Cladribine therapy in refractory celiac disease with aberrant T cells.

BACKGROUND & AIMS: Refractory celiac disease (RCD) may be subdivided into RCD types I and II with phenotypically normal and aberrant intraepithelial T-cell populations, respectively. In RCD II, transition into enteropathy-associated T-cell lymphoma (EATL) is seen frequently. We have evaluated the effect of cladribine (2-CDA), a purine analogue inducing T-cell depletion, on clinical, histopathologic, and immunologic parameters, as well as the toxicity and side effects in a group of RCD II patients. METHODS: Between 2000 and 2005, 17 patients were included (8 men, 9 women). All patients had a clonal rearrangement of the T-cell receptor gamma gene and immunophenotyping showed an aberrant T-cell population lacking surface expression of CD3, CD8, and T-cell receptor alphabeta, in the presence of expression of surface CD103 and intracytoplasmic CD3. Treatment consisted of 2-CDA (0.1 mg/kg/day) intravenously for 5 days, given in 1-3 courses every 6 months depending on the response. RESULTS: All patients tolerated 2-CDA without serious side effects. Six patients (35.8%) showed a clinical improvement (weight gain, improvement of diarrhea, and hypoalbuminemia). In 10 patients (58.8%) a significant histologic improvement and in 6 patients (35.2%) a significant decrease in aberrant T cells was seen. Seven patients (41.1%) developed EATL and died subsequently. One patient died of progressive refractory state with emaciation. CONCLUSIONS: Treatment with 2-CDA in RCD II is feasible, well tolerated, and can induce clinical and histologic improvement as well as a significant decrease of aberrant T cells in a subgroup of patients, albeit it does not prevent EATL development. However, the earlier reported potential risk of precipitating an overt lymphoma should be taken into consideration.     

Initial steps taken by nine primary care practices to implement alcohol screening guidelines with hypertensive patients: the AA-TRIP project.

Many medical conditions are caused or exacerbated by heavy drinking, necessitating alcohol screening and discussion in primary care practices. This is particularly true of hypertension, the most common primary diagnosis in the United States, which has been linked to the regular consumption of 3 or more standard alcoholic beverages a day. The Accelerating Alcohol Screening-Translating Research into Practice (AA-TRIP) project was designed to improve detection and management of alcohol problems in primary care patients with hypertension. Medical providers are being trained using the Practice Partner Research Network's- Translating Research into Practice (PPRNet-TRIP) quality improvement model. This includes a multi-method intervention (electronic medical records, on-site academic detailing, practice feedback reports and annual network meetings) to help practices increase adherence to clinical guidelines. Qualitative analyses of initial steps taken by nine primary care practices toward the routine implementation of alcohol screening guidelines are presented. Organizational factors and provider and patient characteristics all influenced the method and consistency of alcohol screening and intervention. Perceived time constraints, patient sensitivity to questions about alcohol, and possible stigma associated with a diagnosis of alcoholism were also relevant barriers requiring problem solving.     

Sensitive trace-first liquid chromatographic determination of 4-aminopyridine in 3,4-diaminopyridine

For the treatment of human neuromuscular diseases, 3,4-diaminopyridine (DAP) is six to ten times more effective than 4-aminopyridine (AP), but only half as convulsant and toxic. Therefore, there is a need for the determination of AP in DAP. With only conventional equipment, high-pressure liquid chromatography can be used for the extremely sensitive detection of a trace contaminant under one condition: that is, the trace must be eluted before the major component it contaminates. Prior elution presents a trace peak in a fully exploitable form that is maximally efficient and maximally observable. This has already been demonstrated with a Pirkle-concept chiral stationary phase for determination of a chiral trace. However, its application to determination of a nonchiral trace with a reversed phase has not previously been reported. Such an application is reported here. In this demonstrative study, selectivity and loading capability were iteratively improved. Ion pairing with dodecanesulfonate maximized selectivity. It was again shown that using a less concentrated sample in greater volume maximizes loading capability without obscuring the peak of the trace. Eventually, the ability to detect 0.005% AP in DAP was demonstrated. Whether that sensitivity might be improved still more, perhaps with a larger column, was not established.     

Glued-on, rigid gas-permeable contact lens for severe radiation-induced keratitis.

A 68-year-old woman with severe radiation-induced keratoconjunctivitis sicca became progressively unresponsive to conventional medical treatment. Her left eye deteriorated rapidly and required total tarsorrhaphy. In an attempt to stabilize the right eye and preserve some functional vision, we glued a high-Dk rigid, gas-permeable contact lens with tissue-grade cyanoacrylate adhesive to Bowman's membrane. This glued-on contact lens induced rapid and dramatic improvement of the patient's comfort and sight. Recent developments in high-permeability, rigid, contact-lens materials now make artificial replacement of the epithelium a potentially useful treatment for severe ocular surface disease when conventional treatment has failed.     

Gangliosides and sialoglycoproteins in hypothalamus of normal, postnatal, and pre- and postnatal protein undernourished rats.

Total ganglioside and sialoglycoprotein concentrations were determined in the hypothalamus of normal (diet: 25% casein), postnatal undernourished (diet: 8% casein since birth), and pre- and postnatal undernourished rats (diet: 8% casein since pregnancy). Hypothalamic weights for the two low protein diet groups were lower than for the normal diet groups at all ages studied. Total hypothalamic ganglioside and sialoglycoproteins (mumol NANA) of postnatal undernourished rats were lower than control at day 10, while in pre- and postnatal undernourished rats this difference occurred at day 7. The reduction in gangliosides and sialoglycoprotein contents was not solely a consequence of the decrease in hypothalamic weight since, when the data were expressed as nmol NANA/mg tissue, similar reductions were observed principally in the pre- and postnatal protein undernutrition group. These results suggest that the effects of pre- and postnatal undernutrition on hypothalamic gangliosides and sialoglycoproteins are more pronounced than those that occur as a result of postnatal undernutrition.