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Biomedical subjects

S R Baker

Publications and source records attributed to S R Baker.

At least 19 recordsLinked to original sources
PubMed1995

Synthetic and structure/activity studies on acid-substituted 2-arylphenols: discovery of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5- hydroxyphenoxy]-propoxy]phenoxy]benzoic acid, a high-affinity leukotriene B4 receptor antagonist.

Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB4. A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 2-[2-propyl-3-[3-[2-ethyl-4-(4- fluorophenyl)-5-hydroxyphenoxy]-propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 +/- 4.6 nM) and guinea pig lung membranes (IC50 = 6.6 +/- 0.71 nM), inhibition of LTB4-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 = 3.3 +/- 0.81 nM), and inhibition of LTB4-induced contraction of guinea pig lung parenchyma (pKB = 8.7 +/- 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB4-induced airway obstruction in the guinea pig when dosed by the oral (ED50 = 0.40 mg/kg) or intravenous (ED50 = 0.014 mg/kg) routes. A specific LTB4 receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D4 (LTD4), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.

Airway Obstruction↗
PubMed1995

The importance of maintaining the alar-facial sulcus in nasal reconstruction.

The alar-facial sulcus is an important topographical region because it represents a junctional zone of three cosmetic units: the nasal base, the medial aspect of the cheek, and the upper lip. Too often, the sulcus is violated by transposition flaps that have been harvested from the cheek to reconstruct defects of the nasal-alar lobule. When the sulcus is violated by surgery, it is difficult to restore a completely natural appearance. For this reason, we suggest an alternative method of reconstructing the alar lobule through the use of an interpolated flap. When defects extend into the alar-facial sulcus, reconstruction of the sulcus is necessary and should be accomplished with a separate skin flap from that used to repair the nasal component of the defect. When a single flap is used to reconstruct both lobule and sulcus, restoration of a completely natural-appearing sulcus is rarely achieved and usually involves multiple surgical procedures often facilitated by aggressive flap contouring, secondary intention healing, and Z-plasty. We describe our methodology in restoring the alar-facial sulcus after nasal reconstruction.

Female↗
PubMed1995

The Rieger flap for nasal reconstruction.

OBJECTIVE: To repair surgical defects of the middle and distal third of the nose. DESIGN: The anatomic and technical design of the Rieger (dorsonasal) flap is described. CONCLUSION: When performed on properly selected patients, the Rieger flap is an aesthetically predictable, one-stage procedure.

Humans↗
PubMed1995

Second-messenger responses in brain slices to elucidate novel glutamate receptors.

G-Protein-coupled or 'metabotropic' glutamate receptors (mGluRs) are a novel heterogenous family of excitatory amino acid receptors. Activation of mGluRs in the rat hippocampus by the mGluR-selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) leads to multiple changes in second-messenger formation. These include increases in basal phosphoinositide hydrolysis, decreases in forskolin-stimulated cAMP formation, and enhancement of cAMP formation via a potentiation of the effects of endogenous adenosine. These changes in mGluR coupling to phosphoinositide hydrolysis and the formation of cAMP likely reflect the in situ expression of heterogenous populations of mGluRs. A number of electrophysiological studies on the functions of mGluRs in hippocampal circuitry, ontogeny, and cellular functions have also been described. Any or all of these mGluR-mediated changes in second messengers may underlie the reported cellular effects associated with the mGluR activation by 1S,3R-ACPD. However, mGluR agonists that have selectivity for different mGluR second-messenger pathways are needed to sort out the cellular consequences of activating in situ expressed mGluR subtypes linked to specific second-messenger pathways.

Animals↗
PubMed1995

The role of dermabrasion and chemical peels in the treatment of patients with xeroderma pigmentosum.

We describe our experience with two patients with xeroderma pigmentosum who underwent periodic trichloroacetic acid chemical peels. One also received a full-face dermabrasion. The effect of chemical peeling was more transient than dermabrasion but was associated with less morbidity. Both chemical peeling and dermabrasion provided a prophylactic effect against the development of skin malignancies; the latter had a more pronounced effect.

Adolescent↗
PubMed1995

Selective recruitment of lymphocyte subsets to the inflamed appendix.

Total lymphocyte counts and the distribution of lymphocyte subsets were determined in peripheral venous blood and appendiceal mononuclear cells from 60 patients who underwent appendicectomy for the clinical diagnosis of appendicitis. A significant peripheral lymphopenia was observed in the 46 patients with histologically confirmed acute appendicitis which was accompanied by an increase in the appendiceal lymphocyte concentration. There was an even greater depletion of CD45RO+ (memory) T lymphocytes in peripheral blood and an increase in the inflamed appendix. Reciprocal changes were observed in the CD45RA+ (naive) T lymphocyte subset. These changes were reflected in the local arterial and venous CD45RA and CD45RO T lymphocyte subsets. Proliferation studies showed an expanded functional repertoire of T lymphocytes in the inflamed appendix. Selective recruitment of memory T lymphocytes from the peripheral blood to the inflamed appendix was demonstrated.

Acute Disease↗
PubMed1995

Trends in the practice of arterial surgery in Western Australia.

An overview of arterial surgery in Western Australia and the Department of Vascular Surgery at Royal Perth Hospital was undertaken for the ten year period from 1983 to 1992. The annual number of arterial procedures increased 116% from 937 to 2027 and lower limb amputations increased 44% from 335 to 483. Five arterial procedures were examined in detail. There was a marked increase in carotid endarterectomy and angioplasty, a moderate increase in aortic aneurysm repair and a small increase in aortofemoral and femoropopliteal bypass surgery. The major amputation rate was not influenced by bypass surgery. It rose from 113 per million population in 1983 to a peak of 148 in 1986, and then fell to 113 per million population in 1992. From June 1982 to June 1992 the population of Western Australia rose 24%, from 1.34 to 1.66 million (and for persons 60 years and over, rose 38% from 0.16 to 0.23 million). At Royal Perth Hospital similar trends were observed. Mean duration of operation for all vascular procedures and for the individual procedures of carotid endarterectomy, angioplasty, aortic aneurysm repair and aortofemoral and femoropopliteal bypass remained unchanged. Average length of stay decreased for carotid endarterectomy (29%) and angioplasty (74%), but remained unchanged for aortic aneurysm repair and aortofemoral and femoropopliteal bypass.

Angioplasty↗
PubMed1995

Imaging of percutaneous tube gastrostomies: spectrum of normal and abnormal findings.

Enteral alimentation is a crucial component of care for the malnourished patient who cannot eat. Until recently, long-term alimentation was delivered through nasogastric tubes or gastrostomy tubes placed at surgery. In the past few years, percutaneous endoscopic gastrostomy (PEG) has almost completely supplanted these traditional methods. PEG is a safer and better-tolerated procedure. The advantages of PEG over nasogastric tubes include greater social acceptance and improved cosmetic appearance, increased ease of feedings, and decreased nasal alar deformities and gastroesophageal reflux. Complications are less common with PEG than with open gastrostomy but still occur in as many as 15% of cases [1-3]. Percutaneous gastrostomies performed using fluoroscopic guidance have complications in approximately 10% of cases [4]. Despite a rapid increase in the use of percutaneous gastrostomies and their placement by radiologists [4], few published reports have described imaging findings after the placement of such tubes. This pictorial essay illustrates a spectrum of normal and abnormal imaging findings observed with the use of PEG tubes, including tube migration and misplacement, infection, tumor seeding along the PEG tube track, and a variety of gastric wall defects and pseudomasses.

Aged↗
PubMed1995

CT in patients with blunt abdominal trauma: clinical significance of intraperitoneal fluid detected on a scan with otherwise normal findings.

OBJECTIVE: The purpose of this study was to determine the clinical significance of intraperitoneal fluid seen on CT scans with otherwise normal findings in patients with blunt abdominal trauma. MATERIALS AND METHODS: We retrospectively analyzed the CT scans of 60 patients with blunt abdominal trauma who had scans showing normal findings except for the presence of intraperitoneal fluid. The location of the fluid was determined (pouch of Douglas, pelvis, paracolic gutters, mesentery, Morison's pouch, perihepatic or perisplenic spaces). The amount of fluid in each location was categorized as minimal, moderate, or marked. The total volume of fluid in each patient was estimated as small (+1), intermediate (+2), or large (+3) on the basis of the sum of the amount of fluid in the individual peritoneal locations. The amount and location of fluid were compared between patients who required exploratory laparotomy and those who were managed conservatively. RESULTS: In most patients, the total fluid volume was small (44 patients, 73%) as opposed to intermediate (11 patients, 18%) or marked (five patients, 8%). Thirty-seven patients had fluid in one location, 12 patients had fluid in two locations, and 11 patients had fluid in three or more locations. Intraperitoneal fluid tended to accumulate in the pouch of Douglas (67%) and Morison's pouch (33%). Patients requiring laparotomy had a higher total fluid volume score compared with the patients managed conservatively (2.2 versus 1.3, p < .002) and had larger amounts of fluid in the upper abdomen. Laparotomy was required in only one patient (2%) who had a small amount of fluid compared with three patients (27%) with intermediate and two patients (40%) with marked amounts. Mesenteric and/or bowel injuries were noted in all six patients at laparotomy. One patient had a small superficial liver laceration that was not diagnosed with CT. No other injuries to the solid viscera were missed on the scans. Two of the four patients with mesenteric fluid seen on the CT scan had mesenteric lacerations found during surgery, and the remaining two did well with conservative management. CONCLUSION: Patients with blunt abdominal trauma who have small amounts of intraperitoneal fluid as the sole abnormality shown by CT may generally be treated conservatively. However, patients with even a small quantity of mesenteric fluid may benefit from peritoneal lavage to help exclude bowel or mesenteric injury. Intermediate and large amounts of fluid are less common as the sole CT abnormality but have a higher likelihood of being associated with bowel or mesenteric injury.

Abdominal Injuries↗
PubMed1994

Compartment syndrome following prolonged pelvic surgery.

Compartment syndrome is a rare but serious complication of prolonged pelvic surgery. Prompted by two recent cases the authors studied the effect of limb angulation and elevation on Doppler ankle artery pressure and compartment pressure in ten normal subjects. Mean ankle pressure when supine was 130.5 (95 per cent confidence interval (c.i.) 124.5-136.5) mmHg and fell to 77.2 (95 per cent c.i. 64.6-89.8) mmHg in the Lloyd-Davies position with 10 degrees of head-down tilt. Reversing table tilt to bring the ankle elevation to 0 degrees in Lloyd-Davies supports restored mean ankle pressure to 114.3 (95 per cent c.i. 105.5-122.9) mmHg (P < 0.001). Placing the lower limb in calf supports was found to increase the mean intracompartmental pressure from 3.0 (95 per cent c.i. 1.2-4.8) mmHg to 11.6 (95 per cent c.i. 9.1-14.1) mmHg. Reversing table tilt significantly restores limb perfusion in patients undergoing prolonged pelvic surgery with the legs elevated and may protect against subsequent compartment syndrome.

Adult↗
PubMed1994

Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region.

We characterized the breakpoints, gains, and losses of chromosome material in squamous cell carcinomas of the head and neck region from 29 patients. Cell lines were karyotyped in 1/3 of cases, direct preparations or early in vitro harvests in 1/3, and both in 1/3 of cases. GTG-banding was employed in all cases, as were C-banding and RBG- and AgNOR-staining in most. Some tumors were near-diploid and others near-tetraploid, but many had mixed populations, with diploid, tetraploid, and octoploid subclones representing essentially the same karyotypic pattern. The most frequent changes were deletions. Losses affecting 3p13-p24, 5q12-q23, 8p22-p23, 9p21-p24, and 18q22-q23 ranged in frequency from 40% to 60% of tumors. Loss of the short arm of the inactive X occurred in 70% of tumors from female patients, and loss or rearrangement of the Y occurred in 74% of tumors from male patients. Loss of 18q appeared to be associated with short survival, as did the presence of multiple deletions. There was gain (2-5 extra copies) of 3q21-qter, 5p, 7p, 8q, and 11q13-q23 in 28-38% of tumors. Three tumors had an hsr involving 11q13-q21. Gain of material at 11q13 is postulated to be associated with amplification of the PRADI/CCND gene at that locus. A translocation between proximal 1p and either an acrocentric short arm or proximal 8p or 9p was observed in squamous cell carcinomas of the head and neck region but not in female genital tract tumors. No other abnormalities appeared to be site specific, suggesting a pattern of genetic evolution in squamous cell carcinoma that is independent of anatomic site.

Adult↗
PubMed1992

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck.

In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.

Aged↗
PubMed1992

Aetiology of chronic leg ulcers.

This study was undertaken to determine the relative prevalence of the factors causing chronic ulceration of the leg in the general population. Two hundred and fifty-nine patients with chronic ulceration of the leg were found on screening a Western Australian population of 238,000. (The prevalence of chronic ulceration of the leg was 1.1 per 1000 population.) Two hundred and forty-two of these patients (93%) with 286 chronically ulcerated limbs were fully assessed to determine the factors contributing to ulceration. In 239 limbs (84%) ulceration involved the leg; in these limbs venous disease was the most prevalent cause of ulceration (160 limbs). Arterial disease was found in 66 limbs, with both venous and arterial disease present in 35 limbs. Rheumatoid arthritis was a causative factor in 27 limbs and diabetes was found with 29 limbs with ulceration involving the leg. In 47 limbs (16%) ulceration was confined to the foot; arterial disease (35 limbs) and diabetes (23 limbs) were the most prevalent causes of ulceration in these limbs. Venous disease was infrequent (three limbs). No disorder of the circulation was found in 48 limbs (20%) with ulceration involving the leg, and in 58 (20%) of all ulcerated limbs. More than one aetiological factor was present in 93 limbs (33%). A cause for ulceration was not found in 10 limbs (3.5%).

Adult↗
PubMed1991

In vitro radiation resistance among cell lines established from patients with squamous cell carcinoma of the head and neck.

Twenty-five squamous cell carcinoma (SCC) cell lines from 20 patients with head and neck cancer were assessed for radiosensitivity in vitro using a 96-well plate assay. Four non-SCC lines were also tested. Radiation sensitivity of individual cell lines was compared using the area under the survival curve (AUC) as a measure of the mean inactivation dose. Tumor lines were tested with either a cobalt-60 (60Co) gamma-irradiator having a dose rate of 100 cGy/minute or with a 4-meV photon beam having a dose rate of 200 cGy/minute. The mean AUC of the 25 SCC cell lines was 188 +/- 7 (SEM) cGy (range, 100 to 250 cGy) whereas the four non-SCC lines had a mean AUC of 225 +/- 9 cGy. The SCC cell lines with mean inactivation dose values greater than 188 cGy were classified as relatively radioresistant whereas those with values less than 188 cGy were considered relatively radiosensitive. In seven cases SCC cell lines were derived from patients who had already received radiation therapy. In four of these cases the tumor cell lines were radioresistant (AUC, 210 to 250) but in the other three cases the tumor lines were radiosensitive (AUC, 160 to 180). Thus, failure of a tumor to respond to radiation did not always select for radioresistant cells. The mean of the AUC for cell lines from previously irradiated patients (197 +/- 11 cGy) did not differ significantly from that of the cell lines from patients who received no prior radiation therapy (182 +/- 9 cGy). However, among radiation-resistant lines those from the four previously irradiated patients were significantly more resistant (mean AUC = 235 +/- 9) than seven other radioresistant lines from nonirradiated patients (mean AUC, 208 +/- 4) (P = 0.0194). In four cases more than one cell line was derived from different tumor specimens in the same patient. In each of these cases the lines from the same patients were similar to one another in their degree of radioresistance. Based on these observations the authors conclude that the degree of in vitro radiation resistance is an inherent property of some squamous cell tumors.

Adult↗
PubMed1991

Mandible reconstruction with vascularized bone grafts. A histologic evaluation.

To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed.

Bone Transplantation↗
PubMed1991

Epidemiology of chronic venous ulcers.

A metropolitan population of 238,000 in Perth, Western Australia, was screened for chronic ulceration of the leg. Patients with a chronic leg ulcer and a venous abnormality comprised 57 per cent of all patients with a chronic leg ulcer, giving a prevalence of 0.62 per 1000 population. There was an increasing prevalence with age; 90 per cent of patients were 60 years and older. This group comprised 16.7 per cent of the population, and had a prevalence of 3.3 per 1000. Although chronic venous ulcers were more common in women there was no difference in age related prevalence. In 36 per cent of patients with a venous abnormality, there was at least one other aetiological factor contributing to chronic ulceration of the leg; 96 per cent had either a history of deep venous thrombosis or a condition known to predispose to deep venous thrombosis.

Adult↗