Single molecule DNA origami nanoarrays with controlled protein orientation.

The nanoscale organization of functional (bio)molecules on solid substrates with nanoscale spatial resolution and single-molecule control-in both position and orientation-is of great interest for the development of next-generation (bio)molecular devices and assays. Herein, we report the fabrication of nanoarrays of individual proteins (and dyes) via the selective organization of DNA origami on nanopatterned surfaces and with controlled protein orientation. Nanoapertures in metal-coated glass substrates were patterned using focused ion beam lithography; 88% of the nanoapertures allowed immobilization of functionalized DNA origami structures. Photobleaching experiments of dye-functionalized DNA nanostructures indicated that 85% of the nanoapertures contain a single origami unit, with only 3% exhibiting double occupancy. Using a reprogrammed genetic code to engineer into a protein new chemistry to allow residue-specific linkage to an addressable ssDNA unit, we assembled orientation-controlled proteins functionalized to DNA origami structures; these were then organized in the arrays and exhibited single molecule traces. This strategy is of general applicability for the investigation of biomolecular events with single-molecule resolution in defined nanoarrays configurations and with orientational control of the (bio)molecule of interest.

Treatment of low back pain associated with ;;back mice'': a case series.

Back mice are subcutaneous fibroadenomatous nodules that cause low back symptoms. Previous case reports do not provide systematic descriptions of the clinical presentation or long-term follow-up of this problem. This retrospective case series reports syndrome characteristics and treatment outcomes for injection therapy for "back mice." We completed telephone interviews, chart reviews, and written questionnaires for a convenience sample of 35 participants. Participants reported the following symptoms: pain radiating to the lower leg (37%), leg numbness or paresthesias (14%), and a median of 8 weeks of pain before treatment (range 3 weeks to 10 years). Thirty-one participants (89%) received lasting relief from injection of local anesthetic and corticosteroid. Injection therapy relieved both local and radiating symptoms but often did not eliminate the nodules. Thirty participants (86%) were "satisfied" or "very satisfied" with the treatment. There were no adverse events reported. Back mice can cause radiating pain that can be confused with other low back or leg syndromes. Injection treatment seems to be effective, long lasting, and well tolerated. Physicians should search for these nodules in patients with unexplained low back pain and try injection therapy before initiating expensive therapy.

Alcoholism in adolescents and their families. Family-focused assessment and management.

A family-focused approach is the most effective clinical method in the assessment and management of substance abuse in adolescents and their parents. The impact of alcoholism and substance abuse on parents and children, psychosocial risk factors, and indicators of alcoholism are important considerations when using this approach. Education regarding the family-focused approach to the treatment of substance abuse deserves a high priority in the training of pediatricians and other primary care physicians. As Doherty and Baird suggest," . . . the key to this training will not be . . . the development of a more sensitive liver function test, . . . but (rather) will be to help primary care physicians view individual patients as a part of a social context. The challenge will be to train the physicians to evaluate the patient in his or her social and family system for significant disturbances that commonly occur with chemical dependency. By evaluating the presenting patient in a family context, the primary care physician has the means to discover chemical dependency in early stages, when treatment options are less disruptive; when outcome is improved; and when the emotional and economic losses to patient, family and community are reduced."

Validity of the Family APGAR in patients with irritable bowel syndrome.

BACKGROUND: This study explores the validity of the Family APGAR (adaptability, partnership, growth, affection, and resolve), a test of family function, in persons with irritable bowel syndrome (IBS). Previous studies have reported increased stress in persons with IBS in the form of marital and interpersonal relationships. METHODS: The Family APGAR and the MMPI were completed by 198 persons, including 58 who sought care for IBS, 67 with IBS who did not seek care, and 73 who did not have the disorder. Family APGAR scores were compared for the three groups using analysis of variance. Multiple regression analysis was used to compare Family APGAR scores with both IBS group status and MMPI K and L scales. An odds ratio was calculated for the two groups with IBS. RESULTS: Mean Family APGAR scores were in the normal range for all three groups and differed by less than 1 point among the groups. The Family APGAR score did not differentiate among persons with IBS but was strongly related to the MMPI K score, a measure of defensiveness in test taking. CONCLUSIONS: The failure of the Family APGAR to detect the family dysfunction found by psychological interviewing and the strong relationship with the MMPI K scale lead us to question the construct validity of the APGAR. More sophisticated test construction is necessary to measure family dysfunction in patients who may tend to respond defensively.

Dermatologic adverse drug reactions in a family medicine setting.

To determine the prevalence of dermatologic adverse drug reactions in a family medicine outpatient practice setting, identify associated drug classes, and describe associated patient demographics and risk factors, we reviewed the charts of 557 patients in a university-based family medicine center who were diagnosed with a dermatologic condition. The study population included all patients diagnosed during a 1-year period. Thirty-five patients (6.3%) were identified as having dermatologic adverse drug reactions, of which the two most common types were exanthematous eruptions (n = 18 [51.4%]) and generalized erythroderma (n = 6 [17.1%]), with antibiotic use accounting for the majority (n = 21 [60.0%]) of reactions. Patient characteristics most commonly associated with a dermatologic adverse drug reaction were race (African-American), gender (female), and age (70 years and older). These data should provide insight into the types of cutaneous drug reactions commonly seen in community practice. Educational programs in all health-care disciplines, particularly medicine, pharmacy, and public health, that incorporate pharmacoepidemiologic strategies into their curricula are necessary to improve the overall process of monitoring and reporting of adverse drug reactions.

Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome.

We used a pharmacokinetically derived phenobarbital dosing protocol to treat alcohol withdrawal syndrome in patients admitted to a family medicine inpatient service. We describe the protocol and include two case reports documenting its efficacy. Although benzodiazepine agents are considered by many to be the primary agents of choice, based upon our experience and its ease of administration, relative safety, therapeutic efficacy, and lower cost, phenobarbital should be reconsidered as a promising alternative. Comparative trials between these two therapeutic classes will clarify their roles in the treatment of alcohol withdrawal syndrome.

Drug-related admissions to a family medicine inpatient service.

Admissions to a family medicine inpatient service were monitored retrospectively over a one-year period to determine the incidence of drug-related hospitalizations. Of the 293 admissions, 45 (15.4%) were identified as drug related; in 29 admissions (9.9%), a drug-related problem was identified as the primary cause of hospitalization. The two patient characteristics associated with a drug-related admission (DRA) were marital status (divorced) and age (older patients). The two most common types of DRAs were adverse drug reactions (17/45, 37.8%) and drug abuse (14/45, 31.1%), with alcohol being the most commonly abused agent. Adverse drug reactions were most commonly implicated in DRAs for patients over 70 years old, with drug abuse more evenly distributed among age groups. Educational programs that incorporate pharmacoepidemiologic strategies into all health care disciplines are necessary to address this public health issue.

Office glucose analysis.

The advent of dry chemistry techniques has made inexpensive glucose testing equipment available to physicians and their patients. The ability to measure blood glucose concentration quickly, in almost any setting, has eliminated urinary glucose monitoring as the parameter of choice for managing diabetic patients. Blood glucose monitoring has allowed improved control of diabetic patients who avail themselves of one of the techniques. The physician choosing to offer blood glucose testing in the office laboratory has a variety of test equipment from which to choose. Most physicians will want to own and operate an inexpensive, dedicated glucose reflectometer to test glucose samples in the office and to use in patient education. Machines used by both patients and physicians are about the same price. They are easy to learn to use. Office personnel must be trained to perform the procedure, teach it to patients, maintain the machine, and keep adequate quality control records.

Serum drug level utilization review in a family medicine residency program.

A total of 161 tests, comprising six of the most commonly ordered serum drug levels (SDLs) in a family medicine residency program, were audited retrospectively by a review panel. Audit criteria assessed the appropriateness of three factors associated with this laboratory test ordering procedure: (1) indication for the level, (2) procedure and documentation, and (3) physician utilization of the results. There were no statistically significant differences (P less than .05) when comparing the percentage of appropriate indications and uses with the individual drug levels ordered or with the number of years in practice. However, this audit indicated that a large number of therapeutic decisions were based upon information obtained from improperly ordered SDLs. Also, lack of proper documentation and charting of SDLs appeared to hamper optimal continuity of care in a clinic where patients were seen by several physicians. It is suggested that educational and administrative strategies may be effective in promoting better ordering and use of laboratory tests by family physicians in the future.

Laboratory testing in the office of family physicians.

A survey of family physicians was carried out among members of the state academies of family practice and graduates of residency programs in Ohio and North Carolina. Results of the survey demonstrated both an increasing number of laboratories in the offices of all family physicians as well as in increasing variety of laboratory procedures offered. It was found that solo practitioners frequently perform laboratory work themselves, while group practitioners more often delegate laboratory work to other office staff, such as certified laboratory technicians or nurses. Quality control was offered in one-half of the private offices surveyed, and in three-quarters of the office that employed certified laboratory technicians. Results of this study suggest that the increasing number of family practice residency graduates may result in an increased demand for certified laboratory technicians in private office laboratories.