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Biomedical subjects

G V Smith

Publications and source records attributed to G V Smith.

At least 19 recordsLinked to original sources

Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis.

BACKGROUND: beta-Defensins are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces where their production is augmented by infection or inflammation. Helicobacter pylori colonises the gastric epithelium causing persistent gastric inflammation leading to antral and corpus gastritis, and peptic ulcer disease. AIMS: To evaluate the role of beta-defensins in the innate immune response of the gastric epithelium to infection and inflammation, we have assessed mRNA expression and regulation of human beta-defensins 1 and 2 (hBD1, hBD2) by H pylori and proinflammatory stimuli. We have also compared gene and peptide expression of these bactericidal agents in H pylori induced gastritis with that in normal gastric mucosa. METHODS: Modulation of expression of hBD1 and hBD2 by various stimuli was studied in three (AGS, MKN7, MKN45) gastric epithelial cell lines by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR). Defensin mRNA expression was measured by semiquantitative RT-PCR in gastritis tissue and compared with controls. Peptide localisation was assessed by immunohistochemistry. RESULTS: Cytotoxic H pylori and interleukin 1 beta (IL-1 beta) markedly upregulated expression of hBD2 in a dose and time dependent manner in both AGS and MKN7 cell lines. A modest increase in hBD1 expression was also noted during infection. Interestingly, induction of hBD1 gene expression by IL-1 beta was only observed in MKN7 cells. The magnitude of this response was delayed and reduced compared with hBD2 expression. In gastric biopsies, hBD2 was undetectable in normal gastric antrum but a marked increase was observed in H pylori positive gastritis compared with control tissue (p<0.001). Constitutive expression of hBD1 was observed in normal gastric mucosa and there was a significant increase in gastritis (p<0.05). Immunohistochemistry revealed a parallel increase in hBD1 and hBD2 peptide expression in gastritis tissue with positive staining confined to the surface epithelium of the gastric glands. CONCLUSIONS: Modulation of beta-defensin expression by pathogenic and/or inflammatory stimuli and their cellular localisation places these antimicrobial peptides in the front line of innate host defence in the human stomach.

Cell Line↗

Treadmill training improves fitness reserve in chronic stroke patients.

OBJECTIVE: To investigate the hypothesis that treadmill training will improve peak fitness, while lowering the energy cost of hemiparetic gait in chronic stroke patients. DESIGN: Noncontrolled exercise intervention study with repeated-measures analysis. SETTING: Hospital-based senior exercise research center. PARTICIPANTS: Twenty-three patients (mean age +/- standard deviation [SD] 67 +/- 8 yr) with chronic hemiparetic gait after remote (>6 mo) ischemic stroke. INTERVENTION: Three 40-minute sessions of treadmill exercise weekly for 6 months. MAIN OUTCOME MEASURES: Peak exercise capacity (VO2peak) and rate of oxygen consumption during submaximal effort treadmill walking (economy of gait) by open circuit spirometry and ambulatory workload capacity before and after 3 and 6 months of training. RESULTS: Patients who completed 3 months of training (n = 21) increased their VO2peak +/- SD from 15.4 +/- 2.9 mL x kg(-1) x min(-1) to 17.0 +/- 4.4 mL x kg(-1) x min(-1) (p <.02) and lowered their oxygen demands of submaximal effort ambulation from 9.3 +/- 2 mL x kg(-1) x min(-1) to 7.9 +/- 1.5 mL x kg(-1) x min(-1) (p =.002), which enabled them to perform the same constant-load treadmill task using 20% less of their peak exercise capacity (62.3% +/- 17.2% vs 49.9% +/- 19.3%, p <.002). Gains in VO2peak and economy of gait plateaued by 3 months, while peak ambulatory workload capacity progressively increased by 39% (p <.001) over 6 months. CONCLUSIONS: Treadmill training improves physiologic fitness reserve in chronic stroke patients by increasing VO2peak while lowering the energy cost of hemiparetic gait, and increases peak ambulatory workload capacity. These improvements may enhance functional mobility in chronic stroke patients.

Aged↗

Hemiparetic gait parameters in overground versus treadmill walking.

OBJECTIVE: Hemiparetic gait is characterized by high stride-cycle variability, diminished stance time, single-limb stance time, and stance/swing ratio in the paretic limb. Recent studies suggest treadmill (TM) training may improve the motor control underlying these variables, but supporting evidence is sparse. METHODS: This study compared gait patterns of untrained chronic hemiparetic stroke patients (n = 18; mean, 39.5 months poststroke) during overground (OG) and TM walking at matched velocities. Variables included relative stance time, relative single-limb stance time, stance/swing ratio, peak force, and impulse. Within-subject variability of these measures (CV) was used to assess gait pattern stability. RESULTS: OG and TM cycle durations were similar, but CVs differed (TM < OG, p < 0.05). In the paretic limb, differences were seen in relative stance time, relative single-limb stance time, and stance/swing ratio, respectively (TM > OG, p < 0.05). These variables decreased in the nonparetic limb during TM walking (p < 0.05 for all). Improved interlimb symmetry and coordination were evidenced by decreased between-limb differences and improved relative temporal phasing, respectively, in the TM condition (p < 0.05). CONCLUSIONS: Collectively, these results demonstrate that the TM induces an immediate alteration toward a more consistent and symmetric gait pattern. Further investigation is needed to determine whether TM training leads to motor relearning and neuroplasticity in chronic hemiparetic subjects.

Chronic Disease↗

Altered gait profile in subjects with peripheral arterial disease.

The purpose of this study was to determine whether peripheral arterial disease (PAD) subjects had impaired temporal and spatial gait characteristics compared to non-PAD controls at preferred and rapid self-selected walking paces. A total of 28 PAD subjects with intermittent claudication (age = 71 +/- 1; mean +/- SEM) and 15 non-PAD controls with at least one cardiovascular risk factor but no ambulatory leg pain (age = 71 +/- 1) were recruited. Gait parameters consisting of velocity, cadence, stride length, swing time, stance time, single-support time, double-support time, and base of support were recorded at the preferred and rapid walking paces. At the rapid walking pace, velocity was 22% slower (p < 0.001) in the PAD subjects compared with the non-PAD controls (99.9 +/- 3.3 vs. 117.5 +/- 5.3 cm/s) due to an 8% (p = 0.019) slower cadence (99.9 +/- 1.7 vs. 103.3 +/- 2.4 steps/min) and a 14% (p < 0.001) shorter stride length (119.8 +/- 2.9 vs. 135.8 +/- 4.2 cm/stride). The PAD subjects spent 5% less of the gait cycle in the swing phase (p = 0.006) and 3% more in stance (p = 0.006) than their non-PAD counterparts. During the stance phase, the PAD subjects spent 5% less of the gait cycle in single-stance (p=0.004) and 16% more in double-stance (p = 0.007). Similar results were obtained at the preferred walking pace. In conclusion, compared with the controls, PAD subjects adopted an ambulatory pattern that favored greater gait stability at the expense of greater walking speed at either their preferred or rapid self-selected paces.

Aged↗

Effects of aerobic treadmill training on gait velocity, cadence, and gait symmetry in chronic hemiparetic stroke: a preliminary report.

It is widely assumed that only limited improvement in functional mobility is possible beyond the subacute period following ischemic stroke. Contrary to this notion, we studied "neurologically plateaued" stroke patients with chronic hemiparesis to assess whether a "task-oriented" treadmill-training regimen would improve walking speed, cadence, and gait cycle symmetry on a modified "Get-Up and Go" task. Five male patients with a mean age of 60.4 +/- 2.7 years (mean +/- S.D.) status post ischemic stroke (> 6 months prior) participated in this nonrandomized low-intensity treadmill exercise pilot study three times/week for 3 months. All patients had mild to moderate gait asymmetries due to residual hemiparesis. Patients were videotaped before and after 3 months of treadmill aerobic exercise (AEX) while performing a functional task consisting of arising from a chair, walking 3.1 m without an assistive device as fast as safely possible, and returning to sit. Gait events were timed using a 2-D Peak Motus video analysis system. After 3 months AEX training, times for the overall "get-up and return-to-sit" (GURS) task and the "straight-away walk" (SAW) segment decreased from 8.2 +/- 1.4 sec to 6.5 +/- 0.8 sec (mean +/- SEM) (p < 0.05), and from 3.7 +/- 1 sec to 2.8 +/- 0.7 sec (p < 0.05), respectively. These data represent improvements of 21% and 24% for the GURS and SAW segments, respectively. Mean velocity increased from 0.9 +/- 0.2 to 1.2 +/- 0.21 m/sec, a 33% improvement (p < 0.01). Mean cadence (steps/min) increased from 89 +/- 9 to 97 +/- 8, a 9% increase (p < 0.05). Mean stance and swing duration diminished for both paretic (P) and nonparetic (NP) limbs, and the intralimb stance/swing ratio values moved toward normal for both the paretic and nonparetic limbs. However, these latter changes reached significance only for the P limb. Interlimb stance symmetry was unchanged. The more impaired subjects experienced the greatest gains in gait velocity and temporal measures. Collectively, these findings indicate that treadmill exercise improves functional overground mobility in individuals with chronic, stable hemiparesis.

Aged↗

"Task-oriented" exercise improves hamstring strength and spastic reflexes in chronic stroke patients.

BACKGROUND AND PURPOSE: Despite the belief that after cerebral infarction only limited functional gains are possible beyond the subacute period, we tested the hypothesis that a 12-week program of "task-oriented" treadmill exercise would increase muscle strength and decrease spastic reflexes in chronic hemiparetic patients. METHODS: Fourteen subjects, aged 66+/-3 (mean+/-SEM) years, with residual gait deviations due to remote stroke (>6 months), underwent repeated measures of reflexive and volitional (concentric and eccentric) torque with use of isokinetic dynamometry on the hamstring musculature bilaterally. Torque output was measured at 4 angular velocities (30(o), 60(o), 90(o), and 120(o)/s). RESULTS: After 3 months of 3 times/wk low-intensity aerobic exercise, there were significant main effects (2 legs [P<0.01]x2 times [P<0. 01]x4 angular velocities [P<0.05]) for concentric torque production. Torque/time production in the concentric mode also improved significantly in the paretic (50%, P<0.01) and nonparetic hamstrings (31%, P<0.01). Eccentric torque/time production increased by 21% (P<0.01) and 22% (P<0.01) in the paretic and nonparetic hamstrings, respectively. Passive (reflexive) torque/time generation in the paretic hamstrings decreased by 11% (P<0.027). Reflexive torque/time was unchanged in the nonparetic hamstrings (P=0.45). CONCLUSIONS: These findings provide evidence that progressive treadmill aerobic exercise training improves volitional torque and torque/time generation and reduces reflexive torque/time production in the hemiparetic limb. Strength changes associated with improved functional mobility in chronic hemiparetic stroke survivors after treadmill training will be reported in future articles.

Aged↗

Peripheral nerve excitation and plantar flexion force elicited by electrical stimulation in males and females.

STUDY DESIGN: Two-group (gender) posttest only using a sample of convenience. OBJECTIVES: Our study examined the effect of gender on selected stimulus properties, perceived pain thresholds, and maximally tolerated level of contraction of the plantar flexor muscle group. BACKGROUND: There is a dearth of literature regarding gender as a factor that may influence the outcome following the application of neuromuscular electrical stimulation. Data from other disciplines suggest that males and females may not have similar tolerance to electrical stimulation. METHODS AND MEASURES: Eleven women (mean age, 28.3 years +/- 5.6 years) and 9 men (mean age, 33.2 years +/- 6 years) participated in a single session of electrical stimulation. A pair of 4.5 x 4.5 cm, self-adhesive, synthetic, polymer electrodes was placed over the medial and lateral heads of the gastrocsoleus muscle group. Electrical stimulation was provided by a battery-powered pulsatile stimulator generating a symmetric biphasic waveform, 200-mu second phase duration, and pulse rate of 50 pulses per second. During testing, the subjects were seated on a specially constructed chair that incorporated a foot pedal attached to a piezoelectric force transducer to measure plantar flexion force. Stimulation amplitude was increased slowly until 4 thresholds (sensory, motor, pain, and maximal pain) were sequentially achieved. At each threshold, stimulus peak voltage, peak current, and phase charge used to elicit that threshold were recorded. Plantar flexion force was also recorded when stimulation was sufficient to achieve pain and maximal pain thresholds. RESULTS: The peak voltage, peak current, and phase charge needed to elicit the 4 thresholds did not differ between women and men at any threshold examined (2-factor ANOVA; Newman-Keuls post hoc tests). However, significantly higher stimulus peak voltage, peak current, and phase charge were recorded for each of the 4 thresholds (sensory, motor, pain, and maximal pain tolerance) for both groups. The plantar flexion force elicited by electrical stimulation was significantly lower in female subjects than in male subjects at both pain threshold and maximally tolerated stimulation levels. CONCLUSIONS: Gender can influence the magnitude of electrically induced plantar flexion contraction force. We hypothesize that females may require longer conditioning periods to achieve therapeutic levels of muscle contraction.

Adult↗

Treadmill aerobic exercise training reduces the energy expenditure and cardiovascular demands of hemiparetic gait in chronic stroke patients. A preliminary report.

BACKGROUND AND PURPOSE: Elevated energy costs of hemiparetic gait contribute to functional disability after stroke, particularly in physically deconditioned older patients. We investigated the effects of 6 months of treadmill aerobic exercise training on the energy expenditure and cardiovascular demands of submaximal effort ambulation in stroke patients with chronic hemiparetic gait. METHODS: Nine older stroke patients with chronic hemiparetic gait were enrolled in a 6-month program of low-intensity aerobic exercise using a graded treadmill. Repeated measures of energy expenditure based on steady state oxygen consumption during a standardized 1-mph submaximal effort treadmill walking task were performed before and after training. RESULTS: Six months of exercise training produced significant reductions in energy expenditure (n = 9; 3.40 +/- 0.27 versus 2.72 +/- 0.25 kcal/min [mean +/- SEM]; P < .005) during a given submaximal effort treadmill walking task. Repeated measures analysis in the subset of patients (n = 8) tested at baseline and after 3 and 6 months revealed that reductions in energy expenditure were progressive (F = 11.1; P < .02) and that exercise-mediated declines in both oxygen consumption (F = 9.7; P < .02) and respiratory exchange ratio (F = 13.4; P < .01) occurred in a strong linear pattern. These stroke patients could perform the same standardized submaximal exercise task at progressively lower heart rates after 3 months (96 +/- 4 versus 87 +/- 4 beats per minute) and 6 months of training (82 +/- 4 beats per minute; F = 35.4; P < .002). CONCLUSIONS: Six months of low-intensity treadmill endurance training produces substantial and progressive reductions in the energy expenditure and cardiovascular demands of walking in older patients with chronic hemiparetic stroke. This suggests that task-oriented aerobic exercise may improve functional mobility and the cardiovascular fitness profile in this population.

Aged↗

Low-velocity graded treadmill stress testing in hemiparetic stroke patients.

BACKGROUND AND PURPOSE: Coronary artery disease is prevalent in stroke patients and is an important factor affecting rehabilitation and health outcomes. However, the presence of neurological deficits in gait and balance has discouraged systematic application of exercise testing and prescription in the stroke population. We evaluated a novel graded treadmill stress test in paretic stroke patients and tested floor walking as a predictor of adequate neurological function to perform the treadmill test. METHODS: Patients (n = 31) with residual paretic gait deficits after ischemic stroke were evaluated with graded treadmill at gait velocities individualized to functional mobility observed during an initial zero-incline treadmill tolerance test. RESULTS: Most patients (30/31) tolerated testing, achieving mean heart rates of 129 +/- 14 beats per minute (mean +/- SD), representing 84 +/- 10% of maximal age-predicted heart rate. Evidence for asymptomatic myocardial ischemia was found in 29% of those without known coronary artery disease. Exercise termination was more often due to generalized fatigue than cardiopulmonary intolerance (23/31 versus 4/31; P < .0001) or hemiparetic leg fatigue (1/31; P < .0001). Floor walking across a wide range of velocities (0.25 to 2.5 mph) demonstrated a strong linear relation with treadmill velocities (n = 24; r = 80; P < .0001); all patients floor walking at > or = 0.5 mph had adequate neuromotor function to perform the exercise test. CONCLUSIONS: These findings suggest that graded treadmill exercise testing, with proper safety precautions, can be used to assess cardiopulmonary function in paretic stroke patients. A simple floor-walking test predicts adequate neurological function to perform the exercise test. Exercise capacity is most limited by generalized fatigue and not by the paretic limb, supporting a rationale for endurance training in this population.

Aged↗

Peripheral nerve grafts lacking viable Schwann cells fail to support central nervous system axonal regeneration.

Peripheral nerve grafts were implanted bilaterally into the diencephalon of adult hamsters. One graft segment contained both viable Schwann cells and their basal lamina tubes. The Schwann cell population in the second graft segment was killed by freezing prior to implantation. Seven weeks after graft implantations, the extracranial end of each graft segment was exposed, transected and labelled with a fluorescent tracer substance. One week after the labelling procedure each animal was perfused and the diencephalon and midbrain were examined. Ultrastructural analyses of both types of graft demonstrated the persistence of the Schwann cell-derived basal lamina tubes. Retrogradely labelled neurons were found in all cases in which an intact graft remained in place for two months, but were seen in only one case with a frozen graft. Large numbers of myelinated and unmyelinated axons were seen within the intact grafts, but no axons were found in the previously frozen grafts. These results indicate that lesioned CNS axons are able to regenerate vigorously when provided with an environment which includes viable Schwann cells. But, CNS axons regenerate less well, if at all, when Schwann cells are absent. Further, it appears that Schwann cell-derived basal lamina tubes, when isolated from their parent cells, are insufficient to initiate or sustain CNS axonal regeneration.

Animals↗

Delayed diagnosis of duodenal obstruction in Down syndrome.

Four children with Down syndrome (trisomy 21) came to medical attention in late childhood with symptoms of obstruction of the upper gastrointestinal tract. Each patient had radiographic evaluation. The combination of Down syndrome, retained foreign material in the stomach or proximal duodenum, and obstruction resulted in the diagnosis of congenital duodenal stenosis in each patient.

Child↗

Kaposi's sarcoma in renal allograft recipients.

The development of Kaposi's sarcoma in immunosuppressed patients is a rare occurrence, but poses a real threat to the patient due to the rapid progression of the unchecked disease. The suspicion of this disease will prompt early diagnosis by scrutiny of histologic preparations and prompt interruption of antirejection therapy. Four of five patients in whom a diagnosis was made preterminally responded favorably to withdrawal of immunosuppressive agents. In renal allograft recipients with mucocutaneous vascular lesions, Kaposi's sarcoma should be considered as a cause of gastrointestinal bleeding.

Adult↗

Breast feeding and infant nutrition.

Breast feeding is a management problem requiring knowledge of the physiology of lactation, maternal and infant nutritional requirements, and specifics such as drugs which enter the milk. The job of the physician is to allay anxiety; this helps establish the let-down reflex and increases milk production. "Caking," mastitis and even abscesses are not indications for weaning. Rest, warm compresses and frequent nursing are indicated. Breast-fed infants have less tendency to obesity than those who are bottle-fed. Early solid foods in the diet are not needed.

Anxiety↗

Immunochemotherapy of hepatoma in rats.

Immunoglobulin G prepared by immunization of rabbits with rat Novikoff ascites tumor cells was prepared and found to by cytotoxic to Novikoff cells and rat lymphocytes. A chlorambucil conjugate was prepared and found to have similar qualities in vitro. Three day culture systems were prepared with various test substances and the immunoglobulin was shown to markedly depress cell multiplication. The chlorambucil conjugate appeared to be more efficacious than the immunoglobulin alone in inhibiting cell growth. In vivo studies revealed a total inhibition of tumor formation in animals treated with the immunoglobulin-chlorambucil conjugate whereas all control groups had 50 to 100 per cent mortality. No systemic toxicity was apparent. These studies indicate that tumor-specific immunoglobulin bound to chlorambucil presents a feasible method of delivering tumoricidal drugs to cancer in body cavities and of treating tumors with an accessible blood supply.

Animals↗

Neutrophil function in clinical kidney allograft recipients.

The peripheral blood neutrophils from 17 kidney transplant recipients were studied for their ability to phagocytose and kill Pseudomonas aeruginosa in vitro. Practically all of the percent phagocytosis values were within the normal range but many of the neutrophil samples demonstrated a reduced ability to kill ingested P. aeruginosa, particularly within the 3 month period immediately after transplant. Of the 17 patients studied, ten were found to have neutrophils with a reduced capacity to kill the test bacteria. These defects in bactericidal capacity were found in patients who received antihuman-lymphocyte globulin (ALG), large doses of methylprednisolone for rejection, and mostly in subclinical infection with Pseudomonas or other gram-negative bacterial species.

Antibodies↗