Biomedical subjects
Publications and source records attributed to D Hiller.
Atorvastatin 15 mg/week was administered to 21 patients with hypercholesterolemia for 2 months. The mean low-density lipoprotein concentration decreased by 20% after treatment.
OBJECTIVE: To determine the effectiveness of glucosamine in reducing pain from osteoarthritis of the knee. DESIGN: Randomized, double-blind parallel trial of glucosamine 500 mg three times daily or a placebo for 2 months. SETTING: Veterans Affairs Medical Center, Prescott, AZ. PARTICIPANTS: Ninety-eight patients aged 34 to 81 being treated for osteoarthritis of the knee. MAIN OUTCOME MEASURES: Pain intensity both at rest and while walking as assessed by a visual analog scale at baseline and after 30 and 60 days of treatment. RESULTS: Forty-nine patients were randomly allocated to each group. There was no statistical difference between the two groups in scores on the visual analog scale at 30 days for resting (mean [SD] score placebo group 3.5 [2.7] vs 3.3 [2.4] glucosamine group, P = 0.66) or walking (5.1 [2.6] vs 5.3 [2.4], P = 0.69); there was also no difference at 60 days for resting (3.4 [2.5] vs 3.2 [2.5], P = 0.81) or walking (4.9 [2.2] vs 4.9 [2.8], P = 0.90). There was also no statistical difference between groups in the mean change from baseline in scores on the visual analog scale (mean [SD] change for walking at 60 days placebo group -1.5 [2.5] vs glucosamine group -1.4 [3.0], P = 0.77). Two participants taking glucosamine and 4 taking placebo withdrew from the study due to adverse side effects (P = 0.67). CONCLUSION: Glucosamine was no better than placebo in reducing pain from osteoarthritis of the knee in this group of patients.
This study evaluated changes in serum lipids when fluvastatin was substituted for lovastatin using equivalent doses. Results showed that serum lipids, especially low-density lipoprotein cholesterol, significantly increase with this substitution.
The aim of this study is to evaluate and quantify the respiratory dependency of cutaneous laser-Doppler flux motion in two variable innervated sites of the upper extremity (the proximal volar forearm and the fingertip) by using a computer-supported system. Various spontaneous (6-17/ min) and externally triggered (12 or 6/min) respiratory frequencies were used for comparative frequency analysis of the laser-Doppler flux signal. Further, an index (MIRSF) was determined as an indicator of the correlation between flux motion and respiration. The MIRSF is defined as the ratio of the power spectrum of the LDF signal at the specific respiratory frequency divided by the time-averaged LDF for that time period. The MIRSF enables a comparison of different intra- and interindividual flux values. A very high correlation was seen between the respiratory frequency and the MIRSF during spontaneous respiration in the skin of the proximal volar forearm; the lower the spontaneous respiratory frequency, the higher the MIRSF. However, this correlation could not be found in the results of the fingertip. The presence of a constant and therefore externally triggered respiratory frequency increased the modulations of the LDF at both measurement locations. While triggered respiration produced a decline in the taLDF of the fingertip, the taLDF of the forearm was unaffected. Considering the different innervation and hydrostatic effects the results lead to the following conclusion: the finger vessels are richly innervated with adrenoceptors which causes alpha 1-mediated vasoconstriction. In contrast to the vessels of the fingers those of the forearm seem to be under andrenergic as well as cholinergic control. Hydrostatic components appear to be more prevalent in the volar forearm site.
Due to the high risk of amputation they involve, diabetic neuropathic plantar ulcers (DNPU) must be regarded as a late manifestation/complication of diabetes mellitus. The suspected cause of these ulcers--disturbed cutaneous microcirculation--was studied by simultaneously measuring laser-Doppler flux (LDF) and cutaneous oxygen tension (pCUO2) in 14 patients with DNPU at three differently affected sites (dorsal forefoot, ulcer edge, lower leg). Dynamic tests (arterial occlusion, local hyperthermia) as a measure of vascular reactivity showed significantly reduced pCUO2 parameters coinciding with elevated LDF values. This reflects a shift of blood flow from the nutritive capillaries towards deeper vessels. Abolition of normal vasoconstriction in the arteriovenous shunt vessels by diabetic polyneuropathy is the assumed cause of increased AV perfusion, with a consequent rise in LDF values. In a subgroup of the above patients (n = 7) undergoing daily intravenous retrograde perfusion therapy (RVP) over 10 days several basic and dynamic microcirculatory functions were studied before and after this treatment. This subgroup showed on the forefoot and the lower leg a remarkable improvement of the microcirculatory parameters investigated, suggesting a better oxygen supply to the tissues after RVP therapy.
Functional tests simulating local stresses are especially suitable for the evaluation of physiological and pathophysiological patterns in the cutaneous microcirculation, particularly if combined with non-invasive methods such as laser-Doppler fluxmetry and oxygen tension measurements. Arterial occlusion (3 min) and local heating (up to 42 degrees C) are appropriate as stimuli to simulate specific local demands on the cutaneous perfusion similar to those produced by pressure, myokinesis, heat, and inflammation. When the current microcirculatory status is described the initial values (LDF and pO2) and their time-courses during each functional test can be used to determine the so-called post-stimulatory parameters. These-- corresponding to physiological equivalents--allow statements on the vascular reactivity towards hypoxia and ischaemia. Furthermore, dynamic performance parameters can easily be derived from the poststimulatory values. They describe the capacity of cutaneous microcirculation with regard to perfusion reserves and ischaemic tolerance in local stress situations in an appropriate manner. As an example of the usefulness of functional tests for cutaneous microcirculation, the physiological and pathophysiological patterns found in systemic sclerosis are described.
The association of connate, left-sided, extensive epidermal verrucous nevus, multiple isolated bone tumors and vitamin-D-resistant rickets since childhood seen in a 20-year-old male patient corresponded to an epidermal nevus syndrome (ENS). However, other organ involvement occasionally associated with ENS could not be found in this patient, and his intraosseous tumors represented histologically benign hemangiomas. Serum analysis revealed hypophosphatemia (together with phosphaturia), decreased levels of 1,25-dihydroxycholecalciferol and elevated levels of alkaline phosphatase indicating hypophosphatemic osteomalacia. Therefore we suppose that vitamin-D-resistant rickets combined with skeletal tumors represents a peculiar type of osteomalacia caused by unilateral mesenchymomas.
To study disturbed microcirculation involved in the pathogenesis of diabetic neuropathic plantar ulcers (DNPU), we recorded dynamic changes in laser-Doppler flux (LDF) and cutaneous oxygen tension (pcuO2) caused by short-time arterial occlusion and local heating at three different sites (forefoot, ulcer edge, lower leg) in patients (n = 14) with DNPU and healthy controls (n = 18). Significantly reduced dynamic pcuO2 parameters coincided with a significant increase of flux in the patient group. This post-stimulatory "hypoxic hyperemia" indicates a shifting of blood flux, reducing circulation of the nutritive capillaries comparable to an internal "steal effect". This may predispose to the development of DNPU when additional stresses influence the initial borderline balance, characterized by similar pcuO2 and increased flux values compared to controls. Abolishment of normal vasoconstriction in the shunt vessels by diabetic polyneuropathy is the assumed cause of increased arteriovenous perfusion and therefore raised flux values. Non-invasive testing of microcirculatory functions demonstrates characteristic disturbances in DNPU patients and could be used as additional parameters for new therapeutic concepts as the intravenous retrograde perfusion (RVP). After RVP therapy, applied to a subgroup (n = 7) of the patients, some dynamic microcirculatory parameters improved, allowing a preliminary quantitative evaluation of a therapeutic regimen.
The aim of this study was to show and to quantify the breath-dependency of cutaneous fluxmotion in the volar proximal forearm using a new computer-aided system. A meanflux-related index (MI) representing the intensity of the influence of respiration on fluxmotion was calculated. There was a good correlation between MI and the rate of respiration under spontaneous breathing: the lower the rate of respiration, the higher the value of MI. Prescribing a constant breathing rhythm amplifies this frequency-dependent effect. According to occurrence of low rates of respiration (< 12/min) also under physiological conditions the respiration should be simultaneously recorded while assessing fluxmotion.
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To study the functional reactivity of the cutaneous microcirculation in progressive systemic sclerosis (PSS), hyperemic responses after arterial occlusion (3 min) and during local heating (42 degrees C) were investigated with simultaneous measurements of red blood cell flux and cutaneous oxygen tension (pcuO2) of the skin in female patients (n = 19) with PSS and in healthy female controls (n = 15). Additionally, serum levels of 6-keto-prostaglandin 1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, were compared to the microcirculatory data, and both were used to evaluate further a standardized therapy with 10-d intravenous calcitonin (100 IU/d) infusion in six PSS patients. In PSS, the initial mean pcuO2 value was significantly reduced and was inversely proportional to flux and to PGF1 alpha levels, whereas the flux and pcuO2 responses to the above hyperemic stimuli showed significant reductions, revealing a pattern of "hyperemic hypoxia" probably due to exhausted functional reserves of cutaneous perfusion. During calcitonin infusion significant rises in pcuO2 and temporarily in PGF1 alpha and flux were found. After 10 d of therapy, increased pcuO2 was associated significantly with decreased flux, indicating a shifting of blood from deeper regulatory vessels to the subepidermal capillaries. Both clinical improvement and the results of microcirculatory measurements demonstrate a beneficial effect of calcitonin on the cutaneous microcirculation in PSS patients, possibly due in part to a short-term increase in release of endogenous prostacyclin from the vascular endothelium during the infusion. The disturbed reactivity of the dermal vessels in PSS is important for the evaluation of therapeutic concepts and stresses, together with the elevated PGF1 alpha plasma levels, vascular factors in the pathogenesis of PSS.
Necrobiosis lipoidica (NL) is a chronic, skin disease usually localized pretibially and often associated with diabetes mellitus. Primary vascular disturbances are considered pathogenetic for NL. In order to determine microcirculatory alterations in "idiopathic" NL linked with neither arterial hypertension nor diabetes mellitus, we performed simultaneous measurements of laser-Doppler flux (LDF) and oxygen tension (pcuO2) in 10 non-diabetic patients with NL and in 10 age- and sex-matched healthy volunteers. We examined the centre of the pretibial NL plaque, its border and the non-affected skin of the proximal lower leg at probe temperatures of 36 degrees C (flux) and 37 degrees C (pcuO2). Corresponding sites and temperatures were chosen for the controls. In addition, the degrees of hyperaemia caused by arterial occlusion (3 min) and during local heating (42 degrees C) were continuously measured. The initial pcuO2 values were found to be lowered, in contrast to increased fluxes within and around the NL lesions. In addition, responses of both flux and pcuO2 to the hyperaemic stimuli were weaker than in the corresponding skin of the healthy controls. Only minor differences from controls or none at all were found in clinically unaffected lower leg skin of the patients. Our results indicate a local alteration of microcirculation in patients with "idiopathic" NL that occurs independently of diabetes.
In connection with a case of epidemic disease with high morbidity and mortality in a flock of sheep, a pestivirus infection could be diagnosed. Pathological-anatomical abnormalities were very similar to the character of BVD/MD. Scientific findings on pestivirus infections in sheep are discussed.
A modified method combining the two methods of measuring either tissue oxygen tension (pO2) or transcutaneous pO2, which have already been proven in other clinical fields, is presented for application in particular skin diseases. This so-called "cutaneous pO2 measurement" (pcuO2) is based on measurements from commercially available transcutaneous pO2 devices, but produces moderate hyperemia through the lower electrode temperature (e.g., 40.5 degrees C) instead of maximal hyperemia (by 44 degrees-45 degrees C temperature). Values obtained this way depend more upon local skin properties, including peripheral capillary flow, than on the arterial pO2. Thus the data are termed cutaneous pO2 (pcuO2). With this method, over 140 measurements were carried out on 14 healthy subjects and 14 patients with progressive systemic scleroderma (PSS); the measurements were made at various skin sites (interdigital fold II/III, back of mid-hand) and under different conditions (3-min upper arm arterial occlusion, 5-min arm muscle activity, cold stimulus to fingers). The pcuO2 values obtained from the PSS patients were significantly below (0-15 mm Hg) those from the healthy subjects (15-42 mm Hg). Fall and recovery times for pcuO2 (during and after arterial occlusion) were prolonged about twice as long in the patients. The pcuO2 reactions to muscle activity and cold stimulus were also significantly delayed in the patients as compared to the subjects. The modified method of cutaneous oxygen tension measurement presented can be employed for more precise assessment of the degree and severity of vascular disorder in PSS, and it is complementary to other clinical methods.(ABSTRACT TRUNCATED AT 250 WORDS)
A new technique using ultrasound computed tomography is explained. Reconstruction of pictures follows basically the algorithm of radiology CT in one plane. The computed data of several scan planes with different angles of the same subject are used for image reconstruction. In this manner, poor lateral resolution of reflections is eliminated. The improved quality of the CT ultrasound images is shown.
A single dose of 204Tl, representing about 2-3 ng 204Tl per gm/wt was injected into young and adult rats. Rats were killed daily over a period of 10 days and the levels of Tl were estimated in nervous and other tissues. The greatest concentrations of Tl (peak concentration time - PCT) in all tissues in the adult rat occurred 24 hours after injection. In the young rat PCT in the sciatic nerve and spinal cord were 48 hours after injection whereas it occurred 24 hours after injection in the brain and somatic organs. There were differences in biological half-lives of the organs in the young as compared to the adult rats. Tl level in all organs except the kidney, were about 2 pg/mg of tissue. It was concentrated in the cytoplasm of most cells examined. Tl levels then fell rapidly during the few days following the injection, and slowly afterwards. Thirty days after the injection, tracts of 204Tl were present in the cytoplasm of nervous and somatic cells.
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STUDY OBJECTIVE: To assess the efficacy of fluvastatin administered every other day versus an equivalent dose given daily in patients with hypercholesterolemia. DESIGN: Randomized, nonblinded, crossover study. SETTING: Veterans Affairs Medical Center. PATIENTS: Twenty-three patients with low-density lipoprotein (LDL) levels above 160 mg/dl despite diet therapy INTERVENTION: Patients received fluvastatin 40 mg every other day or 20 mg/day, all doses taken at bedtime. Each treatment arm was 6 weeks in duration. MEASUREMENTS AND MAIN RESULTS: A lipid profile was determined at baseline and after each regimen. Both regimens significantly lowered total cholesterol and LDL versus baseline. The LDL levels were lowered by 24% and 21% by fluvastatin 20 mg/day and 40 mg every other day, respectively. There was no statistically significant difference in lipid components between regimens. CONCLUSION: Fluvastatin 40 mg every other day is effective in lowering total cholesterol and LDL in patients with hypercholesterolemia.