Editor's Choice-- A Systematic Review of Endovenous Stenting in Chronic Venous Disease Secondary to Iliac Vein Obstruction.

OBJECTIVES: Deep endovenous stenting to relieve chronic venous disease (CVD) secondary to post-thrombotic or non-thrombotic iliac vein obstruction is becoming increasingly well described. However, current and adequately reported systematic reviews on the topic are lacking. This report aimed to produce a systematic review and meta-analysis of the available data, reported to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register for Controlled Trials databases and key references were searched. RESULTS: Sixteen studies were included (14 before-and-after studies, 1 controlled before-and-after study, and 1 case series) encompassing successful deep venous stenting in 2,373 and 2,586 post-thrombotic or non-thrombotic limbs and patients respectively. The data were too heterogeneous to perform a meta-analysis. There were significant improvements in validated measures of the severity of CVD and venous disease-specific quality of life. Persistent ulcer healing rates ranged from 56% to 100% in limbs that had often already failed conservative management. Primary and secondary stent patency ranged from 32% to 98.7% and 66%-96% respectively. The major complication rate ranged from 0 to 8.7% per stented limb. A GRADE assessment demonstrated the quality of the evidence for five outcomes to be "Very Low" and one to be "Low" (ulcer healing). CONCLUSIONS: The quality of evidence to support the use of deep venous stenting to treat obstructive CVD is currently weak. The treatment does however appear promising and is safe and should therefore be considered as a treatment option while the evidence base is improved.

CXCR3 ligands are augmented during the pathogenesis of pulmonary sarcoidosis.

We and other investigators have hypothesised that the CXC chemokine receptor (CXCR)3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung granulomas; however, significant discrepancies in the current literature remain. In an effort to clarify previous conflicting findings, we performed the largest observational study to date of interferon-inducible ELR(-) (lacking the sequence glutamic acid-leucine-arginine) CXC chemokines in sarcoid bronchoalveolar fluid (BALF). BALF chemokine levels from sarcoid patients (n = 72) and healthy controls (n = 8) were measured with the ELISA method. Immunohistochemical staining was performed for CXCR3 and its ligands. BALF CXC chemokine ligand (CXCL)10 levels from sarcoid patients were not significantly increased compared with controls. BALF CXCL11 levels from sarcoid patients demonstrated a trend towards elevation; subgroup analysis by stage showed significant BALF CXCL11 elevation in stage I sarcoid patients compared with controls. BALF CXCL9 levels were elevated from sarcoid patients compared with controls. CXC11, CXCL9 and CXCR3 were expressed from epithelioid histiocytes, multinucleated giant cells and other inflammatory cells forming sarcoid lung granulomas. Our data suggest that CXCL9 and CXCL11 are important mediators in recruiting CXCR3-expressing cells. Importantly, we have made the novel observation that both lymphocytes and cells of monocyte linage express CXCR3 and are involved in the formation of sarcoid lung granulomas.

Acute abdomen as a cause of death in sudden, unexpected deaths in the elderly.

AIMS: This study profiles patients aged 70 years or above dying suddenly of an 'acute abdomen' and investigates the specific features associated with the conditions and their diagnoses. METHODS: A retrospective study using data obtained from autopsy and police reports held in the Forensic Medicine Section of the University of Edinburgh. RESULTS: From 1997 to 2000, out of 2121 autopsies of patients aged 70 or above, an 'acute abdomen' was considered as a primary cause of death in 111 cases. The number of cases increased over the period of study. Peptic ulcer disease was the commonest underlying cause of death. Twenty-nine (26.1%) cases were due to its complications, namely gastrointestinal haemorrhage and perforation. Sixty-nine (62.2%) patients were seen by a medical practitioner in circumstances arising from the onset of acute abdomen. In 27 (39.1%) cases a provisional diagnosis was recorded. CONCLUSION: The 'acute abdomen' is still an appreciably frequent cause of death in sudden, unexpected deaths in the older age group. Some of the deaths may have been preventable with an early diagnosis. A high level of vigilance and early attention to an 'acute abdomen' by medical practitioners is therefore advocated.

Genetic variation in hepatic glucose-6-phosphatase system genes in cases of sudden infant death syndrome.

Genetic deficiencies of the hepatic glucose-6-phosphatase system, either of the enzyme (G6PC1) or of the glucose-6-phosphate transporter (G6PT1), result in fasting hypoglycaemia. Low hepatic G6PC1 activities were previously reported in a few term sudden infant death syndrome (SIDS) infants and assumed to be due to G6PC1 genetic deficiencies. In preterm infants, failures of postnatal activation of G6PC1 expression suggest disordered development as a novel cause of decreased G6PC1 activity in SIDS. G6PC1 and G6PT1 functional and mutational analysis was investigated in SIDS and non-SIDS infants. G6PC1 hepatic activity was abnormally low in 98 SIDS (preterm, n=13; term, n=85), and non-SIDS preterm infants (n=35) compared to term non-SIDS infants (n=29) and adults (n=9). Mean glycogen levels were elevated, except in term non-SIDS infants. A novel G6PT1 promoter polymorphism, 259C --> T was found; the - 259*T allele frequency was greater in term SIDS infants (n=140) than in term control infants (n=119) and preterm SIDS infants (n=30). Heterozygous and homozygous prevalence of 259C --> T was 38.6% and 7.1%, respectively, in term SIDS infants. In cell-based expression systems, the presence of - 259T in the promoter decreased basal luciferase activity by 3.2-fold compared to - 259C. Glucose-6-phosphatase latency in hepatic microsomes was elevated (indicating decreased G6PT1 function) in heterozygous and homozygous - 259T states. Delayed postnatal appearance of hepatic glucose-6-phosphatase in infants makes them vulnerable to hypoglycaemic episodes and this may occur in some SIDS infants. However, SIDS may be an association of more complex phenotypes in which several genes interact with multiple environmental factors. A UK-wide DNA Biobank of samples from all infant deaths, with an accompanying epidemiological database, should be established by pathologists to allow cumulative data to be collected from multiple genetic investigations on the same large cohort of samples, with the aim of selection of the best combination of genetic markers to predict unexpected infant death.

Suicide by severing the arterio-venous subclavian dialysis catheter.

Haemodialysis access is an essential requirement for haemodialysis treatment in end-stage renal disease. The common forms are arteriovenous fistula (AVF) and arteriovenous grafts in ante-cubital fossa, forearm and upper thigh. Sometimes temporary or immediate access is created via a subclavian catheter or internal jugular catheter. This report is on a 79-year-old man who was suffering from chronic renal failure with a non-functional peripheral AVF; he was being dialysed through a permanent subclavian catheter and he became depressed due to continuing deterioration of his health. He used the easily accessible haemodialysis site as the method of suicide by cutting the tube that connected with the main vessel in his chest and bled to death. This highlights the requirement to assess carefully the patient's mental state in those on chronic haemodialysis, even though very few similar fatal cases have been previously reported.

Medical suicide -- groin stabbing.

This case report concerns a 50-year-old male who died from exsanguination due to self-inflicted stabbing injuries to the groin and cutting injuries to the neck. He was a medical doctor suffering from depression following treatment for cancer. Postmortem examination revealed that stab injuries in the groin were directly over the femoral arteries where the femoral pulse is clinically palpated. The injury pattern of this suicidal stabbing is uncommon and the medical knowledge of this person may have well contributed to the choice of the site.

Hyperphosphorylated tau and amyloid precursor protein deposition is increased in the brains of young drug abusers.

Drug abuse is a major problem worldwide. The incidence of drug-related deaths attributed to opiate abuse is increasing annually. Apart from routine examination, little is known of the neuropathology of drug abuse. We, and others, have shown previously that drug abuse is associated with microglial activation. We hypothesised that neuroinflammation might lead to premature neurodegeneration in drug abusers. We investigated the brains of young opiate abusers (n=34, all<40 years) for the presence of proteins associated with neurodegenerative diseases and compared them with the brains of age-matched, non-drug users (n=16) all of whom died suddenly. Detailed immunohistochemical analysis of the hippocampus, brainstem and basal ganglia for hyperphosphorylated tau, beta-amyloid, beta-amyloid precursor protein (betaAPP) and ubiquitin demonstrated an excess of AT 8-positive neurofibrillary tangles (NFT) in the drug abusers. These were not only more prevalent in the drug abusers than in controls (44%vs. 19%) but also involved more brain areas. In controls NFT were confined to the entorhinal cortex whereas in drug users they were also found in the subiculum, temporal neocortex, nucleus basalis of Meynert and the locus coeruleus. Virtually no amyloid plaques were present but betaAPP positivity was again much more common in drug abusers than controls (73%vs. 20% in the brainstem and 59%vs. 23% in the temporal lobe). There is no suggestion that these drug abusers had displayed major cognitive impairment although detailed neuropsychological assessment is difficult in this subject group. Likely causes of hyperphosphorylated tau deposition in drug abuse include hypoxic-ischaemic injury, microglial-associated cytokine release and possibly drug-associated neurotoxicity or hepatitis. Head injury, which is another major risk factor, does not appear to have contributed to our findings. Genetic factors also merit consideration. It is unclear at present how much of the hyperphosphorylated tau detected in these young drug abusers represents a transitory phenomenon.

The role of bacterial toxins in sudden infant death syndrome (SIDS).

There is increasing evidence for the involvement of bacterial toxins in some cases of sudden infant death syndrome (SIDS), particularly the pyrogenic toxins of Staphylococcus aureus. This had led to the hypothesis that some SIDS deaths are due to induction of inflammatory mediators by infectious agents or their products during a period in which the infant is unable to control these normally protective responses. The genetic, developmental and environmental risk factors identified for SIDS are assessed in relation to frequency or density of mucosal colonisation by toxigenic bacteria and their effects on induction and control of inflammatory responses to the toxins.

Why is smoking a risk factor for sudden infant death syndrome?

Smoking is a major risk factor for both Sudden Infant Death Syndrome (SIDS) and respiratory tract infections. Such infections, both viral and bacterial, also increase the SIDS risk. This study investigated the effect of cigarette smoke at two stages of infection: 1) mucosal surface colonization; 2) induction and control of inflammatory responses. For colonization, RSV or influenza A infected cells bound several bacterial species in significantly higher numbers due to increased expression of host cell antigens. Buccal epithelial cells from smokers bound significantly more bacteria. For Staphylococcus aureus, this was associated with increased tar levels. Some SIDS deaths have been proposed to result from high levels of pro-inflammatory mediators elicited by infection and/or cigarette smoke during a developmental period when infants are less able to control inflammatory responses. Inflammatory reponses were compared between blood samples from smokers (n = 42) and non-smokers (n = 60) stimulated with TSST-1 or LPS. Non-smokers had significantly higher IL-6 (P = 0.011), IFN (P = 0.003) and IL-10 (P = 0.000) baseline levels. Non-smokers had higher IFN (P = 0.008) and IL-1 (P = 0.001, 0.007) responses to LPS and higher IL-10 responses to TSST-1 (P < 0.05) and LPS (P < 0.000). This study highlights that smoking increases the SIDS risk by greater susceptibility to viral and bacterial infections and enhanced bacterial binding after passive coating of mucosal surfaces with smoke components. In animal models, IL-10 reduced the lethal effect of staphylococcal toxins. In this study, smokers had lower IL-10 responses toTSST-1 and LPS. Dose response effects of cigarette smoke exposure needs to be established in relation to inflammatory response control and infantile infections.

Evidence for a genetic component in sudden infant death syndrome.

There is increasing evidence that inflammatory responses have been elicited in some Sudden Infant Death Syndrome (SIDS) infants and that these responses are under genetic control. The objective of this study was to investigate the hypothesis that the cytokine responses of SIDS parents (n = 41) differed significantly from control donors (n = 61). Blood samples were stimulated with the staphylococcal toxin TSST-1 and LPS from Eschericia coli and assessed for production of TNF, IL-1, IL-6, IFN and IL-10. In response toTSST-1 (P < 0.02) and LPS (P < 0.002), SIDS parents produced higher levels of IL-1 than the controls. SIDS parents produced higher levels of IFN in response to TSST-1 compared to LPS (P < 0.001) although in response to LPS, the IFN (P = 0.0008) and IL-6 (P < 0.0002) responses of the SIDS parents were lower than those of the controls. For TNF and IL-10, there was little difference between the two groups unless the effect of smoking was considered. As part of this work, a small pilot genotyping study was carried out using DNA from SIDS parents (n = 10), control donors (n = 10) and Bangladeshi subjects (n = 10). An IFN polymorphism (3/3) was found in 40%,15.4% and 0% of donors respectively. Staphylococcal toxins have been identified in SIDS infants therefore this study highlights the importance of assessing IL-1 levels. Determination of cytokine polymorphisms and consideration of interactions between these and environmental factors such as smoking in high, average and low risk ethnic groups will assist in establishing the contribution of these factors to an infant's susceptibility to SIDS.

Sequence of melanocyte migration into human scar tissue.

Scars of human skin can on occasions provide a very useful ancillary method of identification of an unknown deceased. If the age of any visible scars can be estimated objectively, then this might be of some assistance in the identification procedure. Melanocytes migrate into scar tissue as it ages and their number within the epidermal basal layers alters during the maturation of a scar. A total of 64 scar samples, all from previous surgical sites, were taken in the course of autopsies. Each scar was stained by the H & E method and by an immunohistochemical method using polyclonal S100 antibody. The number of melanocytes in the basal layer was counted in the epidermis overlying the scar and in the adjacent epidermis. This ratio was matched with the documented age of the scar and a statistical evaluation was carried out matching the chronological age of the scars to the melanocyte/basal epidermal cells ratio. Scars with a duration between 1 and 3 years showed a mean ratio of 1.85 and a maximum ratio of 1.94, 1.8 years after a surgical operation. The number of basal melanocytes declined thereafter and reached that of the adjacent epidermis after about 10 years. The immunohistochemical detection of melanocytes can be used for the diagnostic ageing of scars which may be a valuable contribution to improve the identification of unknown deceased persons.

Pedestrian deaths following collisions with heavy goods vehicles.

Pedestrian fatalities following collisions with heavy goods vehicles ('lorries') in south-east Scotland were studied between 1992 and 1998. Data sources included police and ambulance reports, forensic medicine records, hospital casenotes and the Scottish Trauma Audit Group database. All injuries were scored according to the Abbreviated Injury Scale, yielding Injury Severity Scores (ISS). Sixteen pedestrians (mean age 60.2 years) died after being hit by a lorry. Actions of pedestrians were implicated in causing all the collisions--four of which appeared to be suicides. Four of the apparently accidental deaths involved pedestrians with significant blood alcohol levels. Thirteen pedestrians were dead when found. Ten pedestrians had an ISS of 75, having a total of 13 injuries acknowledged to be unsurvivable (Abbreviated Injury Scale = 6), largely to the head and chest. The unsurvivable injuries reflect huge forces, explaining why only a small proportion of the pedestrians survived to hospital. There is little potential to reduce the number of deaths by improving hospital treatment, rather the focus needs to be directed towards injury prevention. Although pedestrians appeared to be responsible for the collisions, the results suggest it may be more feasible and effective to direct injury prevention measures towards lorry drivers.

Quantitative assessment of IgG antibodies to Helicobacter pylori and outcome of ischaemic heart disease.

Criticisms of serological studies on Helicobacter pylori and ischaemic heart disease (IHD) include: undiagnosed heart disease in live controls; no assessment of severity or outcome of IHD; and qualitative not quantitative measurements of IgG to the bacteria. The aim was to assess quantitatively IgG levels specific for H. pylori (ng ml(-1)) among patients who survived a myocardial infarction (MI) with those who died of IHD. Sera were from four groups: (1) men who survived one MI; (2) men matched for age and socioeconomic background to group 1; (3) individuals who died suddenly of IHD; (4) accidental deaths matched for age and sex to group 3. Levels of IgG to H. pylori increased with age (P<0.005) but were not associated with smoking or socioeconomic groups. There was a correlation between IgG to the bacteria and decreasing socioeconomic levels only among group 1 (P<0.01). IgG levels were higher for subjects who died of heart disease (median=151 ng ml(-1)) compared with survivors (median=88 ng ml(-1)) (P=0.034) and higher for survivors compared with their controls (median=58 ng ml(-1)) (P=0.039). Future serological studies of H. pylori in relation to IHD should be quantitative and severity of disease considered in analyses.

A five year study of high falls in Edinburgh.

High falls are a common cause of death and disability. The aim of this study was to obtain an epidemiologically complete picture of all high falls over a 5 year period in Edinburgh, Scotland. Prospectively collected data on hospital survivors and hospital deaths was collected from the Scottish Trauma Audit Group (STAG) database. Data on prehospital deaths was obtained from autopsy reports and detailed police enquiry reports. There were 341 patients in the study, of whom 82% were male. Seventy-four percent survived to hospital discharge. Sixty-three percent of the total deaths appeared to be suicides. Head and chest injuries were responsible for the majority of deaths. Pelvis, limb and vertebral injuries predominated in survivors. In conclusion, prevention may be the most effective method of reducing prehospital deaths. Abdominal injuries were associated with a poor outcome, but survival might improve with immediate surgical exploration in haemodynamically unstable patients.

Necrotizing fasciitis: reports of three fatal cases simulating and resulting from assaults.

Necrotizing fasciitis is a progressive, potentially fatal, rapid, necrotizing infection of the subcutaneous tissues and fascia often caused by a mixture of organisms or by infection with group A Streptococcus pyogenes with or without Staphylococcus aureus. Three cases are presented that have been encountered in forensic pathologic practice. Two cases presented after assaults, and the third simulated an assault and burglary. The history, scene, and pathologic findings are presented with a brief review of the literature.

Plastic bag asphyxia in southeast Scotland.

Death resulting from plastic bag asphyxia has been recognized for >40 years, but relatively little is known about either its epidemiology or its pathophysiology. Over 15 years (1984-1998), 30 deaths were attributed to plastic bag asphyxia among the 14,560 autopsies performed in the Forensic Medicine Unit in Edinburgh. These 30 deaths involved 20 male and 10 female subjects, with an age range of 13 to 81 years. Eleven had some alcohol measurable in the blood, with four having levels >80 mg/dl. Only one individual appeared to have ingested a drug overdose, but inhaled substances within the plastic bag may have contributed to death in five cases. The absence of childhood accidental deaths may reflect successful preventive measures. The 3 accidental deaths involved adults (including 2 who died of autoerotic asphyxia), and the remaining deaths were 27 suicides. Of those who committed suicide, most (59%) had chronic psychiatric illness rather than chronic debilitating or terminal physical illness. In contrast with reports from the United States, publicity associated with "self-deliverance" did not result in an increased number of deaths from plastic bag asphyxia (4 deaths in this series). Analysis of the circumstances of all the deaths revealed them to be difficult to predict and hence prevent.