Sodium iodide symporter (NIS)-mediated radiovirotherapy of hepatocellular cancer using a conditionally replicating adenovirus.

In this study, we determined the in vitro and in vivo efficacy of sodium iodide symporter (NIS) gene transfer and the therapeutic potential of oncolytic virotherapy combined with radioiodine therapy using a conditionally replicating oncolytic adenovirus. For this purpose, we used a replication-selective adenovirus in which the E1a gene is driven by the mouse alpha-fetoprotein (AFP) promoter and the human NIS gene is inserted in the E3 region (Ad5-E1/AFP-E3/NIS). Human hepatocellular carcinoma cells (HuH7) infected with Ad5-E1/AFP-E3/NIS concentrated radioiodine at a level that was sufficiently high for a therapeutic effect in vitro. In vivo experiments demonstrated that 3 days after intratumoral (i.t.) injection of Ad5-E1/AFP-E3/NIS HuH7 xenograft tumors accumulated approximately 25% ID g(-1) (percentage of the injected dose per gram tumor tissue) (123)I as shown by (123)I gamma camera imaging. A single i.t. injection of Ad5-E1/AFP-E3/NIS (virotherapy) resulted in a significant reduction of tumor growth and prolonged survival, as compared with injection of saline. Combination of oncolytic virotherapy with radioiodine treatment (radiovirotherapy) led to an additional reduction of tumor growth that resulted in markedly improved survival as compared with virotherapy alone. In conclusion, local in vivo NIS gene transfer using a replication-selective oncolytic adenovirus is able to induce a significant therapeutic effect, which can be enhanced by additional (131)I application.

Death from inappropriate therapy for Lyme disease.

A 30-year-old woman died as a result of a large Candida parapsilosis septic thrombus located on the tip of a Groshong catheter. The catheter had been in place for 28 months for administration of a 27 month course of intravenous cefotaxime for an unsubstantiated diagnosis of chronic Lyme disease.

Increasing the proportion of women in academic medicine: one institution's response.

OBJECTIVE: To increase gender diversity among the physician consulting staff (PCS) at a major medical center. DESIGN: Because the proportion of female PCS at academic medical centers in the United States has not increased commensurately with increases in the proportion of female graduates from American medical schools, a modeling and graphing technique was developed to analyze this problem and recommend solutions for one large academic medical center. MATERIAL AND METHODS: Personnel data, by gender and year from 1980 through 1994, were collected for all PCS at Mayo Clinic Rochester (MCR). These data were compared with similar data from other US academic medical centers and were used to develop models to predict the proportion of female PCS at MCR yearly until 2005, assuming various hiring and resignation patterns. Novel techniques were developed to illustrate and compare the models. Model-based predictions were compared with national projections, and a realistic target proportion of female PCS was defined on the basis of assumptions about the proportion of female graduates from medical school and internship programs during the next 10 years as well as probable hiring, retention, and resignation rates at MCR. To identify issues critical to recruitment, retention, and professional growth of female PCS at MCR, we used factor analysis to assess responses to a confidential questionnaire sent to all female faculty members. RESULTS: In 1994 and 1995, the proportion of female PCS was 25% at US academic medical centers but only 15% at MCR, and the rate at which this proportion increased from 1980 through 1994 at MCR was also lower than the national rate. Model-based predictions demonstrated that gradually (1.5% per year) increasing the female percentage of new recruits from 26% in 1995 to 40% in 2005 would achieve the targeted 25% female PCS in 13 years. Questionnaire responses from 119 (68%) of the 175 female PCS at MCR identified 6 important recommendations for recruitment and retention of female PCS: survey resignees and candidates who decline positions; appoint more qualified women to policy-making committees; require sensitivity and diversity training for all staff (especially leaders); develop explicit, gender-sensitive criteria for selecting department and division chairs; compare Mayo gender and diversity data with national data at the department or division level; and develop mechanisms for mentoring junior female staff members. CONCLUSION: We developed useful methods for analyzing the PCS gender distribution, defined feasible hiring strategies, and identified specific recommendations to enhance the professional experience of female PCS. These methods can provide a model for other institutions seeking to optimize gender diversity among their staff.

Management of urinary retention: rapid versus gradual decompression and risk of complications.

The literature was reviewed to quantify the risk of complications related to the relief of obstruction in urinary retention. We also sought to determine whether the risk of complications is higher with rapid or gradual decompression (or "clamping") of the obstructed urinary bladder. The medical literature was identified by a search of the MEDLINE database and a manual review of the bibliographies of the identified articles. Studies show that, after quick, complete relief of obstruction, hematuria occurs in 2 to 16% of patients; however, clinically significant hematuria is rare. After relief of obstruction, blood pressure often decreases, but it usually normalizes and does not progress to clinically significant hypotension. Postobstructive diuresis occurs after relief of obstruction in 0.5 to 52% of patients; however, it is easily managed and rarely of clinical significance. We were unable to identify any randomized controlled studies that directly compared quick, complete emptying with gradual emptying of the obstructed bladder. Moreover, we identified no studies supporting the practice of gradual emptying of the obstructed bladder. The available published studies support quick, complete emptying for relief of the obstructed urinary bladder. We conclude that hematuria, hypotension, and postobstructive diuresis may occur after decompression of the obstructed urinary bladder, but these complications are rarely clinically significant. Quick, complete emptying of the obstructed bladder is safe, simple, and effective and is recommended as the optimal method for decompressing the obstructed urinary bladder. Prudent, supportive care is needed for all patients, with special attention to elderly patients and those with hypovolemia.

Laryngeal carcinoma presenting as platypnea.

Platypnea, or dyspnea in the upright position relieved by recumbency, is most commonly associated with cardiac or pulmonary disease. We describe a patient who presented to the emergency department with platypnea due to a laryngeal carcinoma. A tumor of the upper airway should be considered in any patient presenting with platypnea.

A coproporphyria-like syndrome induced by glipizide.

A 49-year-old man with a 1-month history of episodic, severe abdominal pain sought medical attention. The patient's history was remarkable for type II diabetes, for which glipizide therapy had been initiated 2 months earlier. No other medications were being taken at the time the paroxysms of pain began. During the episodes of pain, both examination of the abdomen and abdominal roentgenograms revealed normal findings. Initial assessment, including ultrasonography and computed tomographic scanning of the abdomen, upper gastrointestinal and colon roentgenograms, and esophagogastroduodenoscopy, revealed no cause of the pain. Empiric trials of famotidine, sucralfate, and antacids failed to relieve the pain. Both urine and fecal specimens collected after an attack demonstrated substantially increased coproporphyrins. The glipizide regimen was discontinued; 2 months later, the stool coproporphyrins had decreased to normal levels. At follow-up more than 1 year later, the patient had had no recurrence of abdominal pain. Although other orally administered hypoglycemic agents and other sulfa compounds have been reported to precipitate acute attacks of porphyria, to our knowledge this is the first such case associated with glipizide. We suggest that glipizide be added to the list of medications to be avoided in patients with porphyria.

Incidence of malignant bone and joint tumors in Olmsted County, Minnesota, 1935 through 1981.

During the 47-year period 1935 through 1981, 30 cases of malignant bone and joint tumors (in 20 male and 10 female patients) were identified among Olmsted County, Minnesota, residents. The incidence rates per 100,000 population, age-adjusted to the 1970 US total white population, were 1.0 overall, 1.4 for male subjects, and 0.7 for female subjects. Mortality rates, likewise age-adjusted, were 0.7 overall and 1.1 and 0.3 for male and female subjects, respectively. These rates are similar to those from tumor registries, a finding that suggests that reporting of these tumors is relatively complete. The similarity of the incidence and the mortality rates is consistent with the high case-fatality rate. A comparison of the Olmsted County cases with Mayo Clinic referral cases provides some evidence for referral bias, as the referral patients were significantly younger and had significantly more high-grade tumors.

Fatal hemopericardium due to ruptured solitary myocardial abscess unassociated with infective endocarditis.

A case is presented of hemopericardium and sudden death due to rupture of a solitary myocardial abscess in an elderly woman with cirrhosis and mild urosepsis. If suspected clinically, such myocardial abscesses may be detectable by noninvasive tomographic cardiac imaging.

Severe generalized reactions to ibuprofen: report of a case.

A 46-year-old asplenic, nonatopic woman experienced at least one severe generalized reaction to ibuprofen. During her initial hospitalization for suspected septic shock, several laboratory results suggested disseminated intravascular coagulation. Results of oral dye, preservative, and aspirin challenges and tests for systemic lupus erythematosus were negative. She had remained well since she stopped taking ibuprofen. Awareness of the possibility of severe reactions to ibuprofen should be maintained when this medication is prescribed.