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Biomedical subjects

R Hitchcock

Publications and source records attributed to R Hitchcock.

18 recordsLinked to original sources

Reducing transfer times for coronary angiography in patients with acute coronary syndromes: one solution to a national problem.

BACKGROUND: Patients with acute coronary syndrome (ACS) are at high risk of further cardiac events and benefit from early intervention, as reflected by international guidelines recommending early transfer to interventional centres. The current average waiting time of up to 21 days contravenes evidence based early intervention, creates geographical inequity of access, wastes bed days, and is unsatisfactory for patients. METHODS: A regional transfer unit (RTU) was created to expatriate access of ACS patients referred from other centres to the revascularisation service. By redesigning the care pathway patients arriving on the RTU undergo angiography within 24 hours, and then leave the RTU the following day, allowing other ACS patients to be treated. RESULTS: During the first six months of the RTU, the mean waiting time from referral to procedure decreased from 20 (SD 15) days (range 0-51) to 8 (SD 3) days (range 0-21) for 365 patients transferred from a district general hospital. Ninety seven per cent of patients underwent angiography within 24 hours, 61% having undergone percutaneous coronary intervention at the same sitting, and 78% were discharged home within 24 hours. CONCLUSIONS: Delivering standards laid out in the National Service Framework, reducing inequalities of care across the region, and facilitating evidence based strategies of care represents a challenging and complex issue. For high risk patients suffering ACS who need early invasive investigation, a coordinated network wide approach together with the creation of an RTU resulted in a 62% reduction in waiting times for no extra resources. Further improvements can be expected through increased capacity of this verified strategy.

Angioplasty, Balloon, Coronary↗

Involvement of a herbimycin A-sensitive protein tyrosine kinase in extracellular action of HIV-1 Nef.

Extracellular Nef which has been implicated in disease progression and development of AIDS induces IL-10, a potent immunosuppressive cytokine, in vitro. The present study was designed to examine whether the action of extracellular Nef is a protein tyrosine kinase (PTK)-dependent event. Anti-phosphotyrosine immunoblotting reveals that recombinant HIV-1 Nef induces rapid tyrosyl phosphorylation of several cellular proteins in human peripheral blood mononuclear cells. Pre-treatment of cells with herbimycin A, but not with genistein, significantly abolishes the Nef-induced tyrosine phosphorylation of cellular proteins. Furthermore, ELISA and RNase protection assays show that herbimycin A significantly blocks Nef-induced production of IL-10 at both the protein and the mRNA level. Genistein and aminogenistein have a much less blocking effect on the ability of Nef to induce IL-10. These results provide evidence for the involvement of a herbimycin A-sensitive PTK in the signal transduction pathway for exogenous HIV-1 Nef.

Benzoquinones↗

Immunologic reconstitution following bone marrow transplantation for X-linked hyper IgM syndrome.

X-linked hyper IgM syndrome (XHIM), caused by mutations of the CD40 ligand (CD40L) gene, is characterized by recurrent bacterial and opportunistic infections, an increased incidence of autoimmunity and malignancies, and immunodeficiency due to abnormal T/B cell interaction. Because of poor long-term prognosis, bone marrow transplantation (BMT) has been proposed as an alternative treatment. An 8-month-old boy with XHIM and a splice site mutation of CD40L underwent BMT using a fully matched sibling donor. Markers of engraftment and immunologic reconstitution were measured serially. After BMT, activated T cells expressed functional CD40L, and genomic DNA obtained from circulating white cells contained predominantly wild-type CD40L sequences. Serum immunoglobulin levels including IgE and antibody responses to recall antigens normalized, and immunization with the T-cell-dependent neoantigen, bacteriophage φX174, demonstrated amplification of the response and isotope switching. BMT provides a permanent cure for XHIM if a fully matched sibling donor is available and the procedure is performed before complications have occurred.

Bone Marrow Transplantation↗

Megacystis-microcolon-intestinal hypoperistalsis syndrome: the difficulties with antenatal diagnosis. Case report and review of the literature.

Megacystis on antenatal scan in female fetuses is rare and has serious diagnostic implications. We report two cases of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in female infants in whom antenatal scan abnormalities were identified, but the diagnosis not made until after delivery. MMIHS is a rare autosomal recessive condition which is usually lethal in the first year of life. Prenatal diagnosis is hampered by the lack of specific diagnostic findings on ultrasound and the absence of an identified genetic locus. The prenatal findings in MMIHS are reviewed and contrasted with those of other causes of lower abdominal masses on antenatal ultrasound.

Abnormalities, Multiple↗

Unusual vascular dysplasia presenting as an intra-abdominal catastrophe.

A case of severe, generalised vascular dysplasia presenting as an intra-abdominal catastrophe is reported. Associated clinical features included cutis marmorata telangiectatica congenita, congenital glaucoma, hypertension, and focal fits. The case has been reported in view of its rarity and nature of presentation.

Abdominal Pain↗

Neurological rehabilitation in Indonesia and the UK: differences and similarities.

Both countries face considerable challenges to their rehabilitation services. Although contextually different, the problems and challenges are common to both. Two contrasting views of disability have been presented. In the UK disability may be viewed as a disaster, while in Asia illness and disability may be viewed as inevitable. Personal independence is not a universal goal of rehabilitation, because in some cultures dependence on others is an expected consequence of disability. Disability in Indonesia translates into a large burden of care for the family, whereas English families may expect greater help from the government in caring for their relative. Western rehabilitation is increasingly patient directed, whereas the Indonesian model is more likely to be determined solely by professionals. The problems observed by the team in Indonesia were remarkably similar to those experienced in the UK. A patient centered goal setting approach can be considered vital to neurological rehabilitation, although the focus of the goals set is likely to be very different in these two cultures. The fundamental importance of a multidisciplinary team is recognized in both cultures, although team working may not be easy in either situation. Managerial commitment is essential for the survival of a team, yet both structures sometimes fail to provide the necessary support. Hierarchical leadership can inhibit team development both in the UK and in Indonesia, as can frequent rotation of staff. Prescription of therapy by doctors inhibits the development of therapists in both cultures, and therefore the overall effectiveness of the team. In both the UK and Indonesia, the value of rehabilitation as a specialty is not widely recognized. The absence of life and death situations means that services are often out of the public eye, and poorly understood. However, the prevalence of disability will increase the need for rehabilitation services worldwide. Many challenges remain in both the UK and Indonesia to the development of more effective rehabilitation services. Issues like the lack of recognition of rehabilitation as a specialty, the importance of team work, the paucity of managerial support, and increasing demand for rehabilitation services will need to be recognized and addressed. Despite the different approaches to disability in the two cultures, the problems faced are similar. These problems will need to be solved if there is to be significant progress in this multidisciplinary field.

Attitude to Health↗

Renal agenesis: an acquired condition?

Renal agenesis is a relatively common congenital anomaly, although its etiology is unknown. It is clear that some solitary kidneys are the result of postnatal involution of multicystic dysplastic kidneys. The authors present a series of nine neonates with abnormal prenatal renal ultrasound findings; subsequent postnatal investigations showed an absent kidney. Five children had a prenatal diagnosis of multicystic dysplastic kidney (MDK) and two of hydronephrosis. In five cases (56%) there was a contralateral renal unit anomaly. It appears that MDK, and occasionally hydronephrosis, can involute prenatally, producing the postnatal appearance of renal agenesis.

Congenital Abnormalities↗

Hemodynamic responses to shock in young trauma patients: need for invasive monitoring.

OBJECTIVE: To determine whether early invasive monitoring is necessary in young trauma patients. DESIGN: A prospective study. SETTING: Surgical intensive care unit (ICU) at an inner-city, Level I trauma center. PATIENTS: Thirty-nine patients < 40 yrs of age, who required operative therapy for penetrating trauma and who received > 6 units of intraoperative blood. INTERVENTIONS: Invasive hemodynamic monitoring, with percutaneous insertion of arterial and pulmonary artery catheters. Vital signs, hemodynamic and oxygen transport values, and laboratory tests were obtained at 1, 8, and 24 hrs postoperatively. Oxygen delivery was increased until a normal serum lactate concentration and a state of nonflow-dependent oxygen consumption were achieved. MEASUREMENTS AND MAIN RESULTS: Despite normal heart rate, blood pressure, and urine output, only five (15%) patients achieved an optimized state at 1 hr postoperatively. Of the other 34 patients, two patients achieved an optimized state with volume infusion alone and 32 (82%) patients required inotropes. Five (12%) patients never achieved an optimized state and died within hours of their arrival to the ICU. Two other patients achieved an optimized state but died of sepsis and organ failure. The other 32 (82%) patients achieved an optimized state within 24 hrs and survived. The hemodynamic values of survivors at 1 hr postoperatively showed a significantly lower pulmonary vascular resistance and serum lactate concentration, and a significantly higher oxygen delivery and mixed venous oxygen saturation, when compared with the values of nonsurvivors. At 24 hrs postoperatively, survivors also had a significantly lower pulmonary vascular resistance and serum lactate concentration, and significantly higher oxygen delivery than nonsurvivors. Survivors' oxygen consumption was also higher than the oxygen consumption of nonsurvivors. CONCLUSIONS: Our data demonstrate that young trauma patients have substantial but clinically occult myocardial depression after shock, and most of these patients require inotropes to optimize and clear circulating lactate. Early invasive monitoring is necessary to precisely define the adequacy of the cardiac response and to individually tailor therapy. Patients who do not optimize and clear their lactate within 24 hrs may not survive.

Abdominal Injuries↗

Lactate clearance and survival following injury.

Previous reports cite optimization of O2 delivery (DO2) to 660 mL/min/m2, O2 consumption (VO2) to 170 mL/min/m2, and cardiac index (CI) of 4.5 L/min as predicting survival. We prospectively evaluated 76 consecutive patients with multiple trauma admitted directly to the ICU from the operating room or emergency department. Patients had serum lactate levels and oxygen transport measured on ICU admission and at 8, 16, 24, 36, and 48 hours. Patients were analyzed with respect to survival (S) versus nonsurvival (NS), lactate clearance to normal (< or = 2 mmol/L) by 24 and 48 hours, hemodynamic optimization as defined above, as well as Injury Severity Score (ISS), ICU stay (LOS), and admission blood pressure. All patients achieved non-flow-dependent VO2. There was no difference in CI, DO2, VO2, or ISS when S was compared with NS. All 27 patients whose lactate level normalized in 24 hours survived. If lactate levels cleared to normal between 24 and 48 hours, the survival rate was 75%. Only 3 of the 22 patients who did not clear their lactate level to normal by 48 hours survived. Ten of the 25 nonsurvivors (40%) achieved the above arbitrary optimization criteria. Fifteen of the survivors never achieved any of these criteria. Optimization alone does not predict survival. However, the time needed to normalize serum lactate levels is an important prognostic factor for survival in severely injured patients.

Adolescent↗

Intentional vital root transection: a 52-week histopathologic study in Macaca mulatta.

Past studies dealing with the vascular supply to surgically mobilized dentoalveolar segments have mentioned occasional encounters with vital root transection and have noted varying degrees of pulpal response to this insult. The purpose of this investigation was to observe the pulpal and periapical responses of monkey dental tissues to intentional vital root transection over a 1-year postoperative period. Four adult Macaca mulatta monkeys were used in this study. All roots were surgically transected within the apical third with a bur. Maxillary and mandibular quadrants for 1, 2, 3, 4, 6, 12, 24, and 52 weeks following surgery were obtained after the animals were killed by perfusion of the left ventricle. The tissue blocks were prepared by routine histologic methods. The results demonstrated a disruption of the normal pulpal architecture, with initial pulpal degeneration and subsequent early replacement by the periodontal ligament tissue. A cellular cemental lining of the root canal occurred in all specimens. The periodontal ligament-like tissue continued to deposit cementum, resulting in almost total obliteration of the root canal and pulp chamber and leaving an intact but much reduced blood supply to the pulp chamber containing periodontal tissues.

Animals↗

Vital apicoectomy of the teeth: a 1-4 week histopathological study in Macaca mulatta.

Several studies have reported devitalization of teeth following surgical procedures in the area of the root apices. The purpose of this investigation was to observe the 1-4-week wound healing pattern in monkey dental tissues following intentional vital apicoectomy (IVA). Two adult Macaca mulatta were used in this study. All of the teeth were surgically transected within the apical one-third with a bur. The soft tissues were then closed. At death, a maxillary and a mandibular quadrant for 1, 2, 3 and 4 weeks following surgery were obtained after vascular perfusion. Each quadrant was demineralized in EDTA, processed, serially sectioned at 7 microns and alternately stained with hematoxylin and eosin, Preece's modified trichome, and McKay's bacterial stains. Examination of sequential IVA cuts showed an initial disruption of the pulpal neurovascular supply resulting in pulpal necrosis. The pulpal tissues underwent a process of replacement with PDL-like connective tissues and deposition of cementum on all cut dentin surfaces of the tooth roots as well as in some of the pulp chambers. No abscesses, external resorption or ankylosis were found.

Alveolar Process↗

Radioimmunoassay of serum creatine kinase BB as index of brain damage after head injury.

Brain-type creatine kinase isoenzymes (CK-BB) was measured by radioimmunoassay in the serum of 54 patients with head injuries. CK-BB was not detectable in 476 out of 1006 controls, the remaining 530 normal samples containing a mean of 1.5 +/- SD0.75 microgram/l. The mean CK-BB concentrations in patients with mild, moderate, and fatal head injuries were all significantly higher than the control value (p < 0.01 in each instance). Patients with serious head injury had serum concentrations many times the normal value, in two cases within 30 minutes after impact. Fatally injured patients continued to have high serum concentrations several days after injury. In less serious cases values approached normal within two or three days. Every patient with evidence of cerebral laceration, bruising, or swelling had a serum CK-BB concentration above normal. Raised concentrations were found in 14 out of 22 patients with concussion only. The serum CK-BB concentration appears to be a sensitive index of brain damage and may prove useful in the management and follow-up of head-injured patients.

Adolescent↗

Theoretical and methodological considerations in the measurement of spasticity.

PURPOSE: To discuss the measurement of spasticity in the clinical and research environments, make recommendations based on the SPASM reviews of biomechanical, neurophysiological and clinical methods of measuring spasticity and indicate future developments of measurement tools. METHOD: Using the results of the systematic reviews of the biomechanical, neurophysiological and clinical approaches, methods were evaluated across three dimensions: (1) validity, reliability and sensitivity to change; (2) practical quality such as ease of use and (3) qualities specific to the measurement of spasticity, for example ability to be applied to different muscle groups. Methods were considered in terms of applicability to research and clinical applications. RESULTS: A hierarchy of measurement approaches was identified from highly controlled and more objective (but unrelated to function) to ecologically valid, but less objective and subject to contamination from other variables. The lack of a precise definition of spasticity may account for the problem of developing a valid, reliable and sensitive method of measurement. The reviews have identified that some tests measure spasticity per se, some phenomena associated with spasticity or consequential to it and others the effect of spasticity on activity and participation and independence. CONCLUSIONS: Methods appropriate for use in research, particularly into the mechanism of spasticity did not satisfy the needs of the clinician and the need for an objective but clinically applicable tool was identified. A clinical assessment may need to generate more than one 'value' and should include evaluation of other components of the upper motor neurone syndrome. There is therefore a need for standardized protocols for 'best practice' in application of spasticity measurement tools and scales.

Electromyography↗