18F-Labelling of electron rich iodonium ylides: application to the radiosynthesis of potential 5-HT2A receptor PET ligands.

18F-Labelling of aromatic moieties was limited to electron deficient aromatic systems for many years but recent developments have provided access to the direct labelling of electron rich aromatic systems. Herein we report the synthesis and 18F-labelling of iodonium ylide precursors in the pursuit of 18F-labelled 5-HT2A receptor agonist PET-ligands. Subsequent evaluation in pigs showed high brain uptake of the PET ligands but a blocking dose of ketanserin did not significantly reduce the signal in relevant brain regions - indicating that the ligands do not interact specifically with the 5-HT2A receptor in vivo.

Short-term impact of HbA1c on morbidity and all-cause mortality in people with type 2 diabetes: a Danish population-based observational study.

AIMS/HYPOTHESIS: In a population-based setting, we investigated whether diabetes-related morbidity and all-cause mortality within 2 years of HbA(1c) measurement were associated with that HbA(1c) level in individuals with type 2 diabetes. The main objective was to compare outcomes in those with HbA(1c) ≥ and <7% (53 mmol/mol). METHODS: Individuals with type 2 diabetes from Aarhus County, Denmark, were identified from public data files in a 3 year period (2001-2003). Stratifying the 17,760 individuals by HbA(1c), we estimated HRs for diabetes-related morbidities and all-cause mortality using Cox regression. Results were also stratified by treatment modality. RESULTS: In total, 1,805 individuals experienced at least one diabetes-related morbidity and 1,859 individuals died. In general, the HRs in adjusted analyses of diabetes-related morbidity and mortality were increased for HbA(1c) ≥ 7% (53 mmol/mol): morbidity, HR 1.48 (95% CI 1.34, 1.63); and mortality, HR 1.26 (95% CI 1.15, 1.39). On grouping individuals according to HbA(1c) <5% (31 mmol/mol), 5.0-5.9% (31-41 mmol/mol), 6.0-6.9% (42-52 mmol/mol), 7.0-7.9% (53-63 mmol/mol), 8.0-8.9% (64-74 mmol/mol) and ≥ 9% (75 mmol/mol), the HRs for mortality formed a U shape, with HbA(1c) 6.0-6.9% (42-52 mmol/mol) at the lowest point. For diabetes-related morbidity, a dose-response pattern appeared (lowest for HbA(1c) < 5% [31 mmol/mol]). Patterns of HR differed with treatment modality. CONCLUSIONS/INTERPRETATION: An HbA(1c) level ≥ 7% (53 mmol/mol) was associated with increased morbidity and mortality. Both high and very low levels of HbA(1c) were associated with increased mortality. A dose-response pattern appeared for morbidity. The impact of HbA(1c) level on morbidity and mortality depended on treatment modality.

Improved quality of Type 2 diabetes care following electronic feedback of treatment status to general practitioners: a cluster randomized controlled trial.

AIMS: To evaluate the effect of an electronic feedback system to general practitioners on quality of Type 2 diabetes care. METHODS: A cluster randomized, controlled trial with 15 months follow-up. Eighty-six general practices (158 general practitioners) in a Danish county caring for 2458 people 40-70 years old with Type 2 diabetes were randomized to receive or not to receive electronic feedback on quality of care. People with Type 2 diabetes were identified using a validated algorithm. Primary end-points were processes of care according to guidelines on prescriptions redeemed for Type 2 diabetes treatments, measuring of glycated haemoglobin and cholesterol and visits to ophthalmologists. Secondary end-points were changes in level of glycated haemoglobin and serum cholesterol. Data were analysed using generalized linear models accounting for clustering at practice level. RESULTS: During follow-up, people with Type 2 diabetes in the intervention group more often redeemed recommended prescriptions than people in the control group, respectively, as follows: oral antidiabetic treatment (32.8 vs. 12.0%, P =0.002), insulin treatment (33.8 vs. 12.4%, P < 0.001), lipid-lowering medication (38.3 vs. 18.6%, 0.004) and blood pressure medication (27.6 vs. 16.3%, P = 0.026). There were no differences in mean glycated haemoglobin and serum cholesterol between the two groups. CONCLUSIONS: Electronic feedback to general practitioners on the quality of Type 2 diabetes care resulted in significantly improved quality regarding processes of care according to guidelines. It was not possible to demonstrate any effect on secondary end-point measures within the follow-up period. Electronic feedback on quality of diabetes care can be effective in improving adherence to treatment according to evidence-based guidelines.

Decreased work productivity due to primary palmar hyperhidrosis. What is the cost?

A decrease of 7,2 % in productivity was found in patients suffering from palmar hyperhidrosis. A correction of this could more than pay for the treatment with botulinum-toxins, even 3 or 4 times a year.

Enzymatic generation of hydrogen peroxide shows promising antifouling effect.

The antifouling (AF) potential of hydrogen peroxide (H(2)O(2)) produced enzymatically in a coating containing starch, glucoamylase, and hexose oxidase was evaluated in a series of laboratory tests and in-sea field trials. Dissolved H(2)O(2) inhibited bacterial biofilm formation by eight of nine marine Proteobacteria, tested in microtiter plates. However, enzymatically produced H(2)O(2) released from a coating did not impede biofilm formation by bacteria in natural seawater tested in a biofilm reactor. A field trial revealed a noticeable effect of the enzyme system: after immersion in the North Sea for 97 days, the reference coating without enzymes had 35-40 barnacles, 10% area coverage by diatoms and 15% area coverage by tunicates. The enzyme containing coating had only 6-12 barnacles, 10% area coverage by diatoms and no tunicates. The enzyme system had a performance similar to a copper-based commercial coating and thus appears to have potential as a non-persistent AF agent.

Urinary incontinence in spinal cord injured individuals 10-45 years after injury.

STUDY DESIGN: Epidemiological follow-up study. OBJECTIVE: To evaluate urinary incontinence and its management in a population of individuals with long-term spinal cord injury (SCI). SETTING: Clinic for Spinal Cord Injuries and Department of Urology, Copenhagen University Hospital, Rigshospitalet, Denmark. METHODS: Retrospective data collection from the patient records and information from a follow-up questionnaire of traumatic SCI individuals at least 10 years after injury. A total of 236 patients participated (84.6% response), 82% males and 18% females, 47% tetraplegic and 53% paraplegic, injured between 1956 and 1990. Age at the time of follow-up was 28-84 years (mean 50.5 years). Years of follow-up were 10-45 years (mean 24.1 years). RESULTS: A total of 43% of the participants reported incontinence from less than once a week to daily. There was a significant linear trend across the groups of incontinence with more paraplegics reporting daily incontinence compared with tetraplegics. A higher proportion of participants using clean intermittent catheterization reported incontinence (56%) compared with participants using other bladder-emptying methods. Only 19% of the participants used medication for the management of incontinence. CONCLUSION: Urinary incontinence is a common problem in individuals with SCI. Only a minority of individuals used medication for the treatment of incontinence. SPONSORSHIP: This study was carried out as a part of the primary author's PhD study, financed by the Medicon Valley Academy and Coloplast A/S.

The Danish National Diabetes Register: trends in incidence, prevalence and mortality.

AIMS/HYPOTHESIS: The aim of the study was to describe trends in the incidence rate, prevalence and mortality rate for diabetes in Denmark. METHODS: Healthcare registers at the National Board of Health were used to compile a register of diabetic patients in the Danish population (5.4 million people). Age- and sex-specific prevalence, incidence rates, mortality rates and standardised mortality ratios relative to the non-diabetic part of the population were calculated. RESULTS: The register contains records for about 360,000 persons with diabetes; 230,000 were alive at 1 January 2007, corresponding to an overall prevalence of 4.2%. The prevalence increased by 6% per year. In 2004 the incidence rates were 1.8 per 100,000 at age 40 years and 10.0 per 100,000 at age 70 years. The incidence rate increased 5% per year before 2004 and then stabilised. The mortality rate in the diabetic population decreased 4% per year, compared with 2% per year in the non-diabetic part of the population. The mortality rate decreased 40% during the first 3 years after inclusion in the register. The standardised mortality ratio decreased with age, from 4.0 at age 50 years to 2.5 at age 70 years and just under 2 at age 85 years, identically for men and women. The standardised mortality ratio decreased 1% per calendar year. The lifetime risk of diabetes was 30%. CONCLUSIONS/INTERPRETATION: The prevalence of diabetes in Denmark rose in 1995-2006, but the mortality rate in diabetic patients decreased faster than that of the non-diabetic population. The mortality rate decreased markedly just after inclusion in the register. Incidence rates have shown a tendency to decrease during the last few years, but this finding should be viewed with caution.

Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes.

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.

Improving the compaction properties of roller compacted calcium carbonate.

The effects of roller compaction process parameters, morphological forms of calcium carbonate and particle size of sorbitol on flow, compaction and compression properties were investigated. The morphology of the calcium carbonate and the sorbitol particle size were more influential on the compaction properties than the settings of the roller compactor. The roller compaction process was demonstrated to be robust and stable in regard to flowability and compactibility. The flowability of the granules was improved adequately to facilitate compression in a production scale rotary tablet press. By adding sorbitol to the calcium carbonate, the compressibility - characterized by the Walker coefficient W(ID) - and the compactibility C(P) were improved considerably. A correlation between the consolidation characteristics was demonstrated. Compactibility data from the compaction simulator correlated with the tablet press for two of the calcium carbonates, the cubic form and the ground quality.

High-affinity von Willebrand factor binding does not affect the anatomical or hepatocellular distribution of factor VIII in rats.

UNLABELLED: Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII clearance. Hepatocytes and liver sinusoidal endothelial cells play a key role in FVIII clearance. Anatomical and hepatocellular distribution of FVIII is independent of high-affinity VWF binding. ABSTRACT: Background Von Willebrand factor (VWF) stabilizes factor VIII in the circulation and prevents its premature clearance. Objective To study the effects of VWF on FVIII clearance in rats with endogenous VWF. Methods Anatomical and hepatocellular distribution studies were performed in rats following intravenous administration of glycoiodinated recombinant FVIII (rFVIII) and a FVIII variant, FVIII-Y1680F, lacking high-affinity VWF binding. Radioactivity was quantified in organs, and in distinct liver cell populations. The role of VWF binding was also studied by immunohistochemical staining of rat livers perfused ex vivo with rFVIII alone or with a FVIII-binding VWF fragment. Results The liver was the predominant organ of rFVIII distribution, and a radioactivity peak was also observed in the intestines, suggesting FVIII secretion to the bile by hepatocytes. In the liver, ~60% of recovered radioactivity was associated with hepatocytes, 32% with liver sinusoidal endothelial cells (LSECs), and 9% with Kupffer cells (KCs). When calculated per cell, 1.5-fold to 3-fold more radioactivity was associated with LSECs than with hepatocytes. The importance of hepatocytes and LSECs was confirmed by immunohistochemical staining; strong staining was seen in LSECs, and less intense, punctate staining in hepatocytes. Minor staining in KCs was observed. Comparable anatomical and hepatocellular distributions were observed with rFVIII and FVIII-Y1680F, and the presence of the VWF fragment, D'D3A1, did not change the FVIII staining pattern in intact livers. Conclusions The present data support FVIII clearance via the liver, with hepatocytes and LSECs playing a key role. High-affinity VWF binding did not alter the anatomical or hepatocellular distribution of FVIII.

Studies on the urea cycle enzyme ornithine transcarbamylase using heavy atom isotope effects.

Ornithine transcarbamylase (OTCase) catalyzes the reaction between L-ornithine and carbamyl phosphate in the first step of the urea cycle. 13C isotope effects were measured in carbamyl phosphate, using OTCase obtained from E. coli in a one-column purification which yielded 30 mg of very pure enzyme from 51 of cell culture. At near zero L-ornithine, the 13C kinetic isotope effect was 1.0095, at high levels of L-ornithine (86 mM) the 13C kinetic isotope effect was unity, and 0.83 mM ornithine was found to eliminate half the isotope effect. These results are indicative of an ordered kinetic mechanism in which carbamyl phosphate binds to the enzyme before L-ornithine. Similar experiments were performed using the slow substrate L-lysine in place of L-ornithine. At 90 mM L-lysine the 13C kinetic isotope effect was large, 1.076. This value is most likely the intrinsic kinetic isotope effect with this substrate, and the chemistry of the enzyme catalyzed reaction has become rate limiting.

Feasibility of the fluorometric microculture cytotoxicity assay (FMCA) for cytotoxic drug sensitivity testing of tumor cells from patients with acute lymphoblastic leukemia.

The automated fluorometric microculture cytotoxicity assay (FMCA) was used for chemotherapeutic drug sensitivity testing of fresh and cryopreserved tumor cells from patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse. The technique success rate was 87% for fresh and 81% for cryopreserved samples. Up to 16 different cytotoxic drugs were routinely tested, but neither asparaginase nor methotrexate produced dose-response related cell kill. FMCA data showed good correlation to the well established Disc assay and the drug sensitivity reported by the FMCA was in good agreement with known clinical activity. Samples from children and initial ALL tended to be more drug sensitive than those from adults and ALL at relapse, respectively. For 36 samples clinical outcome was correlated to the quartile position in comparison to all other samples for the most in vitro active drug actually given to the patient. For patients with samples in the first, second, third, and fourth quartiles, the probabilities of complete remission were 89, 57, 38, and 0%, respectively. Using the median value as cut-off line, the sensitivity and specificity of the assay were 87 and 62%, respectively. It is concluded that the FMCA with a minimum of effort and with high success rate report clinically relevant drug sensitivity profiles for ALL.

Interactions between cladribine (2-chlorodeoxyadenosine) and standard antileukemic drugs in primary cultures of human tumor cells from patients with acute myelocytic leukemia.

The semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, was used for in vitro evaluation of Cladribine (2-chlorodeoxyadenosine, CdA) interactions with five standard antileukemic drugs: amsacrine (Am), etoposide (VP16), daunorubicin (Dnr), cytosine arabinoside (AraC), and mitoxantrone (Mit). Samples from 31 patients with acute myelocytic leukemia (AML) were tested with continuous drug exposure. A large heterogeneity with respect to cell kill was observed for all combinations tested. An additive model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) only for CdA+AraC. When the frequency of additive and synergistic interactions were calculated according to the multiplicative concept for drug interactions, the highest frequencies were observed for CdA+AraC and CdA+Dnr. This interaction pattern was confirmed by isobologram analysis. Cross-resistance analysis revealed high correlations between CdA and AraC whereas the correlations were weaker between CdA and the other drugs. The highest frequency of synergistic interactions was obtained for AraC+CdA, despite their cross-resistance. Of the non-cross-resistant drugs tested, Dnr appears to be the most effective adjunct to CdA in terms of interactions at the cellular level.

The effect of penile vibratory stimulation on male fertility potential, spasticity and neurogenic detrusor overactivity in spinal cord lesioned individuals.

PURPOSE: Present the possibility for treatment of male infertility, spasticity, and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals with penile vibratory stimulation (PVS). METHOD: Obtaining reflex-ejaculation by PVS, by using a vibrator developed for this purpose. The stimulation was performed with a vibrating disc of hard plastic placed against the frenulum of the penis (amplitude > or = 2.5 mm). The vibration continued until antegrade ejaculation or for a maximum of 3 minutes followed by a pause of 1 minute before the cycle was repeated, maximally 4 times. RESULTS: >80% SCL men are able to obtain ejaculation with PVS. Pregnancy rates obtained with home PVS and intra-vaginal insemination was 22-62% (4 studies), and with PVS or electroejaculation and intrauterine insemination/in-vitro fertilization/intracytoplasmatic sperm injection 39-64% (9 studies). PVS was demonstrated to decrease spasticity significantly when measured by the modified Ashworth scale. In addition, a decrease of the number of spontaneous EMG events which probably indicate spasms was observed. Increase in bladder capacity at leakpoint following 4 weeks of frequent ejaculation with PVS treatment was likewise demonstrated. CONCLUSION: PVS has proved its importance for SCL male fertility, in the years to come its place in treatment of spasticity and neurogenic detrusor overactivity has to be established.

Fatal Disseminated Toxoplasma gondii Infection in a Captive Harbour Porpoise (Phocoena phocoena).

A 7-year-old female harbour porpoise (Phocoena phocoena), born and held in captivity, suffered from reduced consciousness, imprecise and circling swimming movements and long phases of immobility over a period of 3 weeks. The animal died during treatment in a Danish open sea facility. Pathological examination revealed multifocal pyogranulomatous to necrotizing meningoencephalomyelitis, ganglioneuritis, plexus chorioiditis, myocarditis, hepatitis and adrenalitis with few intralesional protozoal tachyzoites and bradyzoites within cysts. Immunohistochemistry was positive for Toxoplasma gondii antigen within the lesions. Using polymerase chain reaction (PCR), the presence of T. gondii-specific genome fragments was confirmed. A multilocus PCR-restriction fragment length polymorphism analysis using nine unlinked marker regions (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) resulted in the identification of T. gondii type II (variant Apico Type I), which is the T. gondii genotype dominating in Germany. This is the first description of disseminated fatal toxoplasmosis in a captive harbour porpoise that lived in an open sea basin. Surface water contaminated with toxoplasma oocysts is regarded as the most likely source of infection.

Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders.

OBJECTIVES: Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer. DESIGN AND METHODS: Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls. RESULTS: The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls. CONCLUSIONS: MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases.

Reactive hyperemia in cutaneous tissue in generalized scleroderma.

Reactive hyperemia following ischemia in cutaneous tissue of human fingers was studied in 6 normal persons and 9 patients suffering from generalized scleroderma. Ischemia lasting 6 or 12 min was induced by inflating a cuff placed around the proximal phalanx to 300 mm Hg. Blood flow was measured by the local atraumatic 133Xenon wash-out technique. The following parameters were calculated: (1) Maximum blood flow was calculated from the steepest part of the wash-out curve following release of the cuff. (2) Excess cumulative blood flow, i.e., the integrated blood flow from release of cuff until preischemic blood flow values were obtained, minus preischemic blood flow times duration of ischemia. (3) Repayment, i.e., excess cumulative blood flow in percent of preischemic blood flow times duration of ischemia. Maximum blood flow, excess cumulative blood flow and repayment was decreased in the patients compared to normals. This might be due to structural changes of the blood vessel walls and/or functional changes of the vascular smooth muscle cells in scleroderma.

Local regulation of digital blood flow in generalized scleroderma.

A decreasing activity of the vascular bed upon changes in vascular transmural pressure and changes in arterial perfusion pressure head was observed from hand to fingers and from subcutis to cutis in patients suffering from generalized scleroderma. These findings are expressions of deteriorating vascular smooth muscle function. The reactive hyperemia response was decreased in subcutaneous as well as cutaneous tissue in patients fingers and in 4 of 7 patients the response was absent from the finger tip. The reactive hyperemia response of the patients resembled responses obtained in normal fingers during decrease in local perfusion blood pressure, during local cooling or after infiltration of norepinephrine around the digital arteries. This implied an increased digital artery resistance in generalizing scleroderma. A positive feed back loop between cooling, increase in digital artery resistance, increase in blood viscosity and a passive vascular bed is proposed as an important factor in Raynaud's phenomenon.

Blood flow in fingers in generalized scleroderma with Raynaud's phenomenon: influence of arterial blood pressure reduction and proximal vasodilatation.

Maximum reactive hyperemia following vascular occlusion can be taken as an estimate of tissue blood flow capacity. Ten patients with generalized scleroderma and Raynaud's phenomenon and 7 normals were studied. Blood flow was estimated in subcutaneous tissue of fingers by the local 133Xenon washout technique. Blood pressure cuffs were applied around the upper arm and a finger just proximal to the 133Xenon depot. Blood flow was estimated before and after inflation of each cuff. Decrease in arterial perfusion pressure head in fingers was obtained in 3 ways, viz. (a) by proximal vasodilatation, (b) by elevation of the limb, and (c) the combination of (a) and (b). At heart level, maximum 133Xenon washout rate was always lower when the whole arm participated in the hyperemia illustrating the effect of proximal vasodilatation. Maximum blood flow was significantly decreased in the patients as compared to normals. When the fingers were elevated by 40 cm, reactive hyperemia disappeared in the patients. In normals, hyperemia was not abolished until the fingers were elevated by 60 cm. This simple maneuvre might be a suitable provocation test showing the effect of a decrease in arterial perfusion pressure, when organic vascular stenosis exists. Seemingly unimportant lowerings of systemic blood pressure probably are followed by similar changes in finger blood pressure in the patients where they may represent a drastic reduction in blood pressure. This effect may have consequences for the use of systemic vasodilator drugs in late scleroderma.

Evaluation of cutaneous blood flow responses by 133Xenon washout and a laser-Doppler flowmeter.

A new method for noninvasive measurement of cutaneous blood flow is laser-Doppler flowmetry. The technique is based on the fact that laser light is back-scattered from the moving red blood cells, with Doppler-shifted frequencies; these impulses lead to photodetectors and are converted to flow signals. In this work we used a new system with a low noise level. Comparison was made between this technique and the atraumatic epicutaneous 133Xenon technique for measurement of cutaneous blood flow during reactive hyperemia and orthostatic pressure changes. The laser-Doppler flowmeter seems to measure blood flow in capillaries as well as in arteriovenous anastomoses, while the 133Xe method probably measures only capillary flow. A calibration of the laser-Doppler method against the 133Xe method would appear to be impossible in skin areas where arteriovenous anastomoses are present. The changes in blood flow during reactive hyperemia, orthostatic pressure changes, and venous stasis were found to be parallel as measured by the two methods in skin areas without shunt vessels. The laser-Doppler flowmeter would appear to be a useful supplement to the 133Xe washout method in cutaneous vascular physiology, but it is important to keep in mind that different parameters may be measured.