Clinical Chemistry 45: 2200-2206, 1999;
(Clinical Chemistry. 1999;45:2200-2206.)
© 1999 American Association for Clinical Chemistry, Inc.
Influence of Repetitive Finger Puncturing on Skin Perfusion and Capillary Blood Analysis in Patients with Diabetes Mellitus
Jurgen C. de Graaff1,
Geesje J. Hemmes2,
Taco Bruin3,
Dirk T. Ubbink1,a,
Robert P.J. Michels2,
Michael J.H.M. Jacobs1 and
Gerard T.B. Sanders3
Departments of
1
Vascular Surgery,
2
Internal Medicine, and
3
Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands.
a Address correspondence to this author at: Department of Vascular Surgery, Academic Medical Center, Meibergdreef 9, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. Fax 31-20-6914858; e-mail D.Ubbink{at}amc.uva.nl
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Abstract
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Background: Frequent puncturing of fingers to check blood glucose
in patients with type 1 diabetes might alter skin perfusion and, hence,
influence the representativeness of the blood sample. We investigated
the influence of repetitive puncturing on skin microcirculatory
perfusion using laser Doppler fluxmetry and on the preanalytical phase
of capillary blood analysis for small molecules (glucose) and large
particles (cholesterol).
Methods: In 49 patients with long-standing (mean, 21 years) type
1 diabetes, with a mean puncture frequency of three times daily for a
mean duration of 13 years, laser Doppler skin perfusion was measured in
a finger at a frequently punctured site and compared with a similar
site of another finger of the same hand, which was never punctured. In
the supine position with the hand level with the heart, resting flux
(RF), peak flux (PF), and the microcirculatory reserve capacity (MRC;
PF - RF) were assessed. Subsequently, blood samples for capillary
whole blood glucose and cholesterol analyses were taken from the same
sites.
Results: No significant differences were found between the
puncture and control sites in mean RF (2.3 vs 2.0 V;
P = 0.14, paired-samples t-test), PF
(3.3 vs 3.1 V; P = 0.24), MRC (1.0 vs 1.0 V;
P = 0.65), glucose (10.2 vs 10.2 mmol/L;
P = 0.69), or cholesterol (5.1 vs 5.2 mmol/L;
P = 0.26). Power calculation for a RF of 2.0 V and
the SD and n of this study indicate a power (ß) of 80% to detect a
25% change in RF at P <0.05.
Conclusions: Repetitive finger puncturing in
diabetics appears not to injure local skin
microcirculatory perfusion nor to influence results of capillary
blood analysis for glucose and cholesterol.
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Introduction
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Patients with type 1 diabetes usually check their blood glucose by
means of microblood sampling from one or more finger tips. Intensive
therapy in patients with type 1 diabetes delays the onset and slows the
progression of clinically important organ failure (1). For
this purpose, frequent puncturing for glucose analysis is required. The
technique for capillary blood glucose analysis is minimally invasive
and causes minimal lesions. Often, however, the same place is used
several times a day. This practice may hypothetically influence local
skin microcirculation and therefore influence the reliability of the
capillary blood tests.
After skin injury, wound healing consists of three phases: the lag
phase, representing the acute inflammatory response; the proliferative
phase, which is characterized by synthesis and deposition of new
connective tissue matrix; and the remodeling phase, which is the
maturation of the newly deposited tissue. After a short period of
vasoconstriction to prevent excessive bleeding, all three phases are
accompanied by an increased tissue perfusion
(2)(3). Clinical evidence has shown that skin
trauma produces a local hyperemic response as a result of a local
(sterile) inflammatory reaction following a 10-min vasoconstriction
(4).
In general, the extent and duration of the skin response to a local
trauma are influenced by the severity and location of the trauma.
Previous studies showed that the hyperemic response to injury is fast
and the time to peak after injury varies between 15 s
(4) and 15 min (5)(6) The duration of
hyperemia varies with the size and depth of the injury. The response to
a single needle puncture varies between 15 min (4) and
50 h (7)(8), whereas the hyperemia may
exceed more than 1 year in hypertropic scar formation (9).
The duration of the hyperemic response after microblood sampling for
microglucose analysis has never been studied. The frequent puncturing
in diabetics could theoretically lead to a local permanent or
semi-permanent increase of the basal perfusion.
The reliability of laboratory investigations is dependent on the
variation in the preanalytical and analytical phases. The variation in
the analytical phase is declining because of technical improvements;
therefore, the preanalytical variation is gradually becoming the key
factor influencing the reliability of a test. The preanalytical phase
is influenced by biological variation, choice of specimen, specimen
collection, and transport. The biological variation (e.g., diet,
obesity, smoking, exercise, alcohol intake, metabolic state, illness,
and diurnal variation) is most important and averages, for
example, 60% of the total intraindividual variation of cholesterol
determination (10)(11). The biological variation
in cholesterol analysis is influenced by changes in posture,
sympathetic nervous activity, blood volume, and hemoconcentration
(12)(13). Likewise, glucose analysis is related
to hematocrit, sample site (arterial-venous glucose gradients), tissue
perfusion, and temperature (14)(15).
Hypothetically, repetitive puncturing would produce higher skin
perfusion. This putative effect on skin microcirculation may have
important repercussions on the widespread routine assessment of the
serum concentrations of small, water-soluble molecules (glucose) or
larger, non-water-soluble particles (cholesterol) derived from
capillary blood samples. Therefore, we investigated the influence of
repetitive finger puncturing on skin microcirculatory perfusion, using
laser Doppler fluxmetry, and on capillary whole blood glucose and total
cholesterol analysis in patients with longstanding type 1 diabetes.
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Patients and Methods
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patients
A total of 49 patients (22 men and 27 women) were selected from
the outpatient Department of Internal Medicine of the Academic Medical
Center if they had longstanding type 1 diabetes and punctured their
fingers for glycemia checking for at least 3 years. Subjects were
enrolled after giving written informed consent. The mean age was 43
years (range, 24–77 years). The mean diabetes duration was 21 years
(range, 7–39 years). The "finger puncture frequency" was defined
as the number of finger punctures per week divided by the total number
of fingers used for puncturing. The severity of long-term complications
of diabetes mellitus was estimated from medical history scoring the
absence (0 points) or presence (1 point) of retinopathy (as assessed by
an ophthalmologist), nephropathy (microalbuminuria >30 mg/24 h)
(16), and the need for use of angiotensin-converting enzyme
inhibitors irrespective of microalbuminuria, macroangiopathy
(myocardial infarction, cerebrovascular accident, or feet ulcers), and
neuropathy (sensory disturbances of the feet). Thus, the total
score ranged from 0 to 5 points. The extent of macroscopic skin changes
caused by puncturing was classified in two groups: barely and clearly
visible.
skin perfusion
Local skin microcirculatory perfusion was assessed by laser
Doppler fluxmetry (Periflux 4001®, PF 408
standard probe; Perimed) (17), a simple, noninvasive
technique to assess total cutaneous blood flow (18)(19)(20). In
short, laser light with a wavelength of 780 nm is conducted through
optical fibers to the skin where it penetrates the skin to a depth of
1–1.5 mm and is partly reflected. When backscattered by moving objects
(principally erythrocytes), this light undergoes a frequency shift,
which is proportional to the velocity and number of moving objects
(flux), and is expressed in volts [laser Doppler flux
(LDF)1
]. Laser Doppler measures perfusion not only in the
capillaries but also in the subpapillary venular and arteriolar plexus
and arteriovenous shunts (17).
Measurements were performed on the distal phalanx of the finger at the
site most frequently used for microblood sampling and compared with
a similar site of another finger of the same hand never used for this
purpose. Unheated probes were attached to the fingertips with the probe
holder (Perimed) and double-sided adhesive tape. The instrument’s time
constant was set at 3 s. Measurements were performed in the supine
position with the hand level with the heart in a temperature-controlled
environment (22–24 °C) after an acclimatization period of 15 min.
Recordings were sampled on-line and analyzed off-line by means of a
data acquisition system (AcqKnowledge III and MP 100WSW; Biopac
System).
Resting flux (RF) values (in volts) were obtained by averaging the
recording during 5 min. Subsequently, peak flux (PF; in volts) was
assessed during reactive hyperemia following a 3-min arterial occlusion
induced by inflating a cuff around the arm to 200 mmHg. Because it is
known that the spatial variation of laser Doppler measurements is
considerable (CV, 21–51%) (21)(22), the
increase in LDF as a measure of microcirculatory reserve capacity (MRC)
was calculated. The MRC was defined as PF minus RF. In addition, we
performed an evaluation of the LDF differences between the third and
fourth finger of the same hand in a control group of 15 healthy
volunteers. Biological zero as obtained during arterial occlusion was
subtracted from all flux values (23).
capillary blood analysis
Capillary whole blood cholesterol (Lipotrend
C®; Boehringer) (24) and glucose
tests (Glucometer Elite®; Bayer) (25)
were performed at the same measurement sites of both fingers after the
LDF returned to baseline (~5 min). Glucose testing was performed in
only the latter 32 of 49 patients because the test was not available
from the beginning of this study. A 1.4-gauge needle (Brand Safety Flow
Lancets, Microtainer®; Becton Dickinson) was
used for puncturing. The first drop of blood was discarded. Blood was
drawn into the glucose analysis strip and into a heparin-coated
capillary tube (30 µL), after which it was applied to the test zone
and inserted into the instrument for cholesterol analysis. The analyses
were performed according to the manufacturer’s instructions. Both
glucose and cholesterol concentrations were assessed to detect whether
the effect of frequent puncturing on microblood sampling would be
different between small water-soluble molecules (glucose) and larger
non-water-soluble particles (cholesterol). This last factor was also
introduced because it is to be expected that capillary blood analyses
of a wide range of blood substances will be performed increasingly in
clinical chemistry.
statistical methods
The results are expressed as means with SD after testing for
skewness. Differences in laser Doppler parameters and capillary blood
chemistry between the puncture and control sites were analyzed using
the Student t-test for paired samples. Mean differences
(d; control vs puncture site) with SD and 95% confidence intervals
(95% CIs) are presented for all values. Differences between sites
across the range of values were analyzed visually by means of a
difference plot (26).
A possible correlation between finger puncture frequency and
microcirculatory changes (RF, PF, and MRC) was investigated by the
Pearson product–moment correlation coefficient. We assumed a positive
correlation between the finger puncture frequency and RF at the
puncture site and a negative correlation between the finger puncture
frequency and MRC at the puncture site because repetitive puncturing
should produce a semi-permanent reactive hyperemia. Because no adequate
values of the technique used were available before the study, power
analyses for the RF values were performed retrospectively to calculate
the power that can be reached regarding the observed differences.
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Results
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Patients had diabetes mellitus for a mean period of 21 years
(range, 7–39 years), and performed capillary blood sampling for a mean
period of 13 years (range, 3–33 years), with a mean sampling
frequency of 17 times a week (range, 1–50). One to eight
fingers of both hands were used for puncturing. The mean finger
puncture frequency was 5 times a week (range, 1–18 times a week). The
visibility of the puncture sites varied from invisible to clearly
present.
skin perfusion
In control subjects, the CV of differences between the third and
fourth finger was 54% for rest LDF [(SD differences/control
site) x 100%; 1.3/2.4 x 100%], 39% (1.5/3.8 x
100%) for peak LDF, and 36% (0.5/1.4 x 100%) for MRC.
The LDF values at rest and during reactive hyperemia are shown in Table 1
. No significant differences in laser Doppler perfusion
parameters were found between the puncture and control sites. These
flux differences were unequally distributed across the range. The
differences tended to increase with higher flux values (Fig. 1
), in agreement with the greater spatial and temporal variation
that is known to exist at higher flux values (22). The RF,
PF, and MRC did not differ significantly between the sites with barely
and clearly visible puncture marks. Power analysis revealed that in
these 49 patients and with an SD of the mean differences of 1.2
V, a 25% flux difference (0.5 V) between the control (2.0 V) and
puncture site (2.5 V) can be observed with P = 0.05 and
a power (ß) of 80%.
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Figure 1. Scatter plots of the differences (control - puncture
site; y-axis) in RF (A), PF
(B), and MRC (C) vs the mean
(x-axis).
The mean difference (solid line) and the 95% CI (±
1.96 SD; dotted lines) of the differences are
presented.
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capillary blood analysis
The mean (± SD) capillary blood glucose at in the puncture site
(10.1 ± 4.7 mmol/L) was not different (P = 0.69)
from the control site (10.2 ± 4.4 mmol/L): mean (± SD)
difference, 0.09 ± 1.32 mmol/L; 95% CI, -0.19 to 0.28
mmol/L. The same was true for the capillary cholesterol (5.1 ±
1.1 mmol/L for the puncture site vs 5.2 ± 1.0 mmol/L for the
control site; mean difference, 0.07 ± 0.40 mmol/L; 95%
CI, -0.05 to 0.18 mmol/L; P = 0.26).
The distribution was equal across the range of concentrations of
glucose and cholesterol (Fig. 2
), illustrating that neither an actual change in
the control of the diabetes mellitus nor the presence of
hypercholesterolemia produced a greater difference.
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Figure 2. Scatter plots of the differences (control - puncture
site; y-axis) in capillary whole blood glucose
(A) and capillary whole blood cholesterol
(B) vs the mean (x-axis).
The mean difference (solid line) and the 95% CI (±
1.96 SD; dotted lines) of the differences are
presented.
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correlations
A poor correlation was found between finger puncture frequency and
microcirculatory parameters at the puncture and control sites,
indicating that frequent puncturing did not influence skin perfusion
(Table 2
). Small but significant inverse correlations were seen between
both duration of type 1 diabetes and severity of long-term
complications and RF at the puncture site (Table 2
), whereas only a
poor correlation was observed at the control site. The PF showed the
same tendencies, but the correlations were not statistically
significant (P = 0.09 and 0.10).
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Table 2. Correlations1
between laser
Doppler fluxmetry and finger puncture frequency, duration of diabetes
mellitus, and severity of long-term
complications.
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Discussion
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This study presents the first evidence that repetitive finger
puncturing in patients with long-standing insulin-dependent diabetes
mellitus does not influence microcirculatory skin perfusion. Likewise,
the capillary blood glucose and cholesterol concentrations are not
influenced by repetitive puncturing, and thus preanalytical variation
attributable to altered circulation does not need to be considered.
skin perfusion
In contrast to our hypothesis, we did not observe a difference in
skin perfusion between the puncture and control fingers. Both
methodological and pathophysiological factors may contribute to this
observation.
A methodological reason for this could be that the effect on skin
microcirculation was too small to measure with laser Doppler. However,
the rather narrow 95% CIs of the mean differences in LDF values and
the power analyses indicate that the sample size was adequate.
Measurement variability of the laser Doppler is mainly attributable to
the large physiological variation in perfusion rather than the
technical variation of the technique used
(21)(22)(27)(28). The
physiological variation among persons and different anatomic sites is
larger than the within-person variation at identical anatomical sites
of the same limb (22)(28)(29)(30), as was used in
this study. The use of postocclusive hyperemic tests further improves
the reproducibility of the measurement (31). Furthermore, no
differences were observed between the various fingers of the same and
between left and right hands (31). In previous studies, we
demonstrated a difference in laser Doppler perfusion between the stages
of peripheral vascular disease (32)(33) and
reflex sympathetic dystrophy (34), whereas many others have
demonstrated differences in skin perfusion induced by skin injury,
using laser Doppler fluxmetry
(4)(7)(8)(9)(35). Therefore, the laser
Doppler technique is applicable in long-term studies on factors
affecting microcirculatory flow (27) and should be able to
detect important changes in microcirculation if present.
Pathophysiological factors for this lack of difference may
include the following: (a) The injury caused by puncturing
for microblood sampling may not be big enough to induce
longstanding hyperemia. (b) The increase of blood flow that
accompanies wound healing (vasodilatation and neoangiogenesis) might
not be detected by laser Doppler because scar formation increases the
nonperfused part of the 1.5 mm3 of skin measured
by laser Doppler, thereby reducing the backscattered laser Doppler
signal (17). However, there was no significant difference in
perfusion between the fingers with barely and clearly visible
macroscopic changes. (c) The local microcirculatory anatomy,
which varies throughout the body, may contribute to the observed
absence of a difference between the puncture and control site.
Experimental studies have shown that the hyperemic response in skin
areas with a primarily thermoregulatory (arteriovenous) perfusion, such
as the volar sides of the fingers, appears not as pronounced as in
other regions of the skin with primarily nutritive perfusion
(8)(36)(37)(38). (d) Diabetic
microangiopathy may contribute to the results of this study. The
hyperemic response after, for example, needle injury, heating, or
arterial occlusion is known to be reduced in patients with type 1
diabetes (5)(7). The cause of the
inability of the diabetic skin to respond normally to injury is complex
and is part of the microcirculatory changes (increased RF with impaired
reactive hyperemia) that take place in patients with diabetes mellitus
and are called functional diabetic microangiopathy (39). The
influence of diabetic microangiopathy on the reduction of hyperemia
after repetitive puncturing is supported by the inverse correlation we
found between skin perfusion in the puncture site and duration of
diabetes mellitus and severity of long-term complications. However,
this was not observed at the control site, which argues against such an
explanation.
capillary blood analysis
In agreement with the findings in the microcirculation, capillary
blood glucose and cholesterol analysis were not influenced by
repetitive puncturing. Methodological factors (too small an effect or
sample size) may have caused this finding. Nevertheless, if repetitive
puncturing does have an effect on capillary blood analysis, the
influence appears too small to be clinically significant.
conclusions
The results of this study show that, within the limitations of the
used assay, repetitive finger puncturing does not influence skin
microcirculation and, hence, the preanalytical phase of capillary blood
analysis. Apparently, frequent finger puncturing does not induce a
trauma that induces a lasting, local hyperemic response. Even if
puncturing should induce an acute hyperemic response, this appears to
have no lasting effect or may be surpassed by the reduced hyperemic
response caused by diabetic microangiopathy. In conclusion, repetitive
puncturing has no clinical consequences for capillary whole blood
glucose and cholesterol analysis.
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Acknowledgments
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This study was supported by the Dutch Heart Foundation, Grant
96-113. We thank Boehringer Mannheim for providing the materials for
cholesterol analysis.
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Footnotes
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1 Nonstandard abbreviations: LDF, laser Doppler flux; RF, resting flux; PF, peak flux; MRC, microcirculatory reserve capacity; and CI, confidence interval. 
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References
|
|---|
-
Anonymous. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. New Engl J Med 1993;329:977-986.
[Abstract/Free Full Text]
-
Adzick NS. Wound healing: biological and clinical
features. In: Sabiston DC, Lyerly HK., eds. Textbook of surgery. The
biological basis of modern surgical practice, 15 ed. Philadelphia: WB
Saunders, 1997:207–20..
-
Lewis T. The blood vessels of the human skin and their responses 1927:46-80 Shaw and Sons London. .
-
Holloway GA, Jr. Cutaneous blood flow responses to injection trauma measured by laser Doppler velocimetry. J Investig Dermatol 1980;74:1-4.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Rayman G, Williams SA, Spencer PD, Smaje LH, Wise PH, Tooke JE. Impaired microvascular hyperaemic response to minor skin trauma in type I diabetes. Br Med J 1986;292:1295-1298.
-
Walmsley D, Wiles PG. Hyperaemia to skin microtrauma in the foot: a biphasic response [Abstract]. Clin Sci 1988;74(Suppl 18):91P.
-
Walmsley D, Wales JK, Wiles PG. Reduced hyperaemia following skin trauma: evidence for an impaired microvascular response to injury in the diabetic foot. Diabetologia 1989;32:736-739.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Rendell MS, Milliken BK, Finnegan MF, Finney DA, Healy JC. The skin blood flow response in wound healing. Microvasc Res 1997;53:222-234.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Ehrlich HP, Kelley SF. Hypertrophic scar: an interruption in the remodeling of repair–a laser Doppler blood flow study. Plast Reconstr Surg 1992;90:993-998.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Demacker PN, Schade RW, Jansen RT. Intra-individual variation ofserum cholesterol, triglycerides and high density lipoprotein cholesterol in normal humans. Atherosclerosis 1982;45:259-266.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Cooper GR, Myers GL, Smith SJ, Schlant RC. Blood lipid measurements. Variations and practical utility. JAMA 1992;267:1652-1660.
[Abstract/Free Full Text]
-
Miller M, Bachorik PS, Cloey TA. Normal variation of plasma lipoproteins: postural effects on plasma concentrations of lipids, lipoproteins, and apolipoproteins. Clin Chem 1992;38:569-574.
[Abstract/Free Full Text]
-
Howes LG, Krum H, Louis WJ. Increase in plasma cholesterol on subjects’ standing correlates with the increase in plasma norepinephrine. Clin Chem 1988;34:988.[Free Full Text]
-
Kupke IR, Kather B, Zeugner S. On the composition of capillary and venous blood serum. Clin Chim Acta 1981;112:177-185.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Kost GJ, Vu HT, Lee JH, Bourgeois P, Kiechle FL, Martin C, et al. Multicenter study of oxygen-insensitive handheld glucose point-of-care testing in critical care/hospital/ambulatory patients in the United States and Canada. Crit Care Med 1998;26:581-590.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Mogensen CE, Keane WF, Bennett PH, Jerums G, Parving HH, Passa P, et al. Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995;346:1080-1084.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Stern MD, Lappe DL, Bowen PD, Chimosky JE, Holloway GA, Keiser HR, Jr, Bowman RL. Continuous measurement of tissue blood flow by laser-Doppler spectroscopy. Am J Physiol 1977;232:H441-H448.
[Abstract/Free Full Text]
-
Watkins D, Holloway GA, Jr. An instrument to measure cutaneous blood flow using the Doppler shift of laser light. IEEE T Bio-Med Eng 1978;25:28-33.
-
Stern MD. In vivo evaluation of microcirculation by coherent light scattering. Nature 1975;254:56-58.
[Medline]
[Order article via Infotrieve]
-
Ubbink DT, Jacobs MJ, Tangelder GJ, Slaaf DW, Reneman RS. Posturally induced microvascular constriction in patients with different stages of leg ischaemia: effect of local skin heating. Clin Sci 1991;81:43-49.
[Medline]
[Order article via Infotrieve]
-
Lukkari-Rautiarinen E, Lepantalo M, Pietila J. Reproducibility of skin blood flow, perfusion pressure and oxygen tension measurements in advanced lower limb ischaemia. Eur J Vascular Surg 1989;3:345-350.
-
Tenland T, Salerud EG, Nilsson GE, Oberg PA. Spatial and temporal variations in human skin blood flow. Int J Microcirc 1983;2:81-90.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Caspary L, Creutzig A, Alexander K. Biological zero in laser Doppler fluxmetry. Int J Microcirc 1988;7:367-371.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Summerton AM, Summerton N. The use of desk-top cholesterol analysers in general practice. Public Health 1995;109:363-367.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Atkin SH, Dasmahapatra A, Jaker MA, Chorost MI, Reddy S. Fingerstick glucose determination in shock. Ann Intern Med 1991;114:1020-1024.
-
Bland JM, Altman DG. Comparing methods of measurement: why plotting difference against standard method is misleading. Lancet 1995;346:1085-1087.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Sundberg S. Acute effects and long-term variations in skin blood flow measured with laser Doppler flowmetry. Scand J Clin Lab Investig 1984;44:341-345.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Schabauer AM, Rooke TW. Cutaneous laser Doppler flowmetry: applications and findings. Mayo Clin Proc 1994;69:564-574.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Agner T, Serup J. Individual and instrumental variations in irritant patch-test reactions–clinical evaluation and quantification by bioengineering methods. Clin Exp Dermatol 1990;15:29-33.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Bircher A, de Boer EM, Agner T, Wahlberg JE, Serup J. Guidelines for measurement of cutaneous blood flow by laser Doppler flowmetry. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 1994;30:65-72.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Ninet J, Fronek A. Cutaneous postocclusive reactive hyperemia monitored by laser Doppler flux metering and skin temperature. Microvasc Res 1985;30:125-132.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Ubbink DT, Jacobs MJ, Slaaf DW, Tangelder GJ, Reneman RS. Microvascular reactivity differences between the two legs of patients with unilateral lower limb ischaemia. Eur J Vascular Surg 1992;6:269-275.
-
Ubbink DT, Jacobs MJ, Tangelder GJ, Slaaf DW, Reneman RS. The usefulness of capillary microscopy, transcutaneous oximetry and laser Doppler fluxmetry in the assessment of the severity of lower limb ischaemia. Int J Microcirc 1994;14:34-44.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Kurvers HA, Jacobs MJ, Beuk RJ, van den Wildenberg FA, Kitslaar PJ, Slaaf DW, Renemans RS. The influence of local skin heating and reactive hyperaemia on skin blood flow abnormalities in patients with reflex sympathetic dystrophy (RSD). Eur J Clin Investig 1995;25:346-352.
[Web of Science][Medline]
[Order article via Infotrieve]
-
Rayman G, Malik RA, Sharma AK, Day JL. Microvascular responseto tissue injury and capillary ultrastructure in the foot skin of type I diabetic patients. Clin Sci 1995;89:467-474.
[Medline]
[Order article via Infotrieve]
-
Grant RT, Bland EF. Observations on arterio-venous anastomoses in human skin and in the bird’s foot with special reference to the reaction to cold. Heart 1931;15:385-411.
-
Popoff N. The digital vascular system. Arch Pathol 1934;18:295-330.
[Web of Science]
-
Mescon H, Hurley HJ, Moretti G. The anatomy and histochemistry of the arteriovenous anastomosis in human digital skin. J Investig Dermatol 1956;:133-145.
-
Tooke JE. Microvasculature in diabetes. Cardiovasc Res 1996;32:764-771.
[Web of Science][Medline]
[Order article via Infotrieve]
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Abstract
Introduction
