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Biomedical subjects

B Morgan

Publications and source records attributed to B Morgan.

At least 55 records · Page 3Linked to original sources

Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.

The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.

Acquired Immunodeficiency Syndrome↗

Acute pancreatitis complicating a bone marrow harvest.

A patient developing acute pancreatitis with pseudocyst formation after an uncomplicated bone marrow harvest is reported. The diagnosis was confirmed by elevated serum amylase and lipase, and by CT scan. We suggest that the pancreatitis may have been precipitated by spasm of the sphincter of Oddi secondary to opiates administered as premedication and for pain relief.

Abdominal Pain↗

Neonatal welfare and placental transfer of fentanyl and bupivacaine during ambulatory combined spinal epidural analgesia for labour.

To investigate current concerns that potent opioid drugs, such as fentanyl, used for labour regional analgesia may affect neonatal status, maternal and umbilical plasma concentrations of fentanyl and bupivacaine at delivery were measured in 40 nulliparous patients receiving low-dose combined spinal epidural analgesia. Neonatal assessments included Apgar scores, umbilical blood gases and neurobehavioural tests. All maternal and umbilical venous plasma concentrations were low. Maternal and umbilical vein total fentanyl concentrations increased with increasing doses of epidural fentanyl (r = 0.46 and 0.30, respectively, p < 0.01). There were no significant differences between maternal and umbilical venous plasma total or free concentrations of fentanyl. Mean umbilical vein/maternal fentanyl ratios were 1.12 for total drug and 1.20 for free drug and values were unrelated to the last epidural bolus to delivery interval (r = 0.12, p = 0.49). There were no correlations between Apgar scores, umbilical blood gases or neurobehavioural scores and umbilical venous concentrations of either fentanyl or bupivacaine. The dose of fentanyl used for ambulatory combined spinal epidural analgesia would appear to have a negligible effect on neonatal condition.

Ambulatory Care↗

Blood pressure and fetal heart rate changes with patient-controlled combined spinal epidural analgesia while ambulating in labour.

OBJECTIVE: To determine the effect of patient-controlled combined spinal epidural analgesia (PCEA) on maternal pulse and blood pressure, and fetal heart rate in primigravid women, when adapting different positions in labour. DESIGN: A prospective study. SETTING: Queen Charlotte's and Chelsea hospital, London. PARTICIPANTS: Fifty-five primigravid women in labour at > or = 37 weeks of gestation; 40 women had supervised standing top-ups given by an anaesthetist. A further 15 women had PCEA top-ups given in each of standing, sitting and lying positions. MAIN OUTCOME MEASURES: Maternal pulse rate, blood pressure and fetal heart rate changes following epidural top-ups. RESULTS: In the first 40 women there was no clinically significant fall in their blood pressure (< 5 mmHg). The subsequent 15 women who had PCEA top-ups had no fall in blood pressure in the standing and sitting positions, though the average blood pressure fell significantly when a top-up was given in the lying position. Maternal heart rate increased significantly at 12 min post top-up when the women were in the standing position (P = 0.0018). In the 15 women who had PCEA top-ups, the CTG showed improvement in decelerations when women were in the standing position but deterioration when in the lying position (P < 0.01). CONCLUSION: Patient-controlled epidural analgesia top-ups with maternal mobility may be beneficial to the fetus possibly by reducing the hypotension normally associated with top-ups in the lying position.

Analgesia, Epidural↗

An audit of knee radiographs performed for general practitioners.

The Royal College of Radiologists (RCR) has published guidelines concerning indications for imaging investigations. These include plain radiography of the knee, the indications for which are locking or signs of restricted movement. This audit consisted of 1153 knee radiographs in a 9 month period, results of a questionnaire sent to general practitioners (GPs), analysis of radiological reports and returned questionnaires (55% of cases), and subsequent comments from the GPs on receiving these results. Only 50% of cases fall within RCR guidelines, 90% of radiographs were normal or showed degenerative change. In 42% of cases, knee radiographs were requested to confirm previously expected degenerative change, and in 30% patient pressure was a significant factor. Most knee radiographs (87%) result in no significant change in management apart from continuation of symptomatic measures. Application of current guidelines, however, would miss some important diagnoses manifest clinically by persistent pain or effusion, for example loose body or Brodie's abscess. In cases of locking, where a radiograph may miss significant soft tissue abnormality, there was concern that reassurance was often gained by a normal examination. This audit shows that many knee radiographs are unnecessary. The guidelines appear appropriate with the proviso that persistent pain and effusion should be included as indications for investigation. Many GPs report medico-legal considerations as important reasons for unnecessary referrals, although the application of guidelines should be protection against this. The referral rate for knee radiographs before and after the communication of these results has not altered.

Adolescent↗

Novel, cross-restricted, conserved, and immunodominant cytotoxic T lymphocyte epitopes in slow progressors in HIV type 1 infection.

HIV-specific cytotoxic T lymphocytes (CTLs) play an important role in the immune response to HIV infection. Long-term nonprogressors (LTNPs) or slow progressors (SPs) in HIV infection may make qualitatively different CTL responses compared to those generated by seropositive individuals who progress to disease at a faster rate. The class I molecule HLA-B*57 has been identified as one restriction element overrepresented in SP groups studied, and, together with the closely related molecule HLA-B*58, occurs commonly in ethnic groups where HIV is most prevalent. In this study, we have identified five new HLA-B*57-restricted CTL epitopes recognized by SP donors, one of which is also HLA-B*5801 restricted. These HLA-B*57-restricted responses represent the dominant HIV-specific CTL response in each of the SP donors tested. These and other such epitopes may be an important component in future vaccine design.

Amino Acid Sequence↗

Gene expression in the limbless mutant: polarized gene expression in the absence of Shh and an AER.

Limb buds in the limbless chick begin to form normally but fail to form an AER and ultimately degenerate. Wnt7a and LMX-1, which are restricted to the dorsal half of a normal limb bud, are expressed throughout the ectoderm and mesenchyme of the mutant buds, respectively. Engrailed-1, normally expressed in ventral limb ectoderm, is not expressed in the limbless bud. This defect precedes the normal period of AER formation and no localized expression of genes normally found in the AER is observed in limbless buds. Consistent with the lack of molecular specialization of an AER, Shh and BMP-2 are not expressed in the ZPA of the mutant bud. Despite the lack of Shh, FGF-4, or BMP-2 expression, the hoxd genes are expressed at low levels in the posterior mesenchyme of the bud. Forced expression of Shh fails to rescue the positive feedback loop between the AER and the ZPA and does not lead to distal outgrowth. However, Shh does maintain the part of the bud formed during pre-AER stages. These results support the importance of the dorsal/ventral boundary in the initiation of AER formation and imply that Shh is not required for the initial activation of polarized hoxd gene expression during limb development.

Animals↗

Biliary distensibility during per-operative cholangiography as compared to pre-operative ultrasound: a four year follow-up study.

INTRODUCTION: It is well recognized that corrected bile duct diameters, as measured by endoscopic retrograde cholangiography (ERC), are often significantly greater than the corresponding ultrasound measurement. This can be attributed to variation in bile duct distensibility and is particularly noted in post cholecystectomy patients, possibly due to loss of the gall bladder reservoir effect. It has been suggested that increased bile duct distensibility may be related to the post-cholecystectomy syndrome. We have observed a similar discrepancy between ultrasound and per-operative cholangiography (POC). This trial investigates whether the discrepancy between ultrasound and POC measurements has clinical significance. METHOD: Seventy-five patients with normal pre-operative ultrasound and POC undergoing standard open cholecystectomy (with benzodiazepine pre-medication) in 1990 were identified. After allowance for magnification, maximum biliary diameters were obtained for the proximal extra-hepatic bile duct. Follow-up was obtained in 67 patients from clinical case notes and contact with general practitioners. RESULTS: Considerable variation of bile duct distensibility was recorded (range 83% to 410%) with 12 cases having POC biliary diameters outside radiological guidelines (12 mm as recorded on the radiograph). This distension is shown to increase with age. After 4 years, 16 patients had recurrent abdominal pain of which nine had undiagnosed right upper quadrant pain. There were no clinical cases of retained stone post-operatively. There was no correlation between POC measured bile duct diameter or distensibility and post-operative or long term problems. This study suggests that the bile duct has a normal variation of distensibility which increases with age and that radiological guidelines, as regards the upper limit for normal POC biliary diameters can be relaxed.

Adult↗

Hypertrophic osteoarthropathy in staging skeletal scintigraphy for lung cancer.

AIM: To assess the prognostic significance of hypertropic osteoarthropathy (HOA) discovered on routine staging bone scintigraphy in patients with lung cancer. PATIENTS AND METHODS: Between 1989 and 1992 all 99mTc-MDP bone scintigrams performed for the staging of bronchogenic carcinoma were reviewed. HOA was diagnosed by the observation of cortical/periosteal increased uptake in the extremities of the long bones. Follow-up and confirmation of the diagnosis was obtained by hospital computer, histology records, operative records, patient notes and radiological data where available. RESULTS: 164 staging scintigrams for lung cancer were identified. Twenty-eight patients (17%) were observed to have HOA. Patients with and without HOA were well matched for age and sex. There was little difference in the distribution of cell type but the HOA groups has a greater incidence of peripheral tumours. There was no significance in survival between the two groups. Two of three long-term survivors had clinically overt HOA and one presented with arthralgia. CONCLUSION: HOA is often seen on skeletal scintigraphy for staging of lung cancer and has no prognostic significance. The data also support current teaching that a high index of suspicion for HOA, as a cause of arthralgia may lead to early diagnosis of a potentially resectable lung carcinoma.

Aged↗

Maternal expectations and experiences of labour pain and analgesia: a multicentre study of nulliparous women.

Six hospitals with large maternity units in five different European countries were involved in this multicentre study. At least 100 primiparae for each country were examined. All mothers received two standardized interviews, one during the last month of pregnancy, and one 24 h after delivery. Maternal expectations and experiences of pain, pain relief, and satisfaction with analgesia and childbirth were assessed by a 100 mm visual analogue scale (VAS). Almost all mothers were seen regularly by an obstetrician or a midwife during pregnancy, had prepared childbirth classes and received antenatal information on labor analgesia techniques. Differences between the five groups were noted in the level of education and socio-economic status. Maternal expectations of labor pain and the answers to the pre-delivery interview varied significantly between the centers, as did maternal knowledge, expectation and ultimate choice of analgesic technique. Generally speaking the level of maternal satisfaction with analgesia and childbirth experience was high; however, epidural analgesia was more effective than other methods of pain relief (P<0.0001). The most satisfied mothers were those who expected more pain, were satisfied with the analgesia received and had good pain relief after analgesia (P<0.001).

Journal Article↗

Snoring as part of a dose-response relationship between sleep-disordered breathing and blood pressure.

This report addresses the hypothesis that snoring without significant apneas and hypopneas (simple snoring) is associated with elevated blood pressure and cardiovascular disease (CVD). Data on blood pressure, previously diagnosed cardiovascular disease, and sleep-disordered breathing (SDB) status from a population-based sample of 580 adults was analyzed. Systolic and diastolic blood pressures, adjusted for age, sex, and body mass index, increased stepwise across categories of no SDB, simple snoring, mild, moderate, and more severe SDB (p < 0.05). A similar and significant trend was seen for CVD prevalence. The results provide evidence that simple snoring represents the beginning of the SDB severity spectrum and that simple snoring has a proportionately smaller but, nevertheless, significant, risk for elevated blood pressure and CVD.

Adult↗

The correlation of bone scintigraphy and histological findings in patellar tendinitis.

Patellar tendinitis is a chronic overuse injury causing pain and tenderness over the proximal insertion of the patellar tendon. Its management is usually conservative, but in intractable cases surgery is effective. Bone scintigraphy has been suggested as a useful investigation in these patients, although we are aware of no large series supporting this. Thirty-four patients with intractable symptoms of patellar tendinitis were treated surgically. The operative specimens were graded histologically and compared with preoperative radionuclide bone scans. The histological findings confirmed tendon and or tendon sheath abnormalities in all the samples. The predominant abnormalities were increased vascularity, fibroblast proliferation, acid mucopolysaccharide and haemosiderin deposition. Bone scintigraphy showed 24 (71%) patients to have abnormalities on the delayed images, 8 with diffusely increased activity in the patella and 16 with increased activity localized to the lower pole. Patients with abnormal bone scans had significantly more severe histological changes in their tendons. These findings support the use of radionuclide bone scans in the pre-operative assessment of patellar tendinitis correlating well with histopathological severity of the disease process. The 10 false-negative cases (29%), however, suggest that bone scans are unhelpful in the routine diagnosis and management of this condition.

Adolescent↗

Using a mixture model to predict the occurrence of diabetic retinopathy.

Diabetes mellitus is a common condition which has several serious complications associated with it. In this paper a mixture model, based on one previously used to predict the onset of AIDS, is used to predict the onset of one of these complications, diabetic retinopathy, the major cause of adult blindness in the U.K. This model differs from the previous AIDS model by introducing covariates into the model and using a wider choice of mixture distributions. The fit and distributional assumptions of the model are then discussed for this example. The model is fitted to the data by maximum likelihood. It is important that the training set contains balanced numbers of individuals with and without retinopathy.

Acquired Immunodeficiency Syndrome↗