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Biomedical subjects

R Knight

Publications and source records attributed to R Knight.

At least 37 records · Page 2Linked to original sources

Sensory features of variant Creutzfeldt-Jakob disease.

OBJECTIVE: Sensory symptoms are a prominent feature of variant Creutzfeldt-Jakob disease (vCJD), occurring at an early stage of the illness. They are persistent and can be troublesome. Here, they are described in detail and a possible anatomical basis is discussed. METHODS: The first 50 cases of vCJD confirmed by the National CJD Surveillance Unit (NCJDSU) were reviewed. Where possible the patients and their relatives were interviewed and case notes were examined. The presence and nature of sensory symptoms and signs were noted. Results of investigation and types of treatment offered were also reviewed. RESULTS: Of 50 definite cases, 64 % had persistent sensory symptoms, 16 % had no sensory symptoms and 18 % were uncertain. In 2 % there was insufficient information. Of the 32 with definite symptoms, 31 % were symptomatic from the onset of the illness. The symptoms were varied and some patients complained of more than one type of symptom. Limb pain was described in 63 % cases. This was the most common symptom and was often non-specific and poorly localised, usually occurring in the lower limbs. Other symptoms included cold feelings (25 % patients), dysaesthesia (28 % patients), paraesthesia (31 % patients) and numbness (25 % patients). The symptoms were lateralised in 31 % of patients. CONCLUSIONS: Sensory symptoms are a prominent feature of vCJD, occurring in nearly two thirds of cases. They may help distinguish variant from sporadic CJD. They are likely to be of thalamic origin but the recognised MRI changes in vCJD do not correlate with the presence or absence of sensory symptoms. Neuropathological changes in the thalamus, however, show marked astrocytosis and neuronal loss.

Creutzfeldt-Jakob Syndrome↗

An analysis of maternal and fetal hair lead levels.

Lead contamination of the environment is an important public health consideration. There is evidence of declining blood lead levels in Britain, however, there is still concern about chronic exposure of the fetus and young children to low levels of lead and the effect that this has on neurodevelopment. Hair lead levels have been found to correlate well with body lead contamination. This study is the first to document the level of hair lead in pregnant women and their babies from an urban British population. There was no evidence of toxic maternal lead levels and the fetus is protected by the placental barrier.

Adult↗

Epidemiology of variant CJD.

There are 100 confirmed cases of variant CJD (vCJD) in the U.K., with four cases in other countries (France and the Republic of Ireland). In the U.K., The mean age of onset is 28 years (range 12-74) with a median duration of 13 months (range 6-39). There are reported regional variations in incidence in the U.K., with a North/South difference and a 'cluster' of cases in one county, Leicestershire. The incidence of cases in the U.K. is rising. There are concerns about the possibility of secondary, iatrogenic, spread of vCJD, especially given the finding of positive PrP immunocytochemistry in lymphoreticular tissue. Experimental evidence has confirmed the presence of infectivity in blood in transmissible spongiform encephalopathy (TSE) models, but the significance of this in relation to human blood practice is uncertain. The accumulated epidemiological evidence has not shown blood to be a risk factor for sporadic CJD, but variant CJD may behave differently. A Transfusion Medicine Epidemiological Review in the U.K. is collecting data on CJD case donors and recipients, with negative results to date.

Adolescent↗

Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute allograft rejection.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has been shown to play a critical role in the down-regulation of the immune response. We retrospectively examined the association between acute rejection and two polymorphisms in the CTLA4 gene, the dinucleotide (AT)n repeat polymorphism in exon 3 and the single nucleotide polymorphism A/G at position 49 in exon 1, in a cohort of liver and kidney transplant recipients. METHODS AND RESULTS: A total of 207 liver and 167 renal transplant recipients were analyzed. In the case of the (AT)n repeat polymorphism we found an increased incidence of acute rejection in association with allele 3 and 4 in both liver and kidney (P=0.002 and 0.05, respectively). In addition, in liver transplant recipients, allele 7 was associated with acute rejection independent of ethnicity (P<0.05). Allele 1 was less frequently observed in African American as compared with Caucasian liver and kidney transplant recipients, with a frequency of 33.8% and 69%, respectively (P<0.0001). Those patients with allele 1 had a tendency toward a lower rate of rejection at 42% versus 57.8% (P=0.058), suggesting a potential protective effect of allele 1. Analysis of the A/G single nucleotide polymorphism demonstrated no association between either allele and the incidence of acute rejection in the patients studied. CONCLUSION: These initial observations provide the necessary basis to further investigate the risk stratification of transplant recipients based on specific CTLA4 gene polymorphisms.

Abatacept↗

Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischemia/reperfusion injury.

BACKGROUND: Apoptosis contributes to cell loss after ischemia/reperfusion injury in the heart. This study describes the time course and level of apoptosis in different cell types in the intact heart during ischemia/reperfusion injury. METHODS AND RESULTS: Isolated Langendorff-perfused rat hearts were subjected to perfusion alone (control) or to 35 minutes of regional ischemia, either alone or followed by 5, 60, or 120 minutes of reperfusion. Sections were stained by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidium iodide and with anti-von Willebrand factor, anti-desmin, or anti-active caspase 3 antibodies; they were then visualized by confocal microscopy. Sections were also examined by electron microscopy. No TUNEL-positive cells were seen in control hearts or hearts exposed to ischemia alone. Early in reperfusion, TUNEL staining was colocalized with endothelial cells from small coronary vessels. Endothelial apoptosis peaked at 1 hour of reperfusion and, at this time, there was clear perivascular localization of apoptotic cardiac myocytes, whose number was inversely proportional to their distance from a positive vessel. After 2 hours of reperfusion, apoptotic cardiac myocytes assumed a more homogeneous distribution. Active caspase 3 labeling was seen independent of DNA fragmentation during ischemia alone, but it colocalized with TUNEL staining over the 3 time points of reperfusion. Immunocytochemical findings were confirmed by electron microscopy and Western blotting. CONCLUSIONS: In the very early stages of reperfusion, apoptosis is first seen in the endothelial cells from small coronary vessels. The radial spread of apoptosis to surrounding cardiac myocytes suggests that reperfusion induces the release of soluble pro-apoptotic mediators from endothelial cells that promote myocyte apoptosis.

Animals↗

Safety and efficacy of bisphosphonates beyond 24 months in cancer patients.

PURPOSE: Bisphosphonate therapy has decreased the risk of skeletal complications associated with osteolytic bone lesions in patients with breast cancer and multiple myeloma. The large prospective studies have used 21 to 24 months of treatment. We studied the safety and efficacy of bisphosphonates in a subset of patients who received therapy for more than 24 months. PATIENTS AND METHODS: Patients who received bisphosphonates (pamidronate or zoledronic acid) were identified. Data on skeletal events and laboratory parameters were gathered by chart review. RESULTS: We studied 22 patients who received intravenous pamidronate or zoledronic acid for a duration of 3.6 years (range, 2.2 to 6.0 years). Prolonged therapy was well tolerated. No significant calcium, phosphorus, electrolyte, or WBC count abnormalities were encountered. There was a clinically insignificant decrease in hemoglobin and platelet count and an increase in creatinine in these patients. The fracture rate beyond 2 years was no greater than during the first 2 years of treatment. There were no stress fractures of long bones with prolonged therapy. CONCLUSION: Prolonged treatment with the potent bisphosphonates pamidronate and zoledronic acid seems to be well tolerated and should be studied in prospective, randomized studies to document prolonged skeletal efficacy.

Bone Neoplasms↗

Creutzfeldt-Jakob disease: a protein disease.

Creutzfeld-Jakob disease (CJD) is essentially a protein disease. All forms of CJD are characterized by the deposition of an abnormal coformation of a normal cellular protein. This protein (PrPc) is encoded for by the PRNP gene on chromosome 20 in humans. There are important genetic influences on susceptibility to CJD and on the resulting clinico-pathological picture. The abnormal protein (PrPSc), may be the infectious agent itself or the main component of it. However, its precise role in the pathogenesis of disease is not clear. The detection of PrPSc plays a crucial role in the diagnosis of CJD and its electrophoretic characteristics are used to classify different forms of CJD. However, the "molecular diagnosis" of CJD is not without uncertainties.

Creutzfeldt-Jakob Syndrome↗

Delayed penile replantation after prolonged warm ischemia.

We report a case of microsurgical replantation of traumatic self-amputation of penis after prolonged warm ischemia as a result of delayed presentation. At 12 weeks postoperative follow-up evaluation, the patient exhibited good urinary flow, spontaneous erection, and a normal response to pharmacological stimulation.

Humans↗

Prophylactic antibiotics are not indicated in clean general surgery cases.

BACKGROUND: In assigning risk of infection, the traditional wound classification system has been replaced by the National Nosocomial Infection Surveillance (NNIS) system. NNIS classification is determined by procedure length, wound cleanliness, and ASA status. To date, no prophylactic antibiotic guidelines have been proposed for the NNIS system. METHODS: Clean general surgery cases were retrospectively reviewed in our hospital for infection and prophylactic antibiotic use. These cases were then stratified per the NNIS system. RESULTS: One thousand twenty-three clean general surgery cases had 16 (1%) surgical site infections. The infection rate in NNIS class 0, 1, and 2 cases not given prophylactic antibiotics was 1.21%, 3.03%, and 0%, respectively. The infection rate in NNIS class 0, 1, and 2 cases given prophylactic antibiotics was 0.94%, 2.44%, and 6.67%, respectively. CONCLUSIONS: No statistically significant decrease in infection rate was demonstrated by us using prophylactic antibiotics, regardless of the NNIS classification in clean general surgery cases.

Antibiotic Prophylaxis↗

The Patient Care Notebook: quality improvement on a rehabilitation unit.

BACKGROUND: Shortened lengths of stay in acute and rehabilitation hospitals, continuing financial pressures on all postacute care services, and increasing out-of-pocket health care costs for patients and families challenge rehabilitation hospitals' patient education and discharge planning processes. Spaulding Rehabilitation Hospital (Boston) introduced a patient care notebook in a 15-bed satellite unit and pilot tested its contribution to the patient education and discharge planning process. DEVELOPING THE NOTEBOOK: The three-ring binder notebook included sections on medical appointments and phone numbers, understanding illness and medical care, coping with illness, physical activities, recommendations for the home, and community resources, with both standard and patient-specific information. RESULTS: Most of the patients and caregivers who received the notebooks found them to be helpful, and most staff indicated that the notebook improved the teaching process. Telephone calls to the unit after home discharges decreased form 28 calls for 11 discharges to 6 calls for 21 discharges after the notebook began to be used regularly. DISCUSSION: Staff felt that the process of using the notebook helped focus attention on teaching during the entire course of a patient's hospitalization rather than just a day or two before discharge. The patient care notebook process is being introduced to the entire hospital and to all patients, regardless of discharge location and the patient's literacy or proficiency with English. CONCLUSION: In using the notebook, the QI team, and the entire unit staff, learned about the complexities of QI, patient education, and discharge planning. The notebook process was implemented throughout the hospital a little more than a year after the completion of the pilot project.

Aged↗

The role of non-biting flies in the epidemiology of human infectious diseases.

The feeding and reproductive habits of non-biting synanthropic flies make them important mechanical vectors of human pathogens. Synanthropic flies are major epidemiologic factors responsible for the spread of acute gastroenteritis and trachoma among infants and young children in (predominantly) developing countries. House flies are involved in mechanical transmission of nosocomial infections with multiple antibiotic-resistant bacteria in hospital environments.

Acute Disease↗

MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol.

Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle. Characteristic appearances on magnetic resonance imaging (MRI) have been identified in several forms of CJD; sCJD may be associated with high signal changes in the putamen and caudate head and vCJD is usually associated with hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These appearances and other imaging features are described in this article. Using appropriate clinical and radiological criteria and tailored imaging protocols, MRI plays an important part in the in vivodiagnosis of this disease.

Clinical Protocols↗

The selenium status of women with a history of recurrent miscarriage.

OBJECTIVE: To assess the relationship between selenium levels in human blood and hair, and the risk of recurrent miscarriages. DESIGN: Case-control study. PARTICIPANTS: Two groups of non-pregnant women: 18 women with one or more successful pregnancies and no history of miscarriage (control group); 26 women with a history of recurrent miscarriage (> or = 3) with no subsequent successful pregnancies (study group). METHODS: Samples of venous blood and scalp hair were collected and the selenium content analysed by inductively coupled plasma mass spectrometry. RESULTS: No significance difference was found between the level of selenium in the blood samples of the women in each group. There was a significant reduction in the mean hair selenium level in the recurrent miscarriage group compared with the control group (0.14 microg/g vs 0.34 microg/g). Further analysis of the recurrent miscarriage group revealed no relationship between levels of serum or hair selenium with parity. There was a significantly greater proportion of women in the control group who ate cereals, vitamin supplements, and liver or kidney. CONCLUSION: There was evidence of selenium deficiency in women with recurrent miscarriages compared with a control group of women with a good reproductive performance. This difference was seen in hair samples but not serum samples and therefore may not represent a simple nutritional deficiency. The importance of selenium deficiency in miscarriage has still not been determined.

Abortion, Habitual↗