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PubMed2003

Rapid emergence does not explain agitation following sevoflurane anaesthesia in infants and children: a comparison with propofol.

BACKGROUND: Emergence agitation in children is frequently associated with the use of the new highly insoluble volatile anaesthetics. Rapid emergence has been cited as one of the possible causes. Propofol also permits rapid emergence from general anaesthesia but is not associated with agitation. METHODS: The emergence characteristics of children receiving sevoflurane and propofol anaesthesia were examined. After induction with sevoflurane, 53 children, aged 2-36 months, who were undergoing ambulatory surgery, were randomized to receive maintenance anaesthesia with either sevoflurane or propofol. Introperative analgesia with either 2 micro g x kg-1 of intravenous fentanyl or a caudal block with 0.25% bupivacaine was supplied according to surgical procedure. An observer blinded to anaesthetic technique recorded the time to achieve extubation and recovery and assessed emergence behaviour. Data were analysed using Wilcoxon scores, Kruskal-Wallis test, chi-square and multiple regression analysis. RESULTS: The results showed that the time to extubation and recovery were similar between the two study groups, but that emergence agitation was significantly higher in the sevoflurane group compared with the propofol group. No relationship between analgesic technique and agitation scores was found. CONCLUSIONS: Although both sevoflurane and propofol allow for rapid emergence from general anaesthesia, only sevoflurane is associated with a high incidence of emergence agitation in infants and young children. Rapid emergence does not fully explain this phenomena.

Anesthesia Recovery Period↗

PubMed2003

Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation.

Spontaneous healing with no or only very mild ichthyosis distinguishes the "self-healing collodion baby" from other congenital ichthyoses. In two self-healing collodion baby siblings with markedly diminished epidermal transglutaminase 1 activity we found the compound heterozygous transglutaminase 1 mutations G278R and D490G. Molecular modeling and biochemical assays of mutant proteins under elevated hydrostatic pressure suggest significantly reduced activity in G278R and a chelation of water molecules in D490G that locks the mutated enzyme in an inactive trans conformation in utero. After birth these water molecules are removed and the enzyme is predicted to isomerize back to a partially active cis form, explaining the dramatic improvement of this skin condition.

Child, Preschool↗

PubMedDate not supplied

Explaining counter-intuitive clinical outcomes predicted by Kt/V.

Population-based studies of maintenance hemodialysis patients have demonstrated a reproducible relationship between the dose of hemodialysis and mortality and morbidity outcomes. In these analyses, which have aggregated hemodialysis patient subgroups, improved outcomes are associated with greater doses of hemodialysis. However, remarkable counterintuitive findings are observed if patients are analyzed by subgroups based on their race, gender, and anthropometric and blood-based biomarkers of nutritional state. For example, blacks generally receive lower doses of hemodialysis than whites, but enjoy relatively improved survival; patients who receive the highest doses of hemodialysis have an increased death risk; and the dose response curve between hemodialysis and survival is altered based on the patients' body mass index. These seemingly paradoxical relationships between hemodialysis dose and patient survival can be explained because of the use of mathematical urea kinetic constructs as clinical outcome predictors; they integrate a measure of solute removal (K x t) with an anthropometric surrogate of nutrition, the urea distribution volume (V). Both these measures have an independent influence on patient survival and in some clinical circumstances are of unequal power as clinical outcome predictors. These complex interactions must be kept in perspective as clinical care is delivered in the context of hemodialysis dose.

Humans↗

PubMed2002

Explaining adherence to supplemental oxygen therapy: the patient's perspective.

OBJECTIVES: To describe and explain the patterns of adherence to supplemental oxygen in individuals with hypoxemic chronic obstructive pulmonary disease (COPD). DESIGN: Qualitative study of a case-series of patients with COPD who use supplemental oxygen. SETTING: Denver, Colorado. PARTICIPANTS: Community-dwelling, English speaking individuals with hypoxemic COPD receiving long-term supplemental oxygen therapy. MEASUREMENTS: Forced expiratory lung volume, in liters at one second (FEV1), the St. George's Respiratory Questionnaire, Brief Symptom Inventory, semistructured investigator-administered interviews. RESULTS: Respondents from a demographically representative sample with moderate to severe COPD (average age, 69; average FEV1, 1.1) described 3 distinct patterns of adherence to supplemental oxygen therapy: as-needed use, part-time use, and full-time use. For many individuals, the pattern of adherence changed with time and reflected their struggle to optimally manage their health, symptoms, physical function, and social milieu. Adherence to oxygen tended to increase with time and was often associated with significant personal compromises. CONCLUSION: Adhering to oxygen therapy is a complex and difficult task with many barriers, including the physical difficulty of using the oxygen, self-consciousness and a sense of social stigma, lack of perceived benefit, and fear of deleterious side effects from treatment. Improving adherence may involve understanding the process of adapting to oxygen use and addressing the many barriers to therapy.

Aged↗

PubMed2002

Do structural properties explain the anticonvulsant activity of valproate metabolites? A QSAR analysis.

PURPOSE: Differences in potency among valproate (VPA) metabolites could be explained by structural properties. Therefore, a quantitative structure-activity relation (QSAR) analysis was performed to study the relation between structural parameters and the effect of the following VPA metabolites: 4-en-VPA, 2-en-VPA, 3-en-VPA, 2,4'-dien-VPA, 4,4'-dien-VPA, 4-hydroxy-VPA, 3-ceto-VPA, 3-hydroxy-VPA, 5-hydroxy-VPA, and propylglutaric acid. METHODS: By using the CAChe program package for biomolecules (Oxford Molecular, Ltd), we performed molecular modeling. The anticonvulsant activity determined on the threshold for maximal electroconvulsions in mice was obtained from a study of Löscher and Nau. Structural parameters were compared between metabolites with a double bond and metabolites with oxygen at either side chain (unpaired Student's t test). A single linear regression analysis between each structural parameter and the relative anticonvulsant potency was also performed. RESULTS: Similar parameters were found between the cis and trans and R and S isomers. Biologic activity and most of the structural parameters were significantly different between metabolites with a double bond and metabolites with oxygen at either side chain. Activity was directly related to log P(oct) (r(2) = 0.77) and to reactivity parameters and was inversely related to stability parameters and to molecular weight and surface. The most potent metabolites had a log P(oct) value of higher than 2 units. CONCLUSIONS: Similar data were identified between cis and trans, and R and S isomers of VPA metabolites. Anticonvulsant activity was mainly related to log P(oct), probably reflecting the ability of VPA metabolites to cross the blood-brain barrier.

Animals↗

PubMed2002

Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels.

OBJECTIVES: To test whether accelerated sarcopenia in older persons with high interleukin (IL)-6 serum levels plays a role in the prospective association between inflammation and disability found in many studies. DESIGN: Cohort study of older women with moderate to severe disability. PARTICIPANTS: Six hundred twenty older women from the Women's Health and Aging Study in whom information on baseline IL-6 serum level was available. MEASUREMENTS: Self-report of functional status, objective measures of walking performance, and knee extensor strength were assessed at baseline and over six semiannual follow-up visits. Potential confounders were baseline age, race, body mass index, smoking, depression, and medical conditions. RESULTS: At baseline, women with high IL-6 were more often disabled and had lower walking speed. After adjusting for confounders, women in the highest IL-6 tertile (IL-6>3.10 pg/mL) were at higher risk of developing incident mobility disability (risk ratio (RR) = 1.50, 95% confidence interval (CI) = 1.01-2.27), disability in activities of daily living (RR = 1.41, 95% CI = 1.01-1.98), and severe limitation in walking (RR = 1.61, 95% CI = 1.09-2.38) and experienced steeper declines in walking speed (P <.001) than women in the lowest IL-6 tertile (IL-6 < or =1.78 pg/mL). Decline in knee extensor strength was also steeper, but differences across IL-6 tertiles were not significant. After adjusting for change over time in knee extensor strength, the association between high IL-6 and accelerated decline of physical function was no longer statistically significant. CONCLUSIONS: Older women with high IL-6 serum levels have a higher risk of developing physical disability and experience a steeper decline in walking ability than those with lower levels, which are partially explained by a parallel decline in muscle strength.

Activities of Daily Living↗

PubMed1997

Lower antigen site density and weak D immunogenicity cannot be explained by structural genomic abnormalities or regulatory defects of the RHD gene.

BACKGROUND: The weak D phenotype is characterized serologically by a weak or negative agglutination reaction with polyclonal anti-D in an immediate-spin test. Agglutination is enhanced in the indirect antiglobulin test. Red cells that are typed weak D have a much lower number of apparently complete D antigens at their cell surface and are associated with considerably weaker immunogenicity than are red cells with normal D. In a previous study, the number of D sites per cell was determined in eight unrelated weak D individuals to range from 490 to 1870 D sites per cell, which corresponded to 4 to 14.2 percent of the number of D sites in CcDee samples. STUDY DESIGN AND METHODS: The RHD gene was investigated for structural abnormalities by Southern blot experiments and polymerase chain reaction-based RHD typing in these individuals. In addition, abnormalities in the transcription process were studied by sequence analysis of RH transcripts and by comparing the relative amounts of RHD mRNA in weak D to those in CcDee, CcDEe, and -D- samples by using a semiquantitative reverse transcriptase-polymerase chain reaction analysis. RESULTS: The RHD gene in weak D phenotypes does not show any abnormalities at either the genomic or the transcriptional level when compared to the RHD gene in normal D phenotypes. CONCLUSION: The weaker immunogenicity of weak D is not explained by structural difference in the RHD gene itself. The weaker expression of D might be caused by factors involved in the Rh-related complex or by an as yet unidentified suppressor gene. This study supports the concept that weak D phenotypes carry complete D polypeptides and reflect a quantitative rather than a qualitative variation of D.

Antibodies, Monoclonal↗

PubMedDate not supplied

The ability of the stress process model to explain mental health outcomes.

No theory adequately explicates the relationships between stress, social support, and health. The recently developed Stress Process Model incorporates multiple levels of support and stress at the individual, family, and community level, with a focus on predicting mental health outcomes. The purpose of this study was to use an existing database to assess the predictive value of the Stress Process Model in explaining mental health outcomes in community-dwelling subjects with and without panic attacks. This study is a secondary analysis using data obtained in 1990 through 1991 for the Panic Attack Care-Seeking Threshold (PACT) study. Subjects who agreed to participate completed an in-depth interview concerning demographic features, panic characteristics, chronic medical problems, family characteristics, illness attitudes and behaviors, coping strategies, symptom perceptions, psychiatric morbidity, health care utilization, and functional status. The utility of the Stress Process Model is supported by three lines of reasoning. First, most of the relationships predicted by the model were documented in this study. Second, the model accounted for significant amounts of variance in moderating factors, primary and secondary stressors, and mental health outcomes. Finally, two of the three hypotheses were supported by this study. The integration of family and neighborhood variables into the stress process should be attractive to mental health workers in primary care and community settings.

Adaptation, Psychological↗

PubMed2002

Ethnic survival differences after gastrectomy for gastric cancer are better explained by factors specific for disease location and individual patient comorbidity.

INTRODUCTION: Different outcomes after resection of gastric cancer between various ethnic patient groups have been described. It remains unclear whether disparity of treatment forms, disease-related variables, or individual patients accounts for this effect. METHODS: In the 10 years between 1989 and 1999, 75 patients with gastric adenocarcinoma underwent gastrectomy at a single institution, with constant surgical standards during this time period, including complete (R0) resection attempt and extended lymphadenectomy. Ethnicity, disease characteristics, and treatment variables were analysed for their impact on survival. RESULTS: There were 40 males and 35 females, with a median age of 67 years (range 31-97). The gastrectomy extent was total (n=25), proximal (n=18), subtotal (n=17), distal (n=14), and segmental (n=1). The mean lymph-node count was 25+/-17 (SD). There was one post-operative death, and an overall complication rate of 27%; the median hospital stay was 11 days. Overall actuarial 5-year survival was 33% (95% CI: 19-47); potentially curable disease (stage 1A-IIIB) led to a median survival of 49 months. Asian (n=18) and Hispanic patients (n=20) had significantly better survival than Caucasian (n=31) or other patients (n=6) (P=0.01). Ethnicity was linked to the location of the primary tumour ( P=0.002), the gastrectomy extent (P=0.003), and the patient's prior abdominal operation (P=0.01) or tobacco history (P=0.03), but not to resection extent parameters (such as number of lymph nodes retrieved) or differences in pathologic characteristics. When controlling for differences of disease site, stage, R status, and patient comorbidity, ethnicity did not retain an independent prognostic impact on survival. CONCLUSIONS: Obvious survival differences after gastrectomy for gastric adenocarcinoma favouring Asian and Hispanic patients in this experience can be explained by different disease patterns (distal location), the related need for fewer extensive procedures (such as total gastrectomy), and diminished patient risks (tobacco, prior operations, non-cancer deaths). Our therapeutic approach remains an aggressive gastrectomy/lymphadenectomy combination for potentially curable gastric cancer, irrespective of ethnic patient factors.

Actuarial Analysis↗

PubMed1999

Acoustically stimulated transient power scattering explains enhanced detection of the very low velocities in myocardial capillaries by power Doppler imaging: an in vitro study.

BACKGROUND: Although enhanced detection of myocardial perfusion signals by power Doppler imaging during contrast echocardiography has been noted, flow velocities in the coronary microvasculature should generally be below the threshold for Doppler motion detection. It has been suggested that in this situation nonlinear scattering related to acoustically stimulated microsphere oscillation or destruction may be responsible for the detected Doppler shift. METHODS AND RESULTS: This study examined the behavior of MRX 115 (ImaRx Pharmaceuticals) microbubbles during harmonic and nonharmonic power Doppler imaging at varying power outputs (mechanical indexes 0. 3, 0.5, 0.7, and 0.9) in a perfusion tube model under zero-flow conditions. Boluses of MRX 115 0.5-mL suspension were introduced into the model, and flow was halted during each imaging period. Once power Doppler imaging was implemented, a signal was detected as unique sparkling color pixels corresponding to individual bubble destruction events, even in the absence of contrast movement. This phenomenon continued until all contrast bubbles disappeared from the region subjected to power Doppler imaging, usually within 35 to 40 seconds. Off-line videointensity measurements showed that initial power Doppler signal intensity and maximum signal decay rates increased parallel to increasing power output and were substantially greater for nonharmonic than for harmonic imaging modes. CONCLUSION: This relationship between signal intensity and decay rate and acoustic power output suggests that transient scattering related to bubble destruction is responsible for generation of the power Doppler signal in the absence of flow. This would explain the enhanced detection of the very low velocity flows in the myocardial capillaries by power Doppler contrast imaging.

Blood Flow Velocity↗

PubMed2001

Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study.

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.

Adult↗

PubMed2002

Down-regulation of intestinal-type alkaline phosphatase in the tumor vasculature and stroma provides a strong basis for explaining amifostine selectivity.

Strong clinical and experimental evidence indicates that amifostine confers cytoprotection in normal, but not in tumor, tissues. However, the mechanism of such selective action is poorly understood. Intestinal-type alkaline phosphatase (IAP) is a major isoenzyme involved in the hydrolysis of amifostine (WR-2721) to its active thiol form WR-I065. Could differences in IAP expression between normal and malignant tissues account for amifostine's selectivity? Paraffin-embedded material from normal breast, lung, colon, and head and neck tissues, together with their malignant counterparts, were retrieved and stained immunohistochemically for human IAP (antibody 7324, Abcam, Cambridge, UK) and endothelial cell CD31 antigen. Normal tissues (epithelium, fibroblasts, and vessels) consistently displayed strong nuclear and cytoplasmic IAP reactivity. The vascular density (number of positive vessels per x 200 optical field), whether assessed in anti-IAP or anti-CD31 stained sections, was very similar, indicating a strong IAP content for the entire normal vasculature. Therefore, amifostine hydrolysis is ensured in normal tissues and may occur at both vascular and interstitial levels. By contrast, 60% of the tumors analyzed showed a loss of IAP expression in both epithelial cells and stroma, and only 10% to 15% of them demonstrated nuclear/cytoplasmic reactivity, which was confined to the epithelial cells. Similarly, the percentage of tumor vessels exhibiting some IAP reactivity was very low (6% to 17%). This dramatic loss of IAP expression from tumor stroma/vasculature may form a strong basis for explaining amifostine selectivity. In contrast, the abundance of IAP expression in normal tissues, stromal and vascular, ensures an intense hydrolysis of WR-2721 and rapid intracellular accumulation of WR-1065.

Alkaline Phosphatase↗

PubMed2000

Can the pentitol-hexitol theory explain the clinical observations made with xylitol?

The natural dietary carbohydrate xylitol has been used as a source of energy in infusion therapy and found to act curatively in certain clinical situations. Xylitol has also been used as a sweetener in the diabetic diet and as a non- or anticariogenic agent. Xylitol is a sugar alcohol (polyhydric alcohol) of the pentitol type. The various advantageous clinical effects associated with enteral and parenteral administration of xylitol can be considered to result from the five-carbon (pentitol) nature of the molecule and from the molecule's special configuration even when compared with other pentitols. Such effects may be regarded as simple consequences of evolutionary expediency in a situation where human nutrition and man's significant energy-yielding metabolic pathways are associated with the six-carbon nature of D-glucose and the close derivatives and polymers of D-glucose and related sugars, and the physiologic involvement of the five-carbon xylitol in several ancillary pathways. Consequently, most clinical effects occasioned by xylitol cannot be expected to be caused by six-carbon hexitols such as D-mannitol and D-glucitol. A simple pentitol-hexitol theory seems to explain most of the clinical effects associated with the administration of xylitol. This theory is in congruence with the general evolutionary development in which the metabolism of C(6)-based carbohydrates is often inhibited by C(5)-based ones (as manifested in certain bacterial infections in man), or where the presence of the C(5)-based xylitol forwards therapeutically significant metabolic pathways (as observed in parenteral nutrition and treatment of certain enzyme deficiencies). The validity of the theory can be verified in controlled clinical trials.

AMP Deaminase↗

PubMed2000

A theoretical model based upon mast cells and histamine to explain the recently proclaimed sensitivity to electric and/or magnetic fields in humans.

The relationship between exposure to electromagnetic fields (EMFs) and human health is more and more in focus. This is mainly because of the rapid increasing use of such EMFs within our modern society. Exposure to EMFs has been linked to different cancer forms, e.g. leukemia, brain tumors, neurological diseases, such as Alzheimer's disease, asthma and allergy, and recently to the phenomena of 'electrosupersensitivity' and 'screen dermatitis'. There is an increasing number of reports about cutaneous problems as well as symptoms from internal organs, such as the heart, in people exposed to video display terminals (VDTs). These people suffer from subjective and objective skin and mucosa-related symptoms, such as itch, heat sensation, pain, erythema, papules and pustules. In severe cases, people can not, for instance, use VDTs or artificial light at all, or be close to mobile telephones. Mast cells (MCs), when activated, release a spectrum of mediators, among them histamine, which is involved in a variety of biological effects with clinical relevance, e.g. allergic hypersensitivity, itch, edema, local erythema and many types of dermatoses. From the results of recent studies, it is clear that EMFs affect the MC, and also the dendritic cell, population and may degranulate these cells. The release of inflammatory substances, such as histamine, from MCs in the skin results in a local erythema, edema and sensation of itch and pain, and the release of somatostatin from the dendritic cells may give rise to subjective sensations of on-going inflammation and sensitivity to ordinary light. These are, as mentioned, the common symptoms reported from patients suffering from 'electrosupersensitivity'/'screen dermatitis'. MCs are also present in the heart tissue and their localization is of particular relevance to their function. Data from studies made on interactions of EMFs with the cardiac function have demonstrated that highly interesting changes are present in the heart after exposure to EMFs. One could speculate that the cardiac MCs are responsible for these changes due to degranulation after exposure to EMFs. However, it is still not known how, and through which mechanisms, all these different cells are affected by EMFs. In this article, we present a theoretical model, based upon observations on EMFs and their cellular effects, to explain the proclaimed sensitivity to electric and/or magnetic fields in humans.

Electromagnetic Fields↗

PubMed2000

Explaining the variety of human sexuality.

In this paper, the author formulates a theory to explain why human sexual orientation seems to run amok. The 'psychic instrument', as he terms it, is the baby's dreaming mind which interprets or misinterprets input from its sociocultural sexual environment. The baby, already born an omnisexual being, then develops a fantasy life with socially sanctioned or unsanctioned fetishes which are likely to be expressed when certain triggering situations arise.

Adult↗

PubMed2000

Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology?

Pre-clinical and clinical studies have shown that the extract of the leaves of Ginkgo biloba has modest therapeutic potential as a cognitive enhancing drug. The pharmacology of Ginkgo biloba is complex due to its multiple active constituents. While Ginkgo biloba's cognitive enhancing effects have been attributed to its platelet-activating factor antagonistic effects and its free-radical scavenger activity, recent evidence suggests it may have direct effects on the cholinergic system which might explain both its acute and chronic cognitive enhancing effects. Ginkgo biloba's direct cholinergic actions include reduction of scopolamine-induced amnesia, modulation of pre-synaptic choline uptake and acetylcholine release, upregulation of post-synaptic muscarnic receptors and indirect effects on cholinergic function by modulation of the serotonergic system. The overall pharmacodynamic effect of Ginkgo biloba is likely due to a combination of platelet activating factor antagonistic effects, free radical scavenging activity and modulation of cholinergic function.

Acetylcholine↗

PubMed2001

A biochemical theory to explain the cause of bovine spongiform encephalopathy and other encephalopathies.

The purpose of this study is to present a hypothesis to explain the aetiology of bovine spongiform encephalopathy (BSE) which is more credible than any at present available, and to increase its credibility by varying the hypothesis to supply explanations for Alzheimer's disease, Parkinson's disease and certain other conditions. The method used has been to utilize material from biochemical textbooks and similar sources. It has been concluded that BSE is caused by the failure to synthesize sufficient cyclic guanosine monophosphate (cGMP), with the result that neurons die because they are no longer able to prevent the entry of toxic quantities of calcium ions into their cytoplasm. Several causes for the failure to synthesize sufficient cGMP have been identified; these involve selenium and folate deficiencies, and problems with the availability of nicotinamide adenosine dinucleotide (NAD). It is proposed that BSE is initiated by a combination of selenium deficiency and the destruction of NAD by a bacterial toxin of the same type as causes cholera, that folate deficiency is the predominant cause of Alzheimer's disease, and that the failure to synthesize sufficient tetrahydrobiopterin and cGMP from guanosine triphosphate results in Parkinson's disease.

Animals↗

PubMed2001

Nodular goiter and goiter nodules: Where iodine deficiency falls short of explaining the facts.

While the concept of iodine deficiency (ID) still dominates most discussions about the pathogenesis of multinodular goiter (MNG), the present review focuses on those mechanisms that may cause MNG in the absence of ID. Among the many facets of MNG that cannot simply be explained by ID, are the frequent occurrence of the disease in patients not exposed to ID, the autonomous growth of goiters - often accompanied by subclinical or even overt thyrotoxicosis -, the inverse relationship between goiter size and serum TSH, the multifocal, heterogeneous and nodular growth pattern, the heterogeneity of function with the familiar patchy iodine metabolism on scintiscans, the growth of clonal and polyclonal nodules, the prominent genetic predisposition. Even the notoriously low intrathyroidal iodine concentration - common to endemic as well as to sporadic goiter - is a secondary, rather than a primary event. Thus, the fundamental process of goitrogenesis, is independent from ID but operates through mechanisms innate to the hereditary and acquired heterogeneity among the thyrocytes themselves. In this view, goiter nodules and nodular goiters are true benign neoplasias arising by mechanisms common to all benign endocrine and nonendocrine neoplasms. However, superimposed iodine shortage greatly enhances the incidence of MNG and shifts its clinical appearance toward younger ages by adding one more growth factor - presumably enhanced TSH secretion - to an intrinsically activated growth regulating network.

Female↗