Novel DNA-based T-Cell Activator Promotes Rapid T-Cell Activation and Expansion.

Autologous chimeric antigen receptor engineered T-cell therapies are beginning to dramatically change the outlook for patients with several hematological malignancies. Yet methods to activate and expand these cells are limited, often pose challenges to automation, and have biological limitations impacting the output of the injectable dose. This study describes the development of a novel, highly flexible, soluble DNA-based T-cell activation and expansion platform which alleviates the limitations of current technologies and provides rapid T-cell activation and expansion.

Novel cyanine dye-labeled dideoxynucleoside triphosphates for DNA sequencing.

Single color cyanine dye-labeled (Cy 5.0 and Cy 5.5) dideoxynucleoside-5'-triphosphates, or 'terminators', containing different spacer lengths were synthesized and evaluated for efficacy in DNA sequencing methods using a modified thermally stable DNA polymerase. The single color cyanine dye terminators were formulated into two separate sets of sequencing mixes, one for Cy 5.0 and the other for Cy 5.5, and evaluated on different automated sequencing platforms. Each set of mixes included two pyrimidine terminators with 17-atom linkers and two purine terminators with 10-atom linkers between the dye and the nucleotide. The two sets of cyanine dye-labeled terminators chosen for this cycle sequencing study produced improved band patterns with band uniformity similar to that obtained with dye-primer sequencing methods.

Antibiotic prophylaxis: theory and reality in orthopaedics.

Marked differences were found when prophylactic antibiotic regimens and accuracy of administration were compared in the orthopaedic trauma and elective surgery units of one city. Consultants carrying out elective, primary joint replacements advocated similar antibiotic policies. There was 100% compliance in correct prescription and over 99% in administration of antibiotic doses. An audit of eight surgeons who undertook emergency surgery on adult hip fractures found three different prophylactic antibiotic regimens and that half of the consultants wished no antibiotics to be given. Only 33% of the patients were prescribed the schedule that their consultant wished and there were frequent inaccuracies in dose administration. Of 48 doses prescribed, five were omitted and in addition, four were recorded as having been given although they were unprescribed. Whilst antibiotic prophylaxis is universally accepted and the drugs are prescribed and administered accurately in cases of elective joint arthroplasty, the converse is true for emergency hip surgery.

The separation of dentistry and family.

There are times when dentistry and family don't mix. When treating those who are closest to you, you should, at a minimum, observe the same rules you do when treating other, unrelated patients. The wiser course, however, may be to let someone else take care of your loved ones.

Aeromonas septicaemia in Hong Kong species distribution and associated disease.

During a 5-year study of 2211 patients with clinically significant positive blood cultures in Hong Kong. Aeromonas spp. were isolated in 40 cases. Among 26 episodes in which a single species was isolated. 17 (65.4%) were identified as Aeromonas hydrophila. 8 (30.8%) as A. sobria and one (3.8%) as A. caviae. There were 14 episodes with a mixture of species. Of these, nine (64.3%) were identified as A. hydrophila, two (14.3%) as A. sobria, and two (14.3%) as A. caviae. One (7.1%) was an infection with both A. sobria and A. hydrophila. These polymicrobial infections were usually combined with the presence of Enterobacteriaceae. Hepatobiliary disease was the underlying problem in 24 cases (60.0%) and malignant neoplasia in 14 (35.0%) cases. Most patients presented with fever and leucocytosis. The mortality rate for A. sobria septicaemia was not significantly different from the average rate for all septicaemias. A total of 30 isolates was available for sensitivity testing with 17 antibiotics. More than 86.0% were resistant to ampicillin, and the addition of the beta-lactamase inhibitor sulbactam did not restore its activity. All strains tested were sensitive to cefotaxime, ceftazidime, aztreonam, imipenem, norfloxacin and ciprofloxacin.

Aspergillus fungemia: report of two cases and review.

We present two cases of aspergillus infection confirmed by blood culture and review 30 other cases of genuine aspergillus fungemia and 34 cases of aspergillus pseudofungemia. Multiple different media and blood culture systems were used to isolated Aspergillus. The median time to positive blood culture was 8.5 days (range, 1-27 days) in the genuine cases. Genuine aspergillus fungemia was observed more often after cardiac surgery (n = 11 [34%]) or during neutropenia (n = 9 [28%]) than in other settings. In a recent series of fungemia during neutropenia, 7.6% of all episodes were due to Aspergillus. Other patients at risk for aspergillus fungemia were similar to those at risk for invasive aspergillosis, including patients with AIDS. Seven (44%) of 19 patients who were treated survived. In the group of patients with aspergillus pseudofungemia, there were no deaths, and cultures of additional specimens from the same patient were not positive. Criteria that may be applied to ascertain whether the isolation of Aspergillus from blood cultures is clinically significant are put forward.

A hospital outbreak due to Norwalk virus.

An outbreak of diarrhoea and vomiting began at a hospital for the elderly on the 25 October 1991. The symptoms and pattern of spread suggested a viral aetiology from a point source. Electron microscopy confirmed the presence of Norwalk virus. The first wave of illness affected 37 patients and 28 staff. Secondary cases occurred on all wards. Analytical studies of food consumed at three lunchtime meetings by staff and visitors to the hospital demonstrated a clear association between eating sandwiches and subsequent illness. The source of the outbreak was probably a food handler involved in the preparation of sandwiches. Control measures were implemented and the outbreak was declared over on the 11 November 1991. At this time 95 patients and 69 staff (including six visitors) had been affected. The implications for the future investigation and prevention of outbreaks of viral gastroenteritis in closed communities are discussed. An audit of the action taken during the outbreak resulted in the development of standards for the investigation and control of local outbreaks.

The rise of academic orthopaedic surgery during the past 44 years.

In accepting this invitation to write a prefatory chapter as a mini professional autobiography, it has become all too obvious that this has touched a few nerve endings that had healed many years ago. Contemplating personal experiences, thoughts, and philosophies and then writing them should have a purpose. During these past 44 years, I have had the good fortune to share in the breaking away of orthopaedics as a clinical practice, into an academic and scientific subject. Such a radical and difficult birth has been in the presence of many able and good fellow travellers and perhaps, therefore, may serve as a guide for the future by those who care to follow. The mixture of clinical practice with caring for people, teaching, and research has to be bound securely together by academic professors. This has presented the greatest challenge to me and certainly the greatest difficulty, because we have all faced criticism, not always constructive, from these three separate cultures. Even so, our responsibility has been to integrate science and medicine sensibly. Richards described universities as being places of high technology and remoteness from reality. In my experience having spent most of my professional life in British and American universities, the reality has always been too near and real.

Problems in management of health care workers exposed to HBeAg positive body fluids.

A young Asian male was admitted to hospital suffering from severe lower limb and facial injuries. He was subsequently found to be a carrier of hepatitis B virus and HBeAg positive. The management of 38 health care workers with significant blood and body fluid exposure involving this patient is discussed.

Psychiatric consequences of road traffic accidents.

OBJECTIVE: To determine the psychiatric consequences of being a road traffic accident victim. DESIGN: Follow up study of road accident victims for up to one year. SETTING: Emergency department of the John Radcliffe Hospital, Oxford. SUBJECTS: 188 consecutive road accident victims aged 18-70 with multiple injuries (motorcycle or car) or whiplash neck injury, who had not been unconscious for more than 15 minutes, and who lived in the catchment area. MAIN OUTCOME MEASURES: Present state examination "caseness"; post-traumatic stress disorder and travel anxiety; effects on driving and on being a passenger. RESULTS: Acute, moderately severe emotional distress was common. Almost one fifth of subjects, however, suffered from an acute stress syndrome characterised by mood disturbance and horrific memories of the accident. Anxiety and depression usually improved over the 12 months, though one tenth of patients had mood disorders at one year. In addition, specific post-traumatic symptoms were common. Post-traumatic stress disorder occurred during follow up in one tenth of patients, and phobic travel anxiety as a driver or passenger was more common and frequently disabling. Emotional disorder was associated with having pre-accident psychological or social problems and, in patients with multiple injuries, continuing medical complications. Post-traumatic syndromes were not associated with a neurotic predisposition but were strongly associated with horrific memories of the accident. They did not occur in subjects who had been briefly unconscious and were amnesic for the accident. Mental state at three months was highly predictive of mental state at one year. CONCLUSIONS: Psychiatric symptoms and disorder are frequent after major and less severe road accident injury. Post-traumatic symptoms are common and disabling. Early information and advice might reduce psychological distress and travel anxiety and contribute to road safety and assessing "nervous shock."

Septic arthritis in haemophilia.

Septic arthritis has been regarded as rare in haemophiliacs, but its incidence may have increased since HIV infection has become widespread in these patients. We describe six cases treated at one haemophilia unit over a two-year period and discuss their investigation, diagnosis and treatment. Four of the patients were seropositive to anti-HIV.

Dialysis arthropathy of the hip.

Beta 2-microglobulin amyloid deposition is associated with a destructive arthropathy in the hip of chronic hemodialysis patients. Twenty-five hips from 18 patients were assessed for the presence and immunohistochemical type of amyloid. The hemodialysis group was compared with an age- and disease-matched control group that had no evidence of renal failure. Beta 2-microglobulin amyloid deposits were present in all patients who had been on hemodialysis for 18 months or more. Beta 2-microglobulin amyloid deposits were not found in patients who had been on hemodialysis for less than 18 months. Amyloid deposits were seen first in the articular cartilage and later involved the synovial membrane, joint capsule, and subchondral bone as well. The presence and amount of amyloid deposition correlated to the duration of hemodialysis. Severely affected hip roentgenographically had a concentric loss of joint space, periarticular erosions, and cystic lesions in the femoral head and acetabulum. These pathologic and roentgenographic changes suggest that amyloid deposition leads directly to the erosive hip arthropathy occurring in hemodialysis patients.

Bone resorption by cells isolated from rheumatoid synovium.

Cellular mechanisms accounting for the osteolysis of rheumatoid erosions are poorly understood. Cells were isolated and characterised from the synovium of 16 patients with rheumatoid arthritis (RA) and four patients with osteoarthritis and their ability to resorb bone was assessed using a scanning electron microscope bone resorption assay. Macrophages were the major cell type isolated from the synovium of patients with RA. These produced extensive roughening of the bone surface without resorption pit formation. This low grade type of bone resorption was not affected by systemic (calcitonin, parathyroid hormone, 1,25-dihydroxyvitamin D3) or local (interleukin 1, prostaglandin E2) factors influencing bone resorption. Macrophage mediated bone resorption differs qualitatively and quantitatively from that of osteoclasts but is likely to play an important part in the development of marginal erosions in RA.

A five-year prospective study of septicaemia in hospitalized children in Hong Kong.

In a 5-year prospective study in a Hong Kong teaching hospital there were 344 clinically significant episodes of paediatric septicaemia. Many of the microbiological and clinical features were similar to those reported in Japanese and Western studies but there were some important differences. Half of the episodes (or 70% if neonatal infections are excluded) were community-acquired. The commonest organisms found were Salmonella spp (15% of all and 27% of community-acquired infections); this was related to the high local incidence of salmonellosis and typhoid fever. Salmonella typhi, which was responsible for one-third of the salmonella septicaemias, was usually seen in school-age children, while non-typhoid salmonellae were common in infants. Methicillin-resistant Staphylococcus aureus, which are now endemic in Hong Kong hospitals, was a common cause of hospital-acquired septicaemia. Pneumococcal septicaemia accounted for 22% of episodes in infants and pre-school children, but Haemophilus influenzae was uncommon (2% of all episodes) and there was no case of meningococcal septicaemia. The rarity of invasive infection with H. influenzae and Neisseria meningitidis in Hong Kong children is unexplained.