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Biomedical subjects

D H Lewis

Publications and source records attributed to D H Lewis.

At least 109 records · Page 6Linked to original sources

Changes in human forearm blood flow after intravenous regional sympathetic blockade with guanethidine.

The effect of intravenous regional sympathetic blockade with guanethidine on total forearm blood flow and on muscle and skin blood flow in the forearm was studied in healthy humans, using venous occlusion plethysmography, 133Xe-clearance technique and skin temperature recordings. The total blood flow tripled in response to the blockade and the rise persisted for 2-3 days. The increase in blood flow was confined to the skin, with no demonstrable steal effect on muscle blood flow. The observations imply that this type of sympathetic blockade may be of therapeutic value in some vascular disorders of the hand, and as supportive treatment in vascular surgery on the extremities.

Adult↗

Clinical evaluation of injectable biodegradable contraceptive system.

A new long-acting injectable contraceptive system was tested in 24 women. The system consists of microspheres made of biodegradable d,l-polylactic acid in which micronized crystals of norethisterone (NET) are homogeneously dispersed. In previous animal studies we showed that NET is slowly released from the microspheres for 6 months, and after the drug is released, the microspheres biodegrade into lactic acid by the process of hydrolysis. The serum levels of NET, estrogen, and progesterone were monitored by radioimmunoassay, and the effects of treatment on ovarian function and menstrual bleeding were evaluated. The doses ranged from 29 to 370 mg of microspheres containing 7.25 to 94.5 mg of NET or 0.134 to 2.30 mg of NET/kg of body weight. The duration of the NET release was 6 months, and the serum NET profiles in women were similar to those previously described in subhuman primates. Following a small burst, there was a gradual decline in the serum levels of NET over 6 months after treatment. The serum levels of NET varied in proportion to the dose. Doses less than 0.267 mg of NET/kg had no discernible effect on either ovarian function or menstrual bleeding. Doses ranging from 0.419 to 2.30 mg had variable effects on ovarian function and menstrual bleeding. Higher doses caused suppression of ovarian function for longer periods of time, increased the interval between episodes of menstrual bleeding, and decreased the quantity of blood loss during each episode. The treatment was well tolerated by all subjects, and, with the exception of spotting and irregular menstrual cycles, there were no adverse side effects. Based on this initial study, it was determined that doses ranging from 1.33 to 3.45 mg of NET/kg are necessary to suppress ovulation for 6 months. Additional studies with the use of higher doses are currently under way.

Adult↗

Mixed infection in columnaris disease of fish.

In addition to Flexibacter columnaris, Corynebacterium sp was recovered from lesions associated with columnaris disease in catfish. Catfish exposed to pure cultures of the Corynebacterium sp developed circumscribed lesions, which regressed without further adverse effects. Disease signs were not demonstrable in catfish exposed to pure cultures of F columnaris; however, when catfish were exposed to mixed cultures of th Corynebacterium sp and F columnaris, signs of columnaris appeared and the fish died.

Animals↗

The occurrence of paracrystalline mitochondrial inclusions in normal human skeletal muscle.

Two different types of paracrystalline mitochondrial inclusions identical with or very similar to those already described in the literature for a variety of muscle diseases were found in human skeletal muscle biopsies obtained under general anesthesia before ischemia and after various periods of anoxia up to 150 min. As these crystalloids could be observed in seven of 14 healthy subjects and occurred in five of these seven cases either before or only 10 min after onset of ischemia, it is suggested that such mitochondrial inclusions develop not only under the influence of variant noxious stimuli, but may also represent a normal constituent of human skeletal muscle mitochondria.

Adolescent↗

An assessment of recent advances in external maxillofacial materials.

A variety of new materials representing several polymer classes and diverse fabrication procedures are now becoming available for use as external maxillofacial prostheses. Because of the availability of these materials, the severely disfigured patient can now be provided an opportunity to elad a near-normal life in today's society. Remarkable advancements have been made in providing the patient with prostheses which feel and look more like skin. Progress has also been made in simplifying fabrication procedures, thus reducing cost. Much remains to be done in materials research. Processing time is still too long for most of the materials. Some of the materials give variable results in the quality and stability of the prostheses because of sensitivity to contaminants and to lab conditions and operator technique. Extrinsic coloration is extremely tedious and diffult with many of the products. The fitting and attachment of the prosthesis to the patient continues to need much improvement. Margins are difficult to mask even with the best materials. Large prostheses of most of the materials are much too heavy and are poorly retained. Staining of the prostheses by foods, cosmetics, and tobacco is a serious problem. The need for an improved material has been recognized by various government agencies and a few of the industrial suppliers of synthetic polymers. Additional advances are sure to result from these efforts.

Chemical Phenomena↗

Skeletal muscle oxygen pressure fields in rats. A study of the normal state and the effects of local anesthetics, local trauma and hemorrhage.

The MDO (Mehrdraht Dortmund Oberfläche) oxygen electrode was used for studies of oxygen pressure fields in rat skeletal muscle. With this multiwire oxygen electrode, the three-dimensional oxygen pressure field was measured and presented as a two-dimensional frequency distribution, i.e., a histogram. Statistical analysis of the histograms was carried out with the two-sample Kolmogorov-Smirnov test. This eliminated the influence of mean values, since these do not always represent the actual biological situation. The oxygen pressure fields in skeletal muscle of anesthetized normal rats breathing air spontaneously were investigated. When the oxygen pressure in the inspired gas was changed (50% and 95%), changes were seen in muscle oxygen pressure curves. The normal oxygen pressure field histograms were compared with those obtained after local anesthesia, after local trauma to the muscle and after hemorrhage. After local anesthesia the histograms were unchanged. Significant changes in the distribution types of the histograms were found after trauma in all rats studied. After hemorrhage significant changes, similar to those seen after trauma, were found in 15 of the 23 rats studied. Local blood flow was also measured with the 133xenon-clearance method in the hemorrhage experiments. No correlation was found between the changes in the mean oxygen tension values and the changes in 133xenon-clearance.

Animals↗

Skeletal muscle oxygen pressure fields in healthy human volunteers. A study of the normal state and the effects of different arterial oxygen pressures.

The MDO (Mehrdraht Dortmund Oberfläche)oxygen electrode was used for studies of tissue oxygen pressure fields (presented as histograms) in healthy human volunteers breathing room air and gas mixtures with different oxygen concentrations. Forearm blood flow measurements were performed with strain gauge plethysmography, and local blood flow and permeability-surface area product (PS) were studied by the clearances of 133xenon and 51Cr-EDTA. At ordinary arterial oxygen pressure levels the histograms were normal, i.e. their distribution type was approximately Gaussian. Higher arterial oxygen pressures caused changes in tissue oxygenation. However, at arterial oxygen pressure levels above 31 kPa two types of abnormal histogram distribution types were distinguished: scattered multi-population histograms (type a) and a type with predominantly low values (type b). Mean forearm blood flow showed only minor variations, whereas the clearances of 133xenon and 51Cr-EDTA were higher with higher PaO2. A parallel increase was also seen in PS.

Adult↗

Skeletal muscle oxygen pressure fields in artificially ventilated, critically ill patients.

The MDO (Mehrdraht Dortmund oberfläche) oxygen electrode was used in a study of skeletal muscle oxygen pressure fields, presented as histograms, in critically ill patients artificially ventilated with gas mixtures of different oxygen concentrations. The histograms were compared with forearm blood flow measurements performed with strain gauge plethysmography. Local blood flow and permeability-surface area product (PS) were also studied by the simultaneous clearances of 133xenon and 51Cr-EDTA. The histogram distribution type was normal, i.e. approximately Gaussian, at arterial oxygen pressure levels between 10 and 18 kPa. At arterial oxygen pressures outside this range the histogram distribution types were abnormal, i.e. they showed a non-symmetrical distribution of oxygen pressure values, but their mean was approximately the same as in the normal histogram. However, there were significantly higher tissue oxygen pressure mean values in the patients (3.43 kPa) than in a group of healthy human volunteers (2.25 kPa). Mean forearm blood flow and the clearances of 133xenon and 51Cr-EDTA showed marked variations during the measurements both intraindividually and interindividually. Mean forearm blood flow and mean clearances of 133xenon showed opposite trends compared with arterial oxygen pressures. Mean clearances of 51Cr--EDTA and means PS showed only minor variations at the different arterial oxygen pressure levels.

Adult↗

Effect of normovolemic hemodilution of skeletal muscle oxygen pressure fields in atherosclerotic mini-pigs. Preliminary report.

Normovolemic hemodilution with dextran-70 was carried out in 4 Göttingen mini-pigs with induced atherosclerosis. Hematocrit was lowered stepwise to 10--15%. Measurements of the skeletal muscle surface oxygen pressure fields were carried out using the MDO oxygen electrode. Results indicated an optimal PO2 histogram at hematocrit between 21 and 25%, with uniformly abnormal histograms at hematocrit 10%. Cardiac output determinations in 1 animal revealed an initial increase in stroke volume (Hct 29%) followed by increasing heart rate at lower hematocrits. The results indicate that normovolemic hemodilution can be tolerated even in the presence of experimental atherosclerosis and that the matter needs further clinical study.

Animals↗

New long-acting injectable microcapsule contraceptive system.

A new long-acting, injectable contraceptive which provides continuous controlled release of the steroid norethisterone (NET) for a precise period of 6 months following a single intramuscular injection is described. The prototype system consists of microcapsules made of the biodegradable polymer d, l-polylactic acid, in which micronized crystals of NET are homogeneously dispersed. NET is slowly released from the microcapsules following intramuscular injection at a rate of 0.90 microgram NET/day/mg of microcapsule by diffusion of the steroid from the polymer matrix. Three different doses of a standard preparation of microcapsules were tested in normally cycling female babbons (4 to 5 baboons/group). Following injection of either 300, 200, or 100 mg of microcapsules containing 75, 50, or 25 mg of NET, blood samples were collected at selected intervals and analyzed for NET, estrogen, and progesterone by radioimmunoassay. All three doses provided continuous NET release for 6 months following injection. The NET serum profiles for the different doses are parallel, and ovulation was inhibited in all baboons for 6 months following treatment.

Animals↗

A new long-acting injectable microcapsule system for the administration of progesterone.

A long-acting injectable microcapsule system for the controlled-release systemic administration of progesterone (P4) is described. The system consists of microcapsules made of the biodegradable polymer, d,l-polylactic acid, which contain crystalline P4. Following injection, P4 is released from the microcapsules by diffusion and biodegradation of the polymer matrix. The rate of P4 release from the prototype microcapsule system in vivo is 1.3 microgram of P4/day/mg of microcapsules, and the duration of release is 30 days. Vaginal estrous cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following a single injection of P4 microcapsules. The effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent. The utility of the system as a once-a-month injectable contraceptive is established in the baboon model.

Animals↗

Lung uptake of lidocaine in healthy volunteers.

Eleven patients with no known history of heart or lung disease received an i.v. bolus injection of a mixture of lidocaine and indocyanine green dye (Cardiogreen). The dose of lidocaine, given once (or twice 10 min apart), was 0.5 mg/kg b.w. Time concentration curves from the appearance of indocyanine green were constructed for both substances from blood samples taken from the common femoral artery for approx. 50 s at the rate of one sample every 1.2 s. The extraction of lidocaine in each sample and the uptake of lidocaine, when 95% of the injected dose of indocyanine green had been recovered, were calculated. Nine patients showed an initial plateau of high extraction, which was 0.92 +/- 0.02 (mean +/- s.e mean) and 0.91 +/- 0.02 for the first and second injections, respectively, for the entire material. In two cases, however, a short plateau and a rapid decline in the extraction curve were observed. The 95% first pass uptake was 60 +/- 5% in the first injection and 55 +/- 12% for the second injection. Extraction of lidocaine dominated over back diffusion for the approximately 25 s. It is concluded that: (1) The described technique for studying lung uptake gave consistent and reproducible results in human volunteers; (2) Lung uptake of lidocaine in healthy man exceeds that previously observed in anaesthetized pigs; (3) The initial uptake during the first 5 s after appearance of indocyanine green in the arterial samples was more than 90%. (4) The lungs thus have a dampening effect on the arterial concentration, which might be of importance if lidocaine is accidentally injected intravenously.

Adult↗

Displacement of nortriptyline and uptake of 14C-lidocaine in the lung after administration of 14C-lidocaine to nortriptyline intoxicated pigs.

Six anaesthetized Swedish land-race pigs were intoxicated by an intravenous infusion of nortriptyline-HCl (NT) up to a concentration of 4.58 +/- 0.58 (mean +/- S.E.M.) microM in arterial whole blood. A rapid injection of 2 mg/kg b.wt. lidocaine-HCl in the right atrium was followed by a rise in arterial whole blood concentration of NT up to a maximum of 7.32 +/- 0.28 microM NT. Amount displaced NT from the cardio-pulmonary circulation after the 14C-lidocaine bolus, was calculated to be 0.66 +/- 0.03 mumol. Lung uptake of 14C-lidocaine during first-pass through the lung was not influenced to any statistically signficant degree compared to a control group. Thus, first pass uptake (FPU) was 30 +/- 8 (mean +/- S.E.M.)% and 39 +/- 5% respectively. The duration of the QRS-complex of the ECG was increased (P less than 0.01) during the infusion of NT from 0.07 +/- 0.01 (mean +/- S.E.M.) sec. to 0.14 +/- 0.02 sec. when 250 mg NT-HCl had been administered. The QRS-duration was decreased (P less than 0.01) after the injection of the 14C-lidocaine bolus to 0.09 +/- 0.01 sec. Mean arterial blood pressure and heartrate decreased slightly during the infusion of NT, but did not change immediately after the 14C-lidocaine bolus.

Animals↗