Association of HLA-DQA1 and -DQB1 alleles with type I diabetes in Arabs: a meta-analyses.

This study aimed at assessing the nature and significance of associations between various alleles of HLA-DQA1, HLA-DQB1, and type I diabetes (T1D) in Arab populations. Evidence from literature (published before 20 April 2015) was amassed and analysed through multiple meta-analyses, which yielded effect summary odds ratios and 95% confidence intervals for 24 alleles and 4 haplotypes. A total of 1273 cases and 1747 controls from 16 studies were analysed. High levels of significance were obtained to support higher T1D risk when harbouring DQA1*03:01. The alleles DQB1*02:01 and *03:02 and the haplotypes DR3 and DR4 were significant risk factors, albeit with high publication heterogeneity. The protective effects of DQA1*01:01, DQB1*05:03, *06:02, *06:03, and *06:04 were robustly suggested by all indicators of meta-analyses. The haplotypes DR7 and DR11 were strongly suggested to be protective in Arabs. A relatively small number of studies have emerged from Arab countries, mostly with inadequate power on an individual basis. This study fills the gap by providing significant size effect of human leukocyte antigen (HLA) alleles and completes the continuum of global ethnic differences in this context.

A multidirectional fracture stiffness model to determine the principal stiffness properties of a healing human tibia.

A model for the stiffness of a fractured human tibia has been developed. The model is based on Mohr's circle of inertia and relies on tibial fracture stiffness being measured in a number of planes. Using in vitro data, it has been shown that this model can be used to identify the principal stiffness values and their associated planes. It has also been shown that only 4/5 independent measurements are required to generate good correlation between experimental data and fitted data. Initial in vivo experiments show that this model transfers from the laboratory to clinical practice. The model illustrated that the maximum plane for a complete tibia is about 12°-14° relative to anterior-posterior, which correlates with previous publications. It is postulated that the model can be used for further in vitro studies to confirm the most common angle of the minimum stiffness plane. The knowledge of this angle may help orthopaedic surgeons to better assess fracture stiffness and may be the starting point for further discussion about the current minimum value of 15 N m/°.

Clinico-epidemiological study of complicated and uncomplicated chronic suppurative otitis media.

INTRODUCTION: This study aimed to compare the clinical and epidemiological profiles of cases of complicated and uncomplicated chronic suppurative otitis media, based on their prognostic factors. MATERIALS AND METHODS: This was a prospective, cross-sectional study conducted in a tertiary care medical college hospital over a period of two and a half years. The study group comprised 187 ears, out of which 62 had complications while 125 did not. The two groups were compared with respect to nine prognostic variables: age distribution, sex, patient's domicile, literacy status, duration of ear discharge at presentation, ear pathology, predisposing disease focus in the nose or throat, ear swab microbiology, and hearing loss. RESULTS: Patients in the complicated chronic suppurative otitis media group had a higher male predominance and were younger. Rural and illiterate patients had a higher risk of developing complications. Cholesteatoma and granulation tissue were potential risk factors in the complicated chronic suppurative otitis media group. Ears with complications were more prone to develop sensorineural hearing loss. Age, sex, duration of ear discharge, predisposing disease focus in nose or throat, and ear swab microbiology were all less useful prognostic indicators of complications. CONCLUSION: Early detection and timely treatment of chronic suppurative otitis media in rural and illiterate patients may prevent life-threatening complications and reduce their incidence. Ears that harbour relatively large quantities of both cholesteatoma and granulation tissue together require more urgent surgical intervention and more extensive disease clearance in order to prevent complications.

Polymerase-chain-reaction-based detection of fetal rhesus D and Y-chromosome-specific DNA in the whole blood of pregnant women during different trimesters of pregnancy.

OBJECTIVE: The aim of this study was to determine whether or not a noninvasive procedure utilizing maternal peripheral blood as the source of DNA and polymerase chain reaction (PCR) could be used to detect fetal rhesus D (RhD) status as well as fetal gender during different gestational stages of pregnancy. MATERIALS AND METHODS: Maternal blood samples were obtained from 54 RhD-negative pregnant women during the first trimester (6-13 weeks, n = 14), second trimester (14-26 weeks, n = 26) and third trimester (27-40 weeks, n = 14). Genomic DNA was extracted from the whole blood and analyzed by seminested and nested PCR for detection of DNA sequences corresponding to RhD (n = 54) and Y chromosome (n = 48) using RhD and Y-chromosome-specific oligonucleotide primers, respectively. The seminested/nested PCR results were compared with the RhD status and gender of the babies after delivery. RESULTS: The sensitivity and specificity of seminested PCR for detection of fetal RhD positivity in whole blood of pregnant women were 81 and 100%, respectively, while the sensitivity and specificity of nested PCR for detection of male fetuses, using Y-chromosome-specific DNA as a marker, were 96 and 91%, respectively. There were no significant differences in the PCR results with samples obtained from women at different gestational stages of pregnancy. CONCLUSION: Seminested and nested PCRs for detection of fetal RhD and gender status, respectively, by using the blood of pregnant women during different gestational stages of pregnancy, are reliable noninvasive procedures with high sensitivity and specificity.

Detection of Y chromosome-specific DNA in the plasma and urine of pregnant women using nested polymerase chain reaction.

The present study was undertaken to evaluate a nested polymerase chain reaction (PCR) for detection of Y chromosome-specific fetal DNA in maternal plasma and urine of pregnant women during different gestational stages. DNA isolated from plasma and urine samples of 80 pregnant women (between 7 and 40 weeks' gestation) underwent amplification for Y chromosome-specific 198 bp DNA by nested PCR. The postpartum analysis of fetal gender showed that 55 women carried male and 25 female fetuses. Among the 55 women bearing male fetuses, Y chromosome-specific signals were detected in 53 (96%) plasma and 21 (38%) urine samples. Moreover, out of 25 women bearing female fetuses, 3 (12%) and 1 (4%) women had Y chromosome-specific signal in plasma and urine, respectively. Analysis of results with respect to gestational age revealed that there was no significant difference in the detection of Y chromosome-specific DNA between different trimesters in maternal plasma of women bearing male fetuses. These results showed that fetus-specific DNA was detected with high sensitivity (96%) and specificity (88%) in the maternal plasma by nested PCR, and therefore the method could be useful as a non-invasive procedure for fetal sex determination and prenatal diagnosis.

Does heparin coating improve biocompatibility? A study on complement, blood cells and postoperative morbidity during cardiac surgery.

To evaluate whether the effect of heparin coating the extracorporeal circuit resulted in differences in patient outcome and haemostatic alteration, 24 patients undergoing elective, isolated coronary artery bypass were randomized prospectively to cardiopulmonary bypass (CPB) with heparin-coated circuits (group H, n = 12) or uncoated circuits (group C, n = 12). The technique of CPB, heparinization and its reversal were the same in both groups. We studied complement status (C3d, C3, C3d/C3, C4 and C-function), white blood cell counts with differentiation and the postoperative morbidity. The results confirmed that CPB activates complement and increases neutrophils in both the H and C groups. A significantly lower level of leucocytosis was seen in group H compared to the C group (p < 0.05). The complement function via the classical pathway (C-function), expressed as a percentage of the function of a reference serum pool (the values of normal sera were 75-125%), was significantly reduced in both heparin-coated and uncoated circuits (p < 0.05). There was no significant intergroup difference regarding C3, C3d/C3, C4 and C-function during the study period. A lower frequency of postoperative morbidity was present in the H group. We conclude that heparin-coated surfaces elicit less leucocytosis and decrease postoperative morbidity in patients undergoing cardiac surgery but do not cause a significant difference regarding activation of the complement system as reported by many other investigators.

The effect of protamine on the epicardial microflow and the graft flow in open-heart surgery.

To evaluate the effect of coronary revascularization on myocardial perfusion and surgical outcome regarding graft flow, we used laser Doppler flowmetry to assess the epicardial microcirculation in patients undergoing coronary artery bypass grafting (CABG) or valve replacement (VR) and electromagnetic flowmetry to measure graft flow in the CABG group. In the CABG group, the preoperative mean laser Doppler flow rate (LDF) in the epicardium of the left ventricle significantly increased at the end of cardiopulmonary bypass (CPB) (22 +/- 7 arbitrary units (AU) to 60 +/- 13 AU, p < 0.001). This value further increased 10 min after protamine infusion (66 +/- 14 AU, p < 0.01), but was significantly reduced 30 min later (51 +/- 14 AU, p < 0.002). Compared to the post-CPB value (34 +/- 10 ml/min) before protamine infusion, the mean graft flow (ml/min) to this area significantly increased 10 min after protamine infusion (41.3 +/- 10 ml/min, p < 0.001) but significantly decreased 30 min later (29 +/- 9 ml/min, p < 0.001). The preoperative mean LDF in the VR group was significantly higher than in the CABG group (p < 0.01). In the CABG group, there was a positive correlation between the LDF and graft flow at the end of CPB (r = 0.788) and 10 (r = 0.767) and 30 (r = 0.784) min after protamine infusion. This study shows that coronary bypass grafting increases the myocardial microcirculation which, together with graft flow, could give an early indication of the effect of surgery on myocardial microcirculation. Furthermore, protamine was found to be one of the factors contributing to graft flow reduction postoperatively and, therefore, newer methods of heparin reversal may be desirable.

Atypical bronchial carcinoid tumour with amyloid deposition.

The rare association of carcinoid tumors and amyloid deposition has previously been reported. A case of amyloid deposition associated with bronchial carcinoid tumor is presented. The clinical and histopathological findings are discussed.

The effect of prolonged perfusion with a membrane oxygenator (PPMO) on white blood cells.

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% +/- 9, 72% +/- 2 and 76% +/- 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 +/- 1.5, 32.6 +/- 2.2 and 40.3 +/- 8.3 x 10(2)%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 +/- 1.5, 9.7 +/- 1.2 and 13.9 +/- 2.1 x 10(6)/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% +/- 0.3, 23% +/- 0.2 and 14% +/- 0.1 and 14% +/- 0.1 at 24, 48 and 72 hours respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of heparin-coated and uncoated extracorporeal circuits on blood rheology during cardiac surgery.

The effect of heparin-coated perfusion circuits on blood trauma during clinical cardiopulmonary bypass (CPB) was studied in order to find out if traumatic changes in the blood could be minimized. Twenty-four patients undergoing coronary artery bypass surgery were randomized prospectively to CPB with heparin-coated circuits (HCC) or non-coated circuits (NCC). The trauma to blood was assessed by measuring damage to blood cells by estimating red and white cell rheology changes. These were measured as red cell filtration rate (RFR) and white cell filtration rate (WFR) using standard microfiltration methods. Furthermore, changes in plasma hemoglobin (P-Hb), whole blood and plasma viscosity were simultaneously assessed. The RFR was significantly reduced in both groups during CPB by 10% in the HCC and 32% in the NCC groups (p less than 0.01). When comparing the HCC and NCC groups, a significant difference was first seen after 30 minutes of bypass (p less than 0.05) and increased at the end of CPB (p less than 0.01). Similar results were seen regarding WFR (15% and 36%, p less than 0.01). After 30 minutes of bypass, a significant difference was seen between HCC and NCC groups (p less than 0.05). Furthermore, a significant increase in P-Hb levels were seen during CPB in both patient groups. At the end of CPB, there was a significant difference in P-Hb levels (HCC 305+/-90 mg/L; NCC 455+/-78 mg/L, p less than 0.01) when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma protein polymorphisms in Malas and Madigas of coastal Andhra Pradesh, south India.

Four plasma protein polymorphisms: Group specific Component (GC), Haptoglobin (HP), Transferrin (TF) and Caeruloplasmin (CP), have been determined in two endogamous populations (Mala and Madiga) of Visakhapatnam of Coastal Andhra Pradesh, South India. The results were compared between the two caste populations and they revealed no significant differences. The results were also compared with those available from other Andhra populations.

Influence of alprostadil on pulmonary dysfunction after a cardiac operation.

To test the effects of alprostadil on pulmonary dysfunction after cardiac operations, we studied 24 male patients undergoing aortocoronary bypass. Twelve were given an intravenous infusion of alprostadil (synthetic prostaglandin E1), 20 ng.kg-1.min-1, in a double-blind manner during operation; the other 12 were controls. Duration of artificial respirator use and frequent blood gas analyses were used to assess postoperative pulmonary function. Use of the artificial respirator postoperatively was significantly lower in the prostaglandin group (mean time. 5.25 +/- 1.81 hours) compared with the controls (mean time, 8.34 +/- 4.35 hours) (p = 0.047). The proportion of patients with hypercapnia and with hypoxia determined every 4 hours for the first 24 hours after extubation was significantly lower in the prostaglandin group compared with the controls (p less than 0.0001). These results indicate that synthetic prostaglandin E1 may play a role in protecting lung tissue during extracorporeal circulation.

High-dose aprotinin (trasylol) in reducing bleeding and protecting lung function in potential bleeders undergoing cardiopulmonary bypass.

Intraoperative high-dose aprotinin during cardiopulmonary bypass was used to investigate if high-risk bleeders could be changed to bleed normally or less as well as see if aprotinin could preserve lung function. Eleven matched controls were compared with eleven aprotinin patients taking warfarin or aspirin preoperatively. The mean (+/- SEM) 12-h and 24-h postoperative amount of bleeding, volume of blood product transfusion and hemoglobin reduction in the aprotinin group were 328 +/- 45 ml, 418 +/- 63 ml, 341 +/- 99 ml and 1.8 +/- 0.5 g% respectively, which were significantly lower than the respective values of 716 +/- 86 ml (P less than 0.01), 1,029 +/- 115 ml (P less than 0.01), 985 +/- 294 ml (P less than 0.05) and 4.1 +/- 0.4 g% (P less than 0.02) in the controls. There was a 65% blood-saving effect by aprotinin in this study. The hypercapnea rate was 45% in the treated patients, and 82% (P less than 0.05) in the controls reflecting better preservation of pulmonary diffusion function which is clinically important following major surgery.

Gamma globulin prophylaxis to reduce post-transfusion non-A, non-B hepatitis after cardiac surgery with cardiopulmonary bypass.

A prospective, randomized study of immune serum globulin (ISG) for prevention of post-transfusion hepatitis was performed on 196 patients (100 controls without gammaglobulin or placebo and 96 who received ISG) undergoing valve replacement or coronary artery bypass with extracorporeal circulation. The dose of ISG was 2 ml i.m. at premedication and 2 ml i.m. on postoperative day 3. Probable non-A, non-B hepatitis developed postoperatively in ten of the 100 controls and two of the 96 in the ISG group. Two ISG patients and three controls with non-A, non-B hepatitis still have increased serum aminotransferase values after 3-5 years, but liver biopsy revealed hepatitis, which histologically was very mild, in only two control and two ISG patients. Low-dose gamma globulin thus reduced the incidence of acute, probable non-A, non-B hepatitis in cardiac surgery with cardiopulmonary bypass.

The influence of age on the durability of Carpentier-Edwards biological valves. Thirteen years follow-up.

Two hundred and ninety-nine patients received 325 Carpentier-Edwards biological valves from April 1976 to April 1982. Valves were placed in the following positions: 150 aortic (AVR), 120 mitral (MVR), 26 multiple (MR), 2 pulmonary (PR) and 1 tricuspid (TR). The mean age was 54.7 years. The total follow-up time was 2545 patient-years. Patients were divided into different age groups: less than 40, 40-49, 50-59, 60-69 and greater than 70 years and were followed-up for reoperations and tissue failure. Ninety-three operations were performed in 91 patients (30.5%) for valve related dysfunctions. The main cause of reoperation was primary tissue failure (85%). The respective incidence and risk of reoperation in the different age groups were 51.5% and 5%, 41.5% and 4%, 32% and 3%, 18% and 2.5%, and 0% for greater than 70 years of age. The risk of reoperation decreased significantly with increasing age (P less than 0.05). The respective incidence and risk of tissue failure in the age groups were 43.8% and 4.1%, 35% and 4%, 27.3% and 3.2%, and 17.2%, 2.4% and 0%. The freedom from reoperation and tissue failure was significantly higher in the older patient (greater than 60 years) compared to the younger patients (less than 60 years). The commonest cause of failure in young patients was calcification, while in older patients it was cusp rupture. Comparing aortic and mitral bioprostheses in the different age groups showed no difference between these valves in patients less than 50 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood cell filtrability: reference values and clinical applications.

In 500 healthy individuals cell deformability, expressed as cell filtration rate in microliters/s was studied with a microcirculation method in order to determine reference values for this method for various age groups in adults. The overall normal red cell filtration rate (RFR) value in healthy individuals was 69 +/- 11 microliters/s. When one compared the age groups 20-29 and 60-69 years, the reductions for RFR, white cell filtration rate (WFR), plasma-white cell filtration rate (P-WFR) and whole-blood filtration RATE (WBFR) was 26 +/- 3 (p less than 0.01), 32% +/- 5 (p less than 0.01), 28% +/- 4 (p less than 0.01) and 28% +/- (p less than 0.01) respectively. The reduction of RFR was graded into four clinical classes (GCTA = Gothenburg Cardio-Thoracic Association); I = 1-24%, II = 25-49%, III = 50-74%, IV = 75-100%, class I with lowest and class IV with highest reductions. Significant reductions in the mean RFR were noted in patients undergoing heart surgery (36% +/- 3, P less than 0.01, class II), patients with cardiac arrest (55% +/- 5, p less than 0.01, class III), occlusive arterial disease (58% +/- 6, p less than 0.001, class III) diabetes (45% +/- 5, p less than 0.01, class II). None of the patients had a normal RFR value. This study demonstrated a loss of cell deformability with age and disease.

Acute embolic lower limb ischaemia is associated with decreased red cell deformability.

Red cell deformability is an important determinant of peripheral blood flow. In this study the red cell filtration rate (RFR) was measured in 17 patients admitted for acute embolic lower limb ischaemia. The severity of the limb ischaemia on admission was scored from 0 to 6 depending on the degree of pain, and loss of motor and sensibility functions in the ischaemic extremity. Patients who presented with very severe ischaemia on admission underwent early embolectomy whereas those with less severe ischaemia (range from 0 to approximately 3 in ischaemic score) initially were treated conservatively with heparin. Red cell filtration rate was assessed with a standard microfiltration method and expressed in microliters/sec. On admission the RFR averages 30 +/- 5 microliters/sec (mean +/- S.D.), significantly lower than the corresponding value in a normal population of similar age (50 +/- 5 microliters/sec). There was an inverse relationship (r = 0.74, P less than 0.001 by use of linear regression analysis) between the ischaemic score and the RFR on admission, with low RFR values being related to high ischaemic scores. Forty-eight hours after revascularisation, the RFR had improved significantly in the patients having undergone successful revascularisation, whereas it was unchanged in conservatively treated patients. It is concluded that patients with acute embolic lower limb ischaemia have an impaired red cell filtration rate suggesting decreased red cell deformability, the impairment being related to the severity of the ischaemia. A poor red cell filtration rate on admission is related to increased risk of postoperative gangrene and/or cardiac death. Successful revascularisation, but not conservative heparin treatment is associated with increasing deformability.

A method for reconstruction of large full-thickness defects of the bony thorax.

Wide resection in 12 cases of malignant or potentially malignant lesions of the chest wall resulted in full-thickness loss of skeleton and frequently of overlying soft tissues (defect greater than or equal to 15 cm in its smallest diameter or at least 90% of the sternum resected). In reconstruction of the defect, steel bars were used to replace lost ribs and a double layer of Marlex mesh for intercostal spaces. Soft-tissue coverage and primary closure were accomplished with current plastic surgical procedures and good stability of the chest wall was achieved. Protracted respiratory support was required in only one case. Postoperative pain was managed with epidural anesthesia and routine analgesics. Functionally and cosmetically satisfactory long-term results were obtained, with no infection and no need for removal of prosthetic material. The overall 5-year and 10-year actuarial survival rates were 60% and 37.5%. If lesions are radically resectable, the extent of thoracic wall resection need not be restricted because of inability to close the defects.

Long-term follow-up of operative treatment for pulmonary metastases.

From 1954 onwards, 132 patients underwent 165 resections for pulmonary metastases. No other forms of therapy were adopted. The operative mortality was 7.6% (10 patients). After a minimum follow-up of 5 years, the overall survival rate was 20%. The 10- and 15-year survival rates were 6% and 3%, respectively. The major cause of late death was recurrence or spread of the primary disease in 102 patients (83.6%) while 5 patients died of reasons not related to cancer. Fifteen patients (12.3%) are still alive, 13 of whom have no clinical cancer. The presence of symptoms, the disease-free interval of less than 1 year and the number of metastases showed a statistically significant detrimental influence on survival (P less than 0.001, P less than 0.05 and P less than 0.046, respectively). The best 5-year survivals of 42%, 24%, 23% and 23% were noted for metastases from malignancies in the body of the uterus, kidney, bone and colon, respectively. Longterm survival or clinical cure can be achieved with surgery alone by an aggressive approach in selected malignancies.