bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and biochemical studies in Argentinean patients with variegate porphyria
Authors: Rossetti María V , Granata Bárbara X , Giudice Jimena , Parera Victoria E , Batlle Alcira
Published: June 2008

Background

A partial deficiency in Protoporphyrinogen oxidase (PPOX) produces the mixed disorder Variegate Porphyria (VP), the second acute porphyria more frequent in Argentina. Identification of patients with an overt VP is absolutely important because treatment depends on an accurate diagnosis but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death.

Methods

We have studied at molecular level 18 new Argentinean patients biochemically diagnosed as VP. PPOX gene was amplified in one or in twelve PCR reactions. All coding exons, flanking intronic and promoter regions were manual or automatically sequenced. For RT-PCR studies RNA was retrotranscripted, amplified and sequenced. PPOX activity in those families carrying a new and uncharacterized mutation was performed.

Results

All affected individuals harboured mutations in heterozygous state. Nine novel mutations and 3 already reported mutations were identified. Six of the novel mutations were single nucleotide substitutions, 2 were small deletions and one a small insertion. Three single nucleotide substitutions and the insertion were at exon-intron boundaries. Two of the single nucleotide substitutions, c.471G>A and c.807G>A and the insertion (c.388+3insT) were close to the splice donor sites in exons 5, 7 and intron 4 respectively. The other single nucleotide substitution was a transversion in the last base of intron 7, g.3912G>C (c.808-1G>C) so altering the consensus acceptor splice site. However, only in the first case the abnormal band showing the skipping of exon 5 was detected. The other single nucleotide substitutions were transversions: c.101A>T, c.995G>C and c.670 T>G that result in p.E34V, p.G332A and W224G aminoacid substitutions in exons 3, 10 and 7 respectively. Activity measurements indicate that these mutations reduced about 50% PPOX activity and also that they co-segregate with this reduced activity value. Two frameshift mutations, c.133delT and c.925delA, were detected in exons 3 and 9 respectively. The first leads to an early termination signal 22 codons downstream (p.S45fsX67) and the second leads to a stop codon 5 codons downstream (p.I309fsX314). One reported mutation was a missense mutation (p.G232R) and 2 were frameshift mutations: c.1082insC and 1043insT. The last mutation was detected in six new apparently unrelated Argentinean families.

Conclusion

Molecular analysis in available family members revealed 14 individuals who were silent carriers of VP. Molecular techniques represent the most accurate approach to identify unaffected carriers and to provide accurate genetic counselling for asymptomatic individuals. The initial screening includes the insertion search.
Long‐Term Skeletal Effects of Eating Disorders with Onset in Adolescence
Authors: Misra Madhusmita
Published: June 2008

Anorexia nervosa (AN), an eating disorder characterized by severe undernutrition and associated with hypogonadotropic hypogonadism, causes marked deficits in bone mass accrual when the disorder begins in the teenage years. Although bone mass accrual improves with weight gain and menstrual recovery, residual deficits persist. Women with a history of teenage onset of AN are more likely to be osteopenic than age‐matched women without this history, even after many years of weight and menstrual recovery. Non‐recovered women with persistent low weight and amenorrhea have continued decreases in bone density, with a high prevalence of both osteopenia and osteoporosis. Unlike anorexia nervosa, normal‐weight bulimia is not associated with low bone density, unless there is a past history of low weight or amenorrhea. A second possible skeletal effect of teenage‐onset anorexia nervosa is short stature. Duration of illness and time of onset of anorexia nervosa in relation to the pubertal growth spurt are likely important determinants of statural growth. Adolescent boys with anorexia nervosa are more likely than adolescent girls to have short stature, possibly because growth potential persists for two years longer in boys than in girls. Thus, many adolescent girls may have completed growth or be close to growth completion at the time that they develop anorexia nervosa, whereas adolescent boys may still have significant growth potential remaining. This remaining growth potential may be impaired as a consequence of low levels of insulin‐like growth factor‐I (IGF‐I) levels from persistent undernutrition.
Autoimmune Oophoritis in the Adolescent
Authors: Welt Corrine K.
Published: June 2008

Autoimmune oophoritis presents in adolescents as a component of autoimmune polyendocrine syndrome type I or type II. Autoimmune oophoritis can be diagnosed in women with primary ovarian insufficiency in the presence of adrenal cortical or steroid cell antibodies, and/or antibodies to adrenal and ovarian steroidogenic enzymes. The ovaries are cystic macroscopically, with a lymphocytic infiltrate in the steroidogenic theca cells. The immune infiltrate results in low estradiol levels and a compensatory increase in FSH levels. Granulosa cells are spared, and inhibin A and B levels are normal to high. Treatment is aimed at symptom relief with further investigation needed to assess treatment options such as immunosuppression.
Cultural Perceptions and Practices around Menarche and Adolescent Menstruation in the United States
Authors: Stubbs Margaret L.
Published: June 2008

This overview details the persistence of negative characterizations of the menstrual cycle as a feature of the current cultural context in which girls begin menstrual life in the United States. In addition, research on girls' current menstrual attitudes and experiences within this context are reviewed. Current research suggests that girls are not very knowledgeable about menstruation, and that menstrual education continues to provide girls with mixed messages, such as: menstruation is a normal, natural event, but it should be hidden. Girls' attitudes and expectations about menstruation are negatively biased and have been found to contribute to self‐objectification, body shame, and lack of agency in sexual decision‐making. Although preparation has been found to be associated with more positive menarcheal and menstrual experiences, specificity about what constitutes “good” preparation has not been well articulated. Implications for promoting the menstrual cycle among young girls as a vital sign in service of monitoring their health are discussed.
Adolescent Obesity and Puberty: The “Perfect Storm”
Authors: Jasik Carolyn Bradner , Lustig Robert H.
Published: June 2008

Obesity is the most serious long‐term health risk currently facing America's adolescents. Weight gain during adolescence carries a higher risk for adult obesity and the metabolic syndrome. This review highlights early adolescence as a particularly high‐risk time for weight gain due to the synergy of naturally occurring metabolic changes along with increasing behavioral risk factors. One of the first potential health effects of abnormal weight gain during this period is earlier puberty, usually manifested as thelarche. The obesity epidemic is clearly implicated in the national trend toward earlier thelarche, although the data are not as strong in relation to menarche. Leptin activation of the hypothalamic‐pituitary axis, combined with insulin resistance, and increased adiposity may result in the higher estrogen levels that are linked to breast development. Young adolescents also experience a sharp decline in their level of physical activity, worsening nutritional habits, and other important psychosocial and developmental risk factors that may contribute to obesity and estrogen‐dependent disease in later life, including polycystic ovary syndrome and breast cancer. Unfortunately, the very psychosocial factors that contribute to abnormal weight gain during early adolescence make prevention and treatment in this population particularly challenging. Therefore, intervening prior to pubertal onset becomes even more important given the risk factors present once puberty begins.
Psychosocial Development and Puberty
Authors: Short Mary B. , Rosenthal Susan L.
Published: June 2008

The context of adolescent development in which puberty occurs is briefly reviewed, along with the psychosocial impact on timing of puberty, girls' perception of puberty, and the impact of puberty on relationships with parents and on psychological health. This information can be integrated into clinical practice in order to provide the best care for adolescents, but, first, access to confidential and comprehensive care must be available.
Hormone Replacement Therapy for the Adolescent Patient
Authors: DiVasta Amy D. , Gordon Catherine M.
Published: June 2008

Pubertal induction and hormone replacement therapy (HRT) during adolescence are conducted with the aim of closely mirroring the pubertal changes that occur in children with a normal hypothalamic‐pituitary‐ovarian axis. The challenge for the clinician is to determine the most appropriate form, dosing, and duration of replacement therapy to achieve that goal in an individual patient. While the optimal regimen remains unclear and data in adolescents are limited, this review presents the evidence available to clinicians as they care for adolescent girls and young women. Both the goals and phases of HRT are reviewed, and commonly used medication regimens are presented. Both the benefits and risks associated with various methods of HRT are also discussed, as are special issues of concern regarding adolescent HRT, including eating disorders and bone health.
The Pathophysiology of Amenorrhea in the Adolescent
Authors: Golden Neville H. , Carlson Jennifer L.
Published: June 2008

Menstrual irregularity is a common occurrence during adolescence, especially within the first 2–3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen‐deficient or estrogen‐replete. Estrogen‐deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen‐replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise‐induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.
Improving Balance in Regulatory Oversight of Research in Children and Adolescents
Authors: Rosenfield Robert L.
Published: June 2008

The current regulatory environment, designed to protect children, imposes barriers to research in children that are a deterrent to high‐quality clinical research in minors. This article summarizes the special procedures necessary to obtain approval for research in healthy children that poses more than minimal risk according to the code of federal regulations (45 CFR 46.407 and 21 CFR 50.54). The operational realities of the process are illustrated by the case of the most recent research protocol to be reviewed under these rules. The current process poses obstacles to future studies of complex research questions in children and adolescents that require unaffected controls, such as the relationship of adolescent anovulatory disorders to adult illness. It is concluded that current regulatory procedures, while protecting children, increase the potential for the neglect of important research needs of children and are a disincentive to pursuit of a career in clinical research for young clinicians. Suggestions are made for improving the balance between the need for research in children and adolescents and its regulation.
The Menstrual Cycle
Authors: Hawkins Shannon M. , Matzuk Martin M.
Published: June 2008

The basic biology of the menstrual cycle is a complex, coordinated sequence of events involving the hypothalamus, anterior pituitary, ovary, and endometrium. The menstrual cycle with all its complexities can be easily perturbed by environmental factors such as stress, extreme exercise, eating disorders, and obesity. Furthermore, genetic influences such as fragile X premutations, X chromosome abnormalities, and galactose‐1‐phosphate uridyltransferase (GALT) point mutations (galactosemia) also contribute to perturbations of the menstrual cycle. Although not perfect, mouse models have helped to identify and confirm additional components and pathways in menstrual cycle function and dysfunction in humans.
Genetic and Phenotypic Heterogeneity in Ovarian Failure
Authors: Simpson Joe Leigh
Published: June 2008

Ovarian failure is heterogeneous, both in cause and in phenotype. Women whose menses cease prior to age 40 years and have menopausal FSH levels are traditionally considered by clinicians to have the diagnosis of “premature ovarian failure” (POF). In fact, however, the ovarian function in this disorder is in reality a continuum of impairment in ovarian responsiveness. For this reason the term “primary ovarian insufficiency” (POI) has been suggested to be more accurate. It would be yet more desirable to classify this disorder on the basis of aberrant embryonic differentiation rather than the state of ovarian function. Genes that exert known hormonal effects (FSH, FSHR, LH, LHR, CYP17, CYP19) primarily affect follicle function, as do BMP15, GDF9, and GPR3. These genes mutations have occasionally been found in humans, but none are common. Still other genes expressed during oogenesis appear more likely to be characterized by lack of germ cell formation. These include DNA binding proteins and transcription factors like NOBOX and LHX8, and RNA binding proteins like NANOS. Plausible causative mutations have been identified in a few women (NOBOX, GDF9, LDX8), but even then only 1–2% of cases show a perturbation. Thus, considerable heterogeneity—phenotypic as well as etiologic—exists in ovarian failure, irrespective of whether follicles do or do not develop. Analysis of other genes is necessary, including many likely to show novel mechanisms of action.
Menstruation in Adolescents
Authors: Adams Hillard Paula J.
Published: June 2008

The conventional wisdom about menstruation in adolescents, perpetuated in textbooks, requires updating. Recently published national surveys and reviews of large historical databases provide information about menstruation in adolescents, including the following: (1) Girls are experiencing earlier pubertal development than previously noted, suggesting that guidelines for the evaluation of potentially pathologic precocious puberty be reassessed. (2) There are racial differences in pubertal development, with African American girls experiencing earlier signs than Caucasian girls, and Mexican American girls intermediate in pace. (3) The absence of pubertal development by age 14 is associated with a high probability of conditions with impaired reproductive potential. (4) Absence of menarche by age 15 is statistically uncommon and should be evaluated. (5) Parameters for normal menstrual cyclicity indicate that most menstrual cycles for adolescents are between approximately 20 and 45 days. (6) Because menstrual cycles outside of this range are statistically uncommon, consideration should be give to evaluating adolescents with bleeding that is either too frequent or too infrequent. (7) A number of conditions with the potential for significant sequelae in adulthood can present as abnormal menses in adolescence, and thus merit early diagnosis and management.
Cancer Treatment and the Ovary
Authors: Cohen Laurie E.
Published: June 2008

Certain chemotherapeutic drugs (“alkylators”) and radiation therapy are toxic to the ovaries, leading to both loss of sex steroid hormone production and infertility. Higher doses and older age at treatment are both associated with greater damage. Even patients with spontaneous menstrual cycles have evidence of decreased ovarian potential. Adolescents who are treated for cancer with these agents should be counseled about future fertility risks.
Disorders of Sexual Differentiation in the Adolescent
Authors: Lee Peter A. , Houk Christopher P.
Published: June 2008

Disorders of sexual differentiation (DSDs) presenting during adolescence are discussed, and molecular explanations are given for some. DSD conditions are often discovered during early adolescence, an age well known to predispose to high risk for adjustment problems. Presentation may be with lack of or minimal pubertal development, lack of menarche, vaginal, uterine, or breast agenesis and inappropriate sexual development such as virilization in females or feminization (gynecomastia) in males. Most such disorders require life‐long therapy, with many of the medical, surgical and psychological aspects of management being accentuated during adolescence. Regardless of the age at presentation, all require skillful management to promote normal health and well‐being. This care ideally involves specialists in endocrinology and medical therapy, psychology and, if required, surgery. A brief discussion of the needs of the adolescent with DSDs is presented.
Menstrual Cycle Dysfunction Associated with Neurologic and Psychiatric Disorders
Authors: Joffe Hadine , Hayes Frances J.
Published: June 2008

Epilepsy, bipolar disorder, and migraines are common disorders that are often associated with disturbances in menstrual function in adolescent girls. Women with untreated epilepsy are more likely to have irregular menstrual cycles than are nonepileptic controls, indicating that the disease itself plays a role in the etiology of these reproductive abnormalities. In addition, many girls with these disorders require chronic maintenance treatment with agents that may perturb the hypothalamic‐pituitary‐ovarian axis. Valproate is a highly effective antiepileptic drug used widely to treat epilepsy, bipolar disorder, and migraines. Valproate induces features of the polycystic ovary syndrome (PCOS) in approximately 7% of women. Girls with epilepsy, and possibly bipolar disorder, appear particularly susceptible to developing PCOS features on valproate, perhaps on account of the relative immaturity of their hypothalamic‐pituitary‐ovarian axes. Antipsychotics are highly effective drugs used widely to treat adolescents with bipolar disorder, psychotic disorders, and behavioral disturbances. Some, but not all of the antipsychotic, induce hyperprolactinemia, which may result in oligo‐ or amenorrhea. Prolonged amenorrhea in association with hyperprolactinemia incurs significant risks for bone health in adolescent girls. Because of the potential reproductive health risks associated with use of specific antiepileptic drugs and selective antipsychotics, these agents are vital treatments for adolescents with severe illnesses. Use of these agents should be considered and weighed against the risk of using alternative agents, which have their own side effects, or not treating these serious neurologic and psychiatric disorders.
Moving Toward an Understanding of Hormone Replacement Therapy in Adolescent Girls
Authors: Davenport Marsha L.
Published: June 2008

Turner syndrome (TS) is a relatively common disorder of phenotypic females caused by loss of all or part of the second sex chromosome. Most individuals with TS have short stature and gonadal dysgenesis and are at risk for many other medical and learning problems. In the 45,X ovary, germs cells multiply quite normally during fetal development, but there is accelerated atresia of oocytes in the second half of pregnancy that produces gonadal insufficiency by birth. In girls with other karyotypes, especially those mosaic for 45,X/46,XX, gonadal function may be normal or near‐normal. In this chapter, management goals for gonadal insufficiency in girls with TS are presented. The effects of estrogen deficiency and its replacement on three specific problems associated with TS—short stature, cardiovascular disease, and developmental differences in brain structure and function—are explored. General guidelines for estrogen replacement therapy using transdermal estrogen, the most physiologic option, are provided and future research goals are outlined.
Preservation of Menstrual Function in Adolescent and Young Females
Authors: Oktem Ozgur , Oktay Kutluk
Published: June 2008

Every year thousands of young teenagers are afflicted with different types of cancer and receive gonadotoxic chemotherapy and radiotherapy regimens, causing depletion of germ cells in the gonads and premature gonadal failure. In this review, we discuss and outline the current strategies and the future directions of fertility preservation and ovarian cryopreservation and transplantation in adolescents and young females.
From Fire in the Belly to a Boiling Heart
Authors: Hijane Karima , Heyman Carly , Bell Maureen , Busby Mary Beth
Published: June 2008

It has been said that governmental bureaucracies lack the animating life force that is normally provided by the human conscience. Research efforts that include patients and their representatives in the planning and regulatory process can add back this animating life force, a force Friedrich Wilhelm Nietzsche describes “… that your self be in your deed as the mother is in her child—let that be your word concerning virtue.” This paper comprises our invited introductory remarks as patient activists at this symposium, entitled “The Menstrual Cycle and Adolescent Health” and held in Potomac, Maryland in mid October 2007. Attendees included patients, patient advocates, and experts from a variety of fields and disciplines. While our stories have their share of pain, that pain developed into a passion to help others in similar circumstances. A consortium of passionate community activists interested in the menstrual cycle could play the role as a “governmental conscience” around this issue. Developing a community consortium initiated via partnerships between patient advocates and investigators could direct more attention and funding toward menstrual cycle research.
Reflections on Future Research in Adolescent Reproductive Health
Authors: Gordon Catherine M. , Loriaux D. Lynn , Grumbach Melvin M. , Rogol Alan D. , Nelson Lawrence M.
Published: June 2008

A group of basic scientists, clinicians, clinical investigators, psychologists, patient advocacy groups, and representatives from professional societies and governmental agencies met at the National Institutes of Health in October, 2007 with the long‐term goal of having the menstrual cycle accepted and understood as a marker of general health in adolescent girls. An equally important goal was to develop a research agenda for this area of investigation. This chapter comprises the highlights of discussions throughout that meeting, with an emphasis on ideas generated during a final session led by an internationally renowned physician–scientist, in which reports from four breakout groups were presented. The specific goal assigned to each group was to develop an agenda that would set the stage for how research should be conducted over the next 100 years, and to identify the pressing research questions that should be addressed related to the menstrual cycle and adolescent health. The four research areas represented in discussion groups included: emotional health; genetics; metabolism and reproduction; and the promotion of conduct of clinical research. Insights are also provided by five clinical investigators, including two outside experts, on topics of priority for a research agenda in the area of adolescent reproductive health, as well as how the research itself should be conducted.
Passion for Participatory Research on the Menstrual Cycle
Authors: Gordon Catherine M. , Hijane Karima , Heyman Carly , Bell Maureen Lindenhofen , Busby Mary Beth , Nelson Lawrence M.
Published: June 2008

A two‐day symposium entitled “The Menstrual Cycle and Adolescent Health” was held in Potomac, Maryland in mid October 2007. Groups sponsoring the meeting included the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), the National Institute of Child Health and Human Development, the American Society for Reproductive Medicine, the NIH Office of Research on Women's Health, the NIH Office of Rare Diseases, the U.S. Food and Drug Administration Office of Women's Health, the DHHS Office of Women's Health, and Rachel's Well, Inc. Attendees included patients, patient advocates, and experts from a variety of fields and disciplines. The effort identified areas in which there are only sparse data from which to create evidence‐based recommendations for management of menstrual problems in young adolescents. In a final session of the meeting, participants worked together to develop a manifesto regarding research on the menstrual cycle in adolescents, which is the subject of this report. The group reached two major conclusions. First, there is need for a new research model that integrates grass roots community passion for participatory research with research planning and regulatory oversight. Second, there is a need for a coordinated research effort on the menstrual cycle and its disorders in adolescents. This could initially take the form of a Study of Puberty across the Nation (SPAN), similar to the Study of Women across the Nation (SWAN) that addresses the normal menopausal process.
Galactosemia and Amenorrhea in the Adolescent
Authors: Berry Gerard T.
Published: June 2008

Hereditary galactosemia is a biochemical genetic disease due to a deficiency of galactose‐1‐phosphate uridyltransferase (GALT) enzyme activity (OMIM 606999). Acute manifestations occur in the neonatal period and are, with rare exceptions, related to lactose ingestion. They include poor feeding and growth, emesis, jaundice, liver disease, bleeding diathesis, anemia, renal tubulopathy, cataracts, encephalopathy and death from E. coli sepsis. Chronic manifestations, which also develop in prospectively treated patients, involve (a) the brain, resulting in delayed language acquisition, speech defects, and learning problems, and (b) the ovary, in the majority of females, producing hypergonadotropic hypogonadism. The serum FSH level is elevated in infancy/early childhood in many, but not all patients with a severe phenotype. There are few reports of patients with classic galactosemia having undergone pregnancy, labor, and delivery. The pathologic findings in the ovary, including a persistence of primordial follicles and streak gonads, have been variable. The etiology of primary ovarian insufficiency (POI) in galactosemia is unknown. Clinical surveillance includes screening for abnormalities in ovarian function at an early age. Treatment consists of estrogen/progesterone supplementation at the appropriate age. Reduced BMD has been reported. Future research is needed (1) to delineate the mechanisms behind reduced ovarian function in these young women; (2) to determine the timing of the lesion: prenatal, postnatal, and both pre‐ and postnatal; (3) to determine whether elevated galactose‐1‐phosphate is both necessary and sufficient to induce primary ovarian insufficiency; and (4) to understand the mechanism(s) behind the reduced BMD seen in children and adolescents with galactosemia.
Research Involving Adolescents as Subjectsa
Authors: Levine Robert J.
Published: June 2008

Research involving adolescents as subjects is much more difficult to carry out than it ought to be. The excessive burdens in the field are borne by those who design and carry out the research, and also by those who review and monitor such research to ensure compliance with regulations and other policies designed to protect the rights and welfare of research subjects. This chapter is an overview of issues that are specific to research that involves adolescents. Problems and challenges are reviewed, and potential solutions suggested. The chapter also provides suggestions for improving current regulatory policies and practices so as to reduce bureaucratic impediments.
The Menstrual Cycle
Authors: Popat Vaishali B. , Prodanov Tamara , Calis Karim A. , Nelson Lawrence M.
Published: June 2008

Menstruation is the cyclic, orderly sloughing of the uterine lining on account of the interactions of hormones produced by the hypothalamus, pituitary, and ovaries. There is a tendency among parents and clinicians to view oligo‐amenorrhea as a normal variant in the teen years. In fact, the 95th percentile for the time interval between cycles is 90 days. Thus, it is abnormal for an adolescent to be amenorrheic for greater than 3 months, even in the early gynecologic years. Identification of abnormal menstrual patterns throughout adolescence may permit early identification of potential health concerns for adulthood. Few problems in gynecologic endocrinology are as complex or challenging to the clinician as amenorrhea. However, thorough evaluation of menstrual cycle disorders in adolescence provides a window of opportunity for early diagnosis and treatment of conditions affecting the hypothalamic‐pituitary‐ovarian (HPO) axis. Here we discuss a systematic approach to the evaluation and treatment of amenorrhea in adolescents who do not have androgen excess. There is strong evidence that estrogen deficiency is a risk factor for later development of osteoporosis and hip fracture. Delay in the evaluation and treatment of disordered menses in some cases may contribute to reduced bone density. Both patients and clinicians need to view the ovary as an important endocrine organ that helps maintain health, especially bone health.
Autoxidation Resistant Cyclopentyl Methyl Ether
Authors: Hoshino Hayato , Sakakibara Kazuhisa , Watanabe Kiyoshi
Published: June 2008

The bond dissociation energy of the C–H bond at the α-position of an ether oxygen in cyclopentyl methyl ether (CPME) has been evaluated theoretically to be 393.3 kJ/mol by using an isodesmic reaction method. Essential factors accounting for this rather higher bond dissociation energy in CPME comparable to secondary C–H bond have been investigated on the basis of the structures and their thermodynamic data such as heats of formation (ΔHf°) of CPME radical and relevant ether radicals evaluated by the theoretical approach.
Hydrothermal Preparation of Biomineral Botallackite Cu2(OH)3Cl Hollow Nanoarchitectures
Authors: Chen Zhitao , Gao Lian
Published: June 2008

A novel and facile way to produce botallackite (Cu2(OH)3Cl) flower-like solid and hollow architectures with an average diameter of 400 nm is put forward, meanwhile, its probable reaction mechanism is also discussed.
An Improved Synthesis of Methyl Protodioscin: Tautomerization and Direct Access to the 3-O-Substituted Kryptogenin
Authors: Xu Qing-Chun , Liu Yang , Liu Jiao , He Chun-Xian , Yan Mao-Cai , Cheng Mao-Sheng
Published: June 2008

The acid-catalyzed tautomerization of 3-O-substituted kryptogenin 2 was studied, and the effects of acids such as silica gel, TMSOTf, acetic acid, and CDCl3, are discussed. Additionally, a Zn/KI/HOAc reduction based on this tautomerization was adopted, which afforded 2 directly, and provided a facile procedure for the synthesis of methyl protodioscin and other furostanol saponins in a mild way.
Synthesis and Properties of Cyclic [5]meta-Phenyleneacetylene and Its Corresponding Cyclophane Polyone, [25](1,3)Cyclophanedecaone
Authors: Yamakawa Jun , Ohkoshi Masanori , Takahashi Futoshi , Nishiuchi Tomohiko , Kuwatani Yoshiyuki , Nishinaga Tohru , Yoshida Masato , Iyoda Masahiko
Published: June 2008

The cyclic [5]meta-phenyleneacetylene (3) ([5]CMPA) and its corresponding cyclophane polyones 4 and 5 are synthesized. 3, a “missing link” between [4]CMPA and [6]CMPA, shows a fairly pronounced emission, indicating a rigid structure, whereas 5 is colorless in contrast to conventional diarylethane-1,2-diones owing to its conformational mobility and all-s-cis and twisted dione structure.
Single-component CT Crystals Based on 1,4-Benzoquinone Derivatives and TEMPO Radical
Authors: Nobusawa Mitsunori , Akutsu Hiroki , Yamada Jun-ichi , Nakatsuji Shin’ichi
Published: June 2008

Four kinds of TEMPO-substituted 1,4-benzoquinone derivatives were found to afford single-component CT crystals formed by the interactions between a benzoquinone ring and one or two TEMPO groups of the neighboring molecules.
On-site Determination of Trace Nickel in Liquid Samples for Semiconductor Manufacturing by Highly Sensitive Solid-phase Colorimetry with α-Furil Dioxime
Authors: Mizuguchi Hitoshi , Zhang Yan-Fan , Onodera Hirofumi , Nishizawa Saori , Shida Junichi
Published: June 2008

A new, highly sensitive colorimetry for trace NiII at the parts per billion level has been developed. The method is based on effective adsorption of the orange-colored NiII chelate with α-furil dioxime to a membrane filter. There was superior tolerance to coexistence of high concentration of salts such as sodium nitrate in the trace NiII analysis. The proposed method was successfully applied to the NaOH solutions used for the silicon wafer processing and enabled on-site NiII analysis which has been urgently needed in the semiconductor manufacturing.
Palladium-catalyzed Cross-coupling of Benzylic Carbonates with Organostannanes
Authors: Ohsumi Masato , Kuwano Ryoichi
Published: June 2008

The cross-coupling of benzylic carbonates with arylstannanes proceeded in the presence of [Pd(η3-C3H5)Cl]2–DPPPent catalyst, affording the desired diarylmethanes in good yield.
Choriocarcinoma in an AIDS patient – relapsing but not fatal
Authors: Shah Archan M , Tidswell Mark , Prefontaine Michel , Skiest Daniel J , Pantanowitz Liron
Published: June 2008

Summary

Choriocarcinoma is associated with high mortality in immunocompromised patients, in contrast to a good prognosis in immunocompetent individuals. Respiratory failure due to metatstatic choriocarcinoma is associated with high mortality in any patient. We report a case of a woman with AIDS that survived metastatic choriocarcinoma and respiratory failure. We also observed that in contrast to some in vitro studies, the markedly elevated levels of β-subunit of human chorionic gonadotropin in this patient did not have any apparent inhibitory effect on viral replication.
Comparison of cryotherapy to imiquimod 5% in the treatment of anogenital warts
Authors: Stefanaki Christina , Katzouranis Ilias , Lagogianni Eirini , Hagjivassiliou Maria , Nicolaidou Electra , Panagiotopoulos Antonios , Anyfantakis Vassilis , Bethimoutis George , Eustathios Rallis , Antoniou Christina , Katsambas Andreas
Published: June 2008

Summary

The aim of this study was to compare the efficacy of crotherapy versus imiquimod 5% in the treatment of anogenital warts. Eighty HIV-negative males were included in the analysis; 35 of them were treated with imiquimod 5% three times a week for 6–10 hours and 45 of them with cryotherapy once in three weeks. Follow-up appointments were arranged every month for the first three months and then at six and 12 months, or in between whenever the patients noticed any signs of recurrence. Treatment for both groups was continued for a total of 12 weeks or until the warts cleared. At the end of three months, irrespective of the type of treatment, 78.8% of the patients demonstrated 100% improvement. Cryotherapy was more effective, as 86.7% of patients showed 100% improvement compared with 68.6% of patients in the imiquimod group. On the contrary, 17.1% of the imiquimod group did not show any signs of improvement, compared with 2.2% of the cryotherapy group ( P = 0.017). However, patients treated with imiquimod tended to improve earlier than patients on cryotherapy ( P = 0.012). No statistically significant difference was observed regarding the recurrence rate between the two groups ( P = 0.138). Treatment with imiquimod was less painful than cryotherapy ( P = 0.034). Cryotherapy was more effective than imiquimod 5% for the treatment of anogenital warts in males but was more inconvenient.
Multiple aphthoid syphilitic chancres of the oral cavity
Authors: Veraldi S , Lunardon L , Persico M C , Francia C , Bottini S
Published: June 2008

Summary

We describe the case of a 31-year-old man who was affected by three asymptomatic, aphthoid, syphilitic chancres of the oral cavity. These lesions were accompanied by right latero-cervical and chin lymphadenopathy. The infection was previously diagnosed as aphthous stomatitis. The search for Treponema pallidum by means of darkfield microscope examination was positive. The patient was successfully treated with oral erythromycin ethylsuccinate. To our knowledge, this is the first case of multiple aphthoid syphilitic chancres of the oral cavity reported in the literature. We suggest that all patients with a recent history of painless ulcers in the oral cavity, accompanied by regional lymphadenopathy in which the clinical diagnosis has not been confirmed, should undergo a darkfield microscope examination.
Treatment of anal human papillomavirus-associated disease: a long term outcome study
Authors: Nathan M , Hickey N , Mayuranathan L , Vowler S L , Singh N
Published: June 2008

Summary

Treatment for human papillomavirus (HPV)-associated anal canal disease has been unsatisfactory. The objective of our study was to determine the treatment outcome in our cohort with anal HPV disease. Overall, 181 patients were evaluated over a median period of 19.1 months (range = 2.8–125.5). Eighty-eight patients (48.6%) with high-grade anal intraepithelial neoplasia (AIN) and 82 patients (45.3%) with low-grade AIN underwent treatment. One hundred and forty-one patients (77.9%) received laser ablative treatment as an outpatient procedure. The treatment yielded cure, defined as a disease-free state at 12 months after treatment, in 63.0% (114/181). Median time to cure for the cohort was 31.5 months (95% confidence interval: 23.0–40.0). Treatment outcome showed no evidence of being affected by age, sexual preference, history of smoking or presence of high-grade disease. Median time to cure was significantly affected by a positive HIV status ( P = 0.02) and the extent (volume) of the disease ( P = 0.01). Contrary to the current view that treatment of HPV-related anal disease is difficult, unrewarding due to recurrences and may lead to substantial morbidity, we demonstrate that effective treatment is possible for both low- and high-grade AIN. These findings should help with the general desire to introduce screening for AIN for at-risk groups.
Interaction of organic and psychological factors in persistent genital arousal disorder in women: a report of six cases
Authors: Goldmeier David , Leiblum Sandra
Published: June 2008

Summary

There have been a number of case reports published recently describing women who complain of persistent genital arousal. Most of these papers do not report medical data or observations from genital examination. We report in such detail on six cases of persistent genital arousal disorder (PGAD) in women. We further advance the hypothesis that in many cases the objective genital component may be induced by a variety of psychophysiological and pathological factors such as anxiety, genital prolapses and dermatoses. Genital engorgement so produced may not be continuous but when present may be enhanced and perpetuated by both anxiety focussed on the genitals and masturbation used in an attempt to relieve the sensations. Premorbid affective psychological illness negatively colours the subjective perception of this genital engorgement, leading to either elicitation or maintenance of PGAD. We discuss this hypothesis in relation to our six cases.
Characteristics of primary and late latent syphilis cases which were initially non-reactive with the rapid plasma reagin as the screening test
Authors: Singh Ameeta E , Wong Tom , De Prithwish
Published: June 2008

Summary

The aim of the study was to determine the characteristics of primary and late latent syphilis cases that were non-reactive on initial screening by rapid plasma reagin (RPR) but reactive by treponemal tests. RPR test results of all primary and late latent syphilis cases in the province of Alberta, Canada during 1980–2001 were compiled. The proportion of syphilis cases that were non-reactive by RPR testing was compared with reactive cases. Multiple logistic regression was used to identify factors associated with non-reactive RPR results. Among primary syphilis cases, 224 (26%) were non-reactive on initial RPR and were compared with 639 reactive primary cases. Independent factors associated with a non-reactive result were male gender (odds ratio, [OR] = 1.99 [1.22–3.26]), Caucasian ethnicity (OR = 1.77 [1.20–2.61]) and diagnosis during the 1980–1986 syphilis outbreak period in Alberta (OR = 3.13 [1.45–6.74]). Of the late latent cases, 512 (39%) were non-reactive by RPR and 791 were reactive. A non-reactive test for late latent cases was associated with male gender (OR = 2.91 [2.15–3.94]), Canadian Aboriginal (OR = 2.91 [1.59–5.32]), Caucasian (OR = 1.87 [1.35–2.58]), black ethnicity (OR = 1.76 [1.28–2.42]) and diagnosis during the 1980–1986 Alberta syphilis outbreak (OR = 1.67 [1.29–2.16]). RPR testing alone is insufficient to diagnose primary and late latent infections under certain conditions and patient characteristics. Case detection was lower for late latent syphilis when compared with primary syphilis based on the properties of the RPR. Further studies are needed to inform the optimal use of the RPR test in laboratory testing algorithms for the diagnosis of syphilis and to determine the cost effectiveness of better screening tests for syphilis.
Preventing sexually transmissible infections in Australian general practice
Authors: Khan Asaduzzaman , Plummer David , Hussain Rafat , Minichiello Victor
Published: June 2008

Summary

The aims of the present study were to explore aspects of sexually transmissible infections (STI) prevention in general practice and to examine general practitioners' (GPs) perceived barriers to sexual-health promotion. The data from a postal survey of 409 GPs practising in New South Wales, Australia (response rate 45.4%) are analysed to explore the prevention of STI in general practice and to examine practitioners' perceived barriers to sexual-health promotion. About 49% of GPs reported having STI leaflets/pamphlets for patients in their clinic, while 21% had posters on STI displayed in their waiting room. Two-third (67%) of GPs provided STI-specific printed materials/leaflets to patients with STI. Female GPs were more likely to be proactive in STI prevention. Time and funding appear to be the major barriers to sexual-health promotion, followed by inadequate access to counselling. One-fifth (22%) of GPs felt that they had little influence in changing patients' risk behaviour, while about 28% emphasized the need for further preventive care training. The present study identifies inconsistencies in STI-prevention activities in general practice along with barriers to undertake sexual-health promotion. This area warrants further attention if GPs are to contribute fully to the control of STI.
Mortality of the elderly is still exceedingly high at diagnosis of AIDS despite favourable outcomes after highly active antiretroviral therapy in Recife, Brazil
Authors: Lacerda H R , Kitner D
Published: June 2008

Summary

This study aimed to compare the outcome of an elderly group of AIDS patients with that of a younger group and their features at the time of the diagnosis of AIDS. We evaluated 58 patients aged >60 years and 114 aged 20–39 years, followed for 35.3 months. There was an obvious delay in diagnosing the elderly as they had more AIDS-defining diseases at diagnosis and their most frequent opportunistic infection was pulmonary tuberculosis. Mortality at the time of the diagnosis of AIDS was four times higher in the elderly (24.1% versus 6.1%, P < 0.001). However, when comparing only those submitted to highly active antiretroviral therapy, there was a similar frequency of favourable outcomes; 76.9% in the elderly against 83.1% in the young ( P = 0.455). Mean CD4 lymphocyte was 438 cells/mm3 at the end of follow up in the young when compared with 442 cells/mm3 in the elderly ( P = 0.945). The types of antiretroviral schema and the number of antivirals per patient were similar in both groups.
Focal Salmonella enteritidis infection in a patient with HIV infection and other multiple causes of immunodeficiency
Authors: Peppa Dimitra , Sutton Julian K , Bin-Reza Faisal , Morris-Jones Stephen D , Miller Robert F
Published: June 2008

Summary

An HIV-infected man receiving antiretroviral therapy—who also had lupus-like vasculitis and membranous glomerulonephritis (treated with prednisolone and azathioprine), beta-thalassaemia minor trait and post-radiotherapy functional asplenia (mimicking sickle cell disease-induced hyposplenism)—developed focal soft issue and bone infection caused by Salmonella enteritidis at the site of previous mycobacterial infection.
The prevalence of chlamydial infection in Estonia: a population-based survey
Authors: Uusküla A , Kals M , Denks K , Nurm ÜK , Kasesalu L , DeHovitz J , McNutt L A
Published: June 2008

Summary

The aim of this study was to estimate the prevalence of Chlamydia trachomatis infection among Estonian men and women by a cross-sectional study based on the screening of a probability sample of the residents of Tartu using participant-collected, mail-delivered testing for C. trachomatis complemented with the self-administered questionnaire. Full participation as defined by returning both the questionnaire and specimen was 34% ( n = 479; 95% confidence interval [CI] 32–37%). Study participation was 40% ( n = 560; 95% CI 37–43%) for subjects returning either or both the study questionnaire and specimen. After weighing the population distribution, the prevalence estimate for the age group of 18–35 years was 5.4% (95% CI 3.0–7.5%), 6.9% (95% CI 3.6–10.3%) among women and 2.7% (95% CI 0.3–5.0%) among men. The number of sexual partners in the past 12 months was the strongest predictor of infection.
Patient-delivered partner therapy in the UK: what do the professionals think?
Authors: Shivasankar Sivapatham , Challenor Rachel
Published: June 2008

Summary

The aim of this study was to investigate consultant genitourinary (GU) physicians' and health advisers' views regarding acceptability of patient-delivered partner therapy (PDPT) in the United Kingdom (UK). A postal questionnaire was sent to all consultant GU physicians and senior health advisers: 206 (65%) physician questionnaires and 153 (77%) health-adviser questionnaires were returned. One hundred and three (50%) physicians and 31 (22%) health advisers reported ever having used PDPT. Approximately one-third of professionals are strongly opposed to PDPT. However, the majority of both professional groups are cautiously prepared to consider PDPT, but only if there is no other option and only if a health professional first makes contact with the partner. Chief concern among health professionals is the legal status of PDPT in the UK. Here, the current General Medical Council (GMC) guidance on remote prescribing is helpful. The outcome of the Medical Research Council randomized controlled trial on accelerated partner therapy, which fits in with GMC guidance, is eagerly awaited as professionals would welcome evidence-based national guidance.