Gustation in oral submucous fibrosis

The sense of gustation was assessed in a group of fifty oral submucous fibrosis patients. About 24% showed some degree of impairment of taste sensation, which was shown to be related to the severity and extent of the disease. The possible reasons for the loss of gustation in oral submucous fibrosis are discussed.     

Prospective evaluation of combined upper and lower extremity DVT

The clinical importance of upper extremity deep venous thrombosis (UEDVT) has been increasingly demonstrated in recent literature. Not only has the risk of pulmonary embolism from isolated upper extremity DVT been demonstrated, but a significant associated mortality has been encountered. Examination of this group of patients has demonstrated the existence of combined upper and lower extremity deep venous thrombosis (DVT) in some patients who exhibit an even higher associated mortality. As a result of this information, it has become the standard practice at this institution to search for lower extremity DVTs in patients found to have acute thrombosis of upper extremity veins. Since January 1999, there have been a total of 227 patients diagnosed with acute UEDVT. Within this group, 211 (93%) patients had lower extremity studies; 45 of these 211 (21%) had acute lower extremity DVTs by duplex examination in addition to the upper extremity DVTs. Overall, there were 145 women, 66 men, and the average age was 70 +/-1.2 (SEM); 22 of these patients had bilateral lower extremity thrombosis (LEDVT), and 8 patients were found to have chronic thrombosis of lower extremity veins. Of the patients with bilateral upper extremity DVTs, there were 3 with bilateral LE acute DVTs. Finally, 8 of the remaining 166 patients (5%) with originally negative lower extremity studies were found to develop a thrombosis at a later date. These data serve to confirm previous studies, on a larger scale, that there should be a high index of suspicion in patients with UEDVT of a coexistent LEDVT.     

Efficacy and safety of hypoglycemic drugs in children with type 2 diabetes mellitus

STUDY OBJECTIVES: To assess the characteristics of children with type 2 diabetes mellitus and to determine the efficacy and safety of drug therapies for this disease in this population. DESIGN: Retrospective review of medical records. SETTING: Endocrinology specialty clinic at a tertiary teaching children's hospital. PATIENTS: Forty-two children and adolescents with type 2 diabetes examined between January 1996 and December 2001. MEASUREMENTS AND MAIN RESULTS: Demographic information, presenting signs and symptoms, drug history, and laboratory values were obtained in all patients. Presenting signs and symptoms were similar to those seen in adults. Patients were initially treated with metformin (14.3%), sulfonylureas (14.3%), insulin (31.0%), or combination therapy (14.3%). Most drug regimens decreased hemoglobin A 1c (A1C) levels. Overall, patients treated with drugs had a significant decrease in A1C values, from 10.6% +/- 2.7% (mean +/- SD) before treatment to 8.0% +/- 2.0% at 3.2-52.9 months of treatment (p<0.001). Adverse reactions attributed to drugs included hypoglycemia and gastrointestinal distress. CONCLUSION: Drug therapy appears to be effective in lowering A1C values in pediatric patients, although further prospective trials are necessary to determine optimal drug therapy in this population.     

The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

The apicomplexan parasite Toxoplasma gondii can cause severe disease in immunocompromised individuals. Previous studies in mice have focused largely on CD8(+) T cells, and the role of CD4 T cells is relatively unexplored. Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response. To identify the CD4 T cell-stimulating antigens, we generated a T. gondii-specific, lacZ-inducible, CD4 T cell hybridoma and used it as a probe to screen a T. gondii cDNA library. We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells. Immunization of mice with the AS15 peptide provided significant protection against subsequent parasite challenge, resulting in a lower parasite burden in the brain. Our findings identify the first CD4 T cell-stimulating peptide that can confer protection against toxoplasmosis and provide an important tool for the study of CD4 T cell responses and the design of effective vaccines against the parasite.     

Role of Duplex Arteriography as the Sole Preoperative Imaging Modality Prior to Lower Extremity Revascularization Surgery in Diabetic and Renal Patients

The limitations and complications associated with contrast angiography (CA) prior to lower extremity revascularization have led to an increased interest in duplex arteriography (DA) as a potential replacement. We report our experience with DA in patients with diabetes and/or chronic renal insufficiency (CRI) that would particularly benefit from a noninvasive approach to preoperative evaluation of the arterial tree. From January 1998 to November 2000, DA was performed in 145 patients with diabetes mellitus and/or CRI prior to 180 arterial reconstructions. One hundred twenty-one procedures were performed on 91 patients with diabetes alone, 41 on 33 patients with diabetes and CRI, and 18 on 15 patients with CRI alone. Patient ages ranged from 36 to 98 years (mean 72 ± 12 years). Indications for surgery were severe claudication in 33 (18%), rest pain in 37 (21%), nonhealing ischemic ulcers in 52 (29%), and limb gangrene in 58 (32%). Optimal inflow and outflow anastomotic sites were selected according to a diagram based on DA that included arterial tree imaging from mid-aorta to the pedal vessels. Preoperative contrast arteriography was performed in 16 cases (9%) because of extremely poor runoff based on DA and limited visualization of outflow vessels. The distal anastomosis was to the popliteal artery in 89 cases (49%) and to the tibial and pedal arteries in 91 (51%). Intraoperative findings confirmed the preoperative DA results with the exception of one (0.6%) where the distal anastomosis was placed proximal to a significant stenosis requiring an extension graft. The use of DA presents a safe and reliable option to prebypass CA for many patients with diabetes or CRI. The ease of use and favorable patient outcomes achieved by this imaging modality may rival the use of CA for these patients.Presented at the Southern Association for Vascular Surgery, Rio Grande, Puerto Rico, January 26, 2001.     

First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma

Checkpoint inhibitors targeted at programmed cell death‐1 receptor (PD‐1) and its ligand (PD‐L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third‐line setting and beyond based on the KEYNOTE‐059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD‐1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD‐1 blockade and chemotherapy may be important in this disease.     

Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention.

Cytostatic antibiotics of the anthracycline class are the best known of the chemotherapeutic agents that cause cardiotoxicity. Alkylating agents such as cyclophosphamide, ifosfamide, cisplatin, carmustine, busulfan, chlormethine and mitomycin have also been associated with cardiotoxicity. Other agents that may induce a cardiac event include paclitaxel, etoposide, teniposide, the vinca alkaloids, fluorouracil, cytarabine, amsacrine, cladribine, asparaginase, tretinoin and pentostatin. Cardiotoxicity is rare with some agents, but may occur in >20% of patients treated with doxorubicin, daunorubicin or fluorouracil. Cardiac events may include mild blood pressure changes, thrombosis, electrocardiographic changes, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, cardiac failure (left ventricular failure) and congestive heart failure. These may occur during or shortly after treatment, within days or weeks after treatment, or may not be apparent until months, and sometimes years, after completion of chemotherapy. A number of risk factors may predispose a patient to cardiotoxicity. These are: cumulative dose (anthracyclines, mitomycin); total dose administered during a day or a course (cyclophosphamide, ifosfamide, carmustine, fluorouracil, cytarabine); rate of administration (anthracyclines, fluorouracil); schedule of administration (anthracyclines); mediastinal radiation; age; female gender; concurrent administration of cardiotoxic agents; prior anthracycline chemotherapy; history of or pre-existing cardiovascular disorders; and electrolyte imbalances such as hypokalaemia and hypomagnesaemia. The potential for cardiotoxicity should be recognised before therapy is initiated. Patients should be screened for risk factors, and an attempt to modify them should be made. Monitoring for cardiac events and their treatment will usually depend on the signs and symptoms anticipated and exhibited. Patients may be asymptomatic, with the only manifestation being electrocardiographic changes. Continuous cardiac monitoring, baseline and regular electrocardiographic and echocardiographic studies, radionuclide angiography and measurement of serum electrolytes and cardiac enzymes may be considered in patients with risk factors or those with a history of cardiotoxicity. Treatment of most cardiac events induced by chemotherapy is symptomatic. Agents that can be used prophylactically are few, although dexrazoxane, a cardioprotective agent specific for anthracycline chemotherapy, has been approved by the US Food and Drug Administration. Cardiotoxicity can be prevented by screening and modifying risk factors, aggressively monitoring for signs and symptoms as chemotherapy is administered, and continuing follow-up after completion of a course or the entire treatment. Prompt measures such as discontinuation or modification of chemotherapy or use of appropriate drug therapy should be initiated on the basis of changes in monitoring parameters before the patient exhibits signs and symptoms of cardiotoxicity.