Diabetes mellitus is strongly associated with tuberculosis in Indonesia.

SETTING: Diabetes mellitus is a known risk factor for tuberculosis (TB), but no studies have been reported from South-East Asia, which has a high burden of TB and a rapidly growing prevalence of diabetes. OBJECTIVE: To examine if and to what extent diabetes is associated with an increased risk of TB in an urban setting in Indonesia. DESIGN: Case-control study comparing the prevalence of diabetes mellitus (fasting blood glucose level >126 mg/dl) among newly diagnosed pulmonary TB patients and matched neighbourhood controls. RESULTS: Patients and control subjects had a similar age (median 30 years) and sex distribution (52% male), but malnutrition was more common among TB patients (median body mass index 17.7 vs. 21.5 kg/m2). HIV infection was uncommon (1.5% of patients). Diabetes mellitus was present in 60 of 454 TB patients (13.2%) and 18 of 556 (3.2%) control subjects (OR 4.7; 95%CI 2.7-8.1). Adjustment for possible confounding factors did not reduce the risk estimates. Following anti-tuberculosis treatment, hyperglycaemia reverted in a minority (3.7%) of TB patients. CONCLUSION: Diabetes mellitus is strongly associated with TB in young and non-obese subjects in an urban setting in Indonesia. This may have implications for TB control and patient care in this region.     

Technetium-99m labelled liposomes to image experimental arthritis

OBJECTIVES—Liposomes sterically stabilised with polyethylene glycol (PEG) labelled with technetium-99m were tested for their ability to image adjuvant arthritis in a rat model.
METHODS—Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with ^99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
RESULTS—The pharmacokinetics of the radiopharmaceuticals differed considerably (half life in the blood: PEG-liposomes (18 hours) > ^99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/g)>^99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
CONCLUSION—This study shows that ^99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.

     

Mesenteric vein thrombosis associated with primary cytomegalovirus infection: a case report.

In the past few years several studies have supported an interplay between cytomegalovirus infections and a prothrombotic state. We describe a case of primary cytomegalovirus infection in an immunocompetent adult that was complicated with mesenteric vein thrombosis. Transient protein C deficiency, lupus anticoagulant and activated protein C resistance were found, in combination with a heterozygous prothrombin G20210A mutation. We discuss the possible mechanisms of cytomegalovirus-related venous thrombosis.     

Keeping the arm in the limelight: advanced visual control of arm movements in neonates.

To test whether newborn babies have voluntary control over their limbs, spontaneous arm-waving movements were measured in the dark while the baby lay supine with its head turned to one side. A narrow beam of light was shone over the baby's nose or chest in such a way that the arm the baby was facing was only visible when the hand encountered the, otherwise, invisible beam of light. The results showed the babies were capable of precisely controlling the position, velocity, and deceleration of their arms so as to keep the hand visible in the light. The findings indicate that newborns can purposely control their arm movements to meet external demands and that the development of visual control of arm movement is underway soon after birth.     

Vascular proliferation as an unusual cause of hemorrhagic diathesis in myelofibrosis.

One year after splenectomy, a patient with myelofibrosis developed spontaneously large hematomas that were not due to coagulation abnormalities or functionally defective platelets. At autopsy, the liver, muscle, and skin showed extramedullary hematopoiesis associated with capillary proliferation and extravasation of blood. These findings indicate that neovascularization can be an additional cause of bleeding in myeloproliferative disorders and might be induced by neoplastic hematopoietic cells.     

Reoperation for prosthetic heart valve replacement

From 1974 to 1984, 847 heart valve replacement operations were performed with 1005 prosthetic valves. Thirty-nine (4.6%) were reoperations with 43 prosthetic valve replacements (PVR), on 38 patients. Thirty-three patients had received their initial valve replacement in our hospital and 5 elsewhere. Twenty additional cardiac procedures were required, concomitantly with the prosthesis replacement. Twenty-three patients underwent replacement of a mechanical prosthesis (61%) an average of 4.3 years after initial implantation and 15 patients a bioprosthesis (39%) after 2.8 years. Indications for PVR were endocarditis in 15 patients (39%), prosthesis failure in 13 (34%), periprosthetic leak in 7 (18%), thrombosis in 2 (5%), and a left ventricle subannular aneurysm in 1 (3%). Preoperatively 4 patients were in NYHA functional class II (11%), 15 in class III (39%) and 19 in class IV (50%). Six patients died early postoperatively (15.8%) Various risk factors were analyzed. The early mortality rate was 22% for mechanical prosthesis replacement and 7% for bioprosthesis; 11% for aortic position, 13% for mitral position and 50% to 100% for double valve replacement; 23% for non-elective and 6% for elective operations; 10% for patients with only an initial valve replacement and 43% with additional previous valve operations; 18% for active endocarditis, 15% for prosthesis failure, 14% for periprosthetic leak, 0% for thrombosis and 100% for subannular aneurysm; 0% for patients in class II, 7% in class III and 26% in class IV; 6% in patients with an aortic cross-clamp time less than 2 hours and 24% with more; 27% prior to 1981 and 9% during the last 4 years; and finally 50% in patients over the age of 60.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoglobulin G4 antibodies to rat urinary allergens, sensitization and symptomatic allergy in laboratory animal workers

BACKGROUND AND OBJECTIVES: We have previously reported that high rat urinary allergen (RUA) exposure was not associated with increased risk of rat allergy in long-term-exposed laboratory animal (LA) workers. We aimed to assess whether strong allergen-specific IgG4 responses could explain the absence of a dose response in these subjects. We investigated whether IgG4 was associated with allergen exposure and prevalence of sensitization or respiratory symptoms to rats. The longitudinal relation between IgG4 and rat allergy was studied using data obtained during 2 years of follow-up. METHODS: Five hundred and twenty-nine LA workers answered a questionnaire on respiratory symptoms and occupational history and participated in skin prick testing. Blood samples were analysed for specific IgG4 and IgE to RUA. Exposure to RUA was estimated based on personal air samples. The relation between IgG4 and newly occurring sensitization or rat allergy was studied in workers who were not sensitized or did not report respiratory symptoms to rats. RESULTS: IgG4 titres were higher in atopic than in non-atopic subjects, and increased with higher allergen exposure. Titres were highest in subjects who were sensitized and reported respiratory symptoms to rats when compared with those who were not (geometric mean [geometric standard deviation] = 202 [5.7] vs. 8.4 [18.3] AU). The association between IgG4 and sensitization or symptomatic rat allergy was independent of estimated allergen exposure. IgG4 was a strong predictor of newly occurring sensitization and symptomatic rat allergy during follow-up in atopic and rat-sensitized subjects. CONCLUSION: High exposure to RUA is associated with a strong allergen-specific IgG4 antibody response. High anti-RUA IgG4 is a strong predictor of prevalent and incident sensitization and symptomatic rat allergy in atopic and rat-sensitized subjects. IgG4 can therefore not explain the absence of a dose response between allergen exposure and allergy in long-term-exposed workers. We consider anti-RUA IgG4 to be a marker that combines aspects of exposure and susceptibility.     

Bisphosphonate-induced Osteonecrosis of the Jaws: Review, Clinical Implications and Case Report

The introduction of bisphosphonates has increased in the last decade following their indication for metastatic bone diseases, osteoporosis, hypercalcaemia of malignancy and Paget’s disease. Although bisphosphonates have been used clinically for more than three decades there have been no documented long-term complications of their effects on the jaws until recently, where there is now growing evidence of the influence of bisphosphonates on osteonecrosis of the jaws. The aim of this paper is to report a case of this newly described complication, to review this phenomenon, including the clinical implications and to reiterate current clinical guidelines for management of patients in which bisphosphonate therapy is indicated. To the best of our knowledge this is the first reported case of bisphosphonate-induced necrosis of the jaw in South Africa.     

Platelet additive solutions: A future perspective

Platelet additive solutions (PASs) were first developed in the 1980s, and continued to be improved over the following years. The use of PASs as replacement for plasma has a number of benefits, both for the quality of the platelet concentrates and for the patients. However, some PASs have been associated with a lower platelet yield in the PCs, a shorter storage time, and a lower increment in the patient when compared to PCs in plasma. A number of reformulations of the PASs have taken place to counteract these disadvantages. Most PASs use acetate as nutrient for the platelets, which has the benefit of generating bicarbonate when oxidized by the platelets, thus supplying its own buffering capacity. Alternatively, glucose is used, but may cause deterioration of pH in the stored PCs due to the formation of lactic acid. Addition of other buffering substances, such as phosphate, can be added to ensure maintenance of neutral pH. An important finding was the inhibiting effect of potassium and magnesium on platelet activation. The initially developed PASs lacked these two ingredients and showed reduced storage times of the PCs in PAS when compared to those stored in plasma. However, when these constituents are included in the PAS, storage time is similar and even exceeds those seen for PCs in plasma. Considerable research is done in further formulating the optimal PAS. Bicarbonate is being considered as buffer for these PASs. Also, L-carnitine appears to have a favorable effect on stored platelets, including a reduction of platelet metabolism, and inhibition of apoptosis. Another area of optimization is lowering of plasma content needed for maintaining platelet quality. Where current PASs still need at least 30% residual plasma, there is a trend towards lowering the plasma content to less than 5% with the newer PASs. Preservation of purinergic platelet receptor functionality by ADP-degrading activities in plasma appears to play an important role in this respect. Development of PASs are usually based on in vitro studies alone. It is important to realize that only clinical studies can give definitive answers about the quality of platelets stored in PASs. Sofar, only limited clinical evaluations have been published that either studied the effectiveness of platelets in initially-developed PASs, or were specifically done in combination with pathogen reduction technologies. Thus, PASs seem to be an excellent replacement for (part of) the plasma when producing PCs, and allow extended storage with maintenance of quality, but more clinical studies are needed to substantiate in vitro results.