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Biomedical subjects

J H Stevenson

Publications and source records attributed to J H Stevenson.

At least 37 records · Page 2Linked to original sources

Cica-Care gel sheeting in the management of hypertrophic scarring.

A prospective, controlled clinical trial was undertaken to assess the efficacy and safety of two types of silicone gel, Silastic Gel Sheeting (SGS) and Cica-Care (CC), in the management of hypertrophic scars. Forty-two patients were randomly assigned to SGS and CC groups and their hypertrophic scars were divided into treated and control areas. Extensometric measurements were made at monthly intervals for 6 months and significant improvement of the treated areas relative to the control areas was observed. The two gels were not significantly different in efficacy or safety, but CC, being more adhesive and more comfortable than SGS, has advantages in ease of use and patient acceptability.

Adolescent↗

Energy metabolism in cortical synaptic terminals from weanling and mature rat brain: evidence for multiple compartments of tricarboxylic acid cycle activity.

It is well documented that the brain preferentially utilizes alternative substrates for energy during brain development; however, less is known about the use of these substrates by synaptic terminals. The present study compared the rates of 14CO2 production from 1 mM D-[6-14C]glucose, L-[U-14C]glutamine, D-3-hydroxy[3-14C]butyrate, L-[U-14C]lactate and L-[U-14C]malate by synaptic terminals isolated from 17- to 18-day-old and 7- to 8-week-old rat brain. The rates of 14CO2 production from glucose, glutamine, 3-hydroxybutyrate, lactate and malate were 8.55 +/- 0.78, 25.90 +/- 4.58, 42.28 +/- 3.54, 48.42 +/- 2.09, and 9.31 +/- 1.61 nmol/h/mg protein (mean +/- SEM), respectively, in synaptic terminals isolated from 17- to 18-day-old rat brain and 12.95 +/- 1.64, 30.62 +/- 4.19, 16.09 +/- 2.62, 40.33 +/- 6.77, and 8.25 +/- 1.69 nmol/h/mg protein (mean +/- SEM), respectively, in synaptic terminals isolated from 7- to 8-week-old rat brain. In competition studies using unlabelled added substrates, the addition of 3-hydroxybutyrate, lactate or glutamine greatly decreased the rate of 14CO2 production from labelled glucose. Added unlabelled glucose increased the rate of 14CO2 production from 3-hydroxybutyrate in synaptic terminals from 7- to 8-week-old rat brain, but had no effect on 14CO2 production from any other substrates. Lactate also increased 14CO2 production from 3-hydroxybutyrate at 7-8 weeks, whereas the addition of 3-hydroxybutyrate decreased 14CO2 production from lactate only in synaptic terminals from 17- to 18-day-old rat brain. None of the added substrates altered the rate of 14CO2 production from labelled glutamine or malate suggesting that these substrates are metabolized in relatively distinct compartments within synaptic terminals. Overall the data demonstrate that synaptic terminals from both weanling and adult rat brain can utilize a variety of substrates for energy. In addition, the competition studies demonstrate that the interactions of substrates change with age and suggest that there are multiple compartments of energy metabolism (or tricarboxylic acid cycle activity) in isolated synaptic terminals.

Animals↗

Differential effects of serum protein(s) on substrate oxidation by isolated synaptosomes and cultured rat brain astrocytes.

This report extends the finding that serum protein(s) (0.5 mg/ml) caused a 50% decrease in the rate of glucose oxidation by dissociated brain cells with only marginal effects on the oxidation of other substrates. Since dissociated cells represent a heterogeneous population, studies were initiated to determine the effect of serum on the rates of substrate oxidation by isolated synaptosomes and cultured rat brain astrocytes. Experiments revealed that the addition of 5% serum v/v to the reaction mixture resulted in a decrease in the rate of 14CO2 production from [6-14C]glucose by isolated synaptosomes by more than 70%. In contrast, the addition of 5% serum had little or no effect on the 14CO2 production from [U-14C]glutamine by the synaptosomes and only marginal effects (20-25%) on 14CO2 production from [U-14C]lactate and 3-hydroxy[3-14C]butyrate. The effect of serum on the rates of substrate oxidation were similar for synaptosomal preparations obtained from adult animal brains or 18-day-old rats, except that with the latter preparation, 14CO2 production from 3-hydroxy[3-14C]butyrate was more attenuated by the presence of serum than with the former synaptosomal preparation (50 vs. 25%). In contrast to the results with synaptosomes, the presence of 5% serum enhanced the rates of 14CO2 production from [6-14C]glucose, 3-hydroxy[3-14C]butyrate and [U-14C]lactate by 61, 35 and 69%, respectively, in cultured rat brain astrocytes. However, this enhancement did not occur when the cells were grown in chemically defined media or when dibutyryl cAMP was added to the media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: differences revealed using aminooxyacetate.

Several recent studies have demonstrated that the metabolism of energy substrates takes place in multiple compartments in both astrocytes and synaptic terminals from brain. There are a number of differences in the metabolism of astrocytes and synaptic terminals primarily due to the localization of key enzymes such as pyruvate carboxylase and glutamine synthetase in astrocytes. The present study determined the rates of 14CO2 production from several energy substrates by primary cultures of astrocytes and cortical synaptic terminals from rat brain. The rates of 14CO2 production from labelled substrates by astrocytes were 0.96 +/- 0.13, 11.13 +/- 0.67, 10.51 +/- 0.35, 24.92 +/- 1.66 and 4.80 +/- 0.50 for D-[6-14C]glucose, L-[U-14C]lactate, D-3-hydroxy[3-14C]butyrate, L-[U-14C]glutamine and L-[U-14C]ma-late, respectively. The rates of 14CO2 production were also measured in the presence of 5 mM aminooxyacetate (AOAA) to determine the effect of inhibiting the malate-aspartate shuttle and other transaminase reactions on the oxidation of energy substrates. In astrocytes the addition of AOAA decreased the rate of glutamine oxidation 5-fold, consistent with other studies showing that glutamine enters the TCA cycle via transamination. AOAA increased the rate of 14CO2 production from labelled glucose 4-fold, suggesting that inhibition of alanine biosynthesis profoundly alters the utilization of glucose by astrocytes. AOAA also increased the oxidation of lactate and 3-hydroxybutyrate 36 and 58%, respectively. The rates of 14CO2 production from labelled substrates by synaptic terminals were 13.12 +/- 1.05, 35.29 +/- 3.58, 17.66 +/- 1.95, 30.18 +/- 1.10 and 9.95 +/- 1.29, respectively, for glucose, lactate, 3-hydroxybutyrate, glutamine and malate, demonstrating that all substrates were oxidized at a higher rate by synaptic terminals than by astrocytes. The addition of AOAA decreased the rate of 14CO2 production from labelled lactate by 57% suggesting that the use of lactate for energy in synaptic terminals is tightly coupled to the activity of the malate-aspartate shuttle. AOAA had no effect on the rate of 14CO2 production from labelled glutamine, demonstrating that exogenous glutamine enters the TCA cycle in synaptic terminals via glutamate dehydrogenase, not via transamination as is the case with astrocytes. AOAA had no significant effect on the rates of oxidation of glucose, 3-hydroxybutyrate and malate by synaptic terminals. These findings demonstrate that inhibiting transamination with AOAA had very different effects on the oxidation of energy substrates in the two preparations, suggesting that the regulation of metabolism is quite different in astrocytes and synaptic terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

The metabolism of malate by cultured rat brain astrocytes.

Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-[U-14C]malate in primary cultures of rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from 0.01 mM and 0.5 mM malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain. Both the biphasic kinetics and the differential action of many of the effectors on the 14CO2 production from 0.01 mM and 0.5 mM malate provide evidence for the presence of more than one pool of malate metabolism in cultured rat brain astrocytes.

Animals↗

Intractable digital neuroma pain; the ultimate solution?

A case is presented in which, following the failure of several surgical and non-surgical procedures to control the increasingly severe pain in an amputation thumb stump, a toe transfer was carried out, successfully relieving the symptoms without transfer of the pain to the donor site. The patient has remained pain-free for 3 years.

Adult↗

Experience with the free "inverted" groin flap in facial soft tissue contouring; a report on 6 flaps.

Reconstruction of the soft tissue facial contour defect in Romberg's disease and facial lipodystrophy using a free groin flap has been previously reported. However, controversy exists over the optimum placing of this flap within the cheek, i.e. whether it is better to have the dermis or subcutaneous fat side next to the muscle. Our experience with 6 flaps, 3 of which have been followed up for 3 1/2 years, is presented. In all cases the flaps were placed with the dermis side down, i.e. next to muscle. Although not a comparative study, our impression is that in the long term this technique reduces gravitational migration. Our experience with 2 flaps suggests that, in the early postoperative period at least, secure fixation by suturing to the muscle and periosteum is important. We believe that, in addition, this method gives a smoother contour and allows easy and safe secondary adjustments to be made where necessary.

Adolescent↗

Proximal upper limb replantation in children.

Proximal upper limb amputation not only leads to serious local disability but carries with it substantial systemic implications. The replantation of an avulsed limb is all too frequently followed by disappointing functional results. In children, however, with secure bony stability, vascular reconstruction and immediate appropriate nerve repair the results of replantation can be most gratifying. Two such cases have been seen at The Hospital for Sick Children and are reported in detail. The late functional results as illustrated make this complex procedure a very worthwhile undertaking.

Activities of Daily Living↗

Serum effects on substrate oxidation by dissociated brain cells: possible sites of action.

This report is an extension of recent studies indicating the presence of a factor in serum that preferentially inhibits 14CO2 production from labeled glucose. Experiments with dissociated cells revealed that the inhibitory effects of serum were only slightly changed over more than a 50-fold range in initial glucose concentration. Serum had no effect on the rate of glucose transport (uptake of 1,3[3H]2-deoxyglucose). The inhibitory effect of serum was greater on 14CO2 production from [6-14C]glucose than [1-14C]glucose. Other studies revealed that 14CO2 production from [1-14C]pyruvate was more than 5 times the rate obtained using [3-14C]pyruvate; however, the inhibitory effect of serum was much greater on the latter (20% vs 60% inhibition respectively) at 2 mM pyruvate and in the presence of 1% fetal bovine serum. Attempts to characterize the factor using Amicon filtration showed the highest inhibitory activity in a 10,000 mol. wt. fraction, although some inhibitory activity was found in commercial preparations of bovine serum albumin. Delipidation of serum had no effect. Based on these results, we postulate that the observed decrease in labeled CO2 production reflects the regulation of substrate utilization at the pyruvate carboxylase step by one or more factors in serum (with a mol. wt. of approximately 10,000).

Animals↗

Upper limb motor and sensory recovery after multiple proximal nerve injury in children: a long term review in five patients.

Five children who had sustained multiple proximal upper limb nerve injury were reviewed at 18 months to 3 1/2 years after primary repair had been carried out. The findings show that nerve regeneration occurred significantly more rapidly than in adults, with good return of motor and sensory function to the hand, resulting in each of the patients having a useful, painfree and functionally capable upper limb. In two of the cases, the limb had been completely severed. The findings support the view that primary repair of severed proximal nerves in this age group--even in avulsion type injuries--can give good results.

Arm Injuries↗

Functional, mechanical, and biochemical assessment of ultrasound therapy on tendon healing in the chicken toe.

We studied the therapeutic effect of ultrasound treatment on the functional recovery of surgically repaired profundus tendon in the right third toe of mature White Leghorn hens. Ultrasound treatment was given daily for 5 minutes for a total of 20 treatment days, starting immediately after 4 weeks immobilization. Ultrasound (frequency 3.0 mHz; intensity 0.75 W/cm2) was delivered to the right leg by a 5-cm2 probe through distilled water in a bath kept at 35 degrees C. The flexion of the toe was measured preoperatively for 4 consecutive days and daily for 6 weeks after the start of ultrasound treatment for the calculation of percent of functional recovery of the flexor tendon. The non-ultrasound-treated group of birds went through the same manipulations except that no ultrasound was given when the right leg was immersed in the water bath. Ultrasound treatment significantly (p less than 0.01) improved the functional recovery of the repaired tendons (less than 5-mm gap) starting on the third week of treatment (94 +/- 2 percent) compared with the non-ultrasound-treated group (79 +/- 4 percent). Ultrasound treatment had no effect on gap formation or breaking (tensile) strength of the repaired tendons. It is concluded that ultrasound enhanced functional return of repaired flexor tendons in the hen, and the clinical implication is discussed.

Animals↗

Substrate oxidation by isolated rat brain mitochondria and synaptosomes.

The rates of [6-14C]-glucose oxidation by reconstituted systems of cytosol and mitochondria or cytosol and synaptosomes were essentially the same as the rate of oxidation of [3-14C]-3-hydroxybutyrate. However, the rate of [U-14C]-glutamine oxidation by mitochondria was 2.5 times that by synaptosomes. The addition of glutamine (5 mM) caused a reduction in the rates of oxidation [6-14C]-glucose of 20% and 40% by mitochondria and synaptosomes, respectively. Conversely, the addition of glucose (5 mM) had little or no effect on the rate of [U-14C]-glutamine oxidation by either organelle. Amino-oxyacetate decreased [U-14C]-glutamine oxidation by mitochondria more than 35% but had little or no effect on the rate of glutamine oxidation by synaptosomes. When glucose (5 mM) was added to [3-14C]-3-hydroxybutyrate, the rates of oxidation by the mitochondria and synaptosomes were increased by 65% and 77%, respectively. However, in the reverse situation the addition of 3-hydroxybutyrate decreased [6-14C]-glucose oxidation by synaptosomes (35%) but did not decrease the rate by mitochondria. These results suggest that differences in the rates of substrate utilization by mitochondria and synaptosomes and differences in substrate interactions in these two subcellular organelles may contribute to metabolic compartmentation in the brain.

Animals↗

Decreased oxidation of labeled glucose by dissociated brain cells in the presence of fetal bovine serum.

The effect of serum on the rate of substrate oxidation by dissociated brain cells in vitro was examined. At a serum protein concentration of approximately 0.55 milligram per milliliter, oxidation of [6-14C]glucose to 14CO2 was decreased more than 50 percent. Oxidation of [3-14C]-3-hydroxybutyrate and [U-14C]glutamine was decreased much less. Serum from cows, rats, horses, and humans produced similar effects, as did serum from young and old animals and from both sexes. The effect on [6-14C]glucose oxidation was proportional to serum protein concentration, and significant inhibitory activity was obtained with dialyzed serum. Heating (80 degrees C for 10 minutes) significantly reduced the inhibitory activity. These results suggest the presence of a factor in serum that can preferentially decrease glucose oxidation. Such a factor would have profound implications for metabolic regulation in vivo and for studies of cells in vitro in which serum is included in the growth medium.

Animals↗

Competition among oxidizable substrates in brains of young and adult rats. Whole homogenates.

The rates of conversion into 14CO2 of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine were measured in the presence and absence of unlabelled alternative oxidizable substrates in whole homogenates from the brains of young and adult rats. The addition of unlabelled glutamine resulted in decreased 14CO2 production from [6-14C]glucose in brain homogenates from both young and adult rats. In contrast, glucose had no effect on [U-14C]glutamine oxidation. In suckling animals, both 3-hydroxybutyrate and acetoacetate decreased the rate of oxidation of [6-14C]glucose, but in adults only 3-hydroxybutyrate had an effect, and to a lesser degree. The addition of unlabelled glucose markedly enhanced the rates of oxidation of both ketone bodies in adult brain tissue and had little or no effect in the young. The rate of production of 14CO2 from [U-14C]glutamine was increased by the addition of unlabelled ketone bodies in brain homogenates from young, but not from adult rats. In the converse situation, unlabelled glutamine added to 14C-labelled ketone bodies diminished 14CO2 production in young rats, but had no effect in adult animals. These results revealed a complex age-dependent pattern of interaction in which certain substrates apparently competed with each other, whereas an enhanced rate of 14CO2 production was found with others.

3-Hydroxybutyric Acid↗

Burn injury to the face with associated fracture caused by a flare gun: a case report.

A case is presented of a child who sustained a full-thickness burn to the glabella and nose area, associated with an underlying fracture and cerebrospinal fluid leakage. This first reported case of a flare gun injury illustrates some important principles of facial management and soft tissue cover, in both the acute and the reconstructive phases.

Blast Injuries↗

Antiketonemic effect of glycerol during development of the rat.

Glycerol, which decreased circulating levels of ketone bodies in adults, was tested for its antiketonemic action in developing rats. Following intraperitoneal injection of glycerol in rats from 2 to 90 days of age, blood levels of 3-hydroxybutyrate (beta HOB) decreased and reached minimum values in 35-40 minutes. The pattern of recovery in suckling animals (2, 7 and 14 days of age) differed from that of 24-, 35- and 90-day-old rats. Glycerol did not change blood acetoacetate (Ac2) levels in suckling rats but caused marked reductions in fasted older animals. The effect of glycerol on the ration of beta HOB:Ac2 was strikingly different for 90-day-old rats compared to all other groups. Glycerol did not raise blood glucose levels in neonatal or suckling rats. These developmental patterns of response to glycerol differed remarkedly from those to alanine, suggesting differential antiketonemic mechanisms for these two compounds on in vitro rats of beta HOB synthesis in liver homogenates from rats injected with either glycerol or alanine.

3-Hydroxybutyric Acid↗