Burden of cancers attributable to modifiable risk factors in Malaysia.

BACKGROUND: This is a systematic assessment of the burden of cancers in Malaysia in 2018 using epidemiologic approach. The purpose of this study was to identify the proportion of cancers in Malaysia that were attributable to the modifiable risk factors of excess weight, alcohol intake, physical inactivity, tobacco smoking and to estimate the number of cancer cases that could be prevented if the exposure to the modifiable risk factor was reduced. METHODS: We estimated the Population Attributable Fraction (PAF) of the modifiable risk factors to cancers incidences in Malaysia. The two parameters used for the estimation were exposure prevalence from national representative surveys and the relative risk of getting the cancers from worldwide literature review. RESULTS: Among 38,426 cancer incidences in 2018 from Globocan data, we estimated that 22.2% (95% confidence interval (CI):14.9 to 29.6%) of the cancer incidences included in this study were attributable to the investigated modifiable risk factors. 39.1% (95% CI:27.2 to 49.7%) and 10.5% (95% CI:5.8 to 15.7%) of cancers in male and female respectively, were attributable to the studied modifiable risk factors. The top main cancers attributed by the risk factors were lung cancer (65.1%; 95% CI:56.4 to 72.9%), laryngeal cancer (63.6%; 95% CI:39.9 to 80.5%), and oesophageal cancer (51.5%; 95% CI:39.9 to 62.0%). For each risk factor studied across genders, tobacco smoking contributed the most (14.3%; 95% CI:9.9 to 17.3%), followed by excess weight (7.0%; 95% CI:4.1 to 10.2%), physical inactivity (1.0%; 95% CI:0.4 to 1.7%) and alcohol intake (0.6%; 95% CI:0.2 to 1.0%). CONCLUSION: Findings from this study suggests that tobacco smoking and excess weight are the two predominant factors out of the four studied risk factors for cancer cases in Malaysia. Nationwide public health prevention campaigns tailored to these risk factors are recommended. However, the other risk factors such as physical inactivity and alcohol intake shall not be neglected. PAFs are estimated based on the best available data that we have currently. Regular collection of other risk factor exposure prevalence data is vital for future analyses.

Thymus-independent positive and negative selection of T cells expressing a major histocompatibility complex class I restricted transgenic T cell receptor alpha/beta in the intestinal epithelium.

We demonstrate that in the mouse intestinal epithelium the selection of T lymphocytes expressing a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for male antigen (H-Y) in the context of H-2Db depends on the differential expression of H-Y and H-2Db in situ. In H-2Db transgenic males, there is no reduction in the number of intestinal intraepithelial lymphocytes (IEL), and the four main subsets of IEL expressing TCR-alpha/beta, defined by the differential expression of CD4, CD8 alpha, and CD8 beta, are present. Moreover, the level of expression of CD8 alpha and CD8 beta on CD8+ IEL subsets is unaltered. The frequency of CD8 alpha+ IEL expressing CD8 beta, in H-2Db male mice, however, is significantly decreased and these cells do not express the transgenic TCR. In contrast, virtually all CD8 alpha+beta- IEL in the same animals express the transgenic TCR. Still, these potentially autoreactive cells are refractile to H-Y/H-2Db stimulation in vitro. Both H-2Db and H-2Dd transgenic females contain high frequencies of cells expressing the transgenic TCR among CD8 alpha+beta- and CD8 alpha+beta+ IEL. However, two possibly related phenotypic features are peculiar to H-2Db female mice. The frequency of CD8 alpha+ IEL expressing CD8 beta is increased in these mice and, while in H-2Dd females the level of the transgenic TCR alpha chain expressed on CD8 alpha+beta+ IEL is uniformly low, some of the CD8 alpha+beta+ IEL in H-2Db females express a high level of both transgenic TCR chains. It is important to note, the ability of CD8 alpha+beta+ IEL to respond to H-Y/H-2Db stimulation in vitro is restricted to those coexpressing a high level of both transgenic TCR chains. The analysis of athymic radiation chimeras using adult thymectomized recipients of distinct H-Y/H-2 haplotypes, reconstituted with bone marrow from H-2Db transgenic females, demonstrates that all IEL subsets present in unmanipulated transgenic animals develop in the absence of a thymus. These IEL are phenotypically identical to those found in unmanipulated transgenic animals sharing the H-Y/H-2 haplotype of athymic recipients. Taken together, these results demonstrate that in the absence of male antigen, expression of H-2Db in the intestinal epithelium results in the positive selection of functional IEL specific for male antigen, in situ. When both H-Y and H-2Db are expressed in the intestinal epithelium, CD8 alpha+beta+ IEL expressing the transgenic TCR are negatively selected, while the frequency of nonfunctional CD8 alpha+beta- IEL expressing the transgenic CR is increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules.

Transgenic mice that carry on a large fraction of their T cells an alpha/beta T cell receptor that recognizes the male antigen in the context of H-2Db molecules were constructed. An mAb specific for the transgenic receptor was developed and used to analyze T cell subsets in male transgenic H-2b mice. The vast majority of immature CD4+8+ T cells that express the transgenic TCR were deleted in the male transgenic mouse. Nevertheless, the majority of T cells spared by this deletion process expressed a high level of the transgenic TCR. These T cells, however, had an abnormal CD4/CD8 phenotype in that they expressed either no CD8 molecules or only low levels.

Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells.

The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes.

The T cell receptor repertoire of CD4-8+ thymocytes is altered by overexpression of the BCL-2 protooncogene in the thymus.

The bcl-2 gene encodes an intracellular, membrane-associated protein that protects immature cortical thymocytes from a wide variety of apoptotic stimuli, including glucocorticoids, radiation, and anti-CD3 treatment. Since cortical thymocytes are the primary target cells for thymic positive and negative selection processes, and since these processes are associated with cell death, we evaluated the role of bcl-2 in T cell development in two ways. In the first approach, transgenic mice expressing high levels of Bcl-2 in cortical thymocytes were mated with H-Y T cell receptor (TCR) transgenic mice, the latter being a well-defined system for the study of positive and negative selection of T cells. We found that the bcl-2 transgene had a dramatic effect on positive selection. This was manifested by a greatly increased production of mature thymocytes that were highly skewed towards the CD4-8+ lineage. The change involving CD4-8+ thymocytes occurred not only in bcl-2 transgenic mice, but was also observed in H-Y TCR/bcl-2 doubly transgenic mice, regardless of whether the H-Y TCR was expressed in the selecting (H-2b) or nonselecting (H-2d) environments. Furthermore, a large proportion of CD4-8+ thymocytes produced in H-2b H-Y TCR/bcl-2 doubly transgenic female mice expressed endogenous TCR alpha chains rather than the transgenic TCR alpha chain. These observations are consistent with the model that high expression of Bcl-2 in cortical thymocytes overrides the normal apoptotic pathway. This then allows the selection of CD4-8+ thymocytes expressing TCRs that are otherwise nonselectable. However, the bcl-2 transgene did not protect CD4+8+ thymocytes expressing the male-specific TCR from deletion in male doubly transgenic mice. In the second approach, we determined the level of bcl-2 mRNA expression in populations of thymocytes defined by their CD4/CD8 phenotypes using quantitative reversed transcriptase PCR techniques. Our results indicate that bcl-2 mRNA was expressed at a high level in immature CD4-8- thymocytes and in mature CD4+8- thymocytes. There is a dramatic downregulation of bcl-2 mRNA in CD4+8+ thymocytes, particularly those expressing a low level of TCR. CD4+8+ thymocytes that upregulated their TCR, likely as a result of receiving positive selection signals, also upregulated bcl-2 mRNA. This observation suggests that rescue of immature thymocytes from the programmed cell death pathway by positive selection signals is accompanied by the upregulation of bcl-2 mRNA.

Immunoprotective Leishmania major synthetic T cell epitopes.

Using the predictive algorithm of Rothbard and Taylor (1988. EMBO J. 7:93) and the primary structure of gp63 (Button, L., and M.R. McMaster. 1988. J. Exp. Med. 167:724; Miller, R.A., S.G. Reed, and M. Parsons. 1990. Mol. Biochem. Parasitol. 39:267) we have been able to delineate the structures of a number of gp63 T-cell epitopes which stimulate the proliferation of CD4+ cells. One of these synthetic antigens, inoculated subcutaneously with adjuvant, was shown to specifically induce proliferation of the Th1 subset and provided immunoprotection against two species of Leishmania parasites.

Improving B mode ultrasound evaluation of breast lesions with real-time ultrasound elastography--a clinical approach.

Ultrasound elastography using the extended combined auto-correlation method of tissue elasticity allows for real-time strain image visualisation using a free-hand probe with concurrent conventional B mode imaging. Four hundred and fifteen consecutive women with 550 breast lesions confirmed on B mode ultrasound were assessed with elastography using the elasticity score. There were 119 malignant and 431 benign lesions. The elastography sensitivity was 78.0%, specificity was 98.5% and overall accuracy was 93.8%. The median score for malignancy was 5 and that for benign lesions was 2. There was good correlation with B mode BIRADS category. 98.6% of lesions with an elasticity score of 2 or below (95%CI=96.8-99.4) were benign. BIRADS 3 lesions with an elasticity score of 2 or below may be re-classified as BIRADS 2 lesions. We found that 15.3% of BIRADS 2 and 3 lesions with an elasticity score of 3 were malignant. Real-time ultrasound elastography is user-friendly with a high accuracy rate, thereby improving B mode ultrasound assessment.

Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience.

INTRODUCTION: Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies. OBJECTIVE: To evaluate the purity, recovery and viability of CD34+ cells selected from harvested peripheral blood stem cells using the CliniMACS device, as well as to evaluate the T and B cell contents of these products. METHOD: Eight adult patients with malignant haematological diseases (5 non-Hodgkin's lymphomas in 2nd complete remission (CR) and 3 acute myeloid leukaemias in 1st CR) were mobilised with granulocyte colony-stimulating factor (G-CSF) with or without chemotherapeutic regimens. A total of nine leukaphereses for peripheral blood stem cell harvest using the Cobe Spectra cell separator (Cobe BCT Lakewood, CO) were performed. The harvested PBSC were then positively selected for CD34+ cells using the CliniMACS device (Milteny Biotech, Germany). RESULTS: A total of nine leukapheresis products from eight adults with a median pre-selection total CD34+ cell count of 282.2 x 10(6) (range 103.7 - 738.2 x 10(6)) were positively selected with CliniMACS. The median post-selection total CD34+ cell count was 99.5 x 10(6) (range 7.7 - 443.9 x 10(6)) with the median recovery was 66.0% (range 2 - 94%) and median purity of products of 79% (range 18 - 86%). The median total T cell count was reduced dramatically from 3.1 x 10(9) pre-selection to 7.9 x 10(6) post-selection. The selection did not affect the viability of selected cells that was tested with trypan blue exclusion method with a median pre and post selection viabilities of 98% (range 95 - 98%). CONCLUSION: We conclude that positive selection of CD34+ cells using magnetic separation technology by CliniMACS device results in low T-cell content stem cell with acceptable purity and recovery for autologous peripheral blood stem cell transplantation.

Constitutive tyrosine phosphorylation of the T-cell receptor (TCR) zeta subunit: regulation of TCR-associated protein tyrosine kinase activity by TCR zeta.

The T-cell receptor (TCR) zeta subunit is an important component of the TCR complex, involved in signal transduction events following TCR engagement. In this study, we showed that the TCR zeta chain is constitutively tyrosine phosphorylated to similar extents in thymocytes and lymph node T cells. Approximately 35% of the tyrosine-phosphorylated TCR zeta (phospho zeta) precipitated from total cell lysates appeared to be surface associated. Furthermore, constitutive phosphorylation of TCR zeta in T cells occurred independently of antigen stimulation and did not require CD4 or CD8 coreceptor expression. In lymph node T cells that constitutively express tyrosine-phosphorylated TCR zeta, there was a direct correlation between surface TCR-associated protein tyrosine kinase (PTK) activity and expression of phospho zeta. TCR stimulation of these cells resulted in an increase in PTK activity that coprecipitated with the surface TCR complex and a corresponding increase in the levels of phospho zeta. TCR ligations also contributed to the detection of several additional phosphoproteins that coprecipitated with surface TCR complexes, including a 72-kDa tyrosine-phosphorylated protein. The presence of TCR-associated PTK activity also correlated with the binding of a 72-kDa protein, which became tyrosine phosphorylated in vitro kinase assays, to tyrosine phosphorylated TCR zeta. The cytoplasmic region of the TCR zeta chain was synthesized, tyrosine phosphorylated, and conjugated to Sepharose beads. Only tyrosine-phosphorylated, not nonphosphorylated, TCR zeta beads were capable of immunoprecipitating the 72-kDa protein from total cell lysates. This 72-kDa protein is likely the murine equivalent of human PTK ZAP-70, which has been shown to associate specifically with phospho zeta. These results suggest that TCR-associated PTK activity is regulated, at least in part, by the tyrosine phosphorylation status of TCR zeta.

Short QTc in epilepsy patients without cardiac symptoms.

Epilepsy patients have a higher mortality rate than the general population. Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality for these patients. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many previous studies. This study compared the QT interval in epilepsy patients and normal controls, and identified the factors that affected the QT interval. Standard 12-lead ECGs were recorded from 70 consecutive epilepsy patients from the neurology clinic of HUKM and 70 age, race and gender matched controls. The mean QT interval corrected for heart rate (QTc) was calculated and compared. The mean QTc among the epilepsy patients was 0.401 +/- 0.027s. It was significantly shorter than the QTc (0.420 +/- 0.027s) in the control group (p<0.0005). Thirty five epilepsy patients (50%) and 17 matched controls (24.3%) had a mean QTc shorter than 0.40s (p=0.001). Among the epilepsy patients, the mean QTc did not significantly differ between patients in the duration (F=0.836, p=0.438) of the epilepsy, frequency (F=0.273, p=0.845) and types of seizures (p=0.633). There was no significant difference in the mean QTc between the epilepsy patients on different number of antiepileptic agents (F=0.444, p=0.643). Patients with cryptogenic epilepsy had a mean QTc of 0.392 +/- 0.029s, which was significantly shorter than patients with symptomatic epilepsy (QTc = 0.410 +/- 0.027s, p = 0.015). The mean QTc of the same subjects showed no significant interobserver difference (p=0.661). This study, for the first time, demonstrates that epilepsy patients have a significantly shorter QTc than controls, particularly in the subgroup of patients with cryptogenic epilepsy.

Molar pregnancy and glomerulonephritis.

A 17-year-old, sexually active, single, nulliparous young woman presented to us with one week history suggestive of nephrotic syndrome. She was found to have a benign hydatidiform mole confirmed by histopathological examination after suction and curettage. Renal biopsy revealed focal segmental glomerulosclerosis. The renal pathology was most probably due to molar pregnancy due to the close temporal relationship. To our knowledge, this is the first case of focal segmental glomerulosclerosis associated with a gestation trophoblastic disease described in the literature.

Influence of the affinity of selecting ligands on T cell positive and negative selection and the functional maturity of the positively selected T cells.

Interaction of the TCR on immature thymocytes with ligands on antigen presenting cells can lead to different fates including positive and negative selection. The affinity of the selecting ligands plays an important role in determining these outcomes. We used the 2C TCR transgenic model to evaluate the efficacy of ligands with widely differing affinity (3 x 10(3) - 2 x 10(6) M-1) for the 2C TCR in mediating thymic negative and positive selection. Our results support the conclusions that the deletion of immature thymocytes is not only mediated by high-affinity ligands but also by low-affinity/avidity ligands. However, high- and low-affinity ligands differ in their requirements for negative selection. We also present evidence that positive selection is not an all or none process but depending on the strength of interaction between the ligand and the TCR during the positive selection process can result in single positive thymocytes that are at different stages of functional maturity.

Differential regulation of p72syk expression in naive and proliferating CD4-CD8+ T cells.

A well-known consequence of TCR stimulation in proliferating T cells is cell death by apoptosis. We have previously shown that the extent of tyrosine phosphorylation of TCR zeta, CD3 gamma, and CD3 epsilon subunits in proliferating CD4-CD8+ T cells after TCR stimulation was decreased when compared to similarly stimulated naive T cells expressing the same TCR. Furthermore, these differences correlated with a decrease in the specific kinase activity of p56lck and p59fyn, with a corresponding increase in the specific kinase activity of p50rsk, a negative regulator of src-family tyrosine kinases. In this study we determined whether kinases that bind tyrosine phosphorylated TCR zeta chain were differentially regulated in naive and proliferating cells. Chemically synthesized cytoplasmic domains of the TCR zeta chain were fully phosphorylated in vitro with p56lck and used to precipitate TCR zeta binding proteins in naive and proliferating cells. Using this method we found that both ZAP-70 and p72syk bound tyrosine phosphorylated TCR zeta very efficiently. More interestingly, p72syk was found to be expressed only in naive but not proliferating cells. Kinetic studies indicate that more than 48 hr of activation was required for ceasation of p72syk expression. We also showed that the inability to detect p72syk expression in proliferating cells was not due to its translocation to cytoskeletal compartments in proliferating cells. We propose that the differential regulation of ZAP-70 and p72syk in naive and proliferating cells may contribute to the uncoupling of the TCR signaling pathway from downstream signaling events leading to distinct functional outcomes in these two cell types after TCR stimulation.

Increase in the specific activity of p50csk in proliferating T cells correlates with decreased specific activity of p56lck and p59fyn and reduced phosphorylation of CD3 subunits.

Depending on their prior antigen recognition history, mature T cells respond with different functional outcomes to T cell receptor (TCR) stimulation. These functional outcomes include proliferation, anergy and cell death. The biochemical basis underlying differential responses by mature T cells at different stages of their developmental pathway to TCR stimulation remains to be determined. We have previously shown that proliferating but not naive T cells were susceptible to apoptosis after TCR stimulation and that the tyrosine phosphorylation of TCR zeta, CD3 gamma, and CD3 epsilon in proliferating T cells was decreased after TCR stimulation. In this study. We determined whether differences in phosphorylation between naive and proliferating T cells were due to altered regulation of p56lck (Lck) or p59fyn (Fyn) by their positive or negative regulators, CD45 or p5Ocsk (Csk), respectively. We found that Lck was expressed at the same level and had the same phosphotyrosine content in naive and proliferating T cells. However, its autophosphorylation activity was lower in proliferating cells, corresponding to a 2-fold decrease in its specific kinase activity. Similarly, the specific kinase activity of Fyn was also decreased by about 2-fold in proliferating T cells. In contrast, although Csk was expressed at the same level in both cell types its specific kinase activity was increased by 6-fold in proliferating T cells. The tyrosine phosphatase CD45, a positive regulator of src-family kinases, was overexpressed by 3- to 6-fold in proliferating cells. However, the specific activity of CD45 in naive and proliferating T cells was the same. Therefore, although the protein expression level of CD45 was increased in proliferating T cells it only partially compensated for the hyperactivity of Csk resulting in a 2-fold reduction in the specific activity of Lck and Fyn in proliferating T cells.

Production and characterization of monoclonal antibodies specific for the murine T cell receptor zeta chain.

The T cell receptor (TCR) comprises an antigen-specific alpha beta heterodimer non-covalently associated with the CD3 gamma delta epsilon and TCR zeta subunits. Both the CD3 and TCR zeta subunits are proposed to be responsible for the intracellular signal-transduction events. We report here the production of eight monoclonal antibodies (mAbs) that bind in an ELISA assay to a 113 amino acid synthetic peptide corresponding to the cytoplasmic domain of TCR zeta. Western blot analysis of anti-CD8 precipitates of lysates of transfectants expressing chimeric CD8/zeta constructs encoding increasing COOH-terminal truncations of TCR zeta indicates that four of these mAbs recognized the region of TCR zeta chain comprising the last 29 COOH-terminal residues. Thus, this region of TCR theta may encode an immunodominant epitope. Furthermore, one of these mAbs, G3, is capable of precipitating both non-phosphorylated and tyrosine phosphorylated TCR zeta. The G3 mAb should be useful for elucidating the structural and signalling characteristics of the TCR zeta chain.

Intestinal T cells in CD8 alpha knockout mice and T cell receptor transgenic mice.

Intraepithelial lymphocytes (IEL) refer to the T cells located at the epithelium of the intestines. Unlike the T cells in other peripheral lymphoid organs, the majority of IEL express the CD8 cell surface protein. To study the role of CD8 in the ontogeny and the function of IEL, phenotypic analysis of IEL from CD8 alpha knockout mice and normal mice was performed. The CD8 alpha gene in CD8 alpha knockout mice was disrupted by homologous recombination. These mice are defective in thymic maturation of cytotoxic T cells. In normal mice, alpha beta T cells that were CD8 alpha alpha+ or CD4+ CD8 alpha alpha+, and gamma delta T cells that were CD8 alpha alpha+, were the distinct populations found only in IEL. In CD8 alpha knockout mice, the population size of IEL remained normal, but the majority of IEL were CD4- CD8- T cells expressing alpha beta or gamma delta T cell receptors. IEL from the H-Y transgenic mice2, which express the male H-Y antigen specific T cell receptor in a normal and in a CD8 alpha-null background, were also studied. In contrast to thymic derived T cells, CD8 alpha alpha+ IEL with the autoreactive transgenic T cell receptor were not deleted, but clonally expanded in the male transgenic mice. Interestingly, no pathological symptoms were observed in the intestines of these mice. In the absence of CD8 alpha expression, the H-Y specific autoreactive IEL did not accumulate in the intestines. The results suggest that CD8 alpha alpha+ IEL are derived extra-thymically and their responses towards antigens require the CD8 accessory molecule.

Flank pain: is Intravenous Urogram necessary?

AIMS: To determine the diagnostic yield of Intravenous Urogram (IVU) and the values of plain radiograph of kidney, ureter and bladder (KUB) and urinalysis as screening tests, with the objective to improve the cost effectiveness, in the management of patients presenting with flank pain due to urinary lithiasis. PATIENTS AND METHODS: All Intravenous Urogram (IVU) request forms and reports for the month of February 1998 were audited. The case notes, urinalysis, KUB and IVU films were traced and reviewed. RESULTS: There were 110 patients investigated, 61.8% (68) had normal IVU, 38.2% (42) had abnormal IVU. The sensitivity and specificity of KUB alone was 79.4% and 90%. The sensitivity using urinalysis alone was 90.9% and its specificity 33.8%. The sensitivity of combined KUB and urinalysis was 100% and its specificity 26%, with a negative predictive value of 100%. All the patients with both negative KUB and urinalysis in our study were found to have negative IVU. CONCLUSION: Our study shows that in patients with both negative KUB and urinalysis, the yield of IVU is very low and may not be necessary. This is important, as an IVU examination is not without risk. A combination of KUB with urinary analysis and careful evaluation of clinical symptoms will improve the cost-effectiveness of patient management.

Effect of lithium and oral thyrotrophin-releasing hormone (TRH) on serum thyrotrophin (TSH) and radioiodine uptake in patients with well differentiated thyroid carcinoma.

Oral thyrotrophin-releasing hormone (TRH) and lithium were given to patients on follow-up for well-differentiated thyroid carcinoma to see their effect on serum thyrotrophin level (TSH) and radioiodine (I-131) uptake (RAIU). The study was randomised and doubled-blinded and consisted of a total of 19 patients in 3 groups. Group 1 received placebo and TRH, group 2 received lithium and placebo, and group 3 received lithium and TRH. Serum TSH and RAIU at 24 hours were measured before, and after treatment, with TRH, lithium, and/or placebo. In group 1, mean (+/-SEM) TSH increased from 48.9 (+/-15.2) mU/l to 148.2 (+/-48.0) mU/l (p < 0.05); in group 2, the change of 24.9 (+/- 15.9) mU/l to 31.7 (+/-14.1) mU/l in TSH was not statistically significant; and in group 3, TSH increased from 108.1 (+/-13.8) mU/l to 187.0 (+/-39.1) mU/l (p < 0.05). However, despite the significant change in TSH, there was no significant increase in I-131 uptake in any group: 7.70% to 10.43%, 7.15% to 7.43% and 2.49% to 2.61%, in groups 1, 2 and 3 respectively (p > 0.05). We conclude that while oral TRH will increase endogenous serum TSH significantly, there is no significant increase in I-131 uptake. Lithium was not an useful adjunct in increasing serum TSH or I-131 uptake in these patients.

The role of computed tomography in clinically-suspected but equivocal acute appendicitis.

INTRODUCTION: To study the role of contrast-enhanced computed tomography (CT) of the abdomen and pelvis in the evaluation of patients with clinically-suspected but equivocal acute appendicitis. METHODS: The medical records of 206 consecutive patients who had CT of the abdomen and pelvis for equivocal signs and symptoms of acute appendicitis were reviewed. 7 mm collimated axial sections from the diaphragm to the iliac crest and 5mm collimated sections of the pelvis with intravenous and oral contrast were obtained. The criteria used to diagnose acute appendicitis were: (a) a thickened appendix of more than 7 mm or (b) inflammatory changes in the periappendiceal fat. The CT findings were correlated with the histological diagnosis at appendectomy. If the CT findings were negative for acute appendicitis and surgery not performed, the results were correlated with other corroborating diagnostic investigations or clinical follow-up. RESULTS: A total of 206 patients were scanned, of which 39 were excluded due to lack of any follow-up. Of the final 167 that were studied, there were 36 true positives, 127 true negatives, 4 false negatives and no false positives, resulting in a sensitivity of 93.9 percent, specificity of 100 percent and accuracy of 98.5 percent. CONCLUSION: We have found CT to be a safe, reliable and accurate modality in the diagnosis of acute appendicitis in patients with equivocal presentation.

Contrast-enhanced magnetic resonance imaging of the internal auditory canals and posterior fossa.

A retrospective review of 314 cases of contrast-enhanced magnetic resonance imaging (MRI) of the posterior fossa and internal auditory canals was carried out correlating the presenting symptoms with the scan findings. 7.2% of the cases showed findings on the MRI which could account for the patients' symptoms. Patients with sensorineural hearing loss were more likely to have a positive scan than those presenting with vertigo and/or tinnitus without hearing loss. Acoustic schwannoma was the most common lesion detected. Labyrinthine lesions e.g. cochlear schwannoma, labyrinthitis, congenital labyrinthine abnormality, and central lesions e.g. multiple sclerosis, brainstem glioma were some of the other lesions detected.