Diagnostic accuracy of acute diverticulitis with unenhanced low-dose CT.

BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of unenhanced low-dose CT (LDCT) in acute colonic diverticulitis in comparison with contrast-enhanced standard-dose CT (SDCT). METHODS: All patients with clinically suspected diverticulitis who underwent LDCT followed by SDCT between January and October 2017 were evaluated prospectively. CT examinations were assessed for signs of diverticulitis, complications and other differential diagnoses by three independent radiologists (two consultants and one fourth-year resident) using SDCT as the reference method. Sensitivity and specificity were calculated and Cohen's κ coefficient was used for agreement analyses. RESULTS: Of the 149 patients included (mean age 66·7 years, M : F ratio 0·4), 107 (71·8 per cent) had imaging consistent with diverticulitis on standard CT. Sensitivity and specificity values for a diverticulitis diagnosis using LDCT were 95-99 and 86-100 per cent respectively, and respective values for identification of complications were 58-73 and 78-100 per cent. The corresponding κ values among the three readers for diagnosis were 0·984, 0·934 and 0·816, whereas κ values for complications were 0·680, 0·703 and 0·354. Of the 26 patients who presented with other causes of abdominal symptoms identified on standard CT, 23 were diagnosed correctly on LDCT. Missed cases included splenic infarction (1) and segmental colitis (2). CONCLUSION: The diagnostic accuracy of LDCT was high for the presence of acute diverticulitis. However, as signs of complicated disease can be missed using the low-dose protocol, use of LDCT as a primary examination method should not preclude SDCT when complications may be suspected.

ANTECEDENTES: Evaluar la precisión diagnóstica de la tomografía computarizada de dosis baja (low-dose computed tomography, LDCT) sin contraste frente a la TC con dosis estándar (standard-dose CT, SDCT) con contraste en la diverticulitis aguda de colon. MÉTODOS: Todos los pacientes con sospecha clínica de diverticulitis aguda de colon a los que se realizó una LDCT seguida de una SDCT entre enero y octubre de 2017 se evaluaron prospectivamente. Tres radiólogos independientes (dos consultores y un residente de cuarto año) analizaron los signos de diverticulitis, complicaciones y otros diagnósticos diferenciales, utilizando la SDCT como método de referencia. Se calculó la sensibilidad y la especificidad, utilizándose el coeficiente κ de Cohen para los análisis de concordancia entre observadores. RESULTADOS: De los 149 pacientes incluidos en el estudio (edad media 66,7 años, varón/mujer 0,4), 107 (71,8%) presentaban unas imágenes compatibles con diverticulitis en la SDCT. La sensibilidad y la especificidad para el diagnóstico de diverticulitis con la LDCT variaban entre el 95-99% y el 86-100%, respectivamente. La sensibilidad y la especificidad para la identificación de complicaciones oscilaron entre el 58-73% y el 78-100%, respectivamente. Los valores κ entre observadores para el diagnóstico fueron del 0,98, 0,93 y 0,82, respectivamente, mientras que para las complicaciones fueron del 0,68, 0,70 y 0,35. De los 26 pacientes en los que la SDCT identificó otras etiologías como causa de sus síntomas abdominales, 23 fueron diagnosticados correctamente con la LDCT. Los casos con diagnóstico erróneo correspondían a un infarto esplénico y dos colitis segmentarias. CONCLUSIÓN: La precisión diagnóstica de la LDCT fue alta para detectar una diverticulitis aguda. Sin embargo, el protocolo de dosis baja puede no identificar los signos de la enfermedad complicada. Por lo tanto, su utilización como método de exploración primario no debe excluir la SDCT cuando se sospechen complicaciones.

Dual roles of hemidesmosomal proteins in the pancreatic epithelium: the phosphoinositide 3-kinase decides.

Given the failure of chemo- and biotherapies to fight advanced pancreatic cancer, one major challenge is to identify critical events that initiate invasion. One priming step in epithelia carcinogenesis is the disruption of epithelial cell anchorage to the basement membrane which can be provided by hemidesmosomes (HDs). However, the existence of HDs in pancreatic ductal epithelium and their role in carcinogenesis remain unexplored. HDs have been explored in normal and cancer pancreatic cells, and patient samples. Unique cancer cell models where HD assembly can be pharmacologically manipulated by somatostatin/sst2 signaling have been then used to investigate the role and molecular mechanisms of dynamic HD during pancreatic carcinogenesis. We surprisingly report the presence of mature type-1 HDs comprising the integrin α6ß4 and bullous pemphigoid antigen BP180 in the human pancreatic ductal epithelium. Importantly, HDs are shown to disassemble during pancreatic carcinogenesis. HD breakdown requires phosphoinositide 3-kinase (PI3K)-dependent induction of the matrix-metalloprotease MMP-9, which cleaves BP180. Consequently, integrin α6ß4 delocalizes to the cell-leading edges where it paradoxically promotes cell migration and invasion through S100A4 activation. As S100A4 in turn stimulates MMP-9 expression, a vicious cycle maintains BP180 cleavage. Inactivation of this PI3K-MMP-9-S100A4 signaling loop conversely blocks BP180 cleavage, induces HD reassembly and inhibits cell invasion. We conclude that mature type-1 HDs are critical anchoring structures for the pancreatic ductal epithelium whose disruption, upon PI3K activation during carcinogenesis, provokes pancreatic cancer cell migration and invasion.

Manifestations of acute appendicitis: a prospective study on acute abdominal pain.

BACKGROUND/AIMS: The aim of this prospective study was to identify the clinical symptoms and signs most important for the prediction of appendicitis among patients with acute abdominal pain. METHODS: Clinical findings in 2,478 patients admitted to the emergency department of Mora Hospital from February 1997 to June 2000, with acute abdominal pain of up to 7 days' duration, were registered in a database. The medical records were reviewed after 1 year. RESULTS: A total of 432 patients were suspected of having appendicitis and in 221 this diagnosis was confirmed. Some 53 patients, with another preliminary diagnosis, were eventually found to suffer from appendicitis, making a total of 274 patients with appendicitis. Appendectomy was performed in 316 patients and was negative in 14%. Clinical diagnosis of appendicitis had a sensitivity of 0.81, a specificity of 0.90, a positive predictive value of 0.51, a positive likelihood ratio of 8.1, and a diagnostic accuracy of 0.89. The highest odds ratios were found for isolated tenderness in the right iliac fossa (3.29), rebound tenderness (3.00), right-sided rectal tenderness (2.53), migration of pain to the right iliac fossa (2.18), and local guarding (2.11). CONCLUSION: Clinical findings indicating localised inflammation in the right iliac fossa were reliable in predicting acute appendicitis. The patients' history of pain combined with a careful clinical examination still plays an important role in detecting appendicitis among patients with acute abdominal pain.

Estrogen receptor actions on vascular biology and inflammation: implications in vascular pathophysiology.

Whereas hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in menopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required at both a cellular and molecular level. Both the endothelium and the immuno-inflammatory system play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. E2 promotes beneficial actions on the endothelium such as nitric oxide and prostacyclin production. E2 actions are essentially mediated by two molecular targets: estrogen receptor alpha (ER-alpha) and beta (ER-beta), but the former appears to mediate most of the actions of E2 on the endothelium and on the immune system. ER-alpha modulates target gene transcription through two activation functions (AF), AF-1 and AF-2, even though signalling via ER-alpha located at the plasma membrane (responsible for membrane-initiated steroid signalling (MISS)/(extra-genomic)) can also lead to an indirect effect on gene transcription. Recently, we demonstrated that ER-alpha AF-1 is not required for the vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. These results suggest that selective estrogen receptor modulators stimulating ER-alpha with minimal activation of ER-alpha AF-1 could retain beneficial vascular actions, while minimizing the sexual effects.

Impact of time in the development of acute appendicitis.

BACKGROUND: The aim of this study was to elucidate the natural history of appendicitis. METHODS: Data was collected prospectively from consecutive patients admitted to hospital for acute abdominal pain. The degree of appendiceal inflammation in relation to preoperative duration of pain was analysed. RESULTS: The study comprised 253 patients operated on for acute appendicitis that could recall the onset of abdominal pain. There was a longer duration of pre-hospital pain in patients, irrespective of age, with perforated appendicitis compared to patients with phlegmonous or gangrenous appendicitis (p < 0.001). In the multivariate analysis, patient age and preoperative duration of pain were independent risk factors for perforation. CONCLUSION: Patient delay in presentation is the predominant factor determining the incidence of complicated appendicitis, and this delay is not influenced by age or gender.

Role of inflammatory cytokines in the effect of estradiol on atheroma.

1. Although hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in postmenopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. 2. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Although E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo involving several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. The functional role of several cytokines was explored in hypercholesterolemic mice. The atheroprotective effect of E2 was fully maintained in mice deficient in interferon-g or interleukin-12, as well as IL-10. In contrast, the protective effect of estradiol was abolished and even reversed in hypercholesterolemic mice given a neutralizing anti-transforming growth factor-b (TGF-b) antibody. Endothelium is another important target for E2, since it not only potentiates endothelial nitric oxide and prostacyclin production, but also controls trafficking of the populations of the immuno-inflammatory system. 3. To conclude, the respective actions of oestrogens on the cell populations involved in the pathophysiology of atherothrombosis may be influenced, among others, by the timing of HT initiation, the status of the vessel wall and, as recently demonstrated the status of the TGF-b pathway.

Acute diverticulitis--clinical presentation and differential diagnostics.

OBJECTIVE: To describe the clinical presentation of acute diverticulitis in an emergency department and to characterize the natural history of diverticulitis in the short perspective. Comparisons are made with an important differential diagnosis, nonspecific abdominal pain (NSAP). METHOD: Patients admitted to our hospital with abdominal pain of up to 7 days' duration were registered prospectively using a detailed schedule for history, symptoms and signs, from 1 February 1997 to 1 June 2000. Of 3349 patients initially included, 3073 (92%) were eligible for follow up after 1-3 years. RESULTS: Acute diverticulitis was the final diagnosis in 145 patients and NSAP in 1142 patients. The incidence of hospitalized patients with diverticulitis was 47 per year and 100 000 population, with a mean hospital stay of 3.3 days. Patients with diverticulitis, more frequently than NSAP, had a longer history and laboratory signs of inflammatory activity. Isolated left abdominal tenderness was more common in diverticulitis, whereas isolated right abdominal tenderness was more common in NSAP. Duration of symptoms on arrival was independent of age and was not correlated to C-reactive protein, leucocytes or body temperature. Sensitivity of diverticulitis as primary diagnosis was 64% and specificity 97%. Corresponding figures for NSAP were 43% and 90% respectively. Age and gender did not influence diagnostic accuracy or risk of surgery. CONCLUSION: Diverticulitis differs significantly from NSAP in clinical presentation and laboratory parameters. Sensitivity of primary diagnosis for diverticulitis and NSAP was low.

Understanding the oestrogen action in experimental and clinical atherosclerosis.

Whereas hormone replacement/menopause therapy (HRT) in postmenopausal women increases the coronary artery risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of oestradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits in vivo a proinflammation at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for E2, as it potentiates endothelial NO and prostacyclin production, thus promoting the beneficial effects as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appears to be involved in the atheroprotective effect of E2. E2 also accelerates endothelial regrowth, thus favouring vascular healing. Finally, most of these effects of E2 are mediated by oestrogen receptor alpha, and are independent of oestrogen receptor beta. In summary, a better understanding of the mechanisms of oestrogen action not only on the normal and atheromatous arteries, but also on innate and adaptive immune responses is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective oestrogen receptor modulators.

Why do surgeons miss malignancies in patients with acute abdominal pain?

BACKGROUND: The aim of this study was to characterize patients seeking medical advice for acute abdominal pain who were later diagnosed with an intra-abdominal malignancy. PATIENTS AND METHODS: Patients with acute abdominal pain were registered between 1997 and 2000, employing a detailed schedule comprising 111 parameters. The diagnoses (n=2395 patients) were re-evaluated one year later. RESULTS: A total of 66 patients (2.8%) were found to have an intra-abdominal malignancy at follow-up, of whom 37 cases had been undetected at discharge. Malignancy of the liver, biliary tract and pancreas constituted 30% and colorectal cancer 32% of the tumours undetected at discharge. Constipation, intestinal obstruction and non-specific abdominal pain (NSAP) were the most common preliminary diagnoses in patients among whom abdominal malignancy was later detected. CONCLUSION: Except for age and pain duration, the history and clinical investigation provide few clues to suggest an abdominal malignancy in patients with acute abdominal pain. NSAP, of unknown or known etiology, including constipation, should be suspected as a possible sign of abdominal malignancy in all patients over 50 years of age.

Acute abdominal pain among elderly patients.

BACKGROUND: Diagnosis of acute abdominal pain in older persons is a challenge, with the age-related increase in concurrent diseases. In most western countries the number of elderly people is constantly rising, which means that an increasing proportion of patients admitted for abdominal pain at the emergency department are elderly. OBJECTIVE: To characterize differences in clinical presentation and diagnostic accuracy between younger and more elderly patients with acute abdominal pain. METHODS: Patients admitted to Mora Hospital with abdominal pain of up to seven days' duration were registered according to a detailed schedule. From 1st February 1997 to 1st June 2000, 557 patients aged 65-79 years and 274 patients aged > or = 80 years were registered. Patients aged 20-64 years (n = 1,458) served as a control group. RESULTS: A specific diagnosis, i.e. other than 'nonspecific abdominal pain', was established in 76 and 78% of the patients aged 65-79 and > or = 80 years respectively, and in 64% of those aged 20-64 (p < 0.001). Pain duration before admission increased with age (p < 0.003), as did frequency and duration of hospitalization (p < 0.0001). Hospital stay increased from 170 days per 100 emergency admissions in the control group to 320 and 458 days in the younger and older study groups, respectively. At the emergency department, older patients were more often misdiagnosed than control patients (52 vs. 45%; p = 0.002). At discharge the diagnosis was more accurate in the control group (86 vs. 77%; p < 0.0001). Hospital mortality was higher among older patients (23/831 vs. 2/1,458; p < 0.001). The admission-to-surgery interval was increased (1.8 vs. 0.9 days, p < 0.0001) in patients > or = 65 years. Rebound tenderness (p < 0.0001), local rigidity (p = 0.003) and rectal tenderness (p = 0.004) were less common in the older than in the control patients with peritonitis. In patients > or = 65 years, C-reactive protein did not differ between patients operated on and those not, contrary to the finding in patients < 65 years (p < 0.0001). CONCLUSION: Both the preliminary diagnosis at the emergency department and the discharge diagnosis were less reliable in elderly than in younger patients. Elderly patients more often had specific organic disease and arrived at the emergency department after a longer history of abdominal pain compared to younger patients.

Estradiol action in atherosclerosis and reendothelialization.

Whereas hormonal replacement/menopause therapy (HRT) in postmenopausal women increases coronary artery disease risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required. The atheroprotective effect of E2 is absent in mice deficient in mature T and B lymphocytes, demonstrating the crucial role of the endothelium/immune system pair. The immunoinflammatory system appears to play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it elicits in vivo a proinflammation at the level of several subpopulations of the immunoinflammatory system, which could contribute to plaque destabilization. Endothelium appears to be an important target for E2, since it potentiates endothelial NO and prostacyclin production, thus promoting beneficial effects such as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appear to be involved in the atheroprotective effect of E2, which also accelerates endothelial regrowth, thus favoring vascular healing. Finally, most of these E2 effects are mediated by estrogen receptor alpha and are independent of estrogen receptor beta. In summary, a better understanding of the mechanisms of estrogens on the normal and atheromatous arteries is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective estrogen receptor modulators (SERMs).

Hacia unas carreteras sin alcohol en Europa / Towards alcohol free roads in Europe

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Worldwide trends in alcohol and drug impaired driving.

Improved laws, enhanced enforcement, and public awareness brought about by citizens' concern, during the 1980s led to dramatic declines in drinking and driving in the industrialized world. The declines included about 50% in Great Britain, 28% in The Netherlands, 28% in Canada, 32% in Australia, 39% in France, 37% in Germany, and 26% in the United States. Some of these declines may be due in part to lifestyle changes, demographic shifts, and economic conditions. In most countries the declines reversed in the early 1990s and drinking and driving began to increase. By the middle of that decade the increases stabilized and the rates of drinking and driving again began to decline. These decreases were much less dramatic than those in the 1980s. Approaching the end of the 1990s and early in the new century, the record has been mixed. Some countries (France and Germany (until 2002)) continued to reduce drinking and driving while in other countries (Canada, the Netherlands, Great Britain, and the United States), there was stagnation and in some cases small increases or even large increase as was the case in Sweden. Complacency and attention to other issues in recent years have been difficult to overcome in some countries. Harmonization of traffic safety laws in the European Union has strengthened laws in some countries but threatens existing strong policies in others. It may be that the major gains have already been made and that additional progress will require a much greater level of scientific knowledge, use of new and emerging technologies, and political and social commitment to put in place proven countermeasures.

[Psychosocial survey of drunken drivers within the KAPUBRA project. A new interview technique suitable for matching the right treatment with the right client]. / Psykosocial kartläggning av rattfyllerister inom KAPUBRA-projektet. Ny intervjumetod lämplig för att para ihop rätt behandling med rätt klient.

Three different programs for individuals convicted of drunken driving are being evaluated in a randomized design in collaboration between researchers at the Karolinska Institute and the Prison and Probation Service in Sweden. In the years 1996-1998, 912 clients were interviewed by means of a structured interview, the Addiction Severity Index (ASI), which covers seven problem areas (medical status, alcohol use, employment status, drug use, legal status, family/social and psychiatric status). So far about half of the subjects have been re-investigated two years after leave. Initially, the group being investigated had problems particularly in the areas of criminality and alcohol use. Two years later a positive trend in most of the problem areas could be observed for clients in follow-up.

Analysis of the psychrotolerant property of hormone-sensitive lipase through site-directed mutagenesis.

Mammalian hormone-sensitive lipase (HSL) has given its name to a family of primarily prokaryotic proteins which are structurally related to type B carboxylesterases. In many of these alpha/beta hydrolases, a conserved HG-dipeptide flanks the catalytic pocket. In HSL this dipeptide is followed by two additional glycine residues. Through site-directed mutagenesis, we have investigated the importance of this motif for enzyme activity. Since the presence of multiple glycine residues in a critical region could contribute to cold adaptation by providing local flexibility, we studied the effect of mutating these residues on the psychrotolerant property of HSL. Any double mutation rendered the enzyme completely inactive, without any major effect on the enzyme stability. The partially active single mutants retained the same proportion of activity at reduced temperatures as the wild-type enzyme. These results do not support a role for the HGGG motif in catalysis at low temperatures, but provide further validation of the current three-dimensional model of HSL. Rat HSL was found to be relatively more active than human HSL at low temperatures. This difference was, however, not due to the 12 amino acids which are present in the regulatory module of the rat enzyme but absent in human HSL.

FIF [fibroblast growth factor-2 (FGF-2)-interacting-factor], a nuclear putatively antiapoptotic factor, interacts specifically with FGF-2.

Numerous evidence indicates that some of the activities of fibroblast growth factor 2 (FGF-2) depend on an intracrine mode of action. Recently, we showed that three high molecular mass (HMM) nuclear forms of FGF-2 are part of a 320-kDa protein complex while the cytoplasmic AUG-initiated form is included in a 130-kDa complex. Consequently, the characterization of FGF endogenous targets has become crucial to allow the elucidation of their endogenous activities. Through the screening of GAL4-based yeast two-hybrid expression libraries, we have isolated a gene encoding a nuclear protein of 55 kDa, FIF (FGF-2-interacting-factor), which interacts specifically with FGF-2 but not with FGF-1, FGF-3, or FGF-6. In this system, FIF interacts equally well with the NH2-extended 24-kDa FGF form as with the 18-kDa form, indicating that the FIF-binding motif is located in the last 155 amino acids of FGF-2. Nevertheless, coimmunoprecipitation experiments showed an exclusive association with HMM FGF-2. The predicted protein contains a canonical leucine zipper domain and three overlapping hydrophobic heptad repeats. The region spanning these repeats is, together with a region located in the N-terminal part of the FIF protein, implicated in the binding to FGF-2. In contrast to the full-length FIF protein, several deletion constructs were able to transactivate a lac-Z reporter gene. Furthermore, the COOH-terminal part, but not the full-length FIF protein, has previously been shown to exhibit antiapoptotic properties. Thus we discuss the possibility that these activities could reflect a physiological function of FIF through its interaction with FGF-2.

Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.

Hormone-sensitive lipase, the rate-limiting enzyme of intracellular TG hydrolysis, is a major determinant of fatty acid mobilization in adipose tissue as well as other tissues. It plays a pivotal role in lipid metabolism, overall energy homeostasis, and, presumably, cellular events involving fatty acid signaling. Detailed knowledge about its structure and regulation may provide information regarding the pathogenesis of such human diseases as obesity and diabetes and may generate concepts for new treatments of these diseases. The current review summarizes the recent advances with regard to hormone-sensitive lipase structure and molecular mechanisms involved in regulating its activity and lipolysis in general. A summary of the current knowledge regarding regulation of expression, potential involvement in lipid disorders, and role in tissues other than adipose tissue is also provided.

The putative role of the hormone-sensitive lipase gene in the pathogenesis of Type II diabetes mellitus and abdominal obesity.

Impaired lipolysis has been proposed as a pathogenic factor contributing to clustering of abdominal obesity and dyslipidaemia in Type II (non-insulin-dependent) diabetes mellitus--that is, the metabolic syndrome (MSDR). As this syndrome clusters in families, alterations in the hormone-sensitive lipase (HSL) gene could contribute to the genetic predisposition to MSDR. To test this hypothesis we carried out population and intrafamily association studies in individuals with MSDR, using a polymorphic marker (LIPE) in the HSL gene. There was a significant difference in allele frequency distribution between 235 Type II diabetic patients and 146 control subjects (p = 0.002), particularly between 78 abdominally obese Type II diabetic patients with MSDR and the control group (p = 0.010). An extended transmission disequilibrium test (TDT) showed transmission disequilibrium of 66 alleles to 42 nondiabetic, abdominally obese offspring in families with Type II diabetes (p < 0.05). A slight difference in allele frequency distribution was seen between 71 individuals from the lowest and 71 from the highest tertile of isoprenaline-induced lipolysis in fat tissue (p = 0.07). No missense mutations were found with single-strand conformational polymorphism (SSCP) in 20 abdominally obese subjects with MSDR. In conclusion, our population and intrafamily association studies suggest that the LIPE marker in the HSL gene is in linkage disequilibrium with an allele and/or gene which increases susceptibility to abdominal obesity and thereby possibly to Type II diabetes.