformations. Mothers who had lost any such infants responded to a verbal autopsy to ascertain the probable cause of death. Health facilities and local Traditional Birth Attendants were also visited to review maternity records. Of 2985 women of childbearing age (15–49 years) who were interviewed, 343 were pregnant during the mass drug administration. The sensitivity of the last menstrual period in detecting pregnancy and thus being excluded from treatment was 0.854 (293 of 343). Some pregnant women 50 of 343 (14.6%) had thus been inadvertently treated. This represents 1.7% of women in fertile age group (15–49 years). Of the six children found with some congenital malformations in these communities, one had been exposed to the drugs in‐utero. The relative risk for congenital malformation after exposure was 1.05 (P = 1.0). Two of nine reported spontaneous abortions had been exposed to the drugs (P = 0.62). We conclude that the local mode of excluding pregnancy in the current programme, while not perfect, is sufficiently effective and reliable for such a public health intervention; and importantly, that there is no evidence of a higher risk of congenital malformation or abortions in those who are inadvertently exposed.
Treatment costs and work time loss due to episodic adenolymphangitis in lymphatic filariasis patients in rural communities of Orissa, India
Authors: Babu B. V. , Nayak A. N.
Published: November 2003

Objective  To determine the economic loss in terms of treatment costs and loss of productive time because of acute episodes of adenolymphangitis (ADL) caused by lymphatic filariasis (LF) in a rural population of coastal Orissa, India.

Methods  Data on expenditure on treatment and loss of work along with other epidemiological information were collected through a 1‐year surveillance of 113 acute episodes of ADL from 72 individuals of the study population (5.42%). The activity patterns of patients for 24 h of one episode were documented, and data on age‐ and sex‐matched controls were also collected. Standardized Z‐test, paired t‐test, logistic and multiple regressions were used.

Results  Those patients who did incur expenses spent Indian Rupees 92 on average (approximately US$ 1.85) on each episode. The ADL episodes curtailed the productive activity of patients. Patients (88%) were unable to attend to any economic activity compared with 47% of controls who had no history of disease. Similarly during 55% of episodes, females (vs. 8% of controls) could not attend to any domestic work. The mean number of hours spent on economic or domestic activities was significantly lower among patients. Disease status and sex had significant influence on total absenteeism from gainful employment; and similarly, age, family type and disease status influenced total domestic work hours among women.

Conclusions  The results demonstrate the extent of the economic burden caused by acute LF and provide justification for strengthening the ongoing LF elimination programme.
Uncoupling of the order of the S and M phases: effects of staurosporine on human cell cycle kinases
Authors: Stokke T. , Smedshammer L. , Jonassen T. S. , Blomhoff H. K. , Skarstad K. , Steen H. B.
Published: November 2003

The protein kinase inhibitor staurosporine (SSP) was employed to study the involvement of kinases in human cell cycle progression. Thirty to 100 ng/ml SSP blocks entry into S phase and M phase. Lack of entry into S phase is due to impaired activity of the retinoblastoma protein kinase. The requirement for any of the SSP‐sensitive kinases for cell cycle progression can be abrogated in tumour cells. Therefore, these kinases act in a checkpoint network negatively controlling the initiation of S phase, M phase and cytokinesis, rather than being inherent parts of a substrate‐product chain required for the initiation of the cell cycle phases. As a consequence of the lack of certain checkpoint effectors, tumour cells may endoreduplicate or binucleate in the presence of SSP. The latter processes, as well as meiosis, are naturally occurring in specialized cell types, leading to the idea that this checkpoint network controls the order of the cell cycle phases in normal cells. A model is presented where the cell cycle is envisioned as two independently running cycles, the S and the M cycle, which are controlled by intra and intercycle‐dependent checkpoints in human somatic cells. The model accounts for the dependency of S and M phase initiation on the successful completion of the previous M and S phase, respectively, as well as entry into a resting state.
Hexarelin, a synthetic growth hormone releasing peptide, stimulates prolactin secretion in acromegalic but not in hyperprolactinaemic patients
Authors: Ciccarelli E. , Grottoli S. , Razzore P. , Gianotti L. , Arvat E. , Deghenghi R. , Camanni G. , Ghigo E.
Published: November 2003

OBJECTIVE In man, new synthetic peptides such as hexarelin have been shown to have a potent and dose dependent GH releasing activity. Furthermore, a significant PRL releasing activity has also been demonstrated, but this has been investigated in less detail. We have therefore evaluated the effect of hexarelin on PRL and GH secretion in patients with active acromegaly or pathological hyperprolactinaemia.

DESIGN Hexarelin (2 μg/kg i.v.), a modified derivative of GHRP‐6 of the following structure: His‐2‐Me‐D‐Trp‐Ala‐Trp‐D‐Phe‐Lys‐NH2, or placebo, was administered in random order on two separate occasions.

PATIENTS Eight patients with active acromegaly (ACRO, 6 F and 2 M, mean age 61.7 years, range 56–73), 6 with macroadenomas and 2 without radiological signs of tumour, and 6 female patients with pathological hyperprolactinaemia (HPRL, mean age 31.2 years, range 18–47) 5 with microadenomas and 1 with empty sella, were studied. Fourteen normal subjects (NS, 8 F and 6 M, 27.1 years, 24–30) were studied as controls.

MEASUREMENTS GH and PRL levels were evaluated every 15 minutes for 2 hours after hexarelin or placebo. Both hormones were measured using commercial IRMA kits. Basal IGF‐I was measured in all subjects using an RIA following acid–ethanol extraction.

RESULTS Hexarelin induced a significant increase in PRL levels in NS (median, range, Δ peak HEX vs placebo: 150 (−14–402) vs 10 (−34–24) mU/l; Δ AUC HEX vs placebo: 7710 (2 100–3 2540) vs 30 (−2 566–2 040) mU min/l, P < 0.01) and in ACRO (190 (−10–496) vs 6 (−100–34) mU/l; 10 170 (−5 310–51 436) vs−82 (−6 030–1 410) mU min/l, P < 0.02), but not in HPRL (10 (−180–80) vs 50 (−100–240) mU/l; −600 (−16 996–10 140) vs−1 950 (−8 540–14 160) mU min/l). Hexarelin also induced a lower increase of GH in HPRL (60 (30–82) vs 1.8 (−0.2–2.2) mU/l; 2 853 (1 477.6–4 372.6 vs 91.6 (−160.6–174) mU min/l, P < 0.05) than in NS (90.8 (50.6–181) vs 0.8 (−1.2–6.8) mU/l; 6642 (2 004–13 252.6 vs 42 (456–900) mU min/l, P < 0.01) or in ACRO (117.2 (21.2–420.6 vs 3.8 (−2.2–18) mU/l; 6645 (1 554–22 138.6 vs 334.6 (−324–1 065) mU min/l, P < 0.02).

CONCLUSIONS Our data show that the PRL releasing effect of hexarelin is preserved in acromegaly but lost in pathological hyperprolactinaemia. In contrast with acromegaly, the GH releasing effect of hexarelin is also blunted in hyperprolactinaemic patients. These data demonstrate that patients with pathological hyperprolactinaemia are partially refractory to the activity of hexarelin.
Association of HLA‐DQA1*0501 with Graves’ disease in English Caucasian men and women
Authors: Barlow A. B. T. , Wheatcroft N. , Watson P. , Weetman A. P.
Published: November 2003

OBJECTIVE A recent report has demonstrated a stronger association between the HLA‐DQA1*0501 allele and Graves’ disease in Caucasian men than in women. Our aim was to confirm this association in a larger series of male Caucasian patients.

DESIGN Polymerase chain reaction/sequence specific oligonucleotide probing (PCR/SSOP).

PATIENTS Fifty men and 70 women with Graves’ disease were studied as well as a control group consisting of 57 healthy, unrelated men and women.

METHODS Genomic DNA was derived from venous blood samples. Appropriately primed DNA was amplified by PCR and the products were subjected to SSOP. The presence of the allele was demonstrated by enhanced chemiluminescence.

RESULTS A significant association between HLA‐DQA1* 0501 and Graves’ disease was demonstrated among both the men and women as well as in the combined disease cohort, with HLA‐DQA1*0501 conferring a greater relative risk than HLA‐DR3 in all three groups. This association persisted when the results from the DR3‐negative Graves’ patients were analysed in isolation. HLA‐DQA1*0501 was heterogeneously distributed between the sexes with significantly more female Graves’ patients carrying this allele.

CONCLUSIONS There is a significant association between HLA‐DQA1*0501 and Graves’ disease which may be unrelated to the inheritance of this allele on an extended haplotype with HLA‐DR3. In contrast to a recent report, HLA‐DQA1*0501 was significantly more prevalent among women with Graves’ disease than men.
β‐Cell function and glucose and lipid oxidation in Graves’ disease
Authors: Bech K. , Damsbo P. , Eldrup E. , Beck‐Nielsen H. , Røder M. E. , Hartling S. G. , Vølund Aa. , Madsbad S.
Published: November 2003

OBJECTIVE Abnormal glucose metabolism with impaired glucose tolerance has been documented in patients with thyrotoxicosis but the pathogenesis is not fully understood. Therefore, the aim of the present study was to study the β‐cell function and the meal induced oxidative glucose and lipid metabolism in patients with thyrotoxicosis.

DESIGN  After an overnight fast the impact of hyperthyroidism on standard mixed meal induced glucose oxidation, lipid oxidation and β‐cell function was studied.

PATIENTS  Nine untreated patients with Graves’ disease were compared to 9 age and weight matched healthy controls.

MEASUREMENTS  Glucose and lipid oxidation were studied by indirect calorimetry before and after the meal. The insulin secretion rate was calculated by the ‘combined model’ approach, after which the insulin secretion rates and the ambient glucose levels were cross‐correlated. The slope of these regression lines was used as a measure of β‐cell sensitivity to glucose and denotes the insulin secretory capacity. β‐Cell function was further evaluated by measurement of proinsulin and its conversion intermediates. Glucoregulatory hormones were also measured. The findings were correlated to the thyroid hormone levels.

RESULTS  Fasting blood glucose and post‐prandial glucose response were increased in patients (P < 0.01). The hyperthyroid patients displayed a ‘dual’β‐cell defect: (a) inability to increase the insulin response appropriately to hyperglycaemia and (b) increased proinsulin levels both in the fasting state and in response to a meal. Indirect calorimetry showed increased lipid oxidation in the fasting state and at the end of the meal (P < 0.01).

No difference in glucose oxidation was demonstrated in the fasting state but the post‐prandial glucose oxidation was enhanced in the patients (P < 0.01). The adrenaline response was normal, whereas the noradrenaline response was impaired or absent in the patients. The thyroid hormone levels were significantly correlated to fasting levels of blood glucose, insulin, free fatty acids and lipid oxidation, but not to fasting C‐peptide, glucose oxidation or catecholamines.

CONCLUSIONS  Untreated Graves’ disease was associated with glucose intolerance due to quantitative as well as qualitative β‐cell defects. The lipid oxidation was increased in the fasting state and at the end of the meal; after the meal the increase in glucose oxidation was more pronounced in the patients. Thyroid hormones thus increased the oxidation but not by an increase in catecholamines. Indeed, the post‐prandial sympathetic response was blunted.
High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas
Authors: St‐Jean Edith , Blain François , Comtois Ronald
Published: November 2003

OBJECTIVE Large amounts of antigen may produce falsely low values in immunoradiometric assays due to the so‐called high dose, hook effect. The study was designed to identify the clinical and biochemical features of patients with pituitary macroadenomas in whom a high dose PRL hook effect was documented.

DESIGN The clinical and biochemical features of four patients with the high dose PRL hook effect were compared with those of 54 patients with pituitary non‐functioning adenomas and 11 with macroprolactinomas who underwent transsphenoidal microsurgery between 1989 and 1994.

MEASUREMENTS The presence of the high dose PRL hook effect was confirmed by an increase in the initial PRL concentration when the immunoradiometric assay was processed after dilutions of the serum. This phenomenon was observed in 5.8% (4/69) of patients with pituitary macroadenomas. Undiluted median (range) PRL levels were 9140 (l530–83850), 1530 (162–3210) and 2110 mU/l (1470–45 000) in patients with macroprolactinoma, non‐functioning macroadenoma and the hook effect, respectively. In patients with the hook effect, the median PRL levels increased to 384720 (317520–950 000) mU/l when the assay was performed after serum dilution. The proportion of males was 9.9% (1/11) in the macroprolactinoma group, 46.3% (25/54) in the non‐functioning macroadenoma group and 100% (4/4) in patients with the hook effect. Patients with prolactinoma and non‐functioning adenoma had mean tumour sizes of 20±9 and 27±11mm (SD), respectively, while in the hook effect group it was 51±10mm.

CONCLUSION This study suggests that the high dose PRL hook effect is observed particularly in patients with very large tumours. The immunoradiometric PRL assay must be performed with serum dilution in order to overcome the high dose PRL hook effect in all new patients with pituitary macroadenomas who may have a prolactinoma.
Apparent mineralocorticoid excess due to 11β‐hydroxysteroid dehydrogenase deficiency: a possible cause of intrauterine growth retardation
Authors: Kitanaka S. , Tanae A. , Hibi I.
Published: November 2003

A Japanese boy with apparent mineralocorticoid excess (AME) is described. He was born with intrauterine growth retardation (IUGR) and elevated serum level of creatine phosphokinase (CPK). He was studied at 2 years of age because of polyurea and polydipsia of one year’s duration and was found to have hypokalaemic alkalosis and sustained hypertension. His plasma renin activity and aldosterone levels were always low and his ratio of urinary tetrahydrocortisol plus allo‐tetrahydrocortisol to that of tetrahydrocortisone was very high. Therefore, AME due to 11β‐hydroxysteroid dehydrogenase (11β‐HSD) deficiency was diagnosed. He was successfully treated with a combination of spironolactone and nifedipine for at least 16 months. His blood pressure, plasma pH and serum potassium levels were normalized by this treatment, but serum CPK level remained high.

We researched the birth records of previously reported AME cases and found that IUGR is a characteristic feature of AME. The mechanism by which IUGR occurs in AME is discussed and we speculate that 11β‐HSD might be deficient in the placenta and/or fetal tissues, as well as in the kidney, in AME. An explanation for the elevated CPK could not be found.
Exophthalmos in Cushing's syndrome
Authors: Kelly William
Published: November 2003

OBJECTIVE Exophthalmos was noted in 4 of the 12 patients reported by Harvey Cushing in 1932. Although exophthalmos has often been included in clinical descriptions, no previous study has reported actual measurements in patients with active and treated Cushing's syndrome, and in control patients. The aim of this study was to obtain these measurements.

PATIENTS Thirty‐one patients with active Cushing's syndrome (19 iatrogenic), 15 with treated Cushing's syndrome, 18 with Graves' ophthalmopathy, 59 control patients, and 3 patients with active Cushing's syndrome plus a family or personal history of thyroid disease.

DESIGN AND MEASUREMENTS A consecutive series of patients with active and treated Cushing's syndrome were assessed. They were compared with patients with Graves' ophthalmopathy, and with control patients. Exophthalmos was assessed by the author using a Hertel meter. Urinary free cortisol was measured on patients with Cushing's syndrome, and serum thyroxine was estimated for them, and for the patients with Graves' ophthalmopathy.

RESULTS Exophthalmos exceeding 16 mm (>2 SD above normal mean) was found in 45% of active Cushing's syndrome, 21% of iatrogenic Cushing's syndrome, 20% of treated Cushing's syndrome, 2% of normal controls, and 77% of patients with Graves' ophthalmopathy. No patient with Cushing's syndrome had significant symptoms due to exophthalmos.

CONCLUSION Patients with active Cushing's syndrome have statistically significant exophthalmos. This rarely causes symptoms, and diminishes when cortisol concentrations become normal. Cushing's syndrome and autoimmune thyroid disease may coexist in patients with exophthalmos.
Comparison of tests of stress‐released cortisol secretion in pituitary disease
Authors: Orme S. M. , Peacey S. R. , Barth J. H. , Belchetz P. E.
Published: November 2003

OBJECTIVES We wished to compare peak and incremental rise in plasma cortisol in response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon stimulation test (IMGST) and short Synacthen test (SST) in patients with pituitary disease, using a modern radioimmunoassay for cortisol. We compared the three stimulants using receiver operator characteristic (ROC) plots, assuming a cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we used as the standard from which to evaluate the SST and the IMGST.

PATIENTS AND DESIGN We prospectively studied 16 patients (8F, 8M mean age 43.69 ± 3.72 years) admitted to the investigation ward for IIH stress test and who were asked to undergo two additional tests (IMGST and SST) on consecutive days.

MEASUREMENTS We measured serum cortisol at baseline, 30, 45, 60, 90 and 120 minutes during the IIH stress test; baseline, 150 and 180 minutes during GST, and baseline and 30 minutes during the SST.

RESULTS There was a significant rise in cortisol from baseline in all tests (P < 0.001). There was no significant difference among the peak plasma cortisol responses or the incremental rises in plasma cortisol following IMGST, SST and IIH stress test (repeated measures ANOVA F = 0.704, P = 0.503; F = 0.238, P = 0.79). The ROC plots clearly showed that the SST has poor diagnostic utility at both IIH thresholds, compared with the IMGST.

CONCLUSION The peaks and incremental rises in cortisol following all three tests are comparable. Using the insulin induced hypoglycaemia stress test as a reference and peak cortisol thresholds of 500 and 580 nmol/l as discriminating variables, the short Synacthen displayed poor diagnostic utility when compared to the i.m. glucagon stimulation test. The short Synacthen may be misleading if used as a screening test as advocated by a number of authors.
Relationship between growth hormone (GH) status, serum leptin and body composition in healthy and GH deficient elderly subjects
Authors: Gill Matthew S. , Toogood Andrew A. , O'Neill Paul A. , Adams Judith E. , Thorner Michael O. , Shalet Stephen M. , Clayton Peter E.
Published: November 2003

OBJECTIVE

Growth hormone (GH) secretion declines with age and is affected by body composition. The signal that mediates the latter relationship remains ill‐defined. Leptin, the protein product of the adipocyte specific ob gene, is thought to accurately reflect fat mass and could therefore be a candidate to influence GH secretion. We have therefore investigated the relationship between GH status, leptin and body composition in normal and GH‐deficient elderly subjects.

DESIGN

GH secretion was assessed by 20‐minute sampling over 24 hours and serum leptin concentrations were measured in a single morning, fasted sample.

PATIENTS

Twenty‐one GH deficient elderly patients (61–83 years) and 22 gender‐ and BMI‐matched controls (61–88 years).

MEASUREMENTS

Body composition was assessed by dual‐energy X‐ray absorptiometry (DEXA). GH was measured in an ultrasensitive chemiluminescent assay and serum leptin was determined by radioimmunoassay.

RESULTS

Leptin was correlated with percentage body fat in both sexes (male r = 0.75, female r = 0.89, both P < 0.001). Male patients had increased fat mass (FM) (P < 0.01) and leptin concentrations (P < 0.05) but similar lean mass (LM) compared with controls. However, leptin concentration per unit FM was identical in both groups (P = 0.3). In contrast, female patients had lower LM (P < 0.05) but similar FM to controls, yet their leptin concentration per unit FM was twice that of the controls (P < 0.05). In multiple linear regression (MLR) leptin was determined positively by FM and negatively by LM (controls r 2 = 76%; patients r 2 = 73%, both P < 0.0001). When controlled for gender, GH secretion in the controls was correlated negatively with leptin (r = −0.68, P < 0.01) and negatively with percentage body fat (r = −0.73, P < 0.01). In MLR, using leptin as a marker of body composition, 66% of the variability in GH secretion in the controls could be explained by gender (38%) and by leptin (28%).

CONCLUSIONS

Both decreased lean mass and increased fat mass raise serum leptin concentrations in normal and growth hormone‐deficient elderly subjects. Leptin is therefore a marker of body composition rather than fat mass alone. The influence of body composition on growth hormone secretion in the elderly may be mediated through leptin, acting as a peripheral signal from adipose tissue to decrease GH secretion.
Inferior petrosal sinus AVP in patients with Cushing's syndrome
Authors: Yanovski Jack A. , Friedman Theodore C. , Nieman Lynnette K. , Chrousos George P. , Cutler Gordon B. , Doppman John L. , Kalogeras Konstantine T.
Published: November 2003

OBJECTIVE

In both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IPS) contains higher concentrations of AVP and ACTH than the contralateral (non‐dominant) IPS, but ovine corticotrophin‐releasing hormone (oCRH)‐stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oCRH‐releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IPS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome.

PATIENTS

Twenty‐three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin.

MEASUREMENTS

AVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein.

RESULTS

In all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IPS. oCRH significantly increased IPS ACTH only in patients with Cushing's disease (P  <  0.001), whereas it significantly increased dominant IPS AVP levels in all three patient groups (P  <  0.01). However, neither dominant nor non‐dominant IPS AVP (basal or oCRH‐stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH‐stimulated IPS AVP were negatively correlated with urine free cortisol.

CONCLUSIONS

Inferior petrosal sinus AVP levels are similar in all forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH‐stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH‐stimulated AVP.
Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis
Authors: Nagasaka Shoichiro , Sugimoto Hideharu , Nakamura Tomoatsu , Kusaka Ikuyo , Fujisawa Genro , Sakuma Nobuko , Tsuboi Yasushi , Fukuda Shuichi , Honda Kazufumi , Okada Koji , Ishikawa San‐e , Saito Toshikazu
Published: November 2003

OBJECTIVE

Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time‐course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis.

DESIGN

Two year prospective follow‐up study in patients with Graves' disease.

PATIENTS

Ten consecutive patients with Graves' disease (seven males and three females, of mean (±SEM) age 39.3  ±  3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex‐ and age‐matched patients with the disease in remission served as controls.

MEASUREMENTS

Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross‐linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy‐terminal propeptide of type I procollagen (PICP) and alkaline‐phosphatase (ALP) as markers of bone formation.

RESULTS

Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89  ±  0.16 before therapy, higher than those of 0.49  ±  0.12 in the controls (P  <  0.0001); the indices gradually decreased to 1.00  ±  0.20 (12 months) and 0.48  ±  0.12 (24 months). Lumbar BMD Z‐scores increased from −0.22  ±  0.46 to 0.21  ±  0.47 (12 months) and 0.68  ± 0.48 (24 months) (P  =  0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, +396%, P  <  0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months.

CONCLUSIONS

Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4–8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.
Effect of resistance exercise and growth hormone on bone density in older men
Authors: Yarasheski Kevin E. , Campbell Jill A. , Kohrt Wendy M.
Published: November 2003

OBJECTIVE

The purpose of this study was to evaluate whether 16 weeks of heavy resistance exercise training combined with daily growth hormone administration (GH) increases bone mineral density in 64–75‐year‐old men greater than resistance exercise training without GH supplementation.

DESIGN

Eighteen healthy, elderly men (67 ± 1 year) followed a 16‐week progressive resistance training programme (75–90% maximum strength, 5–10 repetitions/set, 4 sets/day, 4 days/week) after double‐blind, random assignment to either a GH (12.5 or 18 μg/kg/day, equivalent to 25 or 36 mU/kg/day, n = 7) or placebo (n = 11) group.

MEASUREMENTS

Before and at the end of 16 weeks of resistance exercise with or without GH administration, body composition, whole body and regional bone mineral density (BMD) were determined by dual‐energy X‐ray absorptiometry. Serum osteocalcin and IGF‐I were determined by radioimmunoassay before, during and at the end of treatment.

RESULTS

Increments in fat‐free mass and training‐specific maximum voluntary muscle strength were similar in both groups after training. Serum insulin‐like growth factor‐I (IGF‐I) and osteocalcin levels were increased (P < 0.05) after exercise training plus GH. In comparison to initial measures, bone mineral density (g/cm2) of the proximal femur (Ward's triangle) was increased (P < 0.05) after 16 weeks of exercise training plus placebo treatment. Sixteen weeks of exercise training plus GH treatment did not increase whole body, spine or hip (femoral neck, trochanter, Ward's triangle) bone mineral density more than exercise plus placebo treatment.

CONCLUSIONS

These findings suggest that in these older men with normal bone mineral density, short‐term resistance exercise training increased regional bone mineral density, but the addition of daily GH administration did not enhance whole body or regional bone mineral density despite GH‐induced increments in serum IGF‐I and osteocalcin. This implies that GH administration during a 16‐week resistance exercise training programme may increase bone turnover without increasing bone mineral accumulation.