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Biomedical subjects

S J Morgan

Publications and source records attributed to S J Morgan.

At least 19 recordsLinked to original sources
PubMed2007

Bcl-2 family proteins are essential for platelet survival.

Platelets are relatively short-lived, anucleated cells that are essential for proper hemostasis. The regulation of platelet survival in the circulation remains poorly understood. The process of platelet activation and senescence in vivo is associated with processes similar to those observed during apoptosis in nucleated cells, including loss of mitochondrial membrane potential, caspase activation, phosphatidylserine (PS) externalization, and cell shrinkage. ABT-737, a potent antagonist of Bcl-2, Bcl-X(L), and Bcl-w, induces apoptosis in nucleated cells dependent on these proteins for survival. In vivo, ABT-737 induces a reduction of circulating platelets that is maintained during drug therapy, followed by recovery to normal levels within several days after treatment cessation. Whole body scintography utilizing ([111])Indium-labeled platelets in dogs shows that ABT-737-induced platelet clearance is primarily mediated by the liver. In vitro, ABT-737 treatment leads to activation of key apoptotic processes including cytochrome c release, caspase-3 activation, and PS externalization in isolated platelets. Despite these changes, ABT-737 is ineffective in promoting platelet activation as measured by granule release markers and platelet aggregation. Taken together, these data suggest that ABT-737 induces an apoptosis-like response in platelets that is distinct from platelet activation and results in enhanced clearance in vivo by the reticuloendothelial system.

Animals↗
PubMed2004

Contraception for teenagers and young adults with cancer.

Adolescence can be an extremely stressful time for all concerned. When this period is then compounded by the development of cancer, formidable and seemingly insurmountable problems may be perceived. Cancer in adolescence is relatively uncommon, with an annual incidence rate in western populations of approximately 150-200 per million. Five-year survival of patients diagnosed around 1990 exceeded 70% in the United Kingdom (UK) and United States of America (USA), and adolescents with cancer are likely to remain fertile. Further advances in therapeutic modalities are creating a generation of adolescents and young adults with cancer who can now aspire to the same sexual and reproductive activities as their healthy peers. This then raises the issue of avoidance of undesired pregnancy during and after treatment. This article aims to address the contraceptive needs of adolescents and young adults undergoing treatment for cancer.

Adolescent↗
PubMed2003

Iliosacral screw fixation of the posterior pelvic ring using local anaesthesia and computerised tomography.

Various techniques have been used for the fixation of the posterior pelvis, each with disadvantages specific to the technique. In this study, a new protocol involving the placement of posterior pelvic screws in the CT suite is described and evaluated. A total of 66 patients with unstable pelvic ring injuries was stabilised under local anaesthesia with sedation. The mean length of time for the procedure was 26 minutes per screw. There were no technical difficulties or misplaced screws and no cases of infection or nonunion. All patients stated that they would choose to have the CT scan procedure again rather than a procedure requiring general anaesthesia. The charges for the procedure were approximately 1840 pounds sterling (2800 dollars) per operation. CT-guided placement of iliosacral screws is a safe, feasible, and cost-effective alternative to radiologically-guided placement in the operating theatre in selected patients.

Adolescent↗
PubMed2002

A novel mutation in KRT12 associated with Meesmann's epithelial corneal dystrophy.

BACKGROUND: The molecular basis of Meesmann's epithelial corneal dystrophy (MECD) has recently been attributed to mutations in the cornea specific keratin genes KRT3 and KRT12. The mechanisms by which these mutations cause the Meesmann's phenotype are not clear. This study presents new data, examines clinical, histological, ultrastructural, and molecular aspects of MECD, and compares the features seen in this condition with those observed in other well studied keratin diseases such as epidermolysis bullosa simplex. METHODS: A two generation family with typical features of Meesmann's epithelial corneal dystrophy (MECD) was studied. All family members were examined under a slit lamp. Biopsy material from elective keratoplasty was studied by histopathological and ultrastructural analysis using standard techniques. Direct automated sequencing of genomic DNA was used for mutation detection, mutations were confirmed by restriction digest analysis. RESULTS: The abnormal corneal epithelium was acanthotic and contained numerous dyskeratotic cells and intraepithelial vesicles. By electron microscopy abnormally aggregated and clumped keratin filament bundles were detected in basal and suprabasal keratinocytes from the centre of the cornea. Direct sequencing of the patients' genomic DNA revealed a novel missense mutation (423T>G) in exon 1 of the cornea specific keratin 12 (KRT12) gene. This mutation predicts the amino acid change N133K within the helix initiation motif of the K12 polypeptide. Comparative studies with well established keratin disorders of other human epithelia underscore the pathogenic relevance of K3 and K12 gene mutations in Meesmann's epithelial corneal dystrophy. The morphological data presented here illustrate the disruptive effects of keratin gene mutations on the integrity of corneal keratinocytes. CONCLUSIONS: A clinical, histopathological, and ultrastructural study of a previously unreported family with MECD is presented. In this family the disease is ascribed to a novel mutation in KRT12. A molecular mechanism is proposed for MECD based on the comparison with other well characterised keratin diseases.

Adult↗
PubMed2001

Patellar tendon rupture 3 years after anterior cruciate ligament reconstruction with a central one third bone-patellar tendon-bone graft.

Use of the central one third bone-patellar tendon-bone autograft is an accepted technique for anterior cruciate ligament (ACL) reconstruction. Patellar tendon rupture following ACL reconstruction is an acknowledged, although rarely reported, complication of this procedure. Of the limited patellar tendon rupture cases reported in the literature, most are described early in the postoperative period. We present a case of late patellar tendon rupture more than 3 years after uneventful ACL reconstruction in a 32-year-old man.

Adult↗
PubMed2001

Evolution of a multidisciplinary clinical pathway for the management of unstable patients with pelvic fractures.

OBJECTIVE: To determine whether the evolution of the authors' clinical pathway for the treatment of hemodynamically compromised patients with pelvic fractures was associated with improved patient outcome. SUMMARY BACKGROUND DATA: Hemodynamically compromised patients with pelvic fractures present a complex challenge. The multidisciplinary trauma team must control hemorrhage, restore hemodynamics, and rapidly identify and treat associated life-threatening injuries. The authors developed a clinical pathway consisting of five primary elements: immediate trauma attending surgeon's presence in the emergency department, early simultaneous transfusion of blood and coagulation factors, prompt diagnosis and management of associated life-threatening injuries, stabilization of the pelvic girdle, and timely insinuation of pelvic angiography and embolization. The addition of two orthopedic pelvic fracture specialists led to a revision of the pathway, emphasizing immediate emergency department presence of the orthopedic trauma attending to provide joint decision making with the trauma surgeon, closing the pelvic volume in the emergency department, and using alternatives to traditional external fixation devices. METHODS: Using trauma registry and blood bank records, the authors identified pelvic fracture patients receiving blood transfusions in the emergency department. They analyzed patients treated before versus after the May 1998 revision of the clinical pathway. RESULTS: A higher proportion of patients in the late period had blood pressure less than 90 mmHg (52% vs. 35%). In the late period, diagnostic peritoneal lavage was phased out in favor of torso ultrasound as a primary triage tool, and pelvic binding and C-clamp application largely replaced traditional external fixation devices. The overall death rate decreased from 31% in the early period to 15% in the later period, as did the rate of deaths from exsanguination (9% to 1%), multiple organ failure (12% to 1%), and death within 24 hours (16% to 5%). CONCLUSIONS: The evolution of a multidisciplinary clinical pathway, coordinating the resources of a level 1 trauma center and directed by joint decision making between trauma surgeons and orthopedic traumatologists, has resulted in improved patient survival. The primary benefits appear to be in reducing early deaths from exsanguination and late deaths from multiple organ failure.

Adult↗
PubMed1999

A new spin on an old model: in vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parameters and histopathology in the adjuvant arthritic rat.

OBJECTIVE: To noninvasively examine the pathogenesis of rat adjuvant-induced arthritis (AIA) by magnetic resonance imaging (MRI), and to correlate MRI indices of disease progression with classic inflammatory parameters and histologic evaluation. METHODS: AIA was established in male Lewis rats following subcutaneous injection in the right hindpaw with 0.5 mg of heat-killed Mycobacterium butyricum suspended in light mineral oil. In vivo MRI evaluations of soft tissue and bony changes in AIA rats with matched histopathology were correlated with changes in left hindpaw volumes, circulating leukocytes, acute-phase reactants, and urinary collagen crosslinks throughout the disease process. RESULTS: MRI of arthritic tibiotarsal joints of the uninjected left hindpaws from AIA rats demonstrated 2 distinct phases of disease activity. The first phase, apparent between days 10 and 18, was characterized by periarticular inflammation with marked synovitis, synovial fibroplasia, and distension of the joint capsule into the surrounding tissue. The secondary phase, occurring between days 18 and 30, was marked by continued soft tissue inflammation, periostitis with osteolysis, and periosteal new bone formation progressing to a state of near complete ankylosis by day 30. These 2 phases of disease activity observed by MRI paralleled biochemical, cellular, and histologic markers of disease progression. CONCLUSION: MRI can be used to noninvasively detect, monitor, and quantify the chronic synovitis and progressive destruction of soft tissue and bone in live AIA rats, thereby improving the ability to evaluate disease progression in this preclinical animal model of rheumatoid arthritis.

Animals↗
PubMed1999

The pathophysiology of chronic laminitis. Pain and anatomic pathology.

The potential pathologic manifestations of chronic laminitis are just as varied, and possibly more so, than the list of possible inciting agents of the disease itself. The extent to which rehabilitation and return to normal function can be attained, cannot always be accurately determined by physical examination. It should be remembered that significant physiologic and pathologic alterations occur in chronic laminitis; thus, even if radiographically the patient returns to a normal appearance, residual morphologic and structural defects are likely to remain.

Animals↗
PubMed1999

The digital pathologies of chronic laminitis.

This review indicates that the patient-to-patient uniqueness commonly seen in chronic laminitis represents the variable presence of the digital pathologies. Although some degree of mechanical failure is always present, the secondary metabolic and growth dysplasias, vascular pathologies, and sepsis may or may not be evident. The presence and severity of these pathologies appear to have a more significant impact on the prognosis of individual cases than does the displacement of the distal phalanx. It should be reiterated that it is often the combined presence of these individual pathologies that gives rise to the patient that is totally refractory to treatment. In the absence of these pathologies, many horses with significant displacement of the distal phalanx are not in pain and are not in need of treatment. It thus follows that a key to the improved rehabilitation of difficult patients is focusing research on the physiopathology and diagnosis of these nonmechanical problems.

Animals↗