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Biomedical subjects

R C Read

Publications and source records attributed to R C Read.

At least 19 recordsLinked to original sources

Invasive pneumococcal disease and the potential for prevention by vaccination in the United Kingdom.

OBJECTIVES: Invasive pneumococcal disease (IPD) is associated with a high mortality despite antimicrobial therapy, but may be preventable by pneumococcal vaccination. The extent of previous exposure to pneumococcal capsular polysaccharide vaccination prior to an episode of IPD in hospitalised adults in the United Kingdom is unclear. METHODS: We conducted a retrospective cohort study in adults with IPD admitted to either of two teaching hospitals in Sheffield, United Kingdom during 1992-2000. Receipt of pneumococcal vaccination, risk factors for IPD, death and disability were determined. RESULTS: The number of cases of IPD was 552 and 187/230 patient records from one site were reviewed. According to UK pneumococcal vaccination guidelines 59% of patients should have received the vaccine and 76% of patients if updated guidelines, which include age>65 years as an indication, are applied. In patients with known risk factors, excluding age, only 8% had been vaccinated. The mortality from IPD was 21% and an additional 6% suffered major complications. CONCLUSIONS: In patients hospitalised with IPD there is a high rate of pre-existing risk factors and a low rate of administration of pneumococcal vaccination. IPD incurs significant mortality, morbidity and economic cost and there is potential for reducing this by improved uptake of pneumococcal vaccination.

Adolescent↗

Haplotype-specific gene expression profiles in a telomeric major histocompatibility complex gene cluster and susceptibility to autoimmune diseases.

The telomeric class III region of the major histocompatibility complex is gene dense, but apart from the three tumour necrosis factor (TNF) superfamily members (TNF, lymphotoxin alpha and lymphotoxin beta) little is known of the expression and function of the majority of the genes. Recent genetic studies in autoimmune diseases, particularly rheumatoid arthritis (RA), have suggested a human leukocyte antigen (HLA)-DR-independent disease effect in this region. To gain further insights into these associations, we used lipopolysaccharide-stimulated human macrophages to examine inducible mRNA expression and genotype-phenotype relationships for genes in this region. Following stimulation in addition to the expected induction of TNF mRNA, a 14-fold increase of ATP6V1G2 at 18 h (P<0.001) was seen, whereas B-associated transcript (BAT)2 (P<0.001) and leucocyte-specific transcript (LST)1 (P<0.001) were both downregulated. By genotyping single-nucleotide polymorphisms spanning a 70 kb interval centred on the TNF locus, we constructed haplotypes and determined associated expression profiles for 10 genes in the cluster using quantitative real-time polymerase chain reaction. Overexpression of BAT1 mRNA was associated with carriers of a haplotype containing the LST1 marker transmitted to RA cases in a family study and also DRB1(*)15 associated with susceptibility to nephritis in systemic lupus erythematosus. The implications of our findings for the understanding of genetic associations with disease susceptibility in this region are discussed.

Autoimmune Diseases↗

British contributions to modern herniology of the groin.

Traditional disdain for groin repair stifled recognition of British innovations. Some, relating to modern herniology, are remembered herein. Morton (1841) and Mackay (1889) showed the epigastric artery piercing Cooper's transversalis fascia (1807). Bilaminarity (Cooper, 1807) was confirmed in 1992 (Read). Thomson's iliopubic tract (1838) became part of Nyhus' repair (1960) [derived from McEvedy's repair (1950)] and laparoscopy (Ger, 1982). Retzius' space (Edinburgh, 1858) with Lister's antisepsis (1865) enabled preperitoneal herniorrhaphy (Annandale, 1876). He participated (1873) in intraperitoneal release of incarceration and reducible protrusions (Tait 1883). Cheyne's pectineus muscle plug (1893) preceded Kelly's marble prosthesis for femoral herniation (1898). Cheatle (1920) introduced posterior preperitoneal repair-ignored, rediscovered (Henry, 1936), and adopted (1952) at the Mayo clinic. Calne (1967) pioneered retrorectus Mersilene and was followed by Stoppa (1969) and Wantz (1989). Brandon (1945) blamed failure of modified Bassini's herniorrhaphies on closure at the intermediate inguinal ring instead of the internal. A similar mechanism may explain interstitial recurrence (Gilbert, 2003) after Amid-Lichtenstein repair. Lytle (1896-1986) described a muscle shutter at the internal ring, course of genitofemoral nerve, and orifice of femoral canal. Russell's congenital saccular theory (1906) was questioned by Keith (1924). Acquired connective-tissue pathology was later shown to play a systematic role in adult groin herniation (Read, 1970), confirmed by Jackson and colleagues (1996) and others.

General Surgery↗

The preperitoneal approach to the groin and the inferior epigastric vessels.

Preperitoneal, a word coined by Nyhus in the 1960s, has been applied not only to posterior approaches that he, Stoppa, and Wantz popularized but to anterior exposures of the groin, which divide the transversalis fascia. This assumes that all give similar views of the easily cleaved space of Bogros. However, accumulated anatomical observations reveal the transversalis fascia as having not one but two layers. The inferior epigastric vessels run between rather than in the preperitoneal space, which is avascular and has its own fascia lining the peritoneum. Historical evidence shows that both the midline Cheatle-Henry and lateral Ugahary-Kugel approaches, which transect the abdominal wall, provide excellent exposure of the avascular preperitoneal space. However, neither the unilateral posterior McEvedy approach nor the anterior approach does, as only part of the musculature and fasciae are retracted. The inferior epigastric vasculature and posterior lamina transversalis fascia, which remain in situ, block the view. Unless they are disrupted or circumvented, neither of the latter approaches or subsequent repairs should be labeled preperitoneal.

Abdominal Wall↗

Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges--updated 10 February 2004.

Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS.

Communicable Diseases, Emerging↗

Lichtenstein vs anterior preperitoneal prosthetic mesh placement in open inguinal hernia repair: a prospective, randomized trial.

Male veterans with unilateral primary inguinal hernia, classified intraoperatively as Gilbert Type III or IV, were randomized to subaponeurotic (Lichtenstein, n=126) or preperitoneal (Read-Rives, n=121) repair under general or spinal anesthesia. The two groups of patients were comparable in age, body weight index, comorbidities, and size and type of hernia. Of the 247 patients enrolled, 224 were followed for at least 2 years (median 82 months, range 24-110 months), 16 were lost to follow-up, and seven died from causes unrelated to the surgery. The average operative time of the Read-Rives repair was 9 min longer than that of the Lichtenstein repair. There were no wound infections, and the frequencies of other short- and long-term complications were low and similar in the two groups. Six patients developed hernia recurrence, five in the Lichtenstein group (4.3%), and one in the Read-Rives group (<1%), ( P=0.21). Both anterior repairs are associated with low postoperative morbidity and recurrence rates. The Lichtenstein repair is technically easier and less time consuming. There is no statistically significant difference in the recurrence rate between the two repairs.

Adolescent↗

Macrophage defences against respiratory tract infections.

Pulmonary macrophages with a key role in defence against respiratory infection are a heterogeneous family of cells with phagocytic, antigen processing and immunomodulatory functions. Macrophages are important in both innate and acquired immunity in the respiratory tract, and have a role in lung defence against viruses, bacteria, mycobacteria and fungi. Interactions of pathogens with lung macrophages is strongly influenced by soluble immune components including complement, collectins and immunoglobulins. Macrophage function can be modulated by cytokines, environmental exposures, recent and chronic infection including HIV infection, drug therapy and gene transfer.

Bacterial Infections↗

Liver abscess in adults: ten years experience in a UK centre.

BACKGROUND: The epidemiology and management of liver abscess (LA) have evolved over time. AIM: To examine our experience over 10 years in a UK teaching centre. DESIGN: Retrospective review of patient records. METHODS: We reviewed the records of all patients aged >16 years discharged from Royal Hallamshire Hospital with a diagnosis of LA between April 1988 and December 1999. RESULTS: There were 69 patients with LA (65 pyogenic, 4 amoebic), giving a crude annual incidence rate of 2.3/100,000/year (18.15/100,000 hospital admissions). Median age was 64 years. Single lesions were found in 41 patients, multiple lesions in 28. Pre-admission, patients were symptomatic for a median 14 days, with the most common symptoms and signs being fever and abdominal pain/tenderness. Pathogens were identified in 74% and predisposing aetiology in 92% of those undergoing investigation. Spread of infection to the liver via the portal venous system was the commonest route of infection (46%), most frequently in patients aged >/=60 years (p=0.019). Abdominal ultrasound (US) was diagnostic for LA in >90% of cases. Treatment with anti-microbial therapy plus interventional radiology was optimal. The case fatality rate was 12.3%, mainly from associated underlying pathology. DISCUSSION: LA is commonly associated with underlying gastrointestinal pathology. Seeking out this underlying aetiology is an integral part of management. We recommend US as the first-line diagnostic tool with guided intervention plus antibiotic(s) as first-line treatment. Prognosis depends chiefly on the underlying pathology.

Adolescent↗

Opsonic phagocytosis of Streptococcus pneumoniae by alveolar macrophages is not impaired in human immunodeficiency virus-infected Malawian adults.

Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis, especially among adults infected with the human immunodeficiency virus (HIV). Alveolar macrophages (AMs) are critical components of cellular defense against bacterial infection and are both infected and affected by HIV. In this study, AMs obtained at bronchoscopy from 44 Malawian adults (24 HIV positive and 20 HIV negative) were exposed in vitro to opsonized S. pneumoniae and coagulase-negative staphylococci. AMs from HIV-positive and -negative volunteers showed no significant difference in binding to or internalization of either S. pneumoniae or coagulase-negative staphylococci. In HIV-positive subjects, the presence of detectable HIV in lung fluid was not associated with AM impairment. AMs from HIV-infected adults did not exhibit impaired pneumococcal phagocytosis in the assay used. This suggests that an alternative mechanism of susceptibility is operating in these individuals.

Adult↗

Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup B.

The influence of the innate immune protein mannose-binding lectin (MBL) on the response of human phagocytes to Neisseria meningitidis was investigated. MBL increased the association of killed meningococci with neutrophils, monocytes, and macrophages by increasing the proportion of cells that recognized bacteria. MBL down-regulated the normal change in expression of the leukocyte adhesion molecules CD11b and CD62L. In an ex vivo model, the addition of MBL to the blood of MBL-deficient donors influenced the production of monocyte-derived inflammatory cytokines. The addition of high concentrations of MBL (>6 microg/mL) profoundly decreased the production of interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha by monocytes in response to meningococci, whereas lower concentrations enhanced the production of IL-6 and IL-1beta. These results suggest that MBL not only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease.

CD11 Antigens↗

Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis.

Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or may represent appropriate host response to infection. Human monocyte-derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria and intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes at levels greater than those in monocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The immune response of macrophages to S. pneumoniae includes a novel form of apoptosis that is associated with successful phagocytosis and bacterial killing. This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.

Amino Acid Chloromethyl Ketones↗

A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease.

Human Toll-like receptor 4 (TLR4) transduces proinflammatory cytokine release by human cells in response to lipopolysaccharide (LPS). This study tested the hypothesis that, if TLR4 is rate limiting for a successful response to bacterial LPS in humans, a human gene polymorphism that results in the amino acid substitution Asp299Gly and causes reduced expression and function of TLR4 should influence susceptibility to or severity of natural gram-negative infection. The allele frequency of the Asp299Gly polymorphism was 5.9% among 879 blood donors, 6.5% among 1047 patients with microbiologically proven meningococcal disease, and 4.1% among 86 patients who died of meningococcal disease. No significant differences were observed, including those analyzed after stratification of the infected population by age and by meningococcal serogroup. Therefore, this functional TLR4 polymorphism does not influence susceptibility to or severity of meningococcal disease.

Adolescent↗

The contribution of Allison and Nissen to the evolution of hiatus herniorrhaphy.

Even though it was not until 1950 that Barrett introduced the term "reflux esophagitis", this entity is now the most common disease afflicting the western world. Diaphragmatic herniation, recognized by Sennertus in 1541, was first repaired by Potemski (1889). Before World-War II, the condition was considered rare; symptomatology, as in external herniae, was ascribed to pinching of the stomach by the hernial ring. Only large protrusions, with signs of impending incarceration, volvulus, or strangulation, were operated upon. Modern understanding derives from studies of short, strictured esophagi. Because of endoscopic "gastric" biopsies in children, Findlay and Kelly considered them congenital "misplacements". However, Allison (1943), finding adults with ulceration and scarring, argued they were acquired. Later (1953) he concluded that the distal esophagus may be lined with metaplastic adenomatous epithelium which can harbor malignancy. His repair, reestablishing the crural pinchcock was, as pointed out by his countryman Collis (who in 1957 constructed a neo-esophagus from the Magenstrasse), inadequate. Nissen performed (1936) gastroesophagectomy in a case of peptic ulceration of the cardia. To avoid leakage he buried the anastomosis. Amazingly, 17 years later he learned that the patient had no reflux. He then successfully performed and reported (1956) fundoplication in a man and woman with gastroesophageal reflux disease. His operation remains the basis for surgical therapy today.

England↗

Bubo masquerading as an incarcerated inguinal hernia.

A 44-year old, male, tattooed, leather jacket clad, Harley-Davidson motorcyclist arrived at the emergency room with a tender, irreducible mass, presenting at the external inguinal ring. In 1998, lung biopsy was read as miliary granuloma. No herniation was found on urgent preperitoneal exploration. Incision of the mass showed acid-fast bacilli. Culture later revealed Mycobacterium avium-intracellulare (MAI). A blood count showed CD4 lymphopenia; HIV was negative and remains so 2 years later.

Adult↗

Differential recognition of obligate anaerobic bacteria by human mannose-binding lectin.

Deficiency of the innate, humoral immune component mannose-binding lectin (MBL) predisposes individuals to a variety of infections, but the importance of MBL in infection by anaerobes has not been addressed. The attachment of MBL to a wide range of anaerobic bacteria associated with human disease and colonization was surveyed. The results suggest that for the species we examined, resistance to MBL binding may be associated with organisms that are more commonly pathogenic and that MBL binding to some bacteria may be phase variable.

Bacteria, Anaerobic↗

Poor hospital infection control practice in venepuncture and use of tourniquets.

Previous studies have indicated that tourniquets may act as reservoirs of pathogenic organisms and could therefore pose a risk to patients through cross-infection. In this study, 200 tourniquets were sampled from health professionals working in a large teaching hospital. A parallel survey of control of infection was also undertaken. Staphylococcus aureus was isolated from 10 (5%) of the tourniquets sampled. Methicillin-resistant S. aureus was not isolated. Seventy-five (37.5%) of the tourniquets sampled had visible blood stains; house officers (72.7%) and laboratory phlebotomists (69.2%) had the highest proportion of blood-stained tourniquets. Tourniquets were owned on average for 1.86 years, with most respondents only obtaining a new tourniquet when the old tourniquet was lost. Three percent of respondents used a separate tourniquet for patients with known infective risk factors, e.g. HIV, MRSA. Twenty-seven percent of respondents did not wear gloves for venepuncture or did so only occasionally. Only 42% washed their hands both before and after venepuncture. Our survey reveals poor infection control practice, but a relatively low frequency of S. aureus contamination of tourniquets.

Blood-Borne Pathogens↗