Diagnosis of pulmonary embolus using ventilation/perfusion lung scintigraphy: more than 0.5 segment of ventilation/perfusion mismatch is sufficient.

BACKGROUND: To determine the optimal diagnostic cut-off point using a simplified criterion for the detection of pulmonary embolus (PE) and to evaluate the criterion's utility and reporter reproducibility. METHODS: Lung scintigraphy was carried out in 924 patients for the diagnosis of PE. This group consisted of 316 men and 608 women with median age of 63 years (range 18-94 years). Ventilation imaging was carried out with Tc-99m Technegas followed by perfusion imaging using 190 MBq Tc-99m macroaggregated albumin. Studies were classified using a 6-category probability criterion of incremental ventilation/perfusion (V/Q) mismatch: A, normal; B, low (minor matched V/Q defects or segmental matched V/Q defects without opacity on chest X-ray); C, low-moderate (a partial segment of V/Q mismatch); D, moderate (1 segment of mismatch); E, moderate-high (1-2 segments of V/Q mismatch) and F, high probability (=2 segments of V/Q mismatch). Clinical end-points at 3 and 6 months were death by PE or PE treated with anticoagulation therapy. Three-reporter reproducibility was determined by kappa statistic on a subgroup of patients (53/924). RESULTS: A total of 122 patients (13%) had a confirmed diagnosis of PE at 3 months and no additional cases were registered at 6 months. The lung scintigraphy probability classification showed: normal 152 (16%), low 620 (67%), low-moderate 20 (2%), moderate 28 (3%), moderate-high 24 (3%) and high 80 (9%). The respective sensitivities and specificities, where the diagnostic cut-offs were established at F, high; E, moderate-high; D, moderate and C, low-moderate probability, were F, 64 and 100%; E, 82 and 99%; D, 95 and 98% and C, 98 and 96%. The respective false-negative cases for F, E, D and C cut-offs were 44, 22, 7 and 3. Using the revised Prospective Investigation of Pulmonary Embolism Diagnosis reporting classification reporter agreement showed kappa values of 0.31-0.48. Using a simplified 2-category (>0.5 segment of V/Q mismatch positive, all others negative) criterion resulted in a higher reporting agreement (kappa 0.74-0.83). There were only 3% of indeterminate cases if this was defined by the D category and a maximum of 8% if categories C, D and E were included. CONCLUSIONS: Using a simplified diagnostic criterion where all studies showing >0.5 segments of V/Q mismatch are regarded as positive and all others as negative, lung scintigraphy, incorporating Tc-99m Technegas ventilation imaging or its equivalent, can achieve a very high diagnostic accuracy for the detection of PE. Using this technique, less than 5% of scans are indeterminate. A simplified, unambiguous approach to reporting is recommended.

The clinical utility of nuclear medicine imaging for the detection of occult gastrointestinal haemorrhage.

Acute gastrointestinal bleeding is often intermittent and the bleeding source may be difficult to locate, resulting in delay of potentially life-saving treatment. The aim of this study was to determine the clinical utility of 99mTc labelled red blood cell imaging and [99mTc]pertechnetate (Meckel's scan) imaging in a series of 137 patients admitted over a 5 year period to hospital for management of acute gastrointestinal bleeding. Of the 137 patients, 70 had positive 99mTc red blood cell studies. Eleven of 24 patients who had imaging performed beyond 3 h had positive scans that would otherwise have been missed. Only 47 patients had a definite final diagnosis at the time of hospital discharge, of which six were negative on 99mTc red blood cell imaging. The correct site of bleeding was localized in seven of 21 patients with foregut bleeding, and 15 of 20 patients with colonic bleeding. Endoscopy yielded a diagnosis in 13 of the 47 patients (28%). Eleven patients had Meckel's scans but all were negative. Angiography was diagnostic in one of 17 patients studied. 99mTc red blood cell imaging is a useful test in the management of acute gastrointestinal bleeding. Imaging beyond 3 h may further improve the bleeding detection rate. This test, however, may be an unreliable means of localization of bleeding, particularly in the foregut.

Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome.

BACKGROUND: The objective of this descriptive analysis of a large cohort of patients with Langerhans cell histiocytosis (LCH) was to add to the understanding of the natural history, management, and outcome of this disease. METHODS: Three hundred fourteen Mayo Clinic patients with histologically proven LCH were categorized into those patients with multisystem disease and those patients with single system disease. Clinical features, treatment, and outcome were determined from the case history notes and tumor registry correspondence. Treatment included chemotherapy, radiotherapy, and surgical excision. The end points were disease free survival, active disease, or death. The median time of follow-up was 4 years (range, 1 month to 47.5 years). RESULTS: The age of the patients ranged from 2 months to 83 years. Of the 314 patients, there were 28 deaths. Multisystemic LCH was found in 96 patients, 25 of whom had continuing active disease after treatment. Isolated bone LCH lesions were observed in 114 of the 314 patients, 111 of whom (97%) achieved disease free survival after treatment. The most common sites of osseous LCH were the skull and proximal femur. Of the 87 patients with isolated pulmonary involvement, only 3 were nonsmokers. After treatment with corticosteroids (+/- cyclophosphamide or busulphan), 74 patients achieved disease free survival, but 10 patients died. Pituitary-thalamic axis LCH, characterized by diabetes insipidus, was found in 44 patients. After treatment, 30 of these patients had disease free survival, but all required long term hormone replacement with desmopressin acetate. Lymph node involvement was found in 21 patients, and mucocutaneous involvement was found in 77 patients. CONCLUSIONS: Patients with isolated bone LCH lesions have the best prognosis compared with patients with LCH involvement of other systems. By contrast, 20% of patients with multisystem involvement have a progressive disease course despite treatment. The identification of prognostic indicators to facilitate appropriate treatment and long term follow-up surveillance is recommended.

99mTc technegas ventilation and perfusion lung scintigraphy for the diagnosis of pulmonary embolus.

UNLABELLED: Lung scintigraphy is used widely for diagnosis of pulmonary embolus (PE). Technegas ventilation imaging has many advantages over other methods, but little outcome data exists on this technique. The aims of this study were to better define the role of lung scintigraphy in the management of patients with suspected PE and to evaluate technegas ventilation imaging by following patient outcomes. METHODS: A group of 717 out of 834 consecutive patients, referred to a university teaching hospital for lung scintigraphy to confirm or refute the diagnosis of PE, was followed for 18-30 mo to determine clinical outcome. The follow-up endpoints were death as a result of PE, death as a result of hemorrhage after treatment for PE, uncomplicated survival, survival with subsequent PE, nonfatal hemorrhage after treatment for PE and recurrence of PE in treated patients. Ventilation imaging was performed using technegas, and perfusion imaging was performed using intravenous 99mTc macroaggregated albumin. The modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) diagnostic criterion was used for interpretation of lung scintigraphy. RESULTS: Diagnostic results included 3.5% normal studies, 67.4% assessed as low probability for PE, 10% as moderate probability for PE and 19.1% as high probability for PE. A total of 231 patents received therapy with heparin, followed by warfarin, including those receiving anticoagulation therapy for other conditions. Ninety-six percent of patients with normal and low probability studies (n = 508) had good outcomes, 6 patients died as a result of PE and 12 subsequently developed PE. The odds ratio for death by PE in this group was 0.2. Of the 72 moderate probability studies, 39 patients were untreated. In this group there was 1 death due to PE, and PE subsequently developed in 2 patients. None of the remaining 33 treated patients died, but 4 patients experienced bleeding complications. The odds ratio for death by PE in the moderate probability group was 0.7. In those patients with high-probability studies, there were 8 deaths by PE, 6 deaths by hemorrhage, 11 nonfatal hemorrhages and 7 patients who experienced recurrences of PE. The odds ratios in this group were 6 and 10 for death by PE, or death by PE and the treatment of PE, respectively. CONCLUSION: The use of the modified PIOPED diagnostic classification is valid for technegas lung scintigraphy. Using technegas, normal/low-probability and high-probability results are highly predictive of respective outcomes. Technegas lung scintigraphy reduces the number of indeterminate studies.

Infected cardiac pacemaker wires demonstrated by Tc-99m labeled white blood cell scintigraphy.

Multiple cardiac pacing wires present a potential source of thrombosis and infection within veins and cardiac chambers. A case is presented where persistent infection involved thrombus on cardiac pacing wires in and around the right subclavian and brachiocephalic veins, which proved difficult to localize and treat. Early Ga-67 and Tc-99m labeled white blood cell imaging were negative but, when the latter test was repeated after 5 weeks, the septic focus was identified. Treatment with antibiotic therapy combined with surgical removal of the infected thrombus and both pacing wires was effective in eradicating infection. Failure to demonstrate an infection focus early in the course of the illness may have related to the size of the infection focus; however, in a later phase of the illness, Tc-99m labeled white blood cell imaging proved helpful in localizing focal infection associated with pacemaker wires.

Increased lymphoscintigraphic flow pattern in the lower extremity under evaluation for lymphedema.

OBJECTIVE: To analyze the clinical and scintigraphic features in four postoperative patients with lower limb edema. DESIGN: Four case reports are presented, and causes of increased lymphatic flow are discussed. MATERIAL AND METHODS: Filtered 99mTc-sulfur colloid (0.1 mL; 20 MBq) was administered by subcutaneous injection into the second web space of each foot. Sequential local (inguinal) and whole-body imaging was performed periodically up to 24 hours after the injections. The patients were three women who were 40, 51, and 86 years of age and an 81-year-old man. RESULTS: Each patient had unilateral lower extremity swelling and had recently undergone an ipsilateral lower limb operation. One female patient had previously undergone proximal femoral vein ligation, and another female patient had venous insufficiency demonstrated by Doppler ultrasonography. The male patient had a history of severe arterial insufficiency, and the remaining female patient had no venous or arterial abnormalities. On lymphoscintigraphy, all patients showed increased lymphatic flow in the edematous lower limb. Only the male patient also demonstrated abnormal dermal backflow pattern. CONCLUSION: Increased lymphatic flow most likely is a normal response to lower limb edema in the presence of normal peripheral lymphatic structures. In the four described cases, a recent lower limb surgical procedure may have resulted in disturbance of normal proximal lymphatic channels. The role of sympathetic innervation of the peripheral lymphatic system is a potential factor determining lymphatic response to trauma or surgical intervention. Increased flow on lymphoscintigraphy may not necessarily represent normal flow, especially if other scintigraphic features of abnormal lymphatic function-such as dermal backflow pattern-are present.

Bilateral axillary lymph node uptake of radiotracer during lower extremity lymphoscintigraphy.

Lymphoscintigraphy is a useful technique for the evaluation of lymphatic function in the presence of limb swelling. The authors report a case where proximal lower limb and genital swelling in a 23-yr-old man was investigated by lymphoscintigraphy. The patient had a history of previous surgery and subsequent infection in the affected groin. Lower limb lymphoscintigraphy showed features of an unusual lymphatic drainage pattern that most likely represented adaptation to chronic lymphatic insufficiency. The drainage pattern was characterized by marked dermal backflow pattern, aberrant lymph node uptake in the abdomen and chest and unexpected avid radiotracer uptake in the axillae bilaterally.

Outpatient management of patients with large multinodular goitres treated with fractionated radioiodine.

The efficacy of fractionated out-patient radioiodine therapy in 38 patients with compressive symptoms due to long-standing large multinodular goitres was assessed. The diagnosis was established by clinical assessment in addition to technetium-99m pertechnetate thyroid scan or computed tomography scan of the thyroid and mediastinum. Oral iodine-131 therapy was administered as a 2.22 GBq (60 mCi) cumulative dose over 4 months (555 MBq per month). All patients were monitored with serum thyroid-stimulating hormone and free thyroxine (+/- free tri-iodothyronine) assays before the treatment and after each dose fraction. Clinical and biochemical follow-up was performed on all patients and ranged from 6 to 45 months after therapy. The patients consisted of 35 female and three male patients with a median age of 59 years (range 37-87 years). Prior to treatment 20 patients were biochemically hyperthyroid and 18 were euthyroid. Overall, 71% of patients reported a subjective improvement in compressive symptoms and 29% reported no change. Clinically assessed reduction in goitre size occurred in 92% of patients while there was no change in 8%. At 3 months of follow-up, 31% of patients had become hypothyroid and at 18 months 66% were hypothyroid. Seven hyperthyroid patients (35%) became euthyroid and 13 hyperthyroid patients (65%) became hypothyroid. Three patients who became hypothyroid experienced neck soreness (transient in one patient, persistent in two patients). There were no differences in outcome between patients who were hyperthyroid and those who were euthyroid prior to treatment. Fractionated out-patient radioiodine therapy showed excellent short- and medium-term safety, was very well tolerated and offered a satisfactory alternative treatment to surgery.

Technical pitfalls in image acquisition, processing, and display.

Optimal image quality is an ideal in nuclear medicine that is not always realized, being subject to a variety of conditions that can act, either singly or in combination, to undermine its accomplishment. These conditions include potential defects and limitations in both the hardware and software used for the acquisition and reconstruction of nuclear medicine images. Factors relating to individual patients can contribute to these obstacles, including limitations in mobility and compliance. Importantly, suboptimal or erroneous technique is a common source of poor imaging results, with loss of diagnostic efficacy. Appropriate test selection and careful attention to patient preparation and procedural details are essential elements in avoiding image flaws and artifacts in nuclear medicine.

Patient-related pitfalls and artifacts in nuclear medicine imaging.

Quality control in nuclear medicine is all important. This applies not only to preparation of the patient and acquisition of the image, but also to interpretation of the study. Although it may seem self-evident, it is important to remain aware of artifacts that are directly related to the patient and need special consideration. Furthermore, at times the distinction between normal variants and artifacts can be difficult. Commonly encountered patient-related artifacts include artifacts caused by attenuation, contamination artifacts, and artifacts caused by intravenous lines, tubes, and catheters. Less commonly, artifacts arise because of the use of multiple isotopes, the presence of fistulas or surgically altered anatomy, and pharmaceuticals and other substances interfering with expected radiopharmaceutical uptake and distribution. The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these patient-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants.

Bone scintigraphy evaluated in diagnosing and staging Langerhans' cell histiocytosis and related disorders.

UNLABELLED: An analysis of patients with proven Langerhans' cell histiocytosis (LCH) was undertaken with the aim of evaluating the role of bone scintigraphy in the diagnosis and staging of LCH. METHODS: Radiographic skeletal surveys and whole-body bone scintigraphy study results were reviewed for all patients treated at the Mayo Clinic in Rochester, Minnesota during 1965-1994 with histologic proven LCH. All available studies were then reported in a randomized and blinded fashion. RESULTS: Of the 73 patients with the histologic diagnosis, 56 (76%) had a definite lesion reported on radiographs and subsequent biopsy-proven bone involvement. For this population, the sensitivity and specificity of radiographic survey were 100% and 61%, respectively, compared to 91% and 55% for bone scintigraphy. Solitary bone lesions were reported on 21 radiographic surveys and 24 bone scintigrams. For solitary lesions, radiograph sensitivity and specificity were 95% and 73%, respectively, compared to 88% and 77% for bone scintigraphy. Bone scintigraphy receiver operating characteristic curves showed the region of greatest diagnostic accuracy to be skull, facial bones and mandible (88% sensitivity, 52% specificity). Radiation dosimetry to adult reproductive organs was less favorable for radiographic skeletal survey compared to bone scintigraphy. CONCLUSION: Our results support the use of radiographic skeletal survey in the initial diagnosis of LCH. Bone scintigraphy may have a role in monitoring a patient's progress in which the initial scintigram and radiographic survey show good correlation.

Evaluation of 201Tl SPET myocardial perfusion imaging in the detection of coronary artery disease after orthotopic heart transplantation.

Accelerated coronary artery disease is a common complication following orthotopic cardiac transplantation. The relationship between acute rejection and accelerated coronary artery disease remains unclear. While thallium-201 (201Tl) imaging has been advocated in the diagnosis of post-transplant coronary arteriopathy, other investigators have found little role for this technique in the evaluation of such patients. We undertook a retrospective review of 13 stress/rest (10 exercise, 2 dobutamine, 1 dipyridamole) and 2 rest/rest 201Tl single photon emission tomographic (SPET) imaging studies performed in seven patients post-cardiac transplantation (mean duration post transplantation = 2.5 years). Four of these patients had serial studies with an average interval between studies of 8.3 months (range 3-14 months). Coronary angiography was performed within 12 months of each 201Tl study (mean = 4.2 months). Using the coronary angiographic diagnostic criterion of > or = 50% stenosis in one or more vessels, one or more fixed or reversible segmental defects were found on 201Tl imaging with a sensitivity of 78% and specificity of 33%. When the angiographic criterion of > 70% stenosis in one or more vessels was used the sensitivity increased to 100%, and where reversible segments were diagnostic the sensitivity was 67% and the specificity range from 42 to 58%. Although based on a small sample of patients, these results suggest that use of appropriate test methods and interpretive criteria may improve the utility of 201Tl SPET myocardial imaging in the diagnosis of coronary artery disease in cardiac transplant patients. Limited specificity may reflect associated pathological processes in these patients, including rejection, oedema and focal inflammation.

Prostatic calcifications detected on Tc-99m MDP bone scan mimicking bone metastasis.

Uptake of Tc-99m MDP tracer was noted within prostatic calcifications in a 48-year-old man with no known malignancy who underwent a three-phase bone scan for left knee and thigh pain. Routine anterior and posterior views of the pelvis demonstrated focal tracer uptake within the right pubic bone, which mimicked a metastatic lesion. Additional imaging showed the uptake to be extraosseous and localized within the prostate in a distribution similar to the extensive prostatic calcifications seen on the corresponding plain film and computed tomography examinations of the pelvis. This unusual presentation illustrates another potential artifact that may be present in scintigraphic bone imaging of the pelvis.

99Tcm-pyrophosphate myocardial scintigraphy: the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction.

The aim of this study was to evaluate the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction (AMI) using 99Tcm-pyrophosphate (99Tcm-PYP) scintigraphy in a diagnostically difficult group of patients. In total, 117 patients were studied using planar, single photon emission tomography (SPET) and 3-D volume-rendered imaging performed 3 h after receiving 555 MBq (15 mCi) of 99Tcm-PYP intravenously. 555MBq (15 mCi) of 99Tcm-PYP intravenously. Two teams of physicians reported in a blinded and random fashion on each planar, SPET and 3-D rotating image study. Individual reports were compared with reports that used all three imaging modalities in combination. Observer reproducibility was between 85 and 90% and inter-observer team agreement was between 87 and 91%. A score based on clinical history, electrocardiography, serum cardiac enzyme levels and cardiac risk factors was validated and used as a de facto 'gold standard' for AMI for 75 of the subjects for whom all these details were available. The sensitivity, specificity and overall accuracy of combined planar, SPET and 3-D rotating image modalities were all 84%. Analysis of each modality in isolation showed SPET imaging to have the highest sensitivity (74%) and specificity (89%). In combination with SPET and planar imaging, 3-D rotation image presentation increases diagnostic sensitivity without appreciably altering overall diagnostic accuracy. 99Tcm-PYP myocardial SPET imaging shows good utility in the diagnosis of AMI in diagnostically difficult patients.

Lymphatic flow rates and first-aid in simulated peripheral snake or spider envenomation.

OBJECTIVES: To demonstrate and define normal lymphatic transit times by lymphoscintigraphy and to evaluate the efficacy of the currently recommended first-aid measures for the management of snake or spider envenomation. SETTING: The nuclear medicine department of a major teaching hospital. PARTICIPANTS AND DESIGN: Twenty-four subjects received either intradermal or subcutaneous injections of 99mtechnetium antimony sulfur colloid (0.1 mL) in both hands/forearms and feet/legs. This simulated a snake or spider bite. Fifteen of the subjects had first-aid in the form of firm bandages and splints applied to an upper and a lower limb immediately after injection. MAIN OUTCOME MEASURES: The progress of the radiotracer was followed with a large field of view gamma camera. If no egress of radiotracer was seen in the bandaged limbs, the subject walked until radioactivity was detected. RESULTS: The mean (+/- SEM) periphery-to-systemic circulation transit time after subcutaneous injection was 58 (+/- 7) minutes. The first-aid was found to be very effective when applied with bandage pressures ranging from 40 to 70 mmHg (5.3-9.3 kPa) in the upper limb and 55 to 70 mmHg (7.3-9.3 kPa) in the lower limb. Lower and higher bandage pressures were ineffective. However, despite first-aid measures, egress of radiotracer, even in the upper limbs, was seen in all subjects who walked for 10 minutes or more. CONCLUSIONS: Firm pressure bandaging is an effective means of restricting the lymphatic flow of toxins after envenomation, provided the bandage is applied within the defined pressure range. Strict limb immobilisation is necessary to minimise lymphatic flow, and walking after upper or lower limb envenomation will inevitably result in systemic envenomation despite first-aid measures.

Calcium channel blocking drug overdose: an Australian series.

1. A descriptive case study of calcium channel-blocking drug (CCB) overdoses in the Hunter Region of NSW was performed to analyse the in-hospital morbidity and mortality of CCB drug overdoses in an Australian population. 2. The patients were admitted to major hospitals within the Hunter Region and treated initially with gastrointestinal decontamination, including the use of oral activated charcoal. Further management was required in most cases and included intravenous calcium, atropine and inotropic support. 3. Of the 15 CCB overdoses, four patients died. Noncardiogenic pulmonary oedema occurred in two other cases. Cardiac conduction defects occurred in 11 cases. 4. Atropine was found to be effective only after intravenous calcium had been administered. 5. Overdose with slow-release verapamil required prolonged treatment with intravenous calcium salts. 6. Overdose with verapamil or diltiazem in doses greater than 300 mg carries a significant risk of death and potentially life threatening arrhythmias occur with lower doses. 7. Recommended initial management includes early, effective gastrointestinal decontamination. High dose intravenous calcium salts should be given to reverse hypotension and bradycardia. Atropine and inotropic support are frequently required.

Digoxin-like immunoreactive substances in the plasma of intensive care unit patients: relationship to organ dysfunction.

Digoxin-like immunoreactive substances are an endogenous group of compounds that cross-react in conventional immunoassays for digoxin. Plasma digoxin-like immunoreactive substance concentrations were estimated using the Abbott TDxll fluorescence polarisation immunoassay kit for digoxin. Digoxin-like immunoreactive substances were measured in one hundred consecutive Intensive Care Unit (ICU) patients who were not treated with digoxin. One hundred healthy blood donors were used as controls. Thirty of the ICU patients had plasma digoxin-like immunoreactive substance concentrations greater than or equal to the greatest value found in the control group (0.22 nmol/l). In the ICU group the median value was 0.17 nmol/l and the range zero to 1.69 nmol/l. In the control group the median was less than the limit of detection of the assay, and the range zero to 0.22 nmol/l. Sixteen ICU patients had coexisting renal and hepatic dysfunction and this group had a median digoxin-like immunoreactive substance concentration of 0.21 nmol/l (range zero to 1.69 nmol/l), while 38 patients with hepatic dysfunction and normal renal function had a median concentration of 0.17 nmol/l (range zero to 0.77 nmol/l). In contrast four patients with renal dysfunction only had a median concentration of 0.05 nmol/l (range zero to 0.34 nmol/l). The remaining forty-two patients had neither hepatic nor renal dysfunction and this group had a median concentration of 0.15 nmol/l (range zero to 0.36 nmol/l). This study has identified the critically ill as a group of patients who exhibit measurable plasma digoxin-like immunoreactive substances using the most commonly used kit for analysis of digoxin.

Age-related responses to influenza vaccination in the Newcastle region during 1983 and 1984.

A study was carried out in Newcastle to assess responses to influenza vaccines in elderly nursing home patients and in younger adults during 1983 and 1984. The decision to vaccinate the elderly subjects was made by their general practitioners. A concurrent randomized placebo-controlled trial of the same vaccine was performed in young adult volunteers. Elderly subjects generally possessed higher levels of pre-existing antibody to the influenzal haemagglutinins that were present in the vaccines than did younger subjects. The highest levels were observed in the 52-63 years' age group. Younger subjects showed significantly greater responses to vaccines compared with elderly subjects (P less than 0.05). Peak responses were noted in the 16-24 years' age group. Of a total of 326 elderly subjects (70% of whom had been vaccinated), six participants, two of whom had been vaccinated, contracted laboratory-proven influenza during 1983. Only one unvaccinated subject of a total of 365 subjects (50% of whom had been vaccinated) contracted influenza during 1984. In both years illness was produced by strain A/Philippines/2/82.