Stephen Hall

Takayasu arteritis: A study of 32 north American patients

Thirty-two patients (26 female, 6 male) with angiographically diagnosed Takayasu arteritis were seen at the Mayo Clinic between 1971 and 1982. Racial composition of this group was 23 North American Caucasians, 4 Mexicans, 3 Orientals, 1 Native American, and 1 patient of Middle Eastern origin. Incidence of the disease in Olmsted County, Minnesota, was 2.6/million/year. Diagnosis was often delayed for long periods of time, with a median delay of 18 months. Patients had both non-vascular symptoms (arthralgias in 56%, fever in 44%, weight loss in 38%) and symptoms of vascular stenosis such as arm claudication (47%) and hypertension due to renal artery stenosis (41%). All patients had either multiple vascular bruits (94%) or absent pulses (50%). Laboratory findings included anemia (44%) and elevations of erythrocyte sedimentation rate (78%). Almost all patients had multiple sites of arterial involvement documented by angiogram with various combinations of stenosis, luminal irregularity and aneurysm formation. Response to corticosteroid treatment was usually very good, with dramatic improvement in non-vascular symptoms and return of pulses in 8 of the 16 patients with absent pulses prior to treatment. Five-year survival rate from time of diagnosis was 94%. Twelve patients underwent surgical procedures involving the carotid arteries (5 cases), subclavian artery (4 cases) and renal arteries (3 cases). Three aneurysms were resected, one had aortic valve replacement for severe aortic regurgitation, and two patients underwent transluminal angioplasty. Pathologic changes were restricted to the media and adventitial layers of the vessel wall and were indistinguishable from those of giant-cell or temporal arteritis. Takayasu arteritis is more common than previously suspected in North America, is not restricted to any one racial group, and is readily treatable with corticosteroids and surgical vascular reconstruction.

Lumbar Spinal Stenosis: Clinical Features, Diagnostic Procedures, and Results of Surgical Treatment in 68 Patients

Our experience with 68 patients with strictly defined, myelographically proven, surgically confirmed lumbar spinal stenosis seen over a 30-month period was reviewed. Pseudoclaudication was the commonest symptom (94%) and was described by patients as pain (93%), numbness (63%), or weakness (43%). Symptoms were frequently bilateral (68%) and generally relieved by flexing the lumbosacral spine. Neurologic abnormalities were found in a minority of patients and were usually mild. Electromyography showed one or more lumbosacral radiculopathies in 34 of 37 patients examined. Radiographic evidence of degenerative disk or joint disease was found in 63 patients. All patients had stenosis on myelography, with narrowing at L2, L3, and L4 being the commonest; 30% had multi-level stenosis. Two of ten computed tomograms were normal. Surgery was extensive; 72% of patients had three or more laminae removed. At a mean of 4 years after surgery, 84% of patients reported that surgery had yielded good to excellent results.

Physiologically based pharmacokinetic modeling in drug discovery and development: A pharmaceutical industry perspective

The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on “how PBPK modeling can be applied in industry” focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.

Respiratory Tract Symptoms as a Clue to Giant Cell Arteritis

Although many manifestations of giant cell arteries are increasingly recognized, little attention has been paid to respiratory symptoms associated with this disorder. We report the cases of 16 patients with giant cell arteritis who had prominent symptoms related to the respiratory tract including cough, sore throat, and hoarseness. These symptoms were the initial finding in 10 patients and obscured the diagnosis in some instances, but resolved quickly when corticosteroids were given. It is estimated that 9% of patients with giant cell arteritis have prominent respiratory tract symptoms, which are the initial manifestation in 4%. This disorder should be considered in an older patient with a new cough or throat pain without obvious cause.

Drug interactions with herbal products and grapefruit juice: A conference report

Shiew-Mei Huang, PhD, Stephen D. Hall, PhD, Paul Watkins, MD, Lori A. Love, MD, PhD, Cosette Serabjit-Singh, PhD, Joseph M. Betz, PhD, Freddie Ann Hoffman, MD, Peter Honig, MD, Paul M. Coates, PhD, Jonca Bull, MD, Shaw T. Chen, MD, PhD, Gregory L. Kearns, PharmD, PhD, and Michael D. Murray, PharmD, MPH Rockville and Bethesda, Md, Indianapolis, Ind, Chapel Hill and Research Triangle Park, NC, Morris Plains, NJ, West Point, Pa, and Kansas City, Mo

Splenectomy Does Not Cure the Thrombocytopenia of Systemic Lupus Erythematosus

Fourteen patients with systemic lupus erythematosus had splenectomies done between 1960 and 1982 for treatment of severe thrombocytopenia. Thrombocytopenia persisted or recurred within 1 month postoperatively in five patients and within 6 months in three others. Three patients had late recurrence (18, 30, and 54 months after splenectomy); in two it was probably related to withdrawal of immunosuppressive agents or corticosteroids. Median lowest platelet count before splenectomy and median platelet count at relapse or failure of splenectomy were both 8000/microL. Only two patients maintained normal platelet counts without need for corticosteroids or other treatment. These results differ from those in patients with idiopathic thrombocytopenic purpura. Other treatments should be tried before splenectomy is done for thrombocytopenia in patients with systemic lupus erythematosus.

Systemic Lupus Erythematosus Developing in Patients with Primary Biliary Cirrhosis

Three patients with biopsy-proven primary biliary cirrhosis subsequently developed a multisystem disorder and serologic abnormalities consistent with systemic lupus erythematosus. In one patient, antimitochondrial antibody titers fell to undetectable levels after the development of the extrahepatic manifestations. No patient had been exposed to D-penicillamine or other drugs capable of inducing a lupus-like condition. These patients further emphasize the difficulties in disease classification and underline the systemic nature of chronic liver diseases such as primary biliary cirrhosis.

Secular trends in the survival of patients with laryngeal carcinoma, 1995-2007

BACKGROUNDnRecent reports suggest a decline over time in the survival of patients newly diagnosed with laryngeal cancer in spite of developments in treatment practices. Our study set out to determine whether the survival of patients with laryngeal cancer in Ontario has changed over time.nnnMETHODSnThis population-based cohort study of patients diagnosed with laryngeal cancer in the province of Ontario between 1995 and 2007 used data extracted from linked provincial administrative and registry databases. Its main outcomes were overall survival, laryngectomy-free survival, and survival ratio relative to an age- and sex-matched general population.nnnRESULTSnThe 4298 patients newly diagnosed with laryngeal cancer during the period of interest were predominantly men (n = 3615, 84.1%) with glottic cancer (n = 2787, 64.8%); mean age in the group was 66 years (interquartile range: 59-74 years). Patient demographics did not significantly change over time. Overall, 5-year survival was 57.4%; laryngectomy-free survival was 45.4%. Comparing patients from three eras (1995-1998, 1999-2003, 2004-2007) and adjusting for age, sex, and comorbidity status, we observed no differences in overall survival or laryngectomy-free survival over time. The 5-year relative survival ratio for patients with laryngeal cancer compared with an age- and sex-matched group from the general population was 81.1% for glottic cancer and 44.5% for supraglottic cancer.nnnCONCLUSIONSnIn patients with a new diagnosis of laryngeal cancer, overall and laryngectomy-free survival have remained unchanged since the mid-1990s. New methods to improve survival and the rate of laryngeal preservation in this patient population are needed.

Treatment of Takayasu's Arteritis

Excerpt To the editor: The prospective analysis by Shelhamer and colleagues (1) of 20 patients seen at the National Institute of Health is a valuable contribution to the study of Takayasus arterit...

A Population-Based Study of 30-day Incidence of Ischemic Stroke Following Surgical Neck Dissection.

AbstractThe objective of this study was to determine the 30-day incidence of ischemic stroke following neck dissection compared to matched patients undergoing non-head and neck surgeries.A surgical dissection of the neck is a common procedure performed for many types of cancer. Whether such dissections increase the risk of ischemic stroke is uncertain.A retrospective cohort study using data from linked administrative and registry databases (1995–2012) in the province of Ontario, Canada was performed. Patients were matched 1-to-1 on age, sex, date of surgery, and comorbidities to patients undergoing non-head and neck surgeries. The primary outcome was ischemic stroke assessed in hospitalized patients using validated database codes.A total of 14,837 patients underwent surgical neck dissection. The 30-day incidence of ischemic stroke following the dissection was 0.7%. This incidence decreased in recent years (1.1% in 1995 to 2000; 0.8% in 2001 to 2006; 0.3% in 2007 to 2012; P for trend <0.0001). The 30-day incidence of ischemic stroke in patients undergoing neck dissection is similar to matched patients undergoing thoracic surgery (0.5%, Pu200a=u200a0.26) and colectomy (0.5%, Pu200a=u200a0.1). Factors independently associated with a higher risk of stroke in 30 days following neck dissection surgery were of age ≥75 years (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05–2.53), and a history of diabetes (OR 1.60, 95% CI 1.02–2.49), hypertension (OR 2.64, 95% CI 1.64–4.25), or prior stroke (OR 4.06, 95% CI 2.29–7.18).Less than 1% of patients undergoing surgical neck dissection will experience an ischemic stroke in the following 30 days. This incidence of stroke is similar to thoracic surgery and colectomy.