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Biomedical subjects

S Walsh

Publications and source records attributed to S Walsh.

At least 19 recordsLinked to original sources
PubMed1995

Expression and secretion of parathyroid hormone-related protein by human bone-derived cells in vitro: effects of glucocorticoids.

We investigated the production of parathyroid hormone-related protein (PTHrP) by cells derived from explants of human bone. Using an immunoradiometric assay (IRMA), PTHrP was detected in conditioned medium from cultures of bone-derived cells from 6 of 7 patients investigated in this study. PTHrP mRNA was identified in human bone cells using reverse transcriptase-linked polymerase chain reaction (RT-PCR) and by Northern analysis. Transcripts for PTHrP were detected in a purified population of alkaline phosphatase positive cells isolated from human bone marrow cultures by flow cytometry, confirming the expression of PTHrP mRNA by cells of the osteoblastic lineage. Production of PTHrP was inhibited by 10(-6) M of the glucocorticoids, prednisolone and desacetylated deflazacort, in a dose-dependent manner. In addition, RT-PCR followed by Southern blot analysis detected a decrease in steady-state PTHrP mRNA in cultures of human bone-derived cells treated with 10(-6) M prednisolone.

Adolescent↗
PubMed1995

Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists.

Assessing the quality of randomized controlled trials (RCTs) is important and relatively new. Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth. We present an annotated bibliography of scales and checklists developed to assess quality. Twenty-five scales and nine checklists have been developed to assess quality. The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs. The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias. There are several shortcomings with these scales. Future scale development is likely to be most beneficial if questions common to all trials are assessed, if the scale is easy to use, and if it is developed with sufficient rigor.

Bias↗
PubMed1995

Osteoblasts and osteoclasts in adult human osteophyte tissue express the mRNAs for insulin-like growth factors I and II and the type 1 IGF receptor.

Insulin-like growth factors (IGFs) are among the most abundant growth factors present in bone. In vitro, bone-derived cells both produce and respond to IGFs I and II, suggesting that these growth factors play an autocrine role in the regulation of bone turnover. In vivo, however, particularly in adult bone, their sites of expression have not been well documented. We have used, therefore, the technique of in situ hybridization to study the expression of the mRNAs for IGFs I and II and the type 1 IGF receptor in adult human osteophyte tissue. Throughout the developing osteophyte there was a strong association between osteogenesis and the expression of all three mRNA transcripts. The highest levels of expression were observed in active osteoblasts. Hybridization signals were weak or absent in flat cells lining quiescent surfaces and in cells of the bone marrow, including those that expressed alkaline phosphatase activity. Osteocytes and cells of the periosteum were negative. At sites of endochondral bone formation newly differentiated and hypertrophic chondrocytes expressed the mRNAs for IGFs and IGF receptor whereas cells of the perichondrium were negative. A striking finding of this investigation was that osteoclasts at sites of bone and calcified cartilage resorption expressed high levels of all three mRNA transcripts. These results support the hypothesis that locally produced IGFs are important regulators of bone formation. The differential expression of all three transcripts among cells of the osteoblast lineage suggests that IGFs may be involved in the maintenance of the mature osteoblast phenotype rather than in inducing the differentiation of marrow precursors or controlling the osteoblast-osteocyte transition.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1995

Complications of day-case angiography using 5F catheters.

Questionnaires were sent retrospectively to patients who had undergone day-case angiography at a British teaching hospital to evaluate the complications suffered after leaving hospital. In 1992, 5F catheters were used in 61 day-case patients. On analysis of the responses and detailed follow-up in areas of concern, no unexpected complication was found. It is concluded that day-case angiography using 5F catheters is associated with low morbidity after discharge home.

Ambulatory Care↗
PubMed1995

The outcome of surgery for colorectal cancer in the elderly: a 12-year review from the Trafford Database.

In this database study of 882 patients with colorectal cancer, elderly patients are of poor physical status on admission and are more likely to be either completely inoperable or require urgent surgery. The operative mortality rate is higher and hospital stay is likely to be longer. However, if the elderly patient is fit for surgery, survives for more than 30 days and a curative resection performed, the 5-year survival and post-operative complication rates are as good as those patients in the younger age groups.

Age Factors↗
PubMed1995

Significant risk factors in elective colorectal surgery.

A prospective study of 618 patients undergoing elective colorectal surgery performed in a district general hospital over a 10-year period is reported. Multivariate analysis has been used in an attempt to identify risk factors. The risk of wound infection was increased if septicaemia, respiratory sepsis or faecal contamination was present, if the surgeon was a consultant and if increased risk of serious complications if the patient was male and of poor physical status. Operative mortality was significantly associated with poor physical status, respiratory sepsis and intra-abdominal abscess. Only three risk factors could be identified preoperatively: patient gender, physical status and seniority of surgeon. However, procedures low in the pelvis are more difficult and in this study group are also associated with a higher risk of wound infection. The majority of these procedures are performed by consultants. In addition, this study group has proportionally more female patients of poor physical status who are selectively being operated on by the consultant, seemingly indicating the 'consultant' as a risk factor.

Adolescent↗
PubMed1994

Monoclonal antibodies with selective reactivity against osteoblasts and osteocytes in human bone.

Monoclonal antibodies (MAb) may provide valuable tools for studying osteoblast differentiation. We therefore raised a panel of MAb reactive with cells of this phenotype using 1,25(OH)2D3-treated human trabecular osteoblast-like cells (HOBS) as the immunogen. Immunohistochemical studies on various tissues, including undecalcified cryostat sections of fetal and adult human bone, identified 11 bone cell-reactive MAb. Of these, 2 demonstrated particularly selective reactivities against osteocytes (OB/M) and osteoblasts (OB/L). These reactivities were also seen in developing bone from rat, rabbit, and marmoset. OB/L and OB/M demonstrated limited reactivity against a small number of human tissues from the extensive panel of substrates tested. Both MAb exhibited reactivity against discrete populations of cells in the large and small intestine. In addition, OB/L reacted with cells in the basal epidermis of skin and OB/M with cells in blood vessel walls. Both antibodies demonstrated reactivity against a variety of cultured osteoblast-like cell lines and other cultured cell types. These MAb may therefore provide a valuable means of studying osteoblast ontogeny.

Adult↗
PubMed1992

Perinatal estradiol benzoate administration affects control of ventilation in adult male rats.

One injection of estradiol benzoate (EB) (100 micrograms) or vehicle was administered to male rat pups 5 days after birth. Two months later ventilation, ventilatory responses to 7% carbon dioxide, and to 580 mg/kg aspartic acid (an agent used as a marker of sexually dimorphism in the control of ventilation) were evaluated and body weight, testes weight, and nose-anus length were measured in animals in each group. The EB-treated rats had similar tidal volumes, frequency of breathing, and minute ventilation as did control male rats. The ventilatory responses of EB-treated rats to hypercapnia were markedly less than those of control animals. Aspartic acid administration depressed ventilation in control animals, but had no effect on ventilation in EB-treated males. Body and testes weights, as well as nose-anus length, were less in EB-treated compared with control rats. However, when body weight was normalized by nose-anus length and testes weight was normalized by body weight, the values were comparable between the two groups. Thus, perinatal EB treatment of male rat pups results in small, hypogonadal adult animals whose ventilation in response to hypercapnia was diminished and whose response to aspartic acid was female-like relative to those of control rats.

Animals↗
PubMed1992

Ventricular tachycardia rate and morphology determine energy and current requirements for transthoracic cardioversion.

BACKGROUND: The electrical current and energy required to terminate ventricular tachyarrhythmias are known to vary by arrhythmia: Ventricular tachycardia (VT) is generally considered to require less energy than ventricular fibrillation (VF). The hypothesis of our study was that current requirements for transthoracic termination of VT are further determined by VT rate and QRS complex morphology. METHODS AND RESULTS: We prospectively studied 203 patients who received a total of 569 shocks for VT or VF by following a current-based protocol. This protocol recommended shocks for VT beginning at 18 A (70 +/- 22 J) and shocks for VF beginning at 25 or 30 A (137 +/- 52 J or 221 +/- 70 J). The ventricular tachyarrhythmias were subclassified as monomorphic VT (MVT): uniform QRS complex morphology on surface electrocardiogram and heart rate greater than 100 beats per minute; polymorphic VT (PVT): nonuniform QRS complex morphology and heart rate less than or equal to 300 beats per minute; or VF: nonuniform QRS complex morphology and heart rate greater than 300 beats per minute. We found that shocks of 18 A and 25 A for terminating MVT had success rates of 69% and 82%, respectively, whereas such low-current shocks were less successful for PVT (33% at 18 A) and for VF (19% at 18 A, 53% at 25 A). High-current shocks of 35 A and 40 A were equally successful for the three ventricular tachyarrhythmias. Subdividing MVT revealed that slower MVT (heart rate less than 200 beats per minute) had a significantly better success rate with low-current shocks of 18 A and 25 A than did faster MVT (greater than 200 beats per minute) (89% versus 72% success, p less than 0.01). Bundle branch block morphology, QRS axis, and duration of ventricular tachyarrhythmia did not alter current requirements. CONCLUSIONS: Heart rate and electrocardiographic degree of organization of ventricular tachycardia are important determinants of transthoracic energy and current requirements for cardioversion and defibrillation. Transthoracic termination of MVT requires relatively low current or energy, but PVT behaves more like VF and requires higher electrical current or energy.

Electric Countershock↗
PubMed1992

Colorectal surgeons in district general hospitals produce similar survival outcomes to their teaching hospital colleagues: review of 5-year survivals in Manchester.

A study of 578 patients treated for colorectal cancer in the North-west region comparing survival after surgery in teaching and non-teaching hospitals was performed. All patients had a minimum of 5 years follow-up. A greater proportion of elderly and emergency patients were treated in the non-teaching hospitals. The number of operative mortalities and 5-year survival figures for all causes of death and for colorectal deaths alone were similar in teaching and non-teaching hospital patients.

Aged↗
PubMed1992

Immobilization alters cell metabolism in an immature ligament.

This investigation examined the metabolic and cellular effects of immobilization on immature rabbit medial collateral ligaments (MCLs). Thirty-two three-month-old rabbits had their right knee pinned in flexion for intervals of two weeks, one month, two months, or three months before being killed for comparison with MCLs from nonpinned contralateral controls and MCLs from 16 normal age-matched controls. Twelve animals were studied by gait analysis after either one month or three months of immobilization and were killed with the others for in vitro analysis of ligament mass, collagen synthesis, plasminogen activator secretion, or DNA content. Immobilized hindlimbs carried less weight than did contralaterals, and MCLs from those hindlimbs synthesized less collagen and secreted less plasminogen activator than did controls at all intervals. Contralaterals also showed some signs of altered cell metabolism compared with normal controls, suggesting that they are not normal by these assessment criteria. With increasing periods of knee immobilization, immobilized MCLs switched progressively from an anabolic to a more catabolic state, apparently contributing to the failure of immobilized ligaments to increase normally in mass. Knee immobilization alters the metabolic behavior of MCLs in both knees in growing rabbits, and, based on these results, either knee joint motion or hindlimb load bearing could be necessary for normal rabbit medial collateral ligament growth and maturation.

Animals↗
PubMed1992

Nature, reliability, and predictive value of muscle performance measures in patients with hemiparesis following stroke.

The purposes of this investigation were to examine among a sample of hemiparetic stroke patients the nature and reliability of selected muscle performance measures and the correlation between the measures and gait speed. Fourteen subjects who met specific entry criteria participated. The Lido Active Rehabilitation System was used to obtain bilaterally all muscle performance measures of knee extension (velocity, isometric torque-peak and time specific, and time to peak torque and 90% peak torque). Gait speed was measured under both "comfortable" and "maximum safe" conditions. In addition to lower torques, the subjects demonstrated slower knee extension speeds and longer times to peak torque and 90% peak torque on the paretic than on the nonparetic side. High intrasession reliabilities were demonstrated for all muscle performance measures except the torque at 0.1 sec on the nonparetic side and the time to peak torque and 90% peak torque measures. Significant correlations were demonstrated between both gait speeds and paretic knee extension torque (except at 0.1 sec), nonparetic knee extension torque at 0.1 sec and 0.2 sec, and time to nonparetic peak torque. Muscle performance measures other than peak torque appeared to offer little advantage (alone) over paretic peak torque for predicting gait speed. Over 74% of the variance in gait speed, however, could be predicted by the peak isometric peak torque of the paretic side and the time to peak torque on the nonparetic side, together. Thus, there may be benefits to testing the muscle performance of both lower extremities when examining patients with stroke.

Aged↗
PubMed1991

A quantitative analysis of matrix alignment in ligament scars: a comparison of movement versus immobilization in an immature rabbit model.

This investigation quantified the alignment of fibrillar matrix in normal rabbit medial collateral ligaments (MCLs) and in healing MCLs from animals treated with or without knee immobilization. Twenty-four immature female rabbits were given complete midsubstance injuries to their right MCLs. Fifteen of them had that knee pin immobilized in flexion, while the remaining nine were allowed unrestricted cage activity. Animals were sacrificed in groups of three at intervals of 3, 6, or 14 weeks after injury, and both healing MCLs and unoperated contralateral controls were fixed in situ for subsequent removal, freeze-fracture, and preparation for scanning electron microscopy (SEM). A random sampling of SEM photographs followed by automated, statistically validated image processing was used to quantify alignment of matrix in all samples. Results showed that nonimmobilized MCL scars in this model do remodel over 14 weeks of healing, returning to normal alignment values in that time. Surprisingly, MCL scars in immobilized knees were even better, with mean matrix alignments falling statistically within normal MCL limits at all healing intervals studied. If not due to an unknown sampling or fixation artifact, these results suggest that gross knee flexion and extension is not a prerequisite for scar matrix alignment in this immature model of ligament healing.

Animals↗
PubMed1991

Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers.

The pharmacokinetics of ampicillin-sulbactam in elderly subjects (65 to 85 years; group 3, n = 8), compared with those in middle-aged (41 to 64 years; group 2, n = 8) and younger (20 to 40 years; group 1, n = 8) subjects, were investigated. A single 2-g dose of ampicillin combined with 1 g of sulbactam in 60 ml of intravenous solution was administered to each subject over a 30-min period. Blood and urine samples were taken at baseline and serially over an 8.5-h period following the infusion. Ampicillin and sulbactam concentrations were assayed by high-performance liquid chromatography on a reversed-phase C-8 column. The mean levels in serum of both ampicillin and sulbactam were significantly higher for samples from group 3: for ampicillin from 1 through 8.5 h, and for sulbactam for the same time interval except at 5.5 h (P less than or equal to 0.05). The mean urinary excretion of both ampicillin and sulbactam was lowest, and urinary concentrations were highest in group 3. The areas under the serum drug concentration-time curve, the half-lives, and the maximum concentrations in serum were greatest, while the total clearance was lowest, for group 3 for both ampicillin and sulbactam. These results are consistent with a prolongation of antimicrobial activity of ampicillin-sulbactam in the elderly compared with that in younger subjects.

Adult↗
PubMed1991

Production and characterization of osteoclast-selective monoclonal antibodies that distinguish between multinucleated cells derived from different human tissues.

Osteoclastoma-derived giant cells were used to produce 11 mouse monoclonal antibodies (MAb) reactive against human osteoclasts on undecalcified sections of adult human bone. All exhibited unique reactivities across a wide range of human tissues. Three in particular demonstrated distinctive reactivities; C35 was highly selective for bone osteoclasts, C27 showed selective reactivity for osteoclasts, tissue macrophages and blood-borne monocytes, and C22 showed selective membrane staining of osteoclasts. Consequently, C22 was used to coat Dynabeads to affinity-purify viable human osteoclasts from osteoclastoma-derived cell suspensions. Immunocytochemical staining of inflammatory osteoarthritic synovium/granulation tissue demonstrated positivity in the majority of giant cells with MAb C22 and C27. In contrast, C35 reacted with only very occasional giant cells. Furthermore, multinucleated cells formed in long-term human bone marrow cultures demonstrated similar selective staining. C27 stained all giant cells and the majority of mononuclear cells. C22 detected only a small proportion of giant cells. In contrast to its staining on bone osteoclasts, C22 demonstrated granular cytoplasmic staining in cultured giant cells. C35 stained no cells at all in these cultures. These MAb can therefore distinguish between giant cells of various origins and authentic mature osteoclasts. Alternatively, they can recognize antigens expressed at different stages of osteoclast differentiation and therefore provide an excellent tool for the study of the human osteoclast lineage.

Antibodies, Monoclonal↗