Surgical strategy in lithium-associated hyperparathyroidism: A population-based study.

BACKGROUND: The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. METHODS: A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). RESULTS: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery. CONCLUSIONS: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.

Kept in the Closet: Structural Stigma and the Timing of Sexual Minority Developmental Milestones Across 28 European Countries.

Structural stigma's role in lesbian, gay, and bisexual (LGB) people's attainment of identity development milestones remains unknown. In a sample of 111,498 LGB people (ages 15 to 65+) living across 28 European countries, associations were investigated between structural stigma measured using an objective index of discriminatory country-level laws and policies affecting LGB people and the timing and pacing of LGB self-awareness, coming out, and closet duration, and subgroup differences in these associations. On average, self-awareness occurred at age 14.8 years old (SD = 5.1), coming out occurred at 18.5 years old (SD = 5.7), and the closet was 3.9 years long (SD = 4.9); thereby highlighting adolescence as a key period for sexual identity development and disclosure. Greater structural stigma was associated with higher odds of never coming out, later age of coming out, and longer closet duration. Gender identity, transgender identity, and sexual identity moderated associations between structural stigma and these developmental milestones. Reducing structural stigma can plausibly promote sexual identity development among LGB populations, especially during adolescence when identity related milestones are often attained.

Neuropsychiatric Comorbidity in Primary Hyperparathyroidism Before and After Parathyroidectomy: A Population Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is often accompanied by neuropsychiatric symptoms. This study aimed to map out psychiatric comorbidity as reflected by medical treatment for psychiatric symptoms. METHODS: A retrospective case-control analysis and a prospective cohort analysis of psychotropic drug utilization before and after PTX. A total of 8279 PHPT patients treated with parathyroidectomy in Sweden between July 1, 2008 and December 31, 2017 compared to a matched control cohort from the total population (n = 82,790). Information on filled prescriptions was collected from the Swedish Prescribed Drug Register (SDR). Socioeconomic data and diagnoses were added by linkage to national patient and population registers. Regression analyses were used to calculate relative drug utilization (OR) within 3 years prior to PTX and relative incidence of drug treatment (RR) within 3 years postoperatively. RESULTS: Utilization of antidepressant, anxiolytic and sleep medication was more comprehensive in PHPT patients compared with the controls prior to PTX. The most common were benzodiazepines [OR 1.40 (95% CI: 1.31-1.50)] and selective serotonin reuptake inhibitors [SSRI; OR 1.38 (95% CI: 1.30-1.47)]. Postoperatively, the excess prescription rate for anxiolytic benzodiazepines decreased within three years from a 30 to 19% excess and for benzodiazepines for sleep from 31 to 14%. No corresponding decrease in excess prescription rate was observed for SSRI. CONCLUSION: PHPT is associated with increased utilization of antidepressive medications and benzodiazepines before PTX. This study implies that psychiatric symptoms should be considered in PHPT patients and continuous medication should be reevaluated after PTX.

Short-term medical treatment of hypercalcaemia in primary hyperparathyroidism predicts symptomatic response after parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism is often associated with non-disease-specific symptoms. The aim of this study was to evaluate whether normalization of hypercalcaemia with short-term medical treatment can be used to predict the effects of parathyroidectomy and guide in surgical decision-making. METHODS: This observational study included patients who received calcimimetic treatment for 4 weeks before parathyroidectomy (30-60 mg daily). A panel of tests was used to assess various aspects of quality of life (European Organisation and Treatment of Cancer QLQ-C30 core questionnaire, Hospital Anxiety and Depression Scale and Positive State of Mind questionnaire), cognitive function (Montreal Cognitive Assessment) and muscle strength (timed-stands test). The tests were carried out at baseline, after 4 weeks of calcimimetic treatment, and at 6 weeks and 6 months after parathyroidectomy. The predictive values of changes during calcimimetic treatment were determined for each test. RESULTS: The study included 110 patients of median age 62 years (91 women). Calcimimetic treatment resulted in normalization of calcium levels and improvements in quality-of-life parameters. The time spent on the timed-stands test was significantly shortened. Eleven of 38 participants with a baseline Montreal Cognitive Assessment score below 26, indicating mild cognitive impairment, reached scores of at least 26 during treatment with calcimimetic. Improvements during treatment with calcimimetic correlated well with postoperative outcomes (positive predictive values 74-96 per cent). CONCLUSION: The method described in this study may be used to aid surgical decision-making for patients with primary hyperparathyroidism and non-disease-specific symptoms by predicting the effects of normalization of hypercalcaemia.

ANTECEDENTES: El hiperparatiroidismo primario (pHPT) a menudo se asocia con síntomas no específicos de la enfermedad. El objetivo de este estudio fue evaluar si la normalización de la hipercalcemia a corto plazo con tratamiento médico se podría usar para predecir los efectos de la paratiroidectomía y guiar la toma de decisiones quirúrgicas. MÉTODOS: Estudio observacional (ClinicalTrials.gov, registro NCT02227264) que incluyó 110 pacientes programados para paratiroidectomía (mediana de edad 62 años; 91 mujeres). Intervención: tratamiento calcimimético, cuatro semanas, 30-60 mg al día. Medidas de resultado: Un panel de pruebas para evaluar los aspectos de la calidad de vida (cuestionario de calidad de vida core 30, QLQ-C30; escala hospitalaria de ansiedad y depresión (HAD) y estado mental positivo (PSOM); función cognitiva (evaluación cognitiva de Montreal, MoCa) y fuerza muscular (Timed-Stands Test, TST). Las pruebas se realizaron cuatro veces: al inicio del estudio (basal), después de cuatro semanas de tratamiento calcimimético, a las seis semanas y seis meses después de la paratiroidectomía. Para cada prueba se determinaron los valores predictivos de los cambios durante el tratamiento calcimimético. RESULTADOS: El tratamiento con fármacos calcimiméticos determinó una normalización en los niveles de calcio y una mejoría en los parámetros de calidad de vida. El tiempo del TST se redujo significativamente. Once de los 38 participantes con una puntuación MoCa basal < 26, definida como deterioro cognitivo leve, alcanzaron puntuaciones ≥ 26 durante el uso de la medicación. Las mejoras observadas durante el tratamiento mostraron una buena correlación con el resultado postoperatorio (valores predictivos positivos 74-96%). CONCLUSIÓN: Este estudio presenta un método basado en la predicción de los efectos de la normalización de la hipercalcemia para ayudar en la toma de decisiones quirúrgicas en pacientes con pHPT y síntomas no específicos de la enfermedad.

microRNA expression signatures of gastrointestinal stromal tumours: associations with imatinib resistance and patient outcome.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is mainly initialised by receptor tyrosine kinase gene mutations. Although the tyrosine kinase inhibitor imatinib mesylate considerably improved the outcome of patients, imatinib resistance still remains a major therapeutic challenge in GIST therapy. Herein we evaluated the clinical impact of microRNAs in imatinib-treated GISTs. METHODS: The expression levels of microRNAs were quantified using microarray and RT-qPCR in GIST specimens from patients treated with neoadjuvant imatinib. The functional roles of miR-125a-5p and PTPN18 were evaluated in GIST cells. PTPN18 expression was quantified by western blotting in GIST samples. RESULTS: We showed that overexpression levels of miR-125a-5p and miR-107 were associated with imatinib resistance in GIST specimens. Functionally, miR-125a-5p expression modulated imatinib sensitivity in GIST882 cells with a homozygous KIT mutation but not in GIST48 cells with double KIT mutations. Overexpression of miR-125a-5p suppressed PTPN18 expression, and silencing of PTPN18 expression increased cell viability in GIST882 cells upon imatinib treatment. PTPN18 protein levels were significantly lower in the imatinib-resistant GISTs and inversely correlated with miR-125a-5p. Furthermore, several microRNAs were significantly associated with metastasis, KIT mutational status and survival. CONCLUSIONS: Our findings highlight a novel functional role of miR-125a-5p on imatinib response through PTPN18 regulation in GIST.

Sickness certification at oncology clinics: perceived problems, support, need for education and reasons for certifying unnecessarily long sickness absences.

Physicians' work with sickness certifications is an understudied field. The aims of this study were to gain knowledge of experiences concerning the sickness certification process among physicians working at oncology clinics. In 2008, all physicians working in Sweden (n = 36 898) were sent a questionnaire concerning sick-listing practices. All respondents working at an oncology clinic (n = 428) were included in the current study. Most of the physicians had sickness certification consultations at least weekly (91.3%). More than one fifth (22.3%) reported that they worked at a clinic with a workplace policy regarding the handling of sickness certification and 61.1% reported receiving at least some support in such cases from their immediate manager. Issuing unnecessary long sickness certificates were related to experiencing delicate interactions with patients and to lack of time. To a moderate degree, further competence was requested regarding: different types of compensation in the social insurance system, responsibilities of the Social Insurance Agency and employers, and sickness insurance rules. The large majority of physicians working in oncology reported regularly having consultations involving sickness certification. Overall, they reported few problems, low level of need for more competence regarding sickness certification, and low frequency of issuing sickness absences for longer periods than necessary.

Prediction of cognitive response to surgery in elderly patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (pHPT) can be associated with potentially reversible cognitive impairment, which is occasionally mistaken for natural ageing and dementia. The aim was to evaluate short-term medical normalization of hypercalcaemia in surgical decision-making for elderly patients with mild cognitive deficiency. METHODS: Patients with pHPT were included in a prospective observational study. A test panel including the Montreal Cognitive Assessment (MoCA) and validated tools for estimation of psychological status (Hospital Anxiety and Depression Scale, HADS), and muscle strength (timed-stands test, TST) was applied at baseline, after 4 weeks of calcimimetic treatment, and after parathyroidectomy. Mild cognitive impairment was defined by a MoCA score below 26. A longitudinal increase in MoCA score of at least 2 points 6 months after surgery was considered clinically meaningful. RESULTS: Of 110 patients who underwent testing, 35 aged 50 years or more were identified to have mild cognitive dysfunction, including 19 who were aged at least 70 years (median MoCA score 23, i.q.r. 21-24). Calcimimetic treatment resulted in normalization of calcium levels, and improvements in MoCA and HADS scores, and TST time. Normal MoCA scores (at least 26) were reached in 17 patients by 6 months after surgery, of whom 10 were aged 70 years or older. Long-term increase in MoCA score correlated with the decrease in ionized calcium concentration (r = -0.536, P = 0.022). Baseline calcium concentration and improvement in MoCA with calcimimetic treatment were identified as independent predictors of favourable outcome after parathyroidectomy. CONCLUSION: Medical normalization of hypercalcaemia can aid in predicting outcome after parathyroidectomy.

Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification.

Parafibromin is a protein product derived from the hyperparathyroidism 2(HRPT2) tumor suppressor geneand its inactivation has been coupled to familial and sporadic forms of parathyroid malignancy. In this study, we have conducted immunohistochemistry on 33 parathyroid carcinomas (22 unequivocal and 11 equivocal) using four parafibromin antibodies directed to different parts of the protein. Furthermore, for a fraction of cases, the immunohistochemical results were compared with known HRPT2 mutational status. Our findings show that 68% (15 out of 22) of the unequivocal carcinomas exhibited reduced expression of parafibromin while the 25 sporadic adenomas used as controls were entirely positive for parafibromin expression. Additionally, three out of the six carcinomas with known HRPT2 mutations showed reduced expression of parafibromin. Using all four antibodies, comparable results were obtained on the cellular level in individual tumors suggesting that there exists no epitope of choice in parafibromin immunohistochemistry. The results agree with the demonstration of a approximately 60 kDa product preferentially in the nuclear fraction by western blot analysis. We conclude that parafibromin immunohistochemistry could be used as an additional marker for parathyroid tumor classification, where positive samples have low risk of malignancy, whereas samples with reduced expression could be either carcinomas or rare cases of adenomas likely carrying an HRPT2 mutation.

RIN14B: a pancreatic delta-cell line that maintains functional ATP-dependent K+ channels and capability to secrete insulin under conditions where it no longer secretes somatostatin.

The delta-cell line RIN14B was characterized with regard to ATP-regulated K+ (K(ATP)) channel activity and hormone release. By applying the patch-clamp technique, dose-response curves for ATP and the sulfonylurea tolbutamide were obtained in inside-out patches. The concentration causing half-maximal K(ATP) channel inhibition was found to be 23.7 and 27.6 microM for ATP and tolbutamide, respectively. ADP and diazoxide stimulated K(ATP) channel activity, an effect dependent on the presence of intracellular Mg2+. The stimulatory effect of diazoxide also required the presence of ATP. The kinetic properties of the K(ATP) channel were analysed in the presence of ATP, a combination of ADP and ATP and in nucleotide-free solutions. The distribution of K(ATP) channel open time could be described by a single exponential function with a time constant of approximately 30 ms in nucleotide-free and in ATP-containing solutions. The presence of both ATP and ADP resulted in the appearance of an additional time constant of > 150 ms. Single-channel unitary current-voltage (i-V) relation was characterised for the K((ATP) channel present in RIN14B cells. The slope conductance, measured at the reversal potential was found to be 19.1 +/- 2.4 pS. The permeability for K+ ions was calculated to be 0.31 x 10(-13) cm3 x s(-1). We have not been able to confirm the somatostatin releasing profile of the RIN14B cells using radioimmunoassays, nor could we find positive somatostatin stain with immunocytochemical techniques. We conclude that the RIN14B cell line, previously characterized as a somatostatin-secreting cell line, contains K(ATP) channels with properties closely resembling the K(ATP) channel described in the pancreatic beta-cell. However, the cell line appears to have dedifferentiated with regard to the ability to secrete somatostatin, maintaining the highly differentiated function of both insulin biosynthesis and exocytosis.

A randomised population-based intervention to examine the effects of the ultraviolet index on tanning behaviour.

The aim of the following study was to examine the effects of the Ultraviolet (UV) Index and a personal ultraviolet radiation (UVR) intensity indicator on tanning behaviour compared with general, written information about sun protection. A population-based random sample in Sweden was randomly assigned to four groups receiving different information packages (n=3200). Questionnaires were sent before and after the summer of 2001. Positive attitudes towards sunbathing as well as tanning and sunburn frequencies decreased. Knowledge about UV radiation and the use of sun protection increased for all groups. There were no between-group differences. Sun-related behaviours and beliefs changed, but information about the UV Index or a personal UVR intensity indicator did not decrease sunbathing and sunburn more than general, written information.

Tanning habits and sunburn in a Swedish population age 13-50 years.

As part of a skin cancer control programme, we studied the occurrence of self-reported outdoor tanning, sunbed use and ultraviolet (UV)-induced erythema in an urban area. A cross-sectional questionnaire study of 6000 adolescents aged 13-19 years, and 4000 adults aged 20-50 years was applied. Non-response was analysed for outdoor tanning and sunbed use. Results, in general, did not differ between responders and non-responders. Females aged 17-29 years tanned outdoors most frequently. Sunbed use and related erythema was twice as common in young females. In males, outdoor tanning was not age-related. In the past 12 months, 55% reported sunburn and/or burn from sunbed use, one-third were burned in Sweden, one-quarter on sunny resorts abroad. Sunburn occurs frequently. Compliance with recommendations for sunbed use is poor, especially among adolescents and young adults. To reduce the occurrence of erythema, the influence of risk settings upon behaviours is a critical issue for exploration.

Mediation of irregular spiking activity by multiple neurokinin-receptors in the small intestine of the rat.

1. We have studied the small intestinal myoelectric response to the natural tachykinins substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and the neurokinin-receptor selective agonists substance P methyl esther (SPME), [beta-Ala8]neurokinin A 4-10, and senktide in conscious rats. 2. The effects of the agonists were studied before and after administration of the selective neurokinin2 (NK2)-receptor antagonist MEN 10,627. 3. Under basal conditions SP, NKA, NKB, as well as the selective NK1-receptor agonist SPME, the NK2-receptor agonist [beta-Ala8]NKA 4-10, and the NK3-receptor agonist senktide, disrupted the interdigestive rhythm with regularly recycling migrating myoelectric complexes and induced a phase II-like irregular spiking activity. 4. MEN 10,627 given alone did not affect the interdigestive rhythm. 5. MEN 10,627 inhibited the response to [beta-Ala8]NKA 4-10 but not to SP, SPME, NKA, NKB or senktide. 6. It is concluded that not only NK2 receptors, but also other receptors, such as NK1 and NK3 receptors, may mediate the motility-stimulating action of different tachykinins in vivo. 7. It is further concluded that MEN 10,627 exerts a selective NK2-receptor antagonism, and may be a valuable tool for assessing the functional role of NK2-receptors in gastrointestinal physiology.

Transtheoretical model: investigation of adolescents' sunbathing behaviour.

The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden as well as in other western countries during the last 20 years. Adolescents are an important group in skin cancer prevention. Interventions targeting this group have been reported to affect knowledge and attitudes, but the effect on sun protection behaviour has been slight. The aim of this study was to investigate the applicability of the Transtheoretical Model (TTM) for skin cancer prevention for adolescents. A random sample of 1200 18-year-olds living in Stockholm County was selected from the national census registry. A questionnaire that included three of the major constructs of the TTM (i.e. stages of change, processes of change and decisional balance) was sent by mail. The majority of the teenagers were in the precontemplation stage for giving up intentional tanning. The relations between the stages of change and two other major constructs of the TTM, processes of change and decisional balance, were consistent with data on other health behaviours. The results may aid in developing successful skin cancer prevention programmes. The results give support for the stages of change measurement used in this study and that utilizing the TTM in skin cancer prevention may be appropriate.

Beliefs, knowledge and attitudes as predictors of sunbathing habits and use of sun protection among Swedish adolescents.

In 1996, a random population sample of 2615 adolescents completed a questionnaire concerning habitual sun-related behaviours, attitudes towards sunbathing, and knowledge about skin cancer. Females, older adolescents, those with less sun-sensitive skin, those with higher knowledge and those with a positive attitude towards sunbathing were more likely to be frequent sunbathers. Younger adolescents, those who today sunbathe moderately, and those with sensitive skin were more likely to believe that they would sunbathe more often in the future. Males, adolescents with less sensitive skin, those with a positive attitude towards sunbathing and those sunbathing often, were less likely to use protection when sunbathing. Interventions to decrease sun exposure among adolescents should focus on changing attitudes toward sunbathing and having a tan, since knowledge of skin cancer and the damaging affect of sunbathing did not seem to effect current sunbathing habits, or use of sun protection.

Stability of questionnaire items measuring behaviours, attitudes and stages of change related to sun exposure.

The use of questionnaires in epidemiological studies needs more methodological research. The time and effort spent on questionnaire design is often limited. Studies on the construction of questionnaires could lead to a higher quality of data, enhanced comparability and improved credibility of epidemiological findings. The aim of the present study was to examine the test-retest reliability of some common items measuring sun-related variables. A sample of 52 female Swedish nurses attending a postgraduate course in research methodology was chosen. They completed a questionnaire on two occasions spaced 3 weeks apart in the winter of 2000. When the results were analysed, items on sun-related behaviours and sunbed use were sufficiently reliable. The items on skin type and sunburn showed moderate stability. Stage of change related to sunlight exposure, items measuring beliefs about sunbathing along with items assessing self-efficacy and risk perception with regards to sunbathing showed lower stability. The results showed that many essential items concerning exposure to ultraviolet radiation and sunburns were sufficiently stable, but other items were less stable and could be improved upon; suggestions for improving these items are presented. The study illustrates the value of reliability testing in the process of item construction. Using methodological studies to improve the reliability and validity of data is an important step toward higher standards for questionnaire surveys.

[Mechanisms of action of peroral antidiabetics. Sulfonylurea preparations block the ATP-dependent potassium channels]. / Perorala antidiabetikas verkningsmekanism. Sulfonylureapreparat stänger ATP-reglerad kaliumkanal.

Although hypoglycaemic sulphonylureas have been used to treat non-insulin-dependent diabetes mellitus (NIDDM) for the past forty years, their mechanisms of action at the molecular level have only recently been elucidated. A combination of electrophysiological and molecular biological techniques showed the target of sulphonylureas to be a sulphonylurea receptor (SUR1) and potassium channel (Kir6.2) complex. Together, these two proteins form the ATP-dependent potassium (KATP) channel occurring in insulin-secreting cells. An increase in the blood glucose level triggers a chain of events in insulin-secreting cells and K(ATP) channel closure which is a prerequisite for insulin secretion. In NIDDM, however, an increase in blood glucose fails to close the K(ATP) channel satisfactorily, but this can be remedied by the administration of sulphonylureas.

Single residue (K332A) substitution in Kir6.2 abolishes the stimulatory effect of long-chain acyl-CoA esters: indications for a long-chain acyl-CoA ester binding motif.

AIMS/HYPOTHESIS: The pancreatic beta cell ATP-sensitive potassium (K(ATP)) channel, composed of the pore-forming alpha subunit Kir6.2, a member of the inward rectifier K+channel family, and the regulatory beta subunit sulfonylurea receptor 1 (SUR1), a member of the ATP-binding cassette superfamily, couples the metabolic state of the cell to electrical activity. Several endogenous compounds are known to modulate K(ATP) channel activity, including ATP, ADP, phosphatidylinositol diphosphates and long-chain acyl coenzyme A (LC-CoA) esters. LC-CoA esters have been shown to interact with Kir6.2, but the mechanism and binding site(s) have yet to be identified. MATERIALS AND METHODS: Using multiple sequence alignment of known acyl-CoA ester interacting proteins, we were able to identify four conserved amino acid residues that could potentially serve as an acyl-CoA ester-binding motif. The motif was also recognised in the C-terminal region of Kir6.2 (R311-332) but not in SUR1. RESULTS: Oocytes expressing Kir6.2DeltaC26 K332A repeatedly generated K(+)currents in inside-out membrane patches that were sensitive to ATP, but were only weakly activated by 1 mumol/l palmitoyl-CoA ester. Compared with the control channel (Kir6.2DeltaC26), Kir6.2DeltaC26 K332A displayed unaltered ATP sensitivity but significantly decreased sensitivity to palmitoyl-CoA esters. Coexpression of Kir6.2DeltaC26 K332A and SUR1 revealed slightly increased activation by palmitoyl-CoA ester but significantly decreased activation by the acyl-CoA esters compared with the wild-type K(ATP) channel and Kir6.2DeltaC26+SUR1. Computational modelling, using the crystal structure of KirBac1.1, suggested that K332 is located on the intracellular domain of Kir6.2 and is accessible to intracellular modulators such as LC-CoA esters. CONCLUSIONS/INTERPRETATION: These results verify that LC-CoA esters interact at the pore-forming subunit Kir6.2, and on the basis of these data we propose an acyl-CoA ester binding motif located in the C-terminal region.

Characteristics of fasting and fed myoelectric activity in rat small intestine: evaluation by computer analysis.

Evaluation of gastrointestinal myoelectric activity has been limited by the assessment techniques and the complexity of the recorded myoelectric signal. Commonly, myoelectric activity is evaluated as motor patterns, which only gives a semiquantitative measure of myoelectric events within the bowel wall. Using myoelectric recordings from the proximal small intestine in rats, a computerized system for acquisition, storage, display and calculation of characteristics for the myoelectric activity was developed. The software was tested in myoelectric recordings from nine rats in fasting and fed states. All migrating myoelectric complexes (MMCs) during fasting and fed myoelectric patterns were recognized in both digital and analog recordings. Reproduction of myoelectric recordings by the computerized system was indistinguishable from that of the analog system. Employing an appropriate cut-off trigger level and a high sampling frequency, spike potentials were recorded in the proximal jejunum with 0.4 (0.3-0.5) spikes 10 s-1 during phase 1 of MMC, 19.5 (15.1-23.9) (P < 0.001) during phase 2, and 103.8 (97.2-110.5) (P < 0.001) during phase 3. In fasted state, MMCs were most frequent in the proximal jejunum whereas fewer were found in the duodenum and distal jejunum. To achieve stable values for MMC cycle length at least four MMCs had to be calculated. After feeding in phase 1, the myoelectric activity increased to 23.8 (13.6-33.9) spikes 10 s-1 (P < 0.001), whereafter the spiking activity decreased over a period of 2 h until a fasting motor pattern was resumed. It is concluded that computerized technology enables evaluation not only of myoelectric patterns, but also of spiking activity per time unit, i.e. the intensity of myoelectric activity in the gut.

Augmented thermic effect of amino acids under general anaesthesia occurs predominantly in extra-splanchnic tissues.

1. Intravenous infusion of amino acid mixtures stimulates human oxidative heat production more effectively under general anaesthesia than in the unanaesthetized state. To analyse the splanchnic and extra-splanchnic regional distribution of this stimulation, whole body and splanchnic oxygen uptake, blood flow and blood temperatures were measured by a catheterization technique in 14 patients undergoing isoflurane anaesthesia for abdominal surgery. During the anaesthesia period, a mixture of 19 amino acids (240 kJ/h) was infused intravenously into seven of the patients while the others served as controls, receiving isovolumic infusions of a nutrient-free saline solution. 2. Whole body oxygen consumption fell by approximately 40% during anaesthesia and surgery in the controls. Approximately 80-95% of the reduction occurred in the extra-splanchnic tissues. The splanchnic oxygen uptake fell by 31 +/- 6% in the controls during the initial phase of anaesthesia, after which it returned to the pre-anaesthesia level. The initial reduction of the controls' splanchnic oxygen consumption accounted for only approximately 23% of the simultaneous anaesthesia-induced reduction in pulmonary oxygen uptake. No initial reduction of the splanchnic oxygen uptake was observed in the patients treated with amino acid. 3. The amino acid infusion stimulated the whole body oxidative heat production by approximately 18 W during anaesthesia and surgery and by approximately 70 W at the emergence from anaesthesia. Approximately 74% of the stimulation occurred in the extra-splanchnic tissues. At awakening, the splanchnic oxygen uptake rose to approximately 64% above the pre-anaesthesia level in the amino acid group. 4. During the entire period of anaesthesia, the whole body heat content fell by 282 +/- 68 kJ in the controls and by 57 +/- 25 kJ in the amino acid group. Amino acid treatment thus prevented approximately 80% of the anaesthesia-induced reduction in whole body heat content. 5. During anaesthesia and surgery, cardiac output was approximately 25% and approximately 16% below the baseline, preanaesthesia levels in the control and amino acid groups, respectively. At awakening, it rose to approximately 44% above baseline in the amino acid group while in the controls it remained unchanged. In both groups the splanchnic blood flow was unaffected by anaesthesia or by amino acid infusions.

Preoperative infusion of amino acids prevents postoperative hypothermia.

Intraoperative infusion of amino acids has been found to stimulate energy expenditure and thereby prevent anaesthesia-induced hypothermia. Rectal temperature and respiratory gas exchange were measured in 24 female patients before and after isoflurane anaesthesia. Sixteen patients had an amino acid mixture of 240 kJ h-1, infused over 1-2 h before anaesthesia and eight control patients received saline. We compared the results with data from six female volunteers treated with amino acids; they were not premedicated or anaesthetized. In lorazepam premedicated patients, amino acids increased the pre-anaesthesia temperature by 0.3 degrees C h-1, twice that observed in the volunteers. At awakening after anaesthesia, energy expenditure increased to 50-60% above baseline in the amino acid treated patients, while in the control patients, receiving saline, no increase occurred, despite vigorous shivering. Amino acid infusion prevented hypothermia by increasing heat accumulation and causing delayed stimulation of heat production. The heat accumulation response to amino acid infusion was increased after premedication with lorazepam.