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Biomedical subjects

K Alexander

Publications and source records attributed to K Alexander.

At least 19 recordsLinked to original sources
PubMed1997

Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease.

BACKGROUND: We studied urinary nitrate and cGMP excretion rates, indices of systemic NO formation, and plasma concentrations of L-arginine and the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) and its inactive stereoisomer, symmetrical dimethylarginine, in 77 patients with peripheral arterial occlusive disease (PAOD) in Fontaine stages IIb through IV and in 47 young and 37 elderly healthy control subjects. METHODS AND RESULTS: Urinary nitrate excretion was 182.0+/-11.4 micromol/mmol creatinine and cGMP excretion was 186.2+/-13.0 nmol/mmol creatinine in young healthy control subjects. In elderly control subjects, both excretion rates were slightly lower (nitrate, 156.0+/-7.8 micromol/mmol creatinine; cGMP, 150.0+/-8.3 nmol/mmol creatinine; P=NS). In PAOD patients, there was a significant, progressive reduction of urinary nitrate (IIb, 138.4+/-11.9; III, 128.6+/-11.3; and IV, 91.9+/-8.0 micromol/mmol creatinine; P<.05) and cGMP (IIb, 139.9+/-25.2; III, 115.6+/-13.1; and IV, 76.9+/-7.9 nmol/mmol creatinine; P<.05) excretion rates related to the Fontaine stage of PAOD. These changes were independent of changes in renal excretory function. Plasma L-arginine concentrations were not significantly different between the groups, but ADMA concentrations were elevated in PAOD patients (young control subjects, 1.25+/-0.11; elderly control subjects, 1.01+/-0.05 micromol/L; IIb, 2.62+/-0.24; III, 3.06+/-0.48; and IV, 3.49+/-0.26 micromol/L; P<.05 for PAOD versus control subjects). There was a significant linear correlation between urinary nitrate and cGMP excretion rates and a significant negative linear correlation between plasma ADMA concentrations and urinary nitrate excretion. CONCLUSIONS: In PAOD patients, there is a progressive reduction in urinary nitrate and cGMP excretion rates, which may be caused in part by accumulation of ADMA, an endogenous inhibitor of NO synthase.

Adult↗
PubMed1997

Treatment of primary Raynaud's syndrome with traditional Chinese acupuncture.

OBJECTIVE: Evaluation of the effects of a standardized acupuncture treatment in primary Raynaud's syndrome. DESIGN: A controlled randomized prospective study. SETTING: A winter period of 23 weeks, angiological clinic of Hannover Medical School. SUBJECTS: Thirty-three patients with primary Raynaud's syndrome (16 control, 17 treatment). INTERVENTIONS: The patients of the treatment group were given seven acupuncture treatments during the weeks 10 and 11 of the observation period. MAIN OUTCOME MEASURES: All patients kept a diary throughout the entire observation period noting daily frequency, duration and severity of their vasospastic attacks. A local cooling test combined with nailfold capillaroscopy was performed for all patients at baseline (week 1) and in weeks 12 and 23, recording flowstop reactions of the nailfold capillaries. RESULTS: The treated patients showed a significant decrease in the frequency of attacks from 1.4 day-1 to 0.6 day-1, P < 0.01 (control 1.6 to 1.2, P = 0.08). The overall reduction of attacks was 63% (control 27%, P = 0.03). The mean duration of the capillary flowstop reaction decreased from 71 to 24 s (week 1 vs. week 12, P = 0.001) and 38 s (week 1 vs. week 23, P = 0.02) respectively. In the control group the changes were not significant. CONCLUSIONS: These findings suggest that traditional Chinese acupuncture is a reasonable alternative in treating patients with primary Raynaud's syndrome.

Acupuncture Therapy↗
PubMed1997

Oxygen-15-water PET assessment of muscular blood flow in peripheral vascular disease.

UNLABELLED: To assess quantitatively regional nutritive muscular blood flow in patients with peripheral vascular disease (PVD), we evaluated the utility of PET with 15O-water. METHODS: Eight healthy volunteers and 16 patients with angiographically proven PVD were studied. Regional blood flow of the calf was measured with 15O-water PET during rest, after intra-arterial infusion of prostaglandin E1 and during ergometry. The studies were quantified using a one tissue compartment model. RESULTS: Normalized mean tracer uptake from 15-60 sec correlated closely (r = 0.98) with absolute blood flow. Scan times longer than 90 sec were required to determine blood flow reliably. The flow values were overestimated by 2% if arterial blood volume was neglected or if the input function delay was corrected globally for parametric imaging. Mean blood flow of calf muscles at rest did not differ significantly between patients (0.017 +/- 0.006 ml/min/ml) and control subjects (0.018 +/- 0.010 ml/min/ml). In PVD patients, blood flow increased by 100% after intra-arterial infusion of PGE1 in the respective leg. In the control subjects, average flow increased by a factor of six during exercise. The increase was more pronounced in the extensor muscles (0.182 +/- 0.031 ml/min/ml) than in flexor muscles (0.121 +/- 0.045 ml/min/ml). Due to the specific type of ergometry, superficial flexors exhibited higher flow values than the profound ones. CONCLUSION: PET with 15O-water enables reliable determination of regional nutritive skeletal muscle blood flow for research and clinical applications in patients with PVD.

Adult↗
PubMed1997

Non-invasive determination of dermal hemoglobin oxygenation and concentration in patients with peripheral arterial occlusive disease.

BACKGROUND: Oxygen saturation (SHB) and concentration (CHB) of dermal hemoglobin are important parameters for the supply of the skin. They may be non-invasively assessed by means of reflection photometry as hemoglobin is predominantly contributing to the skin reflection spectrum. METHODS AND RESULTS: Dermal reflection spectra from the middle of the forefoot and from the tip of the toe of 20 healthy subjects and 61 patients suffering from peripheral arterial occlusive disease (PAOD) were recorded and compared to transcutaneous oxygen pressure (tcPO2). SHB, and tcPO2 were significantly higher in controls: compared to patients (ankle pressure (AP) > 50 mmHg) SHB in the skin of the forefoot was 63.8 vs. 54.5% (p < 0.05), CHB was 0.89 vs. 0.62 aU (p < 0.01). In the great toe SHB was 92.9 vs. 59.9% (p < 0.001), CHB was 2.21 vs. 0.92 aU (p < 0.001). Heating the skin of the forefoot to 44 degrees C yields local dermal vascular reserve capacity: SHB and CHB increased in all healthy subjects (96.4%; 1.44 aU, respectively). SHB decreased at the forefoot in 14 and at the toe in 18 of 21 patients with AP < 50 mmHg. At the toe decrease was found in 50 of 61 patients (sensitivity 82%, specificity 100%). CONCLUSIONS: Local vascular reserve capacity of dermal perfusion is reduced in patients with PAOD, depending on AP. It should be determined preferably in patients with severe PAOD.

Adult↗
PubMed1996

L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia. A randomized, controlled study.

BACKGROUND: L-Arginine is the precursor of endogenous nitric oxide (NO), which is a potent vasodilator acting via the intracellular second-messenger cGMP. In healthy humans, L-arginine induces peripheral vasodilation and inhibits platelet aggregation due to an increased NO production. Prostaglandin E1 (PGE1) induces peripheral vasodilation via stimulating prostacyclin receptors. METHODS AND RESULTS: We investigated the effects of one intravenous infusion of L-arginine (30 g, 60 minutes) or PGE1 (40 microgram, 60 minutes) versus those of placebo (150 mL 0.9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO3- and cGMP excretion rates in patients with critical limb ischemia (peripheral arterial occlusive disease stages Fontaine III or IV). Blood flow in the femoral artery was significantly increased by L-arginine (+42.3 +/- 7.9%, P<.05) and by PGE1 (+31.0 +/- 10.2%, P<.05) but not by placebo (+4.3 +/- 13.0%, P=NS). Urinary NO3- excretion increased by 131.8 +/- 39.5% after L-arginine (P<.05) but only by 32.3 +/- 17.2% after PGE1 (P=NS). Urinary cGMP excretion increased by 198.7 +/- 84.9% after L-arginine (P<.05) and by 94.2 +/- 58.8% after PGE1 (P=NS). Both urinary index metabolites were unchanged by placebo. CONCLUSIONS: We conclude that intravenous L-arginine induces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO3- and cGMP excretion, indicating an enhanced systemic NO production. Increased urinary NO3- excretion may be a sum effect of NO synthase substrate provision (L-arginine) and increased shear stress (PGE1 and L-arginine).

Aged↗
PubMed1996

A new method for the assessment of tissue hemoglobin oxygenation in patients with chronic venous insufficiency.

Venous incompetence often leads to ulceration of the skin of the lower limb due to a disturbance of skin microcirculation. We investigated 10 healthy subjects and 18 patients with chronic venous insufficiency by means of a fast scanning reflection photometer and determined noninvasively the hemoglobin oxygen saturation (S(HB)) and the relative concentration of hemoglobin (C(HB)) in the skin of the forefoot and at the calf, 10 cm proximal of the inner malleolus during positional changes. In supine position no significant differences were found. During sitting and standing S(HB) dropped and was significantly lower in patients at both locations (calf, standing, patients 22.2 +/- 10.6% vs controls 48.2 +/- 13.5%, P < 0.001). C(HB) increased in patients during standing from 0.71 to 2.13 +/- 0.33 aU (in controls from 0.69 to 1.49 +/- 0.28 aU, P < 0.001). Activation of the muscle pump decreased C(HB) and increased S(HB) in patients and in controls. After the movements were stopped, S(HB) decreased again and fell to the initial low values eight times faster in patients (7.4 +/- 5.3 vs 57.5 +/- 19.6 sec, P < 0.001). C(HB) increased four times faster in patients (7.2 +/- 6.1 vs 29.9 +/- 13.6 sec). In sitting and standing positions hemoglobin oxygenation in the skin of the lower limb was markedly reduced in patients, but normal perfusion conditions were restored in supine position, indicating reversibility of the changes. Reflection oxymetry seems a valuable tool for the assessment of chronic venous insufficiency. The substantially reduced oxygenation of dermal hemoglobin in standing patients may contribute to the development of venous ulcers.

Adult↗
PubMed1996

Orthostatic vasoconstrictor response in patients with occlusive arterial disease assessed by laser Doppler flux and transcutaneous oximetry.

Posturally induced microvascular constriction normally causes a decrease of transcutaneous oxygen pressure (tcPO2) and laser Doppler flux (LDF) measured on the forefoot at 37 degrees C. The authors used both methods to assess the vasoconstrictor response (VCR) in 31 patients with various degrees of peripheral arterial occlusive disease (PAOD) and analyzed factors that could have influenced the response. Disturbed VCR was indicated by a signal increase following leg dependency, which occurred significantly more often in tcPO2 than in LDF measurements (69% vs 32%, P < 0.001). Correspondingly the median sitting/supine ratio was 2.4 for tcPO2 and 0.7 for LDF (P < 0.0001). Age and clinical stage had no influence on the VCR. With ankle artery pressures below 50 mmHg an increase of LDF was more probable. TcPO2 predominantly increased with ankle artery pressure up to 100 mmHg, though the sitting/supine ratio of tcPO2 was correlated with ankle artery pressure. In nondiabetics the response of tcPO2 but not of LDF was influenced by the values at rest. Differences between the two methods may be explained in part by their different sample volumes. The authors assume that tcPO2 is predominantly monitoring a local myogenic response while LDF is reflecting venoarteriolar response.

Adult↗
PubMed1996

Hypothenar hammer syndrome successfully managed with intravenous prostaglandin E1 and heparin and with correction of the thrombogenic risk profile. A case report.

A fifty-one-year-old man presented with a history, symptoms, and clinical findings typical of a hypothenar hammer syndrome in his dominant hand. A thrombotic obstruction in the distal section of the ulnar artery with multiple downstream occlusions of proper digital arteries were documented angiographically. Coexistence of additional cardiovascular risk factors (smoking-induced polycythemia, obesity, hypercholesterolemia, and hypertension) was identified. Conservative management with intravenous heparin and prostaglandin E1 together with measures directed at controlling the additional risk factors (repeated venesection, immediate smoking cessation, and low-lipid diet) resulted in a striking clinical and angiographic improvement of the digital perfusion, without resort to interventional measures or thrombolysis.

Alprostadil↗
PubMed1996

Untreated arteriovenous fistula after World War II trauma.

A 76-year-old-patient with severe congestive heart failure due to femoral arteriovenous fistula (AVF) after World War II trauma is presented. He was admitted to our clinic because of increasing dyspnea and vertigo during the last years. Moreover he suffered from chronic venous insufficiency on the lower limb distal of the fistula. History revealed a bullet trauma sustained 50 years ago in 1945 while riding on a train that was taken under fire. In 1973 diagnosis of traumatic AVF was first established by arteriography but the patient did not undergo surgical repair. Actual diagnostic procedure included colour Doppler imaging, chest x-ray, and echocardiography. The patient refused invasive treatment, but drug therapy of congestive heart failure was accepted.

Aged↗
PubMed1996

Thrombosis of the terminal aorta, deep vein thrombosis, recurrent fetal loss, and antiphospholipid antibodies. Case report.

The antiphospholipid syndrome (APS) consists clinically of both arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia associated with antiphospholipid antibodies (aPL). Most of these patients were initially found to suffer from systemic lupus erythematosus (SLE). There is an increasing group of patients who exhibit antiphospholipid antibodies and thrombotic complications without clinical features of SLE or related autoimmune disease termed primary antiphospholipid syndrome (PAPS). The case of a 29-year-old woman with thrombosis of the terminal aorta and deep vein thrombosis, recurrent fetal loss, antiphospholipid antibodies and serological support for an underlying connective tissue disease, probably preclinical SLE is reported.

Abortion, Habitual↗
PubMed1995

[How often is thrombolytic therapy of deep pelvic-leg venous thrombosis indicated?].

BACKGROUND: For patients with deep vein thrombosis new thrombolytic regimes are being proposed and demand evaluation in controlled studies. We tested prospectively, how many patients in internal medicine are candidates for thrombolysis. PATIENTS AND METHODS: All available patients with the diagnosis of deep vein thrombosis (DVT) in lower extremities who were admitted to the service of internal medicine in a medium-sized hospital during one year were prospectively evaluated for the indication of fibrinolysis therapy according to the established criteria. RESULTS: A total of 62 patients were enrolled. Fibrinolysis was not proposed in 25 patients aged over 70 years nor in another 9 patients in whom the thrombosis was restricted to calf veins. Nine additional cases had a recurrence of DVT (n = 4) or a history of more than 14 days. Among the remaining 19 patients, fibrinolysis was not performed in 11 because of advanced malignomas (n =4) or other diseases (n = 3) with limited life expectance, enhanced probability of haemorrhage (n = 3) and obvious non-compliance (n = 1). Eight patients were offered thrombolytic therapy, but 5 of them denied consent after being comprehensively informed. CONCLUSION: Obviously by far most of patients admitted to internal medicine for DVT are candidates for standard heparin therapy only.

Adult↗
PubMed1995

Determination of lansoprazole and five metabolites in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of lansoprazole, a new proton-pump inhibitor, and five of its metabolites in human plasma is described. Lansoprazole, its metabolites, and internal standard (omeprazole) were extracted into diethyl ether-methylene chloride and separation was obtained using a reversed-phase column under isocratic conditions. The method features monochromatic ultraviolet detection at 285 nm, and single extraction, single evaporation sample handling. The lower limit of quantitation, based on standards with acceptable coefficients of variation, was 10 ng/ml for all compounds. No endogenous compounds were found to interfere. This method has been demonstrated to be suitable for pharmacokinetic studies in humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[Traumatically-induced ischemia of the hands].

BACKGROUND: The widely unknown hypothenar hammer syndrome (HHS) is caused by chronic mechanical trauma; in these cases the hypothenar is used as a tool. This may cause intimal lesions of the ulnar artery usually near the hamate bone resulting in thrombosis or aneurysms. PATIENTS: Six patients with HHS are presented. In four cases occupational activities were most probable cause for HHS, in two patients sport activities. DIAGNOSIS: Clinical examination already indicates insufficient blood supply in the supply area of the ulnar artery. Non invasive methods of examination are doppler measurements of hand arteries and occlusion plethysmography of finger arteries. For differential diagnosis capillaroscopy, laboratory tests and hand arteriography can be necessary. THERAPY: Avoiding the releasing cause is main part in therapy of HHS. Only in few patients special medical treatment is indicated. CONCLUSION: Positive evidence of causal relationship between occupational exposure and appearance of HHS has to be acknowledged as occupational disease.

Adult↗
PubMed1995

[A nomogram of duplex ultrasound quantification of peripheral arterial stenoses. Studies of the cardiovascular model and in angiography patients].

BACKGROUND AND METHODS: Blood flow velocity measurements were performed with duplex ultrasound in vitro (flow phantom) and in 62 patients who underwent angiography due to peripheral vascular disease. RESULTS: Intrastenotic peak systolic velocity (PSV) divided by proximally recorded PSV (peak velocity ratio, PVR) exhibited a strong correlation with percent diameter reduction: r2 = 0.86; N = 106 stenoses. A PVR value > or = 2.4 indicated a more than 50% stenosis with a sensitivity of 87% and a specificity of 94%. Calculation of PVR may normalize for patient variation and allow noninvasive quantification of lumen narrowing with high sensitivity and specificity. The intraobserver variability (95% CI) of stenosis quantification using PVR values was 10%. A nomogram simplifies estimation of lumen narrowing after measurement of intrastenotic and proximal PSV values. CONCLUSION: Quantification of peripheral artery stenoses can be performed easily and noninvasively with duplex ultrasound using the peak velocity ratio (PVR).

Aged↗
PubMed1995

Three genes and two isozymes: gene conversion and the compartmentalization and expression of the phosphoglycerate kinases of Trypanosoma (Nannomonas) congolense.

The glycosome, a microbody organelle found only in kinetoplastid protozoa, compartmentalizes the first six enzymes of glycolysis. In order to better understand the regulation and targeting of glycolytic enzymes in trypanosomes, we have cloned and analyzed the three genes of the phosphoglycerate kinase (PGK) complex of Trypanosoma (Nannomonas) congolense. The organization of the genes within the complex is similar to that of Trypanosoma brucei brucei. The nucleotide and amino-acid sequences, including those of the novel high-molecular-weight 56PGK, show substantial cross-species similarity. However, the two downstream genes, c1PGK and c2PGK, encode identical isozymes in T. congolense, while they encode distinct glycosomal and cytoplasmic isozymes in T. brucei. Western analysis also indicated that there are only two isozymes in T. congolense and that these are constitutively expressed. Differential digitonin solubilization of the trypanosomes indicated that 56PGK is primarily localized to the glycosome, as expected, and that c1/c2PGK is cytoplasmic. Northern analysis demonstrates that while 56PGK is constitutively expressed, c1PGK and c2PGK mRNAs are differentially expressed in the T. congolense developmental stages. This work demonstrates that T. congolense has only one PGK isozyme, 56PGK, that is predominantly localized in glycosomes.

Amino Acid Sequence↗
PubMed1995

Skin oxygen pressure histograms in patients with peripheral arterial occlusive disease during intraarterial and intravenous prostaglandin E1 infusions of different dosages and their prognostic value.

Skin surface oxygen pressure fields (tcPO2 [37 degrees C]) reproducibly characterize skin microcirculation in patients with peripheral arterial occlusive disease. These appear suited for investigation of short- and long-term effects of vasoactive drug treatment. The authors studied whether skin surface oxygen pressure histograms change depending on dosage and route of administration of prostaglandin E1 (PGE1), whether they are of predictive value for patients' clinical outcome, and whether they normalize after therapy with PGE1. The authors investigated 15 patients with various degrees of disease and measured forefoot oxygen histograms consisting of at least 80 single tcPO2 (37 degrees C) values before and during intraarterial infusion (1.5, 3, or 6 ng/kg/minute) and intravenous infusion (4.5, or 9 ng/kg/minute). The measurements were repeated two and six hours after the end of intraarterial application of 1.5 ng/kg/minute. Furthermore, the orthostatic vasoconstrictor response was tested. Skin oxygen pressure histograms were controlled after a period of twenty-two (mean) days of intraarterial PGE1 therapy. Resting histograms were left shifted with median tcPO2 (37 degrees C) between 1 and 7 mm Hg. During intraarterial application, histograms were shifted to lower tcPO2 (37 degrees C) values in most patients. Only in 3 diabetic subjects with proximal or acral obliterations was a marked increase observed. The alterations were detectable at least two hours after the end of the infusion. During intravenous infusion, histograms did not change in most cases. After long-term therapy, histograms were substantially unchanged. A pathologic vasoconstrictor response, which was present in 10 patients, could not be restored. Despite a marked deterioration of the histograms the clinical outcome was favorable in 7 patients. Patients with a high resting tcPO2 (37 degrees C) (median 4 mm Hg and more) and those with a vasoconstriction on orthostasis are likely to respond to PGE1 therapy.

Adult↗