Biomedical subjects

P J Fowler

Publications and source records attributed to P J Fowler.

At least 37 records · Page 2Linked to original sources

PubMed1992

Magnetic resonance imaging of reconstructed knee ligaments.

Reconstruction of knee ligaments is now a common orthopedic procedure. Patients are frequently referred for magnetic resonance imaging (MRI) after later reinjury, and the ability to recognize normal reconstructed knee ligaments is therefore becoming increasingly important. This pictorial essay demonstrates various reconstructions of the cruciate and the collateral ligaments, as well as several abnormalities of these ligaments.

Anterior Cruciate Ligament↗

PubMed1992

Subchondral bone infractions in acute ligamentous knee injuries demonstrated on bone scintigraphy and magnetic resonance imaging.

Bone scintigraphy is used to detect radiographically silent fractures. Magnetic resonance imaging (MRI) is currently used to screen knee injuries for cartilage and ligament damage. MRI also delineates bone marrow and fractures. We investigated the bone scintigraphic findings in patients who had subchondral bone injuries demonstrated on MRI. Thirteen patients underwent MRI, three-phase bone scintigraphy with SPECT, and arthroscopic surgery after sustaining acute traumatic hemarthrosis of a knee. They all had clinically unsuspected subchondral bone injuries demonstrated on MRI with normal radiographs and normal overlying articular cartilage at arthroscopy, consistent with occult fractures. All showed focal bone repair on scintigraphy. Two of the 13 patients showed additional bone injuries only on bone scan. Two other patients scintigraphically showed focal bone repair at the medial femoral condyle due to avulsion of the medial collateral ligament. SPECT was easier to interpret than multi-view planar imaging. Bone scintigraphy confirms subchondral fractures demonstrated on MRI but also demonstrates ligament avulsion injuries and additional more subtle bone injuries.

Adolescent↗

PubMed1992

Release of the subscapularis for internal rotation contracture and pain after anterior repair for recurrent anterior dislocation of the shoulder.

Ten patients who had an internal rotation contracture and pain after an anterior repair for recurrent dislocation of the shoulder were treated by release of the subscapularis muscle. For six of the patients, radiographs demonstrated severe osteoarthrotic changes in the shoulder as well. The release was done an average of eleven years after the original procedure, which, for most patients, had been a Putti-Platt repair. After release of the subscapularis, each patient had less pain in the shoulder and an average increase of 27 degrees of external rotation. Release of the subscapularis can offer relief of pain and of functional limitations associated with the symptoms caused by an internal rotation contracture after an anterior repair of the shoulder.

Adult↗

PubMed1991

Human lower oesophageal sphincter relaxation is associated with raised cyclic nucleotide content.

Increases in cyclic adenosine monophosphate and cyclic guanosine monophosphate content accompany relaxation of isolated strips of opossum and canine lower oesophageal sphincter muscle. The aim of this investigation was to characterise these responses in isolated muscle from the human lower oesophageal sphincter. Electrical stimulation of enteric neurons produced a frequency dependent relaxation of the human lower oesophageal sphincter that was sensitive to tetrodotoxin. Furthermore, as previously shown in the opossum and canine lower oesophageal sphincter, cyclic guanosine monophosphate content was significantly raised in muscle strips frozen during maximum electrical field stimulation whereas cyclic adenosine monophosphate content was unchanged. In addition, sodium nitroprusside (EC50 = 0.1 microM) produced a concentration dependent relaxation of human lower oesophageal sphincter, significantly increased cyclic guanosine monophosphate content, but did not alter cyclic adenosine monophosphate content. Zaprinast (M&B 22948) and SK&F 94120, selective inhibitors of cyclic guanosine monophosphate and cyclic adenosine monophosphate phosphodiesterases, respectively, both relaxed human lower oesophageal sphincter with a potency similar to that seen in the dog or opossum lower oesophageal sphincter. Finally, the 8-bromo analogues of both cyclic adenosine monophosphate (EC50 = 420 microM) and cyclic guanosine monophosphate (EC50 = 100 microM) relaxed the human lower oesophageal sphincter. These studies suggest that in the human, as well as the canine and opossum lower oesophageal sphincter, increases in cyclic nucleotide content are associated with relaxation and increases in cyclic guanosine monophosphate are associated with the relaxation induced by stimulation of enteric neurons.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1991

Occult posttraumatic osteochondral lesions of the knee: prevalence, classification, and short-term sequelae evaluated with MR imaging.

The prevalence, characterization, and classification of acute, post-traumatic, occult subcortical fractures of the knee, identified at magnetic resonance (MR) imaging, were evaluated prospectively in 120 consecutive patients first seen with acute posttraumatic hemarthrosis of the knee. Occult subcortical femoral and tibial fractures were identified in 72% of patients. A modified MR imaging classification is suggested based on a combination of the appearances of such lesions at MR imaging and their short-term osteochondral sequelae. Among 67% of a cohort of 21 patients first seen with what have been described as occult geographic subcortical fractures, osteochondral sequelae were seen at follow-up MR imaging 6-12 months later. The evidence from this study indicates that specific subcategories of occult subcortical knee fractures are associated with an inordinately high prevalence of osteochondral sequelae, especially significant cartilage damage.

Adult↗

PubMed1991

Arthroscopic débridement of the knee for osteoarthrosis.

To evaluate outcome after arthroscopic débridement, the records of 171 patients with osteoarthrosis of the knee were reviewed. All patients were unresponsive to conservative management and were treated arthroscopically. Procedures included lavage, meniscectomy, chondrectomy, removal of free bodies and removal of limited osteophytes. Outcome assessment was retrospective, evaluating the need for further surgery, control of pain, improved function and patient satisfaction. Sixty-five percent of patients felt their symptoms were improved. There was excellent control of pain in 38% and improved function in 22%. Subsequent surgical procedures were required in 12% at an average follow-up of 25 months. No factors were identified that correlated with the outcome, including the extent of degenerative changes and of débridement and patient profile. Arthroscopic débridement is a temporizing procedure with good patient satisfaction. Marked, but unpredictable, improvement in symptoms is seen in one patient out of three.

Adult↗

PubMed1990

Cold-restraint stress increases rat fecal pellet output and colonic transit.

Increased fecal pellet output that occurs during cold-restraint stress (CRS) was evaluated systematically. Free-feeding rats, which exhibit a reduced occurrence of gastric ulcers under these conditions, were studied. CRS significantly increased fecal pellet production and fluid content. However, the fecal output produced during CRS was not associated with increased gut secretory activity or somatic motor activity associated with cold restraint and did not occur in anesthetized animals. Cold and restraint stress were additive in producing increased fecal output. Significant dose-related decreases in fecal output were produced by drugs that decrease gut transit (i.e., B-HT 920, clonidine, Lomotil, loperamide, and lidamidine). Anticholinergic-antisecretory drugs, antidepressants, and tranquilizers had little effect on fecal output or fluid content. Changes in gastrointestinal transit did not contribute to the increased fecal output during CRS. Transit in the lower small intestine was not altered, but the cecum tended to empty more contents into the large intestine during CRS. Colonic transit was dramatically affected by CRS, which eliminated retrograde transit and produced the evacuation of the majority of colonic contents. The increased colonic transit produced by CRS was decreased in a dose-related fashion by hexamethonium, nifedipine, loperamide, and B-HT 920. In several time-response and drug-inhibition studies during CRS, both fecal pellet output and colonic transit were affected similarly. These data indicate that CRS appears to change central nervous system output to the colon and that it alters colonic smooth muscle motility in a manner that facilitates colonic transit and evacuation. Small intestinal transit is not involved in this phenomenon and is regulated differently during CRS.

Animals↗

PubMed1990

Anteroposterior radiographs of the osteoarthritic knee.

Destruction of the articular cartilage is the first change seen on gross examination of the knee in osteoarthritis. Weight-bearing radiographs are conventionally taken with the knee in full extension. Biomechanical studies have shown, however, that the major contact stresses in the femorotibial articulation occur when the knee is flexed about 28 degrees. Arthroscopy has confirmed that cartilage loss occurs in a more posterior portion of the femoral condyles than is revealed by radiographs taken in full extension. The 'standing tunnel view' is a weight-bearing postero-anterior radiograph taken with the knee in 30 degrees of flexion. The radiographs of 64 patients have been used to compare the conventional with the standing tunnel view. In 10 knees in which the conventional view suggested normal cartilage the standing tunnel view revealed severe degeneration.

Humans↗

PubMed1989

The predictive value of five clinical signs in the evaluation of meniscal pathology.

One hundred sixty-one consecutive patients with knee pain of at least 1 year's duration were studied on a prospective basis to determine the predictive value of five common clinical tests for the diagnosis of meniscal tears. Each patient had a preoperative examination that evaluated the presence or absence of joint line tenderness, pain on forced flexion, the presence of a positive McMurray test, positive Apley grind and distraction tests, and the presence of a block to extension. The results of these tests were then compared to arthroscopic findings. This study indicates that no one test is predictive for the diagnosis of a meniscal tear; a combination of tests should be used. The presence of anterior cruciate ligament pathology will render these tests less effective for diagnosis of meniscal pathology. Chondromalacia patella is negatively correlated with the presence of joint line tenderness and pain on forced flexion.

Adult↗

PubMed1988

Frequency and predictability of sports injuries in intercollegiate athletes.

This study analyzes injury frequency and predictability in 712 intercollegiate athletes in 24 different male and female sports over the 1984-85 season. The injury rate was 38% for males and 32% for females, with the males suffering more acute injuries. While the men's hockey team had the highest player injury rate, the football team had the greatest absolute number of injuries. Overall, the anatomic location with the highest injury rate was the knee, while sprains were the most common type of injury. Further elaboration of these results are provided in graphic form. By comparing injury occurrence to past history and preparticipation physical findings, this study assesses the predictability of injury. With one exception, no significant relationship was found. It would appear that the preseason exam may play a role in identification, rather than prediction of sports injuries.

Adult↗

PubMed1987

Effects of KC 2450 on the lower esophageal sphincter in vivo and in vitro.

The effect of KC 2450 (racemic 3,5-cis-3-methylamino-2,3,4,5-tetrahydro-1-benzoxepine-5-ol hydrochloride) on lower esophageal sphincter pressure in pentobarbital-anesthetized dogs was determined and compared to the effect of metoclopramide. The ED20 value (i.e. the dose that increased lower esophageal sphincter pressure 20 mm Hg) was 0.72 (0.45-1.04) mg/kg i.v. for KC 2450, significantly different from 2.18 (1.30-3.42) mg/kg i.v. for metoclopramide (P less than 0.01). The superior potency of KC 2450 over metoclopramide also was demonstrated at a dose of 2 mg/kg i.v.; KC 2450 produced an increase in sphincter pressure of 43.2 +/- 4.4 mm Hg and metoclopramide produced an increase in sphincter pressure of only 28.5 +/- 5.4 mm Hg (P less than 0.05). Intraduodenally administered KC 2450 increased lower esophageal sphincter pressure at a threshold dose of 2 mg/kg with 10 mg/kg producing an increase in pressure of 53.2 +/- 9.9 mm Hg. KC 2450-induced increases in sphincter pressure were not affected by bilateral cervical vagotomy or ketanserin, but were eliminated by atropine and reduced by neuronal blockade using tetrodotoxin (TTX). KC 2450 effects also were determined in isolated circular strips of lower esophageal sphincter muscle. KC 2450 produced a concentration-related increase in canine (EC50 = 27 microM) and opossum (EC50 = 199 microM) sphincter muscle strip tension. The KC 2450 concentration-response curve was antagonized by atropine in canine and opossum sphincter muscle strips. Neuronal blockade of canine sphincter muscle with TTX antagonized the KC 2450 concentration-response curve in a non-competitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

DA1 receptor mediates dopamine-induced relaxation of opossum lower esophageal sphincter in vitro.

The objective of the present experiments was to determine the specific receptor subtype through which dopamine (DA) receptor agonists relax the lower esophageal sphincter in vitro. Opossum lower esophageal sphincter smooth muscle strips were placed in oxygenated Krebs' solution containing propranolol and cocaine. The tissues were placed at a tension that gave maximum relaxation to electrical field stimulation and were then pretreated with phenoxybenzamine. The effects of DA, and the DA receptor agonists epinine and apomorphine were determined. In addition, agonist responses were studied in the presence of the selective DA2 receptor antagonist domperidone, a mixed DA1/DA2 receptor antagonist metoclopramide, and the selective DA1 receptor antagonists bulbocapnine and SK&F 83566. The DA agonists relaxed the smooth muscle strips in the following order of potency: DA greater than epinine greater than apomorphine. Domperidone did not antagonize DA- or apomorphine-induced relaxation. Metoclopramide failed to alter DA-induced relaxation. Bulbocapnine and SK&F 83566 significantly inhibited the relaxation induced by DA. These data indicate that DA-induced lower esophageal sphincter relaxation in vitro is mediated by DA1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1986

Selective alpha-2 adrenoceptor blockade by SK&F 86466: in vitro characterization of receptor selectivity.

SK&F 86466 (6-chloro-N-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine) is a potent and selective antagonist at alpha-2 adrenoceptors. Prejunctional alpha-2 adrenoceptor antagonism can be demonstrated either by blockade of the alpha-2 adrenoceptor-mediated neuroinhibitory effect of clonidine or B-HT 920 in the guinea-pig atrium [receptor dissociation constant (KB) = 13-17 nM] or by potentiation of nerve-evoked release of [3H]norepinephrine from prelabeled guinea-pig atria, dog splenic artery or rabbit ear artery. Blockade of the postjunctional alpha-2 adrenoceptor was also seen, as demonstrated by a parallel shift to the right of the concentration-response curve for B-HT 920 as a constrictor agent in the dog saphenous vein. The KB for SK&F 86466 in this test system was 42 nM. The affinity of SK&F 86466 for the alpha-1 adrenoceptor is much lower, with a KB of 900 nM against norepinephrine-mediated constriction in the rabbit ear artery, or 1100 nM vs. SK&F 89748-induced constriction in the dog saphenous vein. The alpha-2/alpha-1 adrenoceptor selectivity ratio of SK&F 86466 is comparable to that obtained with agents such as yohimbine, making SK&F 86466 a useful tool for characterization of alpha-2 adrenoceptors and for investigation of their physiological role.

Adrenergic alpha-Antagonists↗

PubMed1986

Swimming injuries of the knee, foot and ankle, elbow, and back.

The practitioner need not be an expert in swimming but should understand the rudiments of the stroke and training techniques such patients are subjected to. This will aid in proper identification and analysis of the problem. The solution may require the resources of physician, therapist, coach, and parent as well as swimmer.

Ankle Injuries↗

PubMed1985

Reconstruction of the anterior cruciate ligament: historical overview.

The first reported surgical repair of anterior cruciate ligament-deficient knees was done by Mayo Robson in 1895. The earliest anterior cruciate ligament reconstructions were done by Hey Groves in 1917 and by Alwyn Smith in 1918. Both used an intra-articular strip of iliotibial band. At this same time, the first attempt to make an artificial anterior cruciate ligament was done. Corner used wire, while Alwyn Smith used multiple silk sutures. Both methods failed. The first extra-articular procedures to correct instability in anterior cruciate ligament-deficient knees were reported by Bennett in 1926 and Cotton and Morrison and Bosworth and Bosworth in the mid 1930s. All of these surgeons reconstructed the medial side of the knee with free strips of fascia. In 1936, Campbell described the intra-articular use of patellar tendon and stressed the need for anterior cruciate ligament reconstruction in young, athletic individuals with unstable knees. In the 1950s, O'Donoghue also emphasized the early repair of an injuried anterior cruciate ligament and did much to improve the care of the college athlete. The procedures described by Jones, Slocum, Larson, and Nicholas dominated the 1960s and early 1970s. Various rotatory knee instabilities were defined, and the Lachman and pivot shift tests were born. Descriptions of various tendon transfers and intra-articular graft techniques have been published over the last 10 years. Most of these are variations of procedures described decades ago. In 1918, Alwyn Smith used electrical stimulation to decrease postoperative quadriceps atrophy. In 1936, Mauck advised the use of a hinged knee cast after surgery for better rehabilitation. Finally, in 1938, Palmer described a drill guide for more anatomic placement of an anterior cruciate ligament graft in the femur. Although prosthetic materials may have a greater place in the 1980s, the foundation for such research was laid long ago by innovative surgeons such as Hey Groves and Alwyn Smith, the great-grandfathers of anterior cruciate ligament reconstructions.

Humans↗

PubMed1984

The ocular hypotensive action of SK&F 86466 in the conscious rabbit.

SK&F 86466, 6-chloro-3-methyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine, a potent and selective competitive antagonist of the alpha 2-adrenoceptor is of interest as a potential antiglaucoma agent. Following instillation into the rabbit eye, SK&F 86466 produced concentration (0.25 to 10%) dependent reductions in intraocular pressure (IOP). The ocular hypotensive effect of SK&F 86466 was maximal 30-60 minutes post treatment and persisted for at least 90 minutes. The IOP of the contralateral (untreated) eye was significantly decreased only at the 10% concentration. A 10% solution of SK&F 86466 had no significant effect on mean arterial blood pressure (MAP) of rabbits during the time of maximal bilateral ocular hypotensive activity. These results suggest: (1) a selective alpha 2-adrenoceptor antagonist can reduce IOP when applied topically to rabbit eyes and (2) the ocular hypotensive effect of SK&F 86466 is not secondary to a reduction in systemic blood pressure.

Animals↗

PubMed1984

Pharmacological differentiation of postsynaptic alpha adrenoceptors in the dog saphenous vein.

The dog saphenous vein has postsynaptic subpopulations of both alpha-1 and alpha-2 adrenoceptors which are easily demonstrable using selective agonists and antagonists. Specific alpha-1 (methoxamine and SK&F 89748) or mixed alpha-1, alpha-2 (l-norepinephrine and M7) agonists as well as the specific alpha-2 agonist, BHT 920, cause concentration-related contraction of this tissue. However, maximum contractions produced by alpha-2 activation are significantly less than maximum contractions produced by alpha-1 or combined alpha-1, alpha-2 adrenoceptor activation. SK&F 89748-induced contractions are competitively inhibited by prazosin (pA2 = 7.74) and rauwolscine (pA2 = 6.63); BHT 920-induced contractions are unaffected by prazosin but inhibited by rauwolscine (pA2 = 8.93). Contractile responses to l-norepinephrine are inhibited by prazosin, rauwolscine or phenoxybenzamine in a manner that suggests that norepinephrine interacts with two subtypes of alpha adrenoceptors in this tissue. These data indicate that the dog saphenous vein strip is a suitable in vitro preparation for study of drug action at both postsynaptic adrenoceptors inasmuch as either subpopulation of alpha adrenoceptor can be studied independently using specific agonists or antagonists.

Animals↗

PubMed1984

Novel inhibitors of gamma-aminobutyric acid (GABA) uptake: anticonvulsant actions in rats and mice.

SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid] and SK&F 100330A [N-(4,4-diphenyl-3-butenyl)-guvacine] represent a new series of potent, orally active inhibitors of gamma-aminobutyric acid (GABA) uptake. In vitro studies with synaptosome-rich (P2) fractions of rat brain indicated that these compounds were approximately 20 times more potent than the parent amino acids as inhibitors of [3H]GABA uptake. They did not inhibit [3H] muscimol binding at nanomolar concentrations. The present studies demonstrated that these compounds were also potent anticonvulsants when administered either orally or i.p. to rats. Both compounds attenuated the forelimb extensor component of bicuculline-induced convulsions, but had no effect on strychnine-induced convulsions, indicating that they were acting through a GABAergic mechanism in vivo. Two animal models which are known to be indicative of anticonvulsant efficacy in man are inhibition of maximal electroshock seizures (MES) and inhibition of pentylenetetrazol (PTZ) convulsions in either rats or mice. SK&F 89976A, SK&F 100330A and several related compounds were potent inhibitors of PTZ convulsions in rats. SK&F 100330A also inhibited MES convulsions in rats. In contrast, neither compound inhibited MES or electroshock seizure threshold in mice, and whereas both compounds inhibited the tonic phase of PTZ convulsions in approximately 50% of the mice tested, this inhibition was not dose-related. Thus, the rat appears to be a more suitable species for further testing of these compounds. These studies indicate that the family of compounds represented by SK&F 89976A and SK&F 100330A may have clinically relevant anticonvulsant activity.

Animals↗