Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)-3 in the diabetic host.

Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We investigated mycobacterial antigen-stimulated responses in peripheral blood mononuclear cell (PBMC) isolated from healthy endemic controls (EC), those with LTBi, DM groups with and without LTBi, as compared with TB patients. Cytokines were measured using a Luminex-based assay. Gene expression was determined by RT-PCR. In DM-LTBi cases, PPD-stimulated proinflammatory cytokines; IFN-γ, IL-6, IL-2, TNF-α and GM-CSF and anti-inflammatory cytokines, IL-5 and IL-13 were raised as compared with EC. DM-LTBi PPD-stimulated IFN-γ, IL-6 and TNF-α mRNA titres were found raised in DM-LTBi, whilst suppressor of cytokine signalling (SOCS)-3 expression was lowered. Within DM cases, stratification based on HbA1c levels revealed raised IFN-γ but lowered IL-6 gene expression in those with controlled levels as compared with uncontrolled glycaemic levels. Further, SOCS1 expression levels were found higher in DM cases with controlled glycaemia when compared with EC. Overall, we show that diabetics with LTBi manifest raised levels of inflammatory and anti-inflammatory cytokines concomitant with reduced SOCS3 mRNA expression. Reduced glycaemic control results in further inflammatory dysregulation impacting conversing impacting IFN-γ and IL-6 activation. These results suggest that dysregulated immune activation in diabetes is exacerbated by LTBi, lack of glycaemic control may further compromise immunity against MTB infection.

Raised levels of IFN-gamma and IL-13 are associated with pre-diabetes amongst newly diagnosed patients with Tuberculosis.

OBJECTIVE: To investigate pre-diabetes and diabetes in newly-diagnosed tuberculosis patients and to assess the association of serum cytokine levels with diabetes status. METHODS: The cross-sectional study was conducted at Indus Hospital and The Aga Khan University Hospital, Karachi from May to November 2015, and included patients of either gender aged 18 years or more with a confirmed diagnosis of tuberculosis who were either newly diagnosed or had received up to 1 month of anti-tuberculosis therapy were included. Patients were enrolled from among those presenting to the clinics at Indus Hospital, Karachi, and the Department of Medicine, Aga Khan University Hospital (AKUH), Karachi. The patients were tested for glycosylated haemoglobin and random blood glucose. Diabetes was defined as HbA1c >6.5%; pre-diabetes as HbA1c=5.7-6.4%; and normoglycaemic as HbA1c <5.7%. Serum cytokines were investigated using the Bio-plex 27, Bio-Rad assay. SPSS version 19.0 was used for data analysis.. RESULTS: Of the 211 subjects, 110(52%) were females and 101(48%) were males. The overall median age of the sample was 26 years, and 100(47.3%) subjects were underweight. Of the total, 24(11.4%) had diabetes and 45(21.3%) had pre-diabetes. Of the diabetics, only 7(29%) knew their status prior to screening. Interferon-gamma and interleukin-13 were significantly different among tuberculosis patients with diabetes, pre-diabetes and normoglycaemia (p<0.05). Glycosylated haemoglobin levels showed a significant correlation with interferon-gamma levels. CONCLUSIONS: Raised interleukin-13 and interferon-gamma levels in newly-diagnosed tuberculosis patients with pre-diabetes.

Use of medical abbreviations and acronyms: knowledge among medical students and postgraduates.

INTRODUCTION: Inappropriate use of abbreviations and acronyms in healthcare has become an international patient safety issue. The aim of this study was to assess the knowledge of medical abbreviations and acronyms among residents of the department of medicine at a tertiary-care hospital. METHODS: Internal medicine residents (IMRs), subspecialty residents (SRs) and students were asked to complete a self-administered questionnaire which comprised standard abbreviations used in medicine and its various subspecialties. Scores obtained by the residents were classified into three categories: >70% correct answers; 50-69% correct answers; <50% correct answers. RESULTS: A total of 77 IMRs, SRs and medical students participated. Overall, good responses were achieved by 53 (68.8%), 16 (20.8%) attained satisfactory responses, and eight (10.4%) had unsatisfactory scores. The majority of SRs achieved good responses (19/22 (86%)), followed by IMRs (30/40 (75%)) and students (4/15 (26.7%)). Evaluation of their knowledge taken from the list of 'do not use' abbreviations showed that 89.6% reported using 'Q.D.' instead of 'once a day', and 93% used 'IU' instead of the entire phrase 'international unit'. The top five 'not to use' abbreviations were ZnSO4, µg, MgSO4, IU and SC, with the frequency 100%, 96%, 94.8%, 93% and 90%, respectively. CONCLUSIONS: This study showed that there is a knowledge gap among trainees in medicine regarding the meaning and usage of common medical abbreviations. We therefore recommend proper education of trainees in medicine to ensure they understand the meaning of abbreviations and are aware of the list of 'do not use' abbreviations.

Isolated ligamentum flavum ossification in primary hypoparathyroidism.

BACKGROUND: The ligamenta flava can undergo ossification and calcification resulting in myelopathy. Only seven cases of ligamentum flavum ossification in association with hypoparathyroidism have been reported, most of which had concurrent osseous changes in other spinal ligaments. Here, we report a patient with hypoparathyroidism who presented with ligamentum flavum ossification causing both cervical and thoracic myelopathy. CASE DESCRIPTION: A 43-year-old male presented with backache, urinary retention, and lower limb weakness for the last few days. Magnetic resonance imaging scan showed ossification of the ligamentum flavum in the cervical and thoracic regions, with severe spinal stenosis. Following spinal decompressive surgery, the patient made a complete recovery. Primary hypoparathyroidism was found to be the underlying cause for ligamentum flavum ossification. CONCLUSION: Ossification of ligamentum flavum secondary to hypoparathyroidism should be considered as a possible cause of myelopathy in all patients presenting with symptoms of spinal cord compression.

Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome.

OBJECTIVE: To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. METHODOLOGY: Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value <2 in adults and hyperinsulinemia based on fasting insulin levels ≥12 µIU/ml. RESULTS: A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 ±5.5 years. Mean HOMA-IR of women was 3.1 ±1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 ±5.8 µIU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. CONCLUSION: Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMAIR model performed better than hyperinsulinemia alone for diagnosing IR.

Increased Mycobacterium tuberculosis antigen-induced gene expression of interferon-gamma, tumor necrosis factor alpha and interleukin-6 in patients with diabetes.

INTRODUCTION: Pakistan ranks fifth in high tuberculosis (TB)-burden countries and seventh among countries with high prevalence rates of diabetes mellitus (DM). DM is a risk factor for TB and worsens disease outcomes. Furthermore, Mycobacterium tuberculosis (MTB) infection can induce glucose intolerance and worsen glycemic control in diabetes. Suppressor of cytokine signaling (SOCS)-1 and -3 molecules regulate cytokine signaling and are important in maintaining an immune balance. In TB, interleukin (IL)-6 upregulation induces SOCS3, which is also a negative regulator of insulin signaling. This research focuses on the mechanism by which SOCS1 and SOCS3 affect insulin resistance and increased susceptibility to TB. METHODS: We studied gene expression in peripheral blood cells of patients with diabetes (n=10) and healthy endemic controls (EC, n=11) both with and without MTB infection. Mycobacterial antigen (PPD) and mitogen-stimulated SOCS1, SOCS3, interferon-gamma (IFN-γ), IL-6, and tumor necrosis factor alpha (TNFα) mRNA expression levels were determined using real-time polymerase chain reaction. RESULTS: MTB antigen-stimulated mRNA levels of IFN-γ was 10-fold higher, SOCS1 was 4 times greater, TNFα was 10-fold higher, and IL-6 was 2-fold greater in patients with DM than in ECs. Overall levels of PPD-stimulated IL-6 was higher in patients with DM than in ECs (p=.036). Mitogen-induced mRNA levels of IFN-γ were 30-fold higher, SOCS3 was 20 fold higher, and SOCS1 was 4-fold higher in patients with DM than in ECs. CONCLUSION: Increased proinflammatory cytokine production in response to MTB antigens in diabetes would lead to exacerbated pathology and reduced inflammatory control at the site of MTB infection. This would in turn hamper the resolution of inflammation, resulting in unfavorable disease outcomes.

Assessment of diabetes among tuberculosis patients presenting at a tertiary care facility in Pakistan.

OBJECTIVE/BACKGROUND: Pakistan ranks sixth among high-tuberculosis (TB)-burden countries worldwide and fifth worldwide for diabetes incidence. Although both these factors are independently known, the rate of diabetes among TB patients is not well known. We aimed to determine the prevalence of diabetes among patients with TB presenting at tertiary care health centers in Karachi, Pakistan. METHODS: A total of 216 patients with TB were recruited and their blood samples were taken for testing of glycosylated hemoglobin (HbA1c) and random blood sugar. Diabetes was defined as HbA1c>6.5% and random blood sugar>180mg/dL, pre-diabetes as HbA1c 5.7-6.4%, and normoglycemia as HbA1c<5.7%. RESULTS: Data for 211 patients were available and showed that 24 (11.4%) patients had diabetes. Of these, 17 were newly diagnosed, while seven were known diabetics. Prediabetes was identified in 45 (21.3%) cases. Of the TB patients, 165 were newly diagnosed, while 46 were retreatment cases. The majority of patients (60%) were underweight with a body mass index of <18.5. CONCLUSION: This study identified 11.4% diabetics among TB patients presenting to a tertiary care facility. Despite the high diabetes incidence in Pakistan, 71% of the diabetics in the group studied did not know their status. Given the negative impact of diabetes on treatment outcomes of TB, it is important that screening for diabetes be included as initial workup for TB patients. Identification and management of diabetes would result in improved outcomes for TB treatment.

Relationship among fatness, blood lipids, and insulin resistance in Pakistani children.

Observations on associations between fatness and metabolic risks among South-East Asian adults have resulted in devising lower thresholds of body mass index (BMI) for them. Metabolic abnormalities, including type 2 diabetes, are now also appearing in children and are associated with obesity. There has not been much work done to identify indicators of metabolic risks among South Asian children. This study was undertaken to observe the relationship among fatness, blood lipids, and insulin resistance in Pakistani children. Fatness, lipids, and insulin resistance were assessed in 92 middle-class Pakistani school children aged 8-10 years. Height, weight, waist, hips, mid-arm circumference, and triceps skin-fold, measured in school, were used for calculating various indicators of fatness, i.e. BMI, waist hip ratio (WHR), and arm-fat percentage. Fasting blood samples were analyzed for total lipids, triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and insulin levels. Homeostasis model assessment (HOMA) index was calculated to assess insulin resistance. Two separate multiple regression models of various risk indicators (family history, sex, BMI, WHR, arm-fat percentage) showed that only arm-fat percentage had a significant positive association both with insulin levels (b = 2.04, p = 0.044) and LDL (b = 2.11, p = 0.037). Only five children were overweight (BMI-for-age > 85th percentile according to National Center for Health Statistics 2000 reference). Neither overweight children nor those who were in the uppermost tercile of BMI-for-age differed significantly from other children in terms of presence of higher-than-desirable values of lipids or insulin. However, compared to those in the lowest tercile, children who were in the uppermost tercile of armfat percentage had a significantly higher frequency of high blood cholesterol (40% vs 67%, p = 0.027), high LDL (33.3% vs 61.3%, p = 0.026), and markedly higher proportion above average insulin levels (16.7% vs 35.5%, p = 0.083). Arm-fat percentage could be developed as a practical tool for determining the risk status of children. However, further cross-sectional assessments are needed to ascertain accurate relationships among arm-fat percentage, lipid profiles, and insulin resistance in larger and varied groups of children.

Severe rhabdomyolysis due to drug overdose.

A case of a young girl is described who presented in a state of intoxication and later developed acute renal failure secondary to severe rhabdomyolysis. With vigorous fluid therapy she regained normal renal function. Biochemical testing finally confirmed over the counter drug overdose as the cause for this presentation.

Frequency of chronic complications of type II diabetes.

OBJECTIVE: To assess the frequency of chronic complications of type II diabetes in subjects attending a tertiary care unit in Karachi, Pakistan. DESIGN: A cross-sectional analytical study. PLACE AND DURATION OF STUDY: First visit of all type II diabetic subjects attending the outpatient department of Baqai Institute of Diabetology and Endocrinology from September 1996 to December 2001. SUBJECTS AND METHODS: Computerized clinical records of 2199 type II diabetic subjects were analyzed for this study. The clinical and laboratory variables were statistically evaluated with significance at p. RESULTS: Means of glycosylated hemoglobin HbA1c, fasting and random plasma glucose levels, systolic blood pressure, triglycerides and high density lipoproteins (HDL) were higher than the risk indicator value for both genders (p <0.005). Mean body mass index and total blood cholesterol was higher for females only. Hyperglycemia was present in 88%, high HbA1c in 81%, low HDL in 81%, obesity in 66% and hypertriglyceridemia in 54%, neuropathy in 36%, proteinuria in 28% and hypertension in 50% of the subjects. Frequency of obesity, low HDL and hypertension was higher among females (p < 0.001 in each case). Retinopathy (p<0.05), nephropathy (p<0.005), neuropathy (p<0.005) and foot ulcers (p<0.001) were higher among males. Frequency of obesity was significantly higher among those with shorter duration and in younger group while frequency of other complications was higher among those with longer duration and in the older groups. CONCLUSION: Higher rates of complications were observed compared to previous studies. Certain variables showed significant association with gender and age as described above.

Frequency of statin use in type 2 diabetics having macrovascular disease- at a Tertiary Care Hospital of Karachi.

BACKGROUND: During the last two decades with the introduction of statins large reductions in cholesterol concentrations were easily and safely achievable and this led to studies that demonstrated benefits of statin use. But only fewer than one fourth of adults with coronary heart disease were receiving lipid-lowering drugs in a cross sectional health survey done in England. Thus this study was designed to evaluate the frequency of statin use in type 2 Pakistani diabetic subjects with macrovascular disease attending a tertiary care unit in Karachi, Pakistan. METHODS: Records of type 2 diabetic subjects coming to the outpatient department of Baqai Institute of Diabetology and Endocrinology from September 1996 to December 2001 was analyzed for their anthropometric and biochemical characteristics. Patients having any macrovascular disease were identified and frequency of statin use by these subjects was studied. RESULTS: Out of a total of 2152 patients 502 (252 males, 250 females) having macrovascular disease were identified. Only 16.5% of them (44 males, 39 females) were taking statins. Use of statins was higher amongst those who had angina (20%) or myocardial infarction (17%) compared to those who had stroke (10%). Sixty two percent of the users while 52% of the non-users had elevated blood cholesterol. CONCLUSION: Frequency of statin use in the subjects studied was much lower than was warranted with respect to their disease status. Presence of elevated blood cholesterol despite using statins suggested inappropriate treatment in these subjects. Further studies are required to identify the factors leading to low use of statins in type 2 diabetic subjects with macrovascular symptoms.

Fatness, lipids, insulin sensitivity, and life style of children from high and low risk families.

BACKGROUND: Children show variation in certain diabetes related risk factors according to the family history. Early detection of high risk groups could prevent or delay the onset of diabetes. Insulin level and fatness of Pakistani children has never been compared according to family history. This study was designed to observe the differences in insulin sensitivity, lipids and fatness in children from high and low risk families. METHODS: Two groups of 8-10 year old school children were assessed for the differences in insulin sensitivity, lipids, fatness, food and activity habits. The first group had no family history for diabetes (low risk group, n = 40) in any first or second degree relative. The second group had positive family history of diabetes (high risk group n = 40) Data were collected through questionnaire sent to parents and children's interview. Blood test and anthropometric assessments were done at the schools by a physician. RESULTS: The two groups of children had similar level of insulin sensitivity. Children having positive family history for diabetes had markedly higher mean values for BMI, and arm fat % as compared to the controls. Though the low risk group had markedly higher level of total lipids and triglycerides the high risk group had markedly lower HDL and significantly higher LDL (p = 0.008) and HDL-LDL (p = 0.009) ratio than the low risk group. There was no significant difference in food and activity habits of the two groups. CONCLUSION: Marked variations in lipid profile of children from high and low risk families are evident at an early age. Presence of these differences in the absence of differences in food and activity habits and insulin sensitivity suggests that variation in lipid storage and metabolism could precede the appearance of reduced insulin sensitivity in children from high-risk families. Measures to control excessive fat deposition in childhood could be an initial step towards the prevention of diabetes and heart disease in adult life.

Baseline stimulated thyroglobulin level as a good predictor of successful ablation after adjuvant radioiodine treatment for differentiated thyroid cancers.

BACKGROUND: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: This retrospective study accrued 64 patients (23 male and 41 female; mean age of 40±14 years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg<2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. RESULTS: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of ≤14.5 ng/ml was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg≤14.5 ng/ml and 12/36 (33%) patients with baseline STg>14.5 ng/ml ((p value<0.05). Age>40 years, female gender, PTS>2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. CONCLUSIONS: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg <2 ng/ ml, a negative DWBIS and a negative US neck).

A case of Gitelman syndrome with severe hyponatraemia and hypophosphataemia.

Gitelman syndrome (GS) is a renal tubular disorder of the thiazide-sensitive sodium chloride cotransporter, which is located in the distal tubule of the loop of Henle. We present a rare case of GS complicated by severe hyponatraemia and hypophosphataemia. A 17-year-old boy was admitted to our institution with fever and lethargy. The workup revealed typical features of GS, i.e. hypokalaemia, hypomagnesaemia and metabolic alkalosis. In this report, we discuss the differential diagnoses and rationale for accepting GS as the most likely diagnosis. This case was complicated by severe hyponatraemia (115 mmol/L) and hypophosphataemia (0.32 mmol/L). We concluded that the syndrome of inappropriate secretion of antidiuretic hormones could not be ruled out and that respiratory alkalosis was the most likely aetiology of hypophosphataemia. This case report also generates an interesting discussion on water and electrolyte metabolism.

Threshold primary tumour sizes for nodal and distant metastases in papillary and follicular thyroid cancers.

BACKGROUND: In papillary and follicular thyroid cancers (PTC, FTC), nodal and distant metastasis are generally considered important determinants of recurrence and survival, respectively. However, there is no consensus about the threshold primary tumour size (PTS) for these determinants. The aim of this study was to assess size relationships for developing nodal, pulmonary, bone and overall distant metastases. METHODS: This prospective study covered 139 (93 females and 46 males) consecutive biopsy proven patients with PTC (114/139, mean age 41.0 ± 15.7 years, M: F, 35%:65%) and FTC (25/139, mean age 39.2 ± 14.3 years, M: F: 24%:76%). RESULTS: Average primary tumor size was 23.4 ± 11.1 mm and 26.5 ± 13.1 mm for PTC and FTC respectively (p value=0.223). Nodal metastasis was found more common in PTC than FTC (49% vs 28%, p value <0.05), whereas overall distant metastasis was approximately the same (13% and 24%, p value =0.277); however, bone metastasis was significantly higher in FTC than PTC (24% vs 5%, p value <0.05). Cumulative risk for nodal and distant metastases for FTC and PTC starts at PTS <20 mm and may indicate an unusual aggressive tumor behavior in the studied population. Highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC was found to be ≥ 50 mm PTS. CONCLUSION: We conclude that a PTS of <20 mm may indicate an unusual aggressive tumor behavior with highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC with a cutoff of ≥ 50 mm.

Improving diabetes care: multi-component cardiovascular disease risk reduction strategies for people with diabetes in South Asia--the CARRS multi-center translation trial.

AIMS: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in people with diabetes in South Asia. The CARRS Translation Trial tests the effectiveness, cost-effectiveness, and sustainability of a clinic-based multi-component CVD risk reduction intervention among people with diabetes in India and Pakistan. METHODS: We randomly assigned 1146 adults with diabetes recruited from 10 urban clinic sites, to receive usual care by physicians or to receive an integrated multi-component CVD risk reduction intervention. The intervention involves electronic health record management, decision-support prompts to the healthcare team, and the support of a care coordinator to actively facilitate patient and provider adherence to evidence-based guidelines. The primary outcome is a composite of multiple CVD risk factor control (blood glucose and either blood pressure or cholesterol, or all three). Other outcomes include control of the individual CVD risk factors, process and patient-centered measures, cost-effectiveness, and acceptability/feasibility. CONCLUSION: The CARRS Translation Trial tests a low-cost diabetes care delivery model in urban South Asia to achieve comprehensive cardio-metabolic disease case-management of high-risk patients (clinicaltrials.gov number: NCT01212328).

Resistant thyrotoxicosis in a patient with graves disease: a case report.

Background. Conventional management of thyrotoxicosis includes antithyroid drugs, radioactive iodine, and surgery while adjunctive treatment includes beta-blockers, corticosteroids, inorganic iodide and iopanoic acid. Very rarely, patients may be resistant to these modalities and require additional management. Case Presentation. A 50-year-old lady presented with weight loss and palpitations diagnosed as atrial fibrillation. Her past history was significant for right thyroid lobectomy for thyrotoxicosis. Thyroid functions tests at this presentation showed free T4 of 6.63 ng/dl (normal range: 0.93-1.7) and TSH of <0.005 µIU/mL (normal range: 0.4-4.0). She was given aspirin, propranolol, heparin and carbimazole; however free T4 failed to normalize. Switching to propylthiouracil (PTU) did not prove successful. She was then given high doses of prednisolone (1 mg/kg/day) and lithium (400 mg twice daily) which prepared the patient for radioactive iodine treatment by reducing free T4 levels (2.82 ng/dl). Two doses of radioactive iodine were then administered 6 months apart. Subsequently she became hypothyroid and was started on thyroid replacement therapy. Conclusion. This case highlights management options in patients with resistant thyrotoxicosis. Radioactive iodine and surgery are definitive modes of treatment in such complex cases while steroids and lithium play an important role in preparing patients for more definitive treatment.