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Odor of taste stimuli in conditioned "taste" aversion learning.

The present research addresses whether rats can express odor aversions to the odor of taste stimuli. In Experiment 1, saccharin or salt were either mixed in distilled water, so the rats could taste and smell them, or presented on disks attached to the tubes' metal spouts so the rats could only smell them. Aversions were established to taste stimuli under both conditions. The results of Experiment 2 indicate that conditioning was to the odor of the tastes when they were presented on disks in Experiment 1, hence both taste and odor aversions were established by means of "taste" stimuli. Taste aversion learning thus may more properly be termed flavor aversion learning, with flavor referring to both taste and odor components.

Animals↗

Olfactory dysfunction in humans with deficient guanine nucleotide-binding protein.

The guanine nucleotide-binding stimulatory protein (Gs) couples hormone-receptor interaction to the activation of adenylate cyclase and the generation of cyclic AMP. Studies using frog neuroepithelium indicate that the sense of smell is mediated by a Gs-adenylate cyclase system, and this prompted us to test olfaction in the only known model of Gs deficiency in the animal kingdom, Gs-deficient (type 1a) pseudohypoparathyroidism (PHP), which occurs in humans. Such patients are resistant to the cAMP-mediated actions of several hormones. (Although Henkin has reported disturbances in the sense of smell in six patients with PHP, currently available biochemical measurements such as the cAMP response to parathyroid hormone (PTH) and determination of Gs activity were not reported and olfactory testing was limited.) In the present study, we found that all Gs-deficient patients had impaired olfaction when compared with PHP patients who had normal Gs activity (type 1b PHP, in which patients are resistant only to the action of PTH in the kidney). This is the first evidence of human olfactory impairment which can be related to Gs deficiency and suggests that Gs-deficient PHP patients may be resistant to cAMP-mediated actions in other non-endocrine systems.

Cyclic AMP↗

Peritoneoscopic placement of peritoneal dialysis catheter and bowel perforation: experience of an interventional nephrology program.

BACKGROUND: Bowel perforation is an uncommon but serious complication of peritoneoscopic peritoneal dialysis (PD) catheter insertion. The approach to diagnosis of bowel perforation utilizing this technique has not been previously published. The authors report their experience with the diagnosis and management of bowel perforation in the context of peritoneoscopic placement of PD catheters. METHODS: The authors retrospectively reviewed the records of 750 PD catheters inserted over a 12-year period (January 1991 to May 2003) utilizing peritoneoscopic technique. RESULTS: Six (0.8%) patients experienced bowel perforation during the procedure. The diagnosis was made immediately during the procedure in 5 (83%) of the 6 patients. Of these 5, peritoneoscopy confirmed intrabowel position of the cannula by visualizing bowel mucosa (n = 3) and hard stool (n = 1). The fifth patient showed extrusion of fecal matter upon trocar withdrawal before peritoneoscopy. All 5 had emanation of foul-smelling gas through the cannula. Bowel rest and broad-spectrum intravenous antibiotics were initiated. Of the 5, 1 required surgery, whereas the others were discharged home after 3 days. The sixth patient had fever, severe peritoneal irritation, and polymicrobial peritonitis the morning after the procedure. In this patient, no evidence of bowel injury was noted during the procedure except for brief emanation of foul-smelling gas. He required surgical intervention. CONCLUSION: Bowel perforation can be diagnosed immediately in most patients undergoing peritoneoscopic PD catheter insertion. A majority of these patients can be treated medically. The surgical team should be consulted if the patient shows clinical deterioration or has signs of peritoneal irritation.

Abdomen, Acute↗

Clinical double-blind trial on the dermal tolerance and user acceptability of six alcohol-based hand disinfectants for hygienic hand disinfection.

Six commercially available alcohol-based hand rubs [AHD 2000, Desderman, Mucasept A, Manorapid (Poly-Alkohol, Spitacid, and Sterillium] were investigated in a clinical double-blind trial involving 10 participants who had no previous experience of using hand rubs (Group 1), and seven who had substantial professional experience of using hand rubs (Group 2; virology laboratory staff). Group 1 was studied for one week with 20 applications on day 1 and then five applications per day for six days. Transepidermal water loss, dermal water content and superficial sebum content of the skin were measured before and after the seven-day application of the products, as well as user acceptability (self-assessment of smell, speed of drying, emolliant effect, skin dryness). Group 2 used each preparation twice for two weeks in a random sequence, and carried out self assessment at the end of each fortnight. Transepidermal water loss (mean baseline: 18.7 g/m(2)h), dermal water content (mean baseline dorsum: 75.6) and superficial sebum content (mean baseline dorsum: 4.8 microg/cm(2)) did not change significantly. In both groups assessments of the smell and the speed of drying did not reveal any significant differences between the six products. Sterillium had the best emollient effect of all products (P<0.05; Wilcoxon test and Mann-Whitney-U test) and was significantly better than Desderman, AHD 2000, and Mucasept A, causing less skin dryness after seven days use in Group 1 (P<0.05; Mann-Whitney-U test). Manorapid caused significantly less dryness than Spitacid, AHD 2000, and Mucasept A in Group 2 after the first use, but no significant difference was observed after the second use. Thus alcohol-based hand rubs that contain emolliants, irrespective of the type of alcohol (n-propanol, iso-propanol or ethanol), are well tolerated and do not dry out or irritate the skin. Personal assessments showed significant differences for the emolliant effect and the extent of dryness. Both factors are very important, as user acceptability has an impact on compliance. Sterillium is the only hand disinfectant containing mecetronium etilsulphate which has been shown to have an emolliant effect. Future research should focus on user acceptability in order to improve compliance.

Adult↗

Comparison of two micronutrient supplements in children with chronic renal failure.

OBJECTIVE: To compare a newly formulated renal-specific micronutrient (RSM) supplement (vitamins C, E, K, and B complex, copper, zinc) with Ketovite (Paines & Byrnes, Middlesex, UK) tablets (vitamins C, E, K, and B complex) in children with chronic renal failure (glomerular filtration rate [GFR] < 25 mL/min/1.73 m(2)) or on chronic peritoneal dialysis (CPD) and hemodialysis (HD). DESIGN: Children currently prescribed Ketovite tablets were changed to RSM for 3 months. Questionnaires on palatability, acceptability, and ease of administration were assessed while on Ketovite and after 3 months on RSM along with plasma levels of zinc, copper, folate (serum, red cell), vitamin B(12), and homocysteine. SETTING: Regional pediatric nephrology unit. PATIENTS: Fifteen children (10 male) with a mean age of 10.4 years (range, 1.1 to 16 y) were recruited (11 had GFR < 25 mL/min/1.73 m(2), 2 CPD, 2 HD). Two children received overnight gastrostomy button feeding. MAIN OUTCOME MEASURES: Fourteen children (1 child refused RSM after 1 week) and their families completed questionnaires using a Likert scale: 1 (liked) to 7 (disliked). Plasma levels were analyzed at baseline on Ketovite and after 3 months on RSM. RESULTS: Children disliked the smell of Ketovite compared with RSM (P =.004). The size of Ketovite was preferable to the size of the RSM (P =.015) and was believed to be easier to administer (P =.046). There were no differences in patient/parent rating of appearance, texture, or taste, but 8 of 15 patients (53%) expressed a preference for the RSM if available. Plasma values of copper, zinc, folate, and vitamin B(12) were within the normal reference range on Ketovite and showed no significant change on RSM. Mean plasma homocysteine levels were above normal reference ranges in all groups (GFR < 25 mL/min/1.73 m(2), 7.6 [SD, 3.1]; CPD, 11.5 [SD, 1.6]; HD, 12 [SD, 8.7]) on Ketovite and were unchanged after 3 months on RSM. CONCLUSIONS: This pilot study confirms the acceptability of the RSM, particularly in relation to its smell and chewability, but the current size may preclude its widespread use. The incorporation of zinc and copper will be beneficial for many children, but reduction in homocysteine levels may necessitate an increase in folic acid content.

Adolescent↗

A case of Kallmann syndrome associated with Dandy-Walker malformation.

A 19-year-old man was admitted to our hospital for delayed puberty. At birth, he had macrocephalia and showed delayed physical and mental development. At 9 years of age, right cryptorchism was diagnosed. His parents had noticed that he could not recognize any smells since his infancy. Physical examination on admission revealed ocular hypertelorism, high myopia, high arched palate, and intermittent external strabismus. Sense of smell was scaled out by olfactometry. External genitalia were infantile. Neurological examination showed on IQ of 83, and mild truncal ataxia. Magnetic resonance imaging (MRI) showed a cystic distension of the IV ventricle, partial aplasia of the cerebellar vermis, elevation of the tentorium cerebelli, enlargement of the III ventricle, and agenesis of the corpus callosum. These findings revealed that the patient had Dandy-Walker malformation. The basal FSH, LH, and testosterone levels were all low compared with normal adult reference values. The serial LH-RH provocation tests showed stepwise LH and FSH elevation. After the fifth day of LH-RH administration, both LH and FSH responses clearly improved. Olfactory tracts were defective in MRI findings. These findings were consistent with hypogonadotropic hypogonadism of hypothalamic origin with anosmia, and the patient was therefore diagnosed with Kallmann syndrome. Sequence analysis of the KAL1 gene showed no mutation in the coding region. To our knowledge, this is the first case report of the coexistence of Kallmann syndrome and Dandy-Walker malformation in the same patient.

Adult↗

[Special suction tube holder for a laser handpiece in effective smoke suction evacuation. On the problem of smoke suction in external CO2 laser therapy].

Treatment with a CO2 laser causes high smoke production, which leads to reduced view to the surgical field, to bad smell and has potential health hazards. Hitherto the problem of the external smoke evacuation had not been solved sufficiently. Therefore a special sucking-tube holder for a laser handpiece is presented. The end of the sucking tube exactly follows all movements of the handpiece and can be positioned close to the source of smoke. Through a defined angle the smoke can be removed quickly out of the way of the laser beam. According to the practical experiences so far, this special equipment on a laser handpiece guarantees an effective evacuation of smoke, allows the reduction of assisting staff, reduces irritation through bad smell and additionally minimizes the potential risks of smoke caused by an external CO2 laser application.

Condylomata Acuminata↗

The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates.

Olfactory receptors (ORs) located in the cell membrane of olfactory sensory neurons of the nasal epithelium are responsible for odor detection by binding specific odorant ligands. Primates are thought to have a reduced sense of smell (microsmatic) with respect to other mammals such as dogs or rodents. We have previously demonstrated that over 70% of the human OR genes have become nonfunctional pseudogenes, leading us to hypothesize that the reduced sense of smell could correlate with the loss of functional genes. To extend these results, we sampled the OR gene repertoire of 10 primate species, from prosimian lemur to human, in addition to mouse. About 221 previously unidentified primate sequences and 33 mouse sequences were analyzed. These sequences encode ORs distributed in seven families and 56 subfamilies. Analysis showed a high fraction ( approximately 50% on average) of pseudogenes in hominoids. In contrast, only approximately 27% of OR genes are pseudogenes in Old World monkeys, and New World monkeys are almost free of pseudogenes. The prosimian branch seems to have evolved differently from the other primates and has approximately 37% pseudogene content. No pseudogenes were found in mouse. With the exception of New World monkeys, we demonstrate that primates have a high fraction of OR pseudogenes compared with mouse. We hypothesize that under relaxed selective constraints, primates would have progressively accumulated pseudogenes with the highest level seen in hominoids. The fraction of pseudogenes in the OR gene repertoire could parallel the evolution of the olfactory sensory function.

Animals↗

Multiple chemical sensitivity in male painters; a controlled provocation study.

The purpose of the present study was to examine whether male painters reporting multiple chemical sensitivity (MCS) differ from their matched controls (male painters without such sensitivity) during controlled chamber challenges to singular and mixtures of odorous chemicals with respect to: (1) Subjective rating of symptoms (i.e., symptoms related to central nervous system (CNS) and symptoms related to irritation) and sensations of smell elicited by low-level chemical exposures. (2) Changes in serum prolactin and cortisol levels, changes in nasal cavity and eye redness as a result of the various exposures. Moreover, background assessments were made regarding mental well-being, sense of coherence (SOC) as well as state of anxiety and depression in both groups. The MCS and control group consisted of 14 and 15 male painters respectively. Regarding background assessments of mental well-being, anxiety, depression and SOC, statistically significant differences were obtained between painters with MCS and their controls. During the controlled chamber challenges, neither difference regarding sensations of smell nor development of CNS related symptoms were seen between MCS and control group. In contrast, subjective rating of symptoms related to irritation (i.e., eyes, nose, throat, skin, and breathing difficulties) was significant higher in subjects with MCS. No differences between the groups as a result of the different exposures were seen concerning nasal cavity, eye redness and serum cortisol levels. However, a trend (P = 0.056) between the groups was measured regarding a decline of serum prolactin levels in the MCS group. This is a relatively small study with a limited number of volunteers; and no definitive conclusions can be drawn concerning the above findings. But it is the first controlled challenge study that incorporates similarly exposed groups (painters) recruited from a community rather than from a clinical population.

Adult↗

Clinical relevance of nasal polyps in individuals recruited from a general population-based study.

OBJECTIVE: To compare the clinical presentations of individuals with nasal polyps detected by endoscopy in a general population sample with those of patients with nasal polyp disease seeking medical attention. MATERIAL AND METHODS: A total of 38 individuals with nasal polyps from a population-based sample were compared with 38 matched controls and a third group consisting of 44 patients who presented to an outpatient clinic with symptoms and diagnosed nasal polyps Upper and lower airway symptoms were registered. Polyp size, peak nasal inspiratory flow (PNIF), olfactory function and health-related quality of life were measured. RESULTS: Compared with the individuals with nasal polyps in the population sample, patients actively seeking medical care for nasal polyposis experienced more symptoms of nasal blockage and an impaired sense of smell, and had more extensive polyps and reduced PNIF. There were equal frequencies of asthma symptoms in these two groups. Compared with the controls, the individuals with nasal polyps in the population sample had a greater frequency of asthma symptoms and aspirin intolerance and also experienced an impaired sense of smell. CONCLUSION: Nasal polyps alone, as seen occasionally, are indicative of airway disease involving the upper and lower respiratory tracts.

Adult↗

Women with nausea and vomiting in pregnancy demonstrate worse health and are adversely affected by odours.

The objectives of this study were (1) to determine aversive stimuli that are related to nausea and vomiting in pregnancy (NVP); (2) to determine food and fluid intake in early pregnancy; and (3) to explore relationships between aversive stimuli and health measures. A total of 273 women in an antenatal setting completed a questionnaire survey, incorporating the Nausea and Vomiting in Pregnancy Instrument (NVPI); the General Health Questionnaire (GHQ); measures of perceived mood and illness; food and fluid intake; and open-ended questions relating to perceived aversive and helpful stimuli. Data was subjected to quantitative and qualitative analysis. A total of 57% of women reported aversive stimuli. Of these, the primary sense implicated was olfaction, with 72% reporting food smells. A number of women were affected by the odours of drinks (26%) and other products (31%). Women who were adversely affected by odours had higher severities of NVP, perceived illness and psychopathology scores on the GHQ. In conclusion, odour appears to be an important stimulus related to NVP, with perceived aversive smells related to the severity of nausea. Women severely affected by NVP demonstrated worse health. The role of olfaction in pregnancy and specifically in sufferers of severe NVP should be evaluated further.

Female↗

Cognitive deficits in obsessive-compulsive disorder on tests of frontal lobe functions.

Individuals with obsessive-compulsive disorder (OCD) display frontal lobe deficits, but there are inconsistencies between various tests of frontal lobe functions and between the results from different studies. The objective of this work was to characterize frontal lobe dysfunctions in OCD patients. Fifteen patients and 17 control subjects matched for age, sex and intelligence were tested on classic tests of frontal lobe functions [Wisconsin Card Sorting Test (WCST) and tests of fluency], a smell identification test and one computerized test: the Intra/Extra Dimension test. The Intra/Extra Dimension test showed a significant difference between the two groups in reversal of response. The test of Figural fluency showed a significant difference between the two groups in numbers of produced figures. There were no differences on the WCST, verbal fluency and the smell identification test.

Adult↗

Galen's ideas on neurological function.

Galen was the leading physician of the Roman empire during the last half of the second century. Unlike some of his predecessors, Galen concluded that the brain controlled cognition and willed action. The initial evidence for this doctrine was that the brain was the site of termination of all of the five senses: touch, taste, smell, sight, and hearing. Galen presumed that the information from these five senses was organized by a part of the brain that generated a concept of an object common to all senses; this part of the brain he considered to be the area of common sense. Galen thought that he could differentiate sensory from motor nerves (not nerve fibers) by palpation. Sensory nerves were soft because they needed to be impressed with the essence of the object seen, heard, felt, smelled, or tasted. Motor nerve fibers were very hard because they needed to carry the force of the will from the brain to the muscles. Strong willed people had especially firm motor nerve fibers; hence, the modern term that a person with great bravery has 'nerves of steel'. Galen considered that common sense, cognition, and memory were functions of the brain. Personality and emotion were not generated by the brain, but rather by the body as a whole (or perhaps by the heart and liver). Galen's studies of respiration and of the recurrent laryngeal nerve solidified the knowledge that the brain, not the chest, was the site of the rational power that guides human behavior. This doctrine has continued from Galen's time to the present.

Brain↗

Sensations from initial exposure to nicotine predicting adolescent smoking in China: a potential measure of vulnerability to nicotine.

Sensations derived from initial exposure to nicotine are a potential indicator of an individual's vulnerability to nicotine. This study assessed whether sensations experienced during the first lifetime exposure to nicotine could predict current and established cigarette smoking. Data from 210 respondents who reported having ever tried cigarette smoking in Wuhan, China, were obtained for this study from 610 students in 10th grade at two schools. Subjects were participants in a multipurpose pilot survey for an adolescent smoking prevention trial. The survey was administered in a classroom setting using a paper-and-pencil questionnaire. Sensations reported were cigarette smell (59.2%), coughing (54.1%), dizziness (52.1%), nausea (42.5%), relaxation (19.1%), and pleasurable buzz/rush (9.0%). After controlling for confounders, multiple logistic regression analyses identified three sensations significantly associated with smoking: (a) Cigarette smell (OR for days smoked in the past 30 days=2.93, p<.05, OR for number of cigarettes smoked per day=2.69, p<.05, and OR for 100-cigarette smoking=5.40, p<.01), (b) pleasurable buzz/rush (OR for 100-cigarette smoking=11.09, p<.05), and (c) relaxation (OR for past 30-day smoking measures ranged from 3.69 to 4.48, p<.01, and OR for 100-cigarette smoking=4.12, p<.05). A dose-response relationship was observed between the sensations and cigarette smoking. Self-reported sensations from initial exposure to nicotine may be a useful indicator of an individual's vulnerability to nicotine. This information can be used for adolescent smoking prevention and cessation interventions.

Adolescent↗

"Do-it-yourself" dementia testing: issues regarding an Alzheimer's home screening test.

The Early Alert Alzheimer's Home Screening Test (AHST) is a variant of the Smell Identification Test (SIT) and the Cross-Cultural Smell Identification Test (CC-SIT), and recently became available for purchase by the general public. The validity and the practical utility of routine screening for individuals with asymptomatic cognitive impairment has not been established. There are considerable specific methodological concerns regarding the use of the AHST including the association of olfactory impairment with (a) age in the absence of cognitive impairment, (b) numerous acute and/or chronic medical conditions, and (c) lifestyle habits and social and/or demographic variables. General public misunderstanding of the difference between a screening and a diagnostic test, primary care physicians' frequent confusion about follow-up mechanisms for newly diagnosed patients with dementia, the possible lack of perceived counseling options for those self-diagnosed, and abuse of test findings create distinct possibilities for misuse of this test. The marketing of the AHST and its general use without appropriate public health educational safeguards is inappropriate and may be unethical.

Aged↗

Conversion of dietary choline to trimethylamine and dimethylamine in rats: dose-response relationship.

Trimethylamine (TMA) and dimethylamine (DMA) are normal components of human urine and are precursors of dimethylnitrosamine, a potent carcinogen. In part, DMA and TMA are products of the metabolism of dietary choline by intestinal bacteria. Most TMA formed in the intestinal tract is later oxidized and excreted as trimethylamine oxide (TMAO). Humans treated with large doses of choline smell "fishy" (the odor of TMA). Humans ingest choline as part of foods, and yet rarely smell fishy, suggesting that TMA formation must depend upon the dose of choline ingested. We found that, in adult rats, at low doses of choline (1.5 mmol/kg body wt) only 9 mumol choline (6% of the dose) reached the part of the intestine which is colonized by bacteria (the cecum and colon). After administration of 15 mmol choline/kg body wt, 237 mumol (16% of the dose) reached the cecum and colon. At both doses, 64-65% of the administered choline was absorbed from the intestine by 3 h after the dose. We found that orally administered choline slightly increased TMA and TMAO excretion at doses of choline smaller than 7 mmol/kg body wt, but that there was a disproportionately large increase in TMA excretion per 24 h when larger doses were administered (from 11 mumol TMA and 100 mumol TMAO per kg body wt in controls to 226 mumol TMA and 3617 mumol TMAO per kg body wt in rats treated with 15 mmol choline/kg body wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute giardiasis: an improved clinical case definition for epidemiologic studies.

In June 1983, an outbreak of waterborne giardiasis occurred in a group of 93 university students and faculty participating in a geology field course in Colorado. All cases occurred in one subgroup of persons who were heavily exposed to untreated stream water on a field trip, and the risk of illness was strongly related to the amount of untreated stream water consumed. The median incubation period from a brief exposure to the first symptom was 7 days. The authors compared symptoms and stool sample results among 31 Giardia-positive persons in the exposed group and 36 Giardia-negative participants in an unexposed group to assess several case definitions for acute giardiasis. Diarrhea, abdominal cramps, flatulence, foul-smelling stools, nausea, excessive tiredness, bloating, anorexia, and chills were each significantly more common in the first group than in the second. A giardiasis case definition of 5 days or more of diarrhea--the definition used in many epidemiologic studies of giardiasis--had a specificity of 100 percent but a sensitivity of only 32.2 percent compared with a definition based on results of stool examinations. When a case was defined as an illness lasting 7 days or more, with a combination of two or more of six symptoms (diarrhea, flatulence, foul-smelling stools, nausea, abdominal cramps, and excessive tiredness), sensitivity rose to 73 percent, with a specificity of 88 percent. Such a case definition may be an improvement over that of 5 days of diarrhea, especially in outbreaks where there is good laboratory documentation that Giardia is the etiologic agent. The definition should be validated in other outbreaks and in situations where giardiasis must be distinguished from gastrointestinal disease caused by other agents.

Colorado↗

Brain cholecystokinin tetrapeptide levels are increased in a rat model of anxiety.

Rats exposed to the smell of a predator adopted the freezing posture indicative of anxiety. Correlatively, the concentration of cholecystokinin tetrapeptide (CCK-4) was increased in the olfactory bulb, frontal and central cortex, dorsal and ventral striatum, central amygdala and the nucleus of the solitary tract. The concentration of CCK-8 was increased only in the ventral striatum. Glutamate was increased in the cortex and the striatum and dopamine was increased in the cortex. Intraperitoneal injection of CCK-4 increased brain levels of CCK-4 and replicated, in part, the behavioural effect of the smell of the predator. Injection of a CCK-B-receptor antagonist had the opposite behavioural effect. The results support a role for CCK-4 in anxiety.

Animals↗