Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Addition of a foreign oligopeptide to the major capsid protein of poliovirus.

Insertion mutants of type 3 poliovirus (Sabin strain) were constructed that encode additional amino acid sequences at the level of residue 100 of the capsid polypeptide VP1 within the neutralization site 1, corresponding to a loop on the capsid surface. The addition of a tri- or hexapeptide did not hamper virus viability. The antigenic pattern of insertion mutants was only modified locally: all mutants lost reactivity of neutralization site 1 with the corresponding monoclonal antibodies, while the reactivity of sites 2 and 3 was unaffected by the insertion. We have shown for one of the mutants--vFG68--that the antigenic specificity of the neutralization site 1 was replaced by a new one. Although vFG68 differs from its parental Sabin strain only by the addition of three amino acids within VP1, neutralizing antibodies specific for vFG68 were induced by the native virion as well as by the heat-denatured mutated virions. Our results demonstrate that an oligopeptide of three or six amino acids can lengthen VP1 at the level of antigenic site 1 without affecting virus multiplication and that this foreign peptide is exposed on the virion surface.     

Review: Head and neck squamous cell carcinoma in sub-Saharan Africa

Aim

Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa.

Methods

Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed.

Results

Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare.

Conclusions

The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol.     

Abrupt propranolol withdrawal in angina pectoris: effects on platelet aggregation and exercise tolerance.

Data collected before the initial reports of myocardial infarction following sudden withdrawal of propranolol are presented here to evaluate possible mechanisms for this phenomenon. Twenty patients with angina pectoris were randomized into placebo and propranolol (160 mg./day) treated groups and followed for 50 weeks at which time treatment was abruptly discontinued. Measurements of exercise tolerance, the product of heart rate and blood pressure at exercise end-point (HR × BP), and platelet aggregation thresholds in response to ADP and epinephrine were made before, during, and after treatment. Prior to propranolol, mean total work performance was 765 ± 125 k.p.m., HR × BP (heart rate-blood pressure product) was 16,800 ± 1,535. Mean platelet aggregation threshold with ADP was 1.32 μM¹; with epinephrine 1.26 μM¹. Patients treated with propranolol demonstrated significant improvement in exercise performance (1,790 ± 285 k.p.m., p < .01), reduction in HR × BP (12,000 ± 895, p < .01), and an elevation in platelet aggregation threshold; with ADP 3.43 μM¹ (p < .01); with epinephrine 12.9 μM¹ (p < .01). Following abrupt cessation of propranolol, exercise tolerance and HR × BP fell below pretreatment levels (630 ± 117 k.p.m. and 15,500 ± 513, respectively). Similarly platelet aggregation threshold fell to 1.0 μM¹ with ADP and 0.57 μM¹ with epinephrine. In six patients platelets were significantly more hyperaggregable than prior to therapy. Anginal frequency increased in all, but no acute infarction was observed. Abrupt withdrawal of propranolol may be deleterious in patients, sometimes causing “rebound” platelet hyperaggregability associated with increasing anginal frequency and decreasing exercise tolerance.     

Cryoglobulinemia due to chronic viral hepatitis infections is not a major problem in clinical practice

Background: Essential mixed cryoglobulinemia (EMC) is a systemic disease frequently associated with chronic viral hepatitis. This study was conducted in order to assess the prevalence of EMC in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. We also evaluated the possible associations of EMC with (1) the clinical, virological, and histological status of liver disease; (2) the presence of EMC-related symptoms; and (3) the response rate to interferon-alpha (IFN-alpha) treatment, in an attempt to address whether EMC is a major problem in hepatitis patients. Methodology: A total of 154 consecutive patients (104 with HBV and 50 with HCV infection) were investigated for the presence of rheumatoid factor (RF), cryoglobulins, and EMC-related manifestations. Sixty-two HBV patients were chronic carriers of hepatitis B surface antigen, 29 had chronic hepatitis B, and 13 HBV cirrhosis. Thirty-five HCV patients had chronic hepatitis C and 15 HCV cirrhosis. HCV genotyping was performed in 44 patients. Results: The prevalence of cryoglobulins was significantly higher (P<0.001) in HCV patients (46%) than in HBV patients (13.4%). EMC was associated with a high frequency of RF detection, older age, and longer duration of viral diseases. Weakness or malaise, arthralgias, and purpura were significantly more frequent in cryoglobulin-positive patients. These manifestations, however, were mild in most of the patients. The EMC-related symptoms were significantly associated with the presence of HCV infection, increased levels of cryoglobulins, and RF detection (P<0.01, P<0.05, and P<0.000005, respectively). Worse liver histology was unrelated to a higher prevalence or increased levels of cryoglobulins in both HBV and HCV infection. There was no relationship between EMC and a specific HCV genotype. IFN-alpha therapy led to the disappearance of cryoglobulins and EMC-related manifestations in most cases. The response rate to IFN-alpha was similar in both groups of patients (with and without EMC). Conclusions: A higher prevalence of EMC was observed in HCV patients than in HBV patients. However, this finding was unrelated to overt clinical manifestations of EMC, a specific HCV genotype, or worse liver histology. The latter suggests that EMC does not contribute to liver injury and vice versa, that EMC pathogenesis is rather unrelated to the degree of liver injury. From a clinical point of view, testing for cryoglobulins seems reasonable only for HCV patients with EMC-related manifestations, since this may have therapeutic consequences. RF detection could be used primarily as a surrogate marker for the existence of cryoglobulins.     

Intimate Partner Violence and Food Insecurity Predict Early Behavior Problems Among South African Children over 5-years Post-Birth

Households experiencing intimate partner violence (IPV) and food insecurity are at high risk of lifelong physical and behavioral difficulties. Longitudinal data from a perinatal home-visiting cluster-randomized controlled intervention trial in South Africa townships were used to examine the relationships between household settings and mothers’ histories of risk and children’s behavior problems at 3 and 5 years of age. IPV, food insecurity, maternal depressed mood, and geriatric pregnancy (at age of 35 or older) were consistently associated with children’s internalizing and externalizing behavior problems. Aggressive behavior was more prevalent among 3- and 5-year olds boys, and was associated with maternal alcohol use. The effects of these factors on child behavior were more prominent than maternal HIV status. There is a continuing need to reduce IPV and household food insecurity, as well as supporting older, depressed, alcohol using mothers in order to address children’s behavioral needs.

     

Quality of life in Greek family members living with leg ulcer patients

Leg ulcers have been shown to have a significant impact on a patient's quality of life (QoL). Little is known, however, about the secondary impact of the disease on the QoL of the relatives and partners of patients with leg ulcers. The aim of this study was to explore the impact of chronic leg ulcers on the lives of both patients and their family members. Two hundred sixteen patients with leg ulcers and their family members were recruited. All patients entered were evaluated for QoL using the Dermatology Life Quality Index (DLQI) scale, and family members were similarly evaluated using the Family Dermatology Life Quality Index (FDLQI).The study included 56 female and 52 male patients, and 50 female and 58 male family members. The FDLQI score for the latter group was 14.37 ± 2.46 with over 96% of family members reporting a large effect on their QoL due to their relative's disease. The DLQI score in patients with leg ulcers was 13.18 ± 2.88. A significant positive and high correlation between DLQI and FDLQI scores (r = 0.71, p < 0.001) was documented, while DLQI contributed significantly to the prediction of FDLQI (standardized β = 0.71, p < 0.001). Our study results indicate that the QoL of the family was also affected by the patient's condition of chronic leg ulcers and clearly associated with that of the patients.     

Clinics in diagnostic imaging (162). Meckel’s diverticulum

A 28-year-old Chinese man presented with acute bleeding per rectum. Computed tomography showed a posterior outpouching arising from the distal ileum. The outpouching had hyperaemic walls, but no active contrast extravasation was detected. Technetium-99m pertechnetate scintigraphy showed focal areas of abnormal uptake in the right side of the pelvis, superior and posterior to the urinary bladder. These areas of uptake appeared simultaneously with the gastric uptake and demonstrated gradual increase in intensity on subsequent images. The diagnosis of Meckel’s diverticulum was confirmed on surgery and the lesion was resected. The clinical and imaging features of Meckel’s diverticulum are discussed.