Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Consensus Development Conference Panel.
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Comorbidity↗
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Surgical considerations for invasive breast cancer.
The 1992 NIH Consensus Development Conference reported that "breast conservation treatment is an appropriate method of primary therapy for the majority of women with stage I and II breast cancer and is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast." This conclusion has been solidly confirmed by recent updates of all of the prospective clinical trials performed. The uneven utilization of this BCS indicates the personal discomfort of some surgeons in recommending it or in communicating their recommendations to patients. The appropriate candidate for mastectomy is the patient in whom it is evident that BCS will not control the tumor. This conclusion may be drawn after one or even two attempts at revision have shown more extensive microscopic disease. The experience with preoperative chemotherapy programs such as NSABP Protocol B-18 shows that even for larger tumors primary excision or excision after preoperative chemotherapy provides reasonable rates of local control with no evidence of diminished distant control or survival. Very large tumors, often accompanied by other grave signs, are best treated by primary chemotherapy, because they are essentially not stage I or stage II disease. Although recognizing that better long-term cure rates are a function of the treatment of micrometastases with adjuvant chemotherapy, surgeons should remember the need to balance cosmetic factors with techniques required for good local control. Cosmetic factors are always important, but the primary concern is adequate removal of the primary tumor with pathologically negative margins. The best way to prevent the need for a salvage mastectomy following local recurrence is to obtain adequate control at the initial procedure, but this does not mean that aggressive local surgery is needed, and it certainly does not mean that a primary mastectomy is needed except in unusual cases.
Attitude of Health Personnel↗
Diagnosis and treatment of attention deficit hyperactivity disorder (ADHD).
OBJECTIVE: The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder (ADHD). The statement provides state-of-the-art information regarding effective treatments for ADHD and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas of study that deserve further investigation. Upon completion of this educational activity, the reader should possess a clear working clinical knowledge of the state of the art regarding this topic. The target audience of clinicians for this statement includes, but is not limited to, psychiatrists, family practitioners, pediatricians, internists, neurologists psychologists, and behavioral medicine specialists. PARTICIPANTS: Participants were a non-Federal, nonadvocate, 13-member panel representing the fields of psychology, psychiatry, neurology, pediatrics, epidemiology, biostatistics, education and the public. In addition, 31 experts from these same fields presented data to the panel and a conference audience of 1215. EVIDENCE: The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: Attention deficit hyperactivity disorder or ADHD is a commonly diagnosed behavioral disorder of childhood that represents a costly major public health problem. Children with ADHD have pronounced impairments and can experience long-term adverse effects on academic performance, vocational success, and social-emotional development which have a profound impact on individuals, families, schools, and society. Despite progress in the assessment, diagnosis, and treatment of ADHD, this disorder and its treatment have remained controversial, especially the use of psychostimulants for both short and long-term treatment. Although an independent diagnostic test for ADHD does not exist, there is evidence supporting the validity of the disorder. Further research is needed on the dimensional aspects of ADHD, as well as the comorbid (coexisting) conditions present in both childhood and adult forms. Studies, (primarily short term, approximately three months) including randomized clinical trials, have established the efficacy of stimulants and psychosocial treatments for alleviating the symptoms of ADHD and associated aggressiveness and have indicated that stimulants are more effective than psychosocial therapies in treating these symptoms. Because of the lack of consistent improvement beyond the core symptoms and the paucity of long-term studies (beyond 14 months), there is a need for longer term studies with drugs and behavioral modalities and their combination. Although trials are underway, conclusive recommendations concerning treatment for the long term cannot be made presently. There are wide variations in the use of psychostimulants across communities and physicians, suggesting no consensus regarding which ADHD patients should be treated with psychostimulants. (ABSTRACT
Adult↗
Rehabilitation of persons with traumatic brain injury.
OBJECTIVE: The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Rehabilitation of Persons with Traumatic Brain Injury. The statement provides state-of-the-art information regarding effective rehabilitation measures for persons who have suffered a traumatic brain injury (TBI) and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas that deserve further investigation. Upon completion of this educational activity, the reader should possess a clear working clinical knowledge of the state of the art regarding this topic. The target audience for this statement includes, but is not limited to, pediatricians, family practitioners, internists, neurologists, physiatrists, psychologists, and behavioral medicine specialists. PARTICIPANTS: Participants were a non-Federal, nonadvocate, 16-member panel representing the fields of neuropsychology, neurology, psychiatry, behavioral medicine, family medicine, pediatrics, physical medicine and rehabilitation, speech and hearing, occupational therapy, nursing, epidemiology, biostatistics and the public. In addition, 23 experts from these same fields presented data to the panel and a conference audience of 883. EVIDENCE: The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. A compendium of evidence was prepared by the panel which included a contribution from a patient with TBI, a report from an Evidence Based Practice Center of the Agency for Health Care Policy and Research, and a report from the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: Traumatic Brain Injury (TBI) results principally from vehicular incidents, falls, acts of violence, and sports injuries, and is more than twice as likely in males as in females. The estimated incidence rate is 100 per 100,000 persons with 52,000 annual deaths. The highest incidence is among persons 15 to 24 years of age and 75 years and older, with an additional less striking peak in incidence in children ages 5 and younger. Since TBI may result in lifelong impairment of an individual's physical, cognitive, and psychosocial functioning and prevalence is estimated to be 2.5 million to 6.5 million individuals, TBI is a disorder of major public health significance. Furthermore, mild TBI is significantly under diagnosed and the likely societal burden therefore even greater. Given the large toll of TBI and absence of a cure, prevention is of paramount importance. However, the focus of this conference was the evaluation of rehabilitative measures available for the cognitive and behavioral consequences of TBI. Although studies are relatively limited, available evidence supports the use of certain cognitive and behavioral rehabilitation strategies for individuals with TBI. This research needs to be replicated in larger, more definitive clinical trials. (ABSTRACT TRUNCATED)
Adolescent↗
Osteoporosis prevention, diagnosis, and therapy.
OBJECTIVE: The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Osteoporosis Prevention, Diagnosis, and Therapy. The statement provides state-of-the-art information and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas of study that deserve further investigation. The target audience of clinicians for this statement includes, but is not limited to, family practitioners, internists, gerontologists, orthopaedic surgeons, rheumatologists, obstetricians and gynecologists, and preventive medicine specialisits. PARTICIPANTS: A nonfederal, nonadvocate, 13-member panel representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopaedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. In addition, 32 experts from these same fields presented data to the panel and a conference audience of approximately 700. EVIDENCE: The literature was searched using MEDLINE and an extensive bibliography of references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: Osteoporosis occurs in all populations and at all ages. Though more prevalent in white postmenopausal females, it often goes unrecognized in other populations. Osteoporosis is a devastating disorder with significant physical, psychosocial, and financial consequences. The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions known to be associated with secondary osteoporosis. Clinical risk factors have an important, but as yet poorly validated, role in determining who should have BMD measurement, in assessing risk of fracture, and in determining who should be treated. Adequate calcium and vitamin D intake are crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation of these two components in bioavailable forms may be necessary in individuals who do not achieve recommended intake from dietary sources. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce the risk of falls in older individuals. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary goal in the treatment of patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures. These include therapies that enhance bone mass and reduce risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for the presence of osteoporosis and given appropriate therapy.
Adolescent↗
An update from the latest workshop on asymptomatic primary hyperparathyroidism.
Considerable data have accumulated since 1990 concerning the natural history of asymptomatic primary hyperparathyroidism,the extent of target organ involvement, techniques for preoperative localization of parathyroid glands, and new surgical approaches for parathyroidectomy. Therefore a Workshop on Asymptomatic Primary Hyperparathyroidism: a Perspective for the Twenty-first Century was held in April 2002 with a goal of reevaluating the conclusions from the 1990 National Institutes of Health (NIH)Consensus Development Conference. This article presents the recommendations of the workshop panel and discusses the evidence leading to the changes in the recommendations of the 1990 NIH conference.
Bone Density↗
NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake.
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Adolescent↗
NIH consensus conference: Total hip replacement. NIH Consensus Development Panel on Total Hip Replacement.
OBJECTIVE: To provide physicians with a current consensus on total hip replacement. PARTICIPANTS: A nonfederal, nonadvocate, 13-member consensus panel representing the fields of orthopedic surgery, rehabilitation and physical medicine, biomechanics and biomaterials, internal medicine, public health, geriatrics, biostatistics, and a public representative. In addition, 27 experts in orthopedic surgery, rehabilitation and physical medicine, biomechanics and biomaterials, rheumatology, geriatrics, and epidemiology presented data to the consensus panel and a conference audience of 425. EVIDENCE: The literature was searched through MEDLINE and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS: The panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. CONSENSUS STATEMENT: The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. CONCLUSIONS: Total hip replacement is an option for nearly all patients with diseases of the hip that cause chronic discomfort and significant functional impairment. Most patients have an excellent prognosis for long-term improvement in symptoms and physical function. At this time, a cemented femoral component using modern cementing techniques, paired with a porous-coated acetabular component, can give excellent long-term results. Revision of a total hip replacement is indicated when mechanical failure occurs. Continued periodic follow-up is necessary to identify early evidence of impending failure so as to permit remedial action before a catastrophic event.
Hip Prosthesis↗
National Institutes of Health (NIH) to host a consensus development conference on screening and management for phenylketonuria (PKU).
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Consensus Development Conferences, NIH as Topic↗
Methods for voluntary weight loss and control. NIH Technology Assessment Conference Panel. Consensus Development Conference, 30 March to 1 April 1992.
One quarter to one third of Americans are overweight; as many as 40% of women and 24% of men are trying to lose weight at any given time; many have tried a variety of methods, such as diets, exercise, behavior modification, and drugs. In controlled settings, participants who remain in weight loss programs usually lose approximately 10% of their weight. However, one third to two thirds of the weight is regained within 1 year, and almost all is regained within 5 years. For many overweight persons, achieving and maintaining a healthy weight is a lifelong challenge. Successful weight loss improves several cardiovascular risk factors and diabetic control; effects on mortality are not clear. Several epidemiologic studies have found that weight loss is associated with increased mortality but the reasons for weight loss were not known. Survey data also confirm that many Americans who are not overweight, particularly young women, are trying to lose weight, which may have adverse physical and psychological consequences. Because of the importance of these issues, research on weight and on weight loss and control should assume a high priority on the nation's health agenda.
Appetite Depressants↗
Adjuvant therapy for breast cancer: practice patterns of community physicians.
PURPOSE: We evaluated the use of adjuvant therapy for breast cancer using the National Institutes of Health (NIH) Consensus Development Conference statements as guideposts for assessing how rapidly community physicians adopt recommended therapies. PATIENTS AND METHODS: Women with stage I through IIIA breast cancer diagnosed in 1987 through 1991 and in 1995 were randomly sampled from the population-based National Cancer Institute Surveillance, Epidemiology, and End-Results program. A total of 8,106 women were included in the study with younger women, < or = 50 years, being oversampled. Their treating physicians were asked to verify whether chemotherapy, hormonal therapy, or both were given. RESULTS: After adjusting for clinical and nonclinical factors, the use of 1985 recommendations for adjuvant therapy in women with node-positive disease was already high at 80% in 1987 and increased slightly to 84% by 1995. Use of combined multidrug chemotherapy plus tamoxifen increased. In contrast, the use of 1990 recommendations for adjuvant therapy for node-negative disease was slightly less than 13% in 1987 and increased markedly to 57% by 1995. For women with node-negative tumors > or = 1 cm in size diagnosed in 1995, 40% received tamoxifen, 16% combination chemotherapy, and 7% both, an increase from 10%, 5%, and 0.4%, respectively, in 1987. CONCLUSION: Community physicians began prescribing adjuvant chemotherapy and hormonal therapy in advance of publication of the NIH consensus statement in 1990. Adoption of recommended treatments for node-negative disease has been less complete compared with node-positive tumors, perhaps reflecting the more complex nature of the clinical trials data or the smaller anticipated benefit from adjuvant therapy for this disease subset.
Aged↗
Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: a national survey of endocrine surgeons.
A 1991 NIH Consensus Development Conference statement provided recommendations for the management of patients with asymptomatic and minimally symptomatic primary hyperparathyroidism (primary HPT), but adherence to these guidelines has not been documented. We conducted a cross-sectional survey of North American members of the American Association of Endocrine Surgeons inquiring about surgeon and primary HPT patient characteristics, thresholds for surgery, and clinical outcomes. Multivariate regression was used to assess the relationship of physician characteristics to practice patterns and outcomes. Of 190 surgeons surveyed, 147 (77%) responded; 109 provided complete responses (57%). These surgeons spend 66% of their time in patient care and perform an average of 33 (range, 1-130) parathyroidectomies/yr. More than 72% of primary HPT patients who underwent surgery were asymptomatic or minimally symptomatic. High volume surgeons (>50 cases/yr) had significantly lower thresholds for surgery with respect to abnormalities in preoperative creatinine clearance, bone densitometry changes, and levels of intact PTH and urinary calcium compared to their low volume colleagues (1-15 cases/yr). Overall reported surgical cure rates were 95.2% after primary operation and 82.7% after reoperation. Compared to high volume surgeons, low volume endocrine surgeons had significantly higher complication rates after primary operation (1.9% vs. 1.0% respectively; P < 0.01) and reoperation (3.8% vs. 1.5%; P < 0.001) as well as higher in-hospital mortality rates (1.0% vs. 0.04%; P < 0.05). Endocrine surgeons operate on a large number of asymptomatic or minimally symptomatic primary HPT patients. Even among a group of highly experienced surgeons who typically see patients after referral from endocrinologists, clinical outcomes and criteria for surgery vary widely and appear to be associated with surgeon experience. Their criteria for surgery diverge from NIH guidelines. These results implore the endocrine community to examine the evidential basis for decisions made in the management of primary HPT.
Female↗
The Roles and Controversies of Radiation Therapy in Breast Conserving Therapy for Breast Cancer.
Breast conserving therapy (BCT) is defined as a combination of conservative surgery for resection of the primary tumor, followed by radiation therapy (RT) for the eradication of residual microscopic disease in the breast. At NIH Consensus Development Conference in 1990, BCT was recognized as the preferred treatment for the majority of women with Stage I and II breast cancer. RT is a potent locoregional treament and its role in BCT in reducing local recurrence is already established. On the other hand, the influence of RT on survival outcome has not yet been closely demonstrated so far. RT appears to be useful as neoadjuvant therapy, and also as exclusive local treatment for patients achieving complete regression (CR) after neoadjuvant chemotherapy. The other possible role of RT is to use it as an alternative to axillary dissection in patients with clinically uninvolved nodes. The question of the appropriateness of using RT in all BCT cases is raised. Since the subgroup of patients who would not deserve any benefit by RT has not yet identified, RT should be delivered as standard treatment following breast conserving surgery for early stage breast cancer.
Journal Article↗
Rationale for treatment.
Based on substantial evidence, the 1984 NIH Consensus Development Conference concluded that the treatment of total and low-density lipoprotein (LDL) cholesterol elevations with diet and, when necessary, with drugs, can reduce the risk of coronary artery disease (CAD). Accordingly, in 1988 the National Cholesterol Education Program (NCEP) published guidelines for defining moderate-, borderline-high-, and high-risk categories for CAD. Many clinical trials have supported the benefits of antihyperlipidemic therapy. Evidence from the Coronary Primary Prevention Trial gave rise to the "2:1 ratio," i.e., that a 1% reduction in total cholesterol level is associated with a 2% decrease in CAD events. The Helsinki Heart Study results indicated that additional benefit may be obtained by raising high-density lipoprotein (HDL)-cholesterol levels. Dramatic reductions in LDL and total cholesterol were achieved by the Program on the Surgical Control of the Hyperlipidemias, which also achieved a 35% reduction in CAD events and a two-thirds reduction in both coronary bypass operations and angioplasties. Long-term benefits of cholesterol lowering in terms of cardiovascular and all-cause mortality have been shown in the Coronary Drug Project and the Multiple Risk Factor Intervention Trial. Two major studies that have documented angiographic changes as a result of cholesterol lowering are the Cholesterol-Lowering Atherosclerosis Study (CLAS) and the Familial Atherosclerosis Treatment Study (FATS). In both CLAS and FATS, there was a decrease in the development of new lesions and a lowering of the rate of progression of existing lesions. In FATS, there was also evidence that aggressive antihyperlipidemic therapy will decrease existing lesions in some CAD patients.
Cholesterol↗
Cardiovascular risk status and oral contraceptive use: United States, 1976-1980.
Data from the second National Health and Nutrition Examination Survey, conducted in 1976-1980, were analyzed for the prevalence of cardiovascular risk factors (cigarette smoking, serum cholesterol, and blood pressure) among 2,342 premenopausal women ages 20-44 years, stratified by oral contraceptive use. For oral contraceptive users and non-users, adjusted means were serum cholesterol, 205 vs 188 mg/dl (P less than 0.05); systolic blood pressure, 116 vs 113 mm Hg (P less than 0.01); and diastolic blood pressure, 74 vs 73 mm Hg (NS). The prevalence of cigarette smoking was significantly higher among oral contraceptive users (44% compared with 36% among nonusers; P less than 0.05). Using the 1984 NIH Consensus Development Conference Statement on Lowering Blood Cholesterol to define risk levels for serum cholesterol, 23% of the oral contraceptive users were at high risk compared with 12% of the nonusers, and 16% of the oral contraceptive users vs 11% of the nonusers were at moderate risk. For users and nonusers, the respective prevalence of a blood pressure at or above 140/90 mm Hg was 5.3% vs 8.8% (unadjusted) and 8.6% vs 8.0% (age adjusted). The percentage of women with multiple risk factors was also higher among oral contraceptive user; 14% of the users had two or more risk factors vs 7% of the nonusers (P less than 0.05). These cross-sectional national data support data from clinical studies regarding the effect of oral contraceptives on cholesterol and blood pressure levels. In addition, since the use of oral contraceptives is widespread in the population and users tend to see physicians more regularly than other women, the data suggest that users of the pill are a good target group among which to screen and monitor cardiovascular risk factors.
Adult↗
Helicobacter pylori in duodenal and gastric ulcer disease.
The decision to treat a patient should in general always be based on potential risk and advantage. Widespread and uncontrolled use of all kinds of anti-H. pylori regimens may promote development of antimicrobial resistant strains. In particular, antimicrobial monotherapy is associated with failure to eradicate H. pylori and induction of resistant strains. Polychemotherapy is much more effective and has a lower risk for development of antimicrobial resistant H. pylori strains but carries the risk of significant drug-related side effects. If the prescribed anti-H. pylori regimen is not effective in at least 80%, or if the patient is not compliant, this type of therapy should not be considered. Also if reinfection is to be expected, the risk may outweigh potential benefits (Graham, 1993). Guidelines published in 1990 by an international working party during the World Congress of Gastroenterology recommended H. pylori eradication only in patients where duodenal ulcer was a serious management problem requiring lifelong maintenance therapy, and in whom complications (bleeding, perforation) had occurred or surgery was considered (Tytgat et al, 1990). Recently less stringent guidelines were recommended. A National Institutes of Health (NIH) Consensus Development Conference has recommended that all patients with gastric or duodenal ulcer who are H. pylori infected should be treated with antimicrobials including patients presenting with an ulcer for the first time. In addition, patients on maintenance antisecretory medication should also be contacted and treated for H. pylori infection (Anonymous, 1994). The ulcer relapse rate during prolonged follow-up after H. pylori eradication is very low. Despite this, it is advised that antisecretory medication is continued after successful H. pylori eradication in patients with previous ulcer complications. In all other patients maintenance antisecretory medication can be stopped after successful eradication. It is not known whether H. pylori eradication lowers the risk of NSAID-induced ulceration or whether the risk of ulcer complications is reduced.
Anti-Inflammatory Agents, Non-Steroidal↗
Surgical anatomy of hepatic transplantation.
Hepatic transplantation was pioneered by the work of Starzl and colleagues, first at the University of Colorado and later at the University of Pittsburgh. With the meeting of the National Institutes of Health (NIH) Consensus Development Conference in June of 1983, and their conclusion that liver transplantation was no longer experimental, orthotopic liver transplantation entered the "modern era." The release of cyclosporine by the US Food and Drug Administration (FDA) to transplant centers around the country, at the end of 1983, allowed for significant expansion of hepatic transplantation programs. Hepatic transplantation remains, however, the most difficult and complex of all solid organ transplants. A thorough grounding in the anatomic variations of hepatic segmental, arterial, venous, and ductal anatomy is only the first step in the successful completion of this challenging procedure.
Bile Ducts↗
Dopamine genes and ADHD.
Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.
Alleles↗