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Biomedical subjects

S Walsh

Publications and source records attributed to S Walsh.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

Chromosome Mapping↗

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↗

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↗

The ventilatory response to carbon dioxide in high risk infants.

PURPOSE: To examine the ventilatory response to inspired carbon dioxide in infants considered to be at risk for sudden infant death syndrome or apnea. DESIGN: Clinical data measurement. SETTING: Infant apnea evaluation program of a university division of neonatology. PATIENTS: Fifty nine infants were full term characterized by the following diagnoses; siblings of infants who had died from sudden infant death syndrome (SIDS) (n = 7), apparent life threatening event (ALTE) (n = 24), apnea/cyanosis in the newborn nursery (n = 21), and controls. Sixty-nine infants were preterm and consisted of patients suffering from idiopathic apnea (n = 61), and bronchopulmonary dysplasia (n = 8). MEASUREMENTS: The ventilatory response to carbon dioxide was measured with a computerized waveform analyzer. MAIN RESULTS: Among full term infants no significant differences in the ventilatory slope in response to CO2 was seen. The range of mean slope was 19.4 +/- 7.6 in siblings of SIDS and 36 +/- 17 in control infants. Greater number of sibling of SIDS had slopes less than 20 ml/kg/min/mmHg in comparison to control infants. Sibling of SIDS had less increase in minute ventilation and inspiratory flow in response to CO2 administration in comparison to control infants. Preterm infants had similar slopes with a mean of 33 ml/kg/min/mmHg in infants with idiopathic apnea and 28 ml/kg/min/mmHg in infants with bronchopulmonary dysplasia. CONCLUSIONS: The large intragroup variability in the ventilatory response to inspired CO2, confirming previously reported data, comprises the benefit of this test. Thus, ventilatory response to CO2 administration is not useful in unselected patients at risk of SIDS or apnea.

Apnea↗

Knee immobilization inhibits biomechanical maturation of the rabbit medial collateral ligament.

In this investigation, the effect of immobilization on the structural biomechanical properties of the immature rabbit medial collateral ligament (MCL) was quantified. The right hindlimbs of ten, three-month-old female New Zealand White rabbits were immobilized. The hindlimbs of the first group (n = 5) were immobilized for one month, until the rabbits were four months of age. The hindlimbs of the second group (n = 5) were immobilized for three months, until the rabbits were six months of age. Left hindlimbs were not surgically treated and served as contralateral controls. Fifteen normal animals were kept in similar cages until they were killed in subgroups at three, four, or six months of age. Biomechanical investigations after the animals were killed included the testing of a number of MCL structural properties, including prefailure and strength tests. Results showed that the maturation of MCL structural properties were inhibited during immobilization with signs of structural degradation becoming more obvious at the longer period of immobilization. Results also demonstrated that the structural mechanical properties of the contralateral MCLs were significantly altered. These results suggest that knee mobility is essential to the normal maturation of MCL mechanical properties and that contralateral MCLs cannot be used as normal controls in this immature rabbit model of immobility.

Age Factors↗

Blood transfusion does not have an adverse effect on survival after operation for colorectal cancer.

The effect of perioperative blood transfusion on cancer progression remains controversial because retrospective clinical studies have produced conflicting results. We have collected data prospectively on 379 patients undergoing curative surgery for colorectal adenocarcinoma and assessed the effect of variables, including blood transfusion, on survival. Univariate and multivariate survival analysis has been carried out. When the end-point for analysis used was death due to recurrent colorectal carcinoma and non-cancer deaths were censored, there was no difference in cancer-specific survival between transfused and non-transfused patients. Survival analysis was also carried out without censoring the non-cancer deaths and clearly demonstrated how the statistical analysis and data interpretation could be distorted by age-related non-cancer deaths. The incidence of recurrence of colorectal carcinoma was not greater in the transfused group than in the non-transfused group. We conclude that blood transfusion should not be withheld in colorectal surgery for fear of worsening the prognosis.

Adenocarcinoma↗

A randomized and longitudinal study of human menopausal gonadotropin with intrauterine insemination in the treatment of infertility.

OBJECTIVE: To study in a randomized and longitudinal manner the efficacy of human menopausal gonadotropin (hMG) superovulation combined with intrauterine insemination (IUI) versus IUI alone in the treatment of various causes of infertility in the presence of normal ovulation. METHODS: An initially randomized and subsequently longitudinal study of infertile couples was performed at a university-based clinical research center. One hundred nineteen couples with longstanding infertility (average duration 3.7 years) associated with male factor infertility, unexplained infertility, and/or endometriosis were enrolled. All patients were randomized in the initial cycle to treatment with either hMG/IUI or urine LH-timed IUI alone. They were then followed longitudinally as they alternated subsequent cycles between the two modalities. Outcome indices measured were cycle fecundity, pregnancy outcome, and cumulative pregnancy rates evaluated by life-table analysis. RESULTS: Human menopausal gonadotropin/IUI therapy was consistently more effective than IUI alone in the treatment of endometriosis, male factor infertility, and unexplained infertility, with cycle fecundities ranging from 7.1-19.0% versus 0-6.7%, respectively, during the first seven cycles. CONCLUSION: Human menopausal gonadotropin/IUI is a more effective therapy for enhancing fertility than is IUI alone for the treatment of endometriosis, male factor infertility, and unexplained infertility.

Adult↗

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↗

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↗

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↗

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↗

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↗