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Biomedical subjects

S Walsh

Publications and source records attributed to S Walsh.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

Similarities and differences between MMPI and MMPI-2 applications to the assessment of posttraumatic stress disorder.

The purpose of this study was to address the question: Is the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) comparable to the original MMPI in its applicability to the assessment of posttraumatic stress disorder (PTSD) among Vietnam combat veterans? The question was addressed by administering both the original MMPI and MMPI-2 to 29 subjects classified as meeting Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria for PTSD and comparing MMPI and MMPI-2 scores in terms of: degree of association, code-type congruence, diagnostic hit rates (when compared to two other clinical samples, and one normal sample), and congruence of the Keane PTSD Scale (PK). Results reveal highly significant correlations between MMPI and MMPI-2 basic scales for the PTSD sample as well as congruence in 2-point codes comparable to previous studies. The MMPI-2 was found to identify effectively PTSD subjects from the other groups. Results also showed a high degree of association between the MMPI and MMPI-2 in regard to PK scores, although minor differences were found in PK raw scores between the two tests. Overall, the findings suggest a high degree of comparability between the MMPI and MMPI-2 in the assessment of PTSD.

Adult↗

Large granular T lymphocytes, neutropenia and polyarthropathy: an underdiagnosed syndrome?

Thirteen patients with expansion of an unusual subset of T lymphocytes, defined by large size, cytoplasmic granularity and CD3+ CD8+ Leu 7+ surface phenotype, are reported. Although morphologically and/or phenotypically abnormal lymphocytes were found in all patients, only five had an absolute peripheral blood lymphocytosis. Ten patients had a bone marrow lymphocytosis. As in previous series, there was a strong association with neutropenia (12 patients) and polyarthropathy (seven patients). The latter group displayed a wide range of articular disease: classical or definite rheumatoid arthritis in four patients and milder non-erosive disease in the remainder. All 13 patients showed evidence of abnormal B cell function: IgM rheumatoid factor was present in nine patients, neutrophil-specific antibodies in six and all showed an increased level of at least one immunoglobulin isotype. These patients may be difficult to distinguish from those with idiopathic neutropenia and Felty's syndrome. Such a distinction may not be made on clinical grounds alone: critical assessment of lymphocyte morphology, bone marrow examination and analysis of lymphocyte phenotype should be considered in all patients with unexplained neutropenia, particularly in the context of arthritis. It is suggested that the true prevalence of this syndrome may have been greatly underestimated.

Aged↗

Effects of oxidants on lens transport.

Hydrogen peroxide is associated with the development of cataracts. As an oxidant, it can act on the sulfhydryl groups of proteins and alter the transport properties of membranes. A nearly impermeant sulfhydryl binding agent is p-chloromercuriphenylsulfonate (p-CMPS). The changes in the current-voltage relationship of the equatorial potassium current produced by hydrogen peroxide and p-CMPS are similar. The authors studied the effects of p-CMPS to determine the possible effects of binding extracellular sulfhydryl groups. With a vibrating probe and microelectrodes, the authors saw three sequential effects of 0.5-5.0 microM p-CMPS. The first phase was a shift of the reversal potential, which is equivalent to the potassium equilibrium potential, to more negative values. The current-voltage relationship (J vs PD) shifted in a manner opposite to that produced by ouabain. The 86Rb uptake was stimulated. Ouabain blocked this initial phase. The second phase was a decrease in the resistance. The effects seen were similar to those described in other tissues after the intracellular injection of small amounts of Ca++. This second phase was inhibited by the removal of Ca++ from the medium and also by the addition of quinine to the medium. The third phase consisted of a depolarization of the lens. This effect has been described by others with larger concentrations of p-CMPS and is accompanied by an influx of Na+ and Ca++. The results suggested that micromolar quantities of extracellular p-CMPS sequentially stimulate the Na, K-pump; activate Ca(++)-dependent K+ channels; and open nonspecific channels. It is suggested that the second phase may play a role in cateractogenesis.

4-Chloromercuribenzenesulfonate↗

Curative resection: the major determinant of survival in patients with large bowel cancer.

Data collected prospectively from 578 patients with colorectal cancer managed by 12 Manchester surgeons were analysed to evaluate the effects on survival of prognostic, clinical and pathological factors. Available preoperative and perioperative factors were included in a stepwise regression analysis and curative resection was found to be most strongly associated with patient survival. Other variables ranked according to their relative importance were performance status, weight loss and sex. The finding of the study supports the need to establish an early diagnosis if long-term survival results are to improve.

Activities of Daily Living↗

Risk factors and operative mortality in surgery for colorectal cancer.

The operative mortality rate after surgery for colorectal carcinoma remains significant. A series of 578 patients has been studied prospectively. The features which most significantly affect operative mortality are the age of the patient, a history of loss of weight, limited preoperative patient mobility and the presence of intestinal obstruction with perforation of the bowel. By identifying high-risk groups of patients, attention may be focused on particular patients at risk, in order to reduce operative mortality.

Activities of Daily Living↗

EGTA modulates equatorial currents in frog lenses.

A combination of a vibrating probe with microelectrodes was used to study the effects on the equatorial K+ current, J, of perturbing the frog lens by removing Ca2+ from the bathing medium. The results were different in the absence and presence of EGTA. In the absence of EGTA the reversal potential (PDJ = 0) remained near the Nernst potential; the input resistance, R, and the resistance of the segment of the K+ current loop being studied, RJ, decreased; the driving force (PD - PDJ = 0) increased; and J increased fourfold. In the presence of EGTA J did not increase more than twofold; the current-voltage relationship became linear; RJ did not decrease and both the PD and the reversal potential, PDJ = 0, became less negative with time. These findings, which are dependent on the use of the vibrating probe, were unexpected, and they were explored by studying the effects of removing Na+ from the medium. Substituting TMA for Na+ did not increase J. Removal of Ca2+ and the addition of EGTA to a Na+-free medium in which frog lenses were bathed resulted in a decrease in RJ, and an increase in J; J varied inversely with the concentration of Na+ in the medium. The changes were reversible. A mechanism to account for the changes is proposed.

Animals↗

An investigation of the effects of heat and water exchange in the recovery period after exercise in children with asthma.

It has been reported that asthma provoked by breathing subfreezing air during exercise is enhanced when air at BTPS is inhaled in the recovery period (1). It was concluded that the rate of airway rewarming is an important event in asthma provoked by exercise. It is also possible, however, that the enhanced response was due to hypo-osmolarity caused by condensation of water from inspired air at BTPS on the cooled mucosa. We examined, in a group of boys with asthma, the response to rapid rewarming of the airways after exercise, with and without the potential for condensation. On two test days, two exercise tests were performed 4 h apart on a cycle ergometer. On Day 1 (n = 17), the inspired air during exercise was -5 degrees C, dry. During recovery, the air was either -5 degrees C, dry or 50 degrees C, 23 mg H2O/L. On Day 2 (n = 11), the inspired air during exercise was -15 degrees C, dry, and during recovery was either -15 degrees C, dry or at BTPS. We did not find enhancement of the response with either condition designed to cause rapid airway rewarming. On Day 1 the mean (+/- 1 SD) percent fall in FEV1 was 23 +/- 22 (-5 degrees C, dry) and 24 +/- 21 (50 degrees C, 23 mg H2O/L) (r = 0.92), and on Day 2 it was 19 +/- 17 (-15 degrees C, dry) and 18 +/- 17 (BTPS) (r = 0.96).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of Ca++ depletion on lens equatorial currents in frog lenses.

The combination of the vibrating probe measuring the outward equatorial current (J) with microelectrodes measuring PD and the response to injected current provides one of the best means of relating macro findings of lens currents to the micro data that have been reported using the patch clamp technique. In standard frog Ringers solution the equatorial current appears to be a relatively pure K+ current with a reversal potential of -95 mV. This agrees with the reversal potential of the 45 pS K+ channel. When Ca++ is removed from the medium bathing the lens the input resistance (R) decreases, the PD becomes less negative and the current J increases. This process can be reversed by adding Ca++ or Mn++ to the Ca++ deficient medium. When all Ca++ is removed from the medium by adding EGTA in the absence of Ca++, the increase in J is less than expected. However, if Na+ is replaced by TMA in the Ca++ depleted EGTA medium the current is seven times as great. These changes are consistent with those found in non-selective cation channels in the absence of Ca++.

Animals↗

Postpartum depression: a clinical view.

Recent studies identify a much higher incidence of postpartum depression than had previously been acknowledged and show that a mother's depression may have a highly deleterious effect on the early development of her infant. Although a variety of theories exist concerning the etiology of postpartum depression, many writers now accept a transactional model of causality. This article suggests that for many women early depriving or abusive experiences are necessary but not sufficient conditions to explain the development of severe postpartum depression. Four different types of postpartum depression are presented with widely differing prognoses and needs for treatment. It is suggested that a wide range of treatment modalities may be needed with the more serious depressions and that such services are lacking in most communities.

Depressive Disorder↗

Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital.

Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections.

Aged↗

An ELISA for the detection of anti-acetylcholine receptor antibodies using biotinylated alpha-bungarotoxin.

An antibody-capture enzyme immunoassay has been developed for the detection of anti-acetylcholine receptor (AChR) antibodies in tissue culture supernatants using biotinylated alpha-bungarotoxin (B alpha BGT). Immunoglobulins in culture supernatants were bound indirectly to microtitre plates via an anti-globulin antibody already coupled to polyvinyl plates. Anti-AChR antibodies were then detected by incubation with AChR crude extract. Bound AChR was revealed by incubation with B alpha BGT followed by horseradish peroxidase-conjugated avidin. This assay is specific, more sensitive than the commonly used double antibody radioimmunoassay, avoids the use of radioactive material, is practical for large numbers of samples and is particularly suitable for detecting anti-AChR antibodies in tissue culture supernatants.

Animals↗

Operative mortality rate and surgery for colorectal cancer.

Different authors use different definitions of operative mortality rate when reporting results of their operations. Four definitions used in current literature were applied to our own series of 578 patients with colorectal carcinoma. The operative mortality rate was found to vary from 7.3 per cent to 12.2 per cent, depending on the definition used. 'Death within 30 days of the last operation' was the definition which best reflected true operative deaths. We urge that this definition of operative mortality rate be adopted as a standard for all operations.

Cause of Death↗