Adolescents with Type 1 diabetes mellitus experience psychosensorial symptoms during hypoglycaemia.

AIM: To describe mood and psychosensorial symptoms of hypoglycaemia in adolescents with Type 1 diabetes mellitus in two countries with different cultures, Turkey and the USA. METHODS: We developed a 68-item questionnaire assessing physical, behavioural, mood and psychosensorial symptom frequency and ratings ['good', 'bad', or 'both' (sometimes good, sometimes bad)]. Adolescents with Type 1 diabetes were recruited from paediatric diabetes clinics at the University of North Carolina at Chapel Hill in the USA and Kocaeli University in Turkey. The percentages of participants at each clinic who endorsed individual symptoms, symptom categories and symptom ratings were calculated and compared. RESULTS: Cronbach's α values were > 0.7 for each real symptom category. No symptom items were excluded from the questionnaire analysis based on item-total correlation results which were all > 0.2. Data were collected from 132 participants (69 from University of North Carolina, 63 from Kocaeli University, 54% male). The mean (SD) age of the participants was 14.9 (1.9) years, HbA1c level was 8.7 (1.8) % and duration of Type 1 diabetes was 5.8 (3.7) years. On average, each physical symptom was experienced by 65.2% of participants, each behavioural symptom by 46.5%, each mood symptom by 42.8%, and each psychosensorial symptom by 48.9%. On average, each physical, behavioral, mood and psychosensorial symptom was rated as 'good' or 'both' by 23.0, 29.1, 36.9 and 37.2% of participants, respectively. There were no symptom differences between the groups in each country. CONCLUSIONS: In addition to the classic physical symptoms experienced during hypoglycaemia, adolescents with Type 1 diabetes report psychosensorial, mood and behavioral symptoms, and some describe them as positive experiences. Symptom experiences were similar in these two countries with different cultures.

Bifocal versus unifocal right atrial pacing under plasma level controlled sotalol to prevent atrial fibrillation in patients with symptomatic sinus bradycardia and paroxysmal atrial fibrillation.

AIMS: Bifocal right atrial pacing (BP) has been reported to increase arrhythmia-free intervals in patients with paroxysmal atrial fibrillation (PAF) under antiarrhythmic drugs. This study compares AF burden with unifocal pacing (UP) vs BP under sotalol. METHODS: In 19 patients with PAF a DDDR pacemaker with right atrial lateral and CS ostial leads was implanted. Sotalol was initiated. After a 3 month back-up pacing period patients were randomized to continuous UP or BP for 3 months and crossed over for 3 more months. Primary endpoint was AF burden. Secondary endpoints included number of episodes, time to first recurrence and safety of BP. RESULTS: The intention to treat analysis revealed 12.4% AF during back-up, 6.2% during UP and BP (p=0.91 UP vs BP, p=0.08 back-up vs UP and p=0.07 back-up vs BP). Per protocol analysis showed no advantage of either pacing mode (UP 4.8% and BP 5.4% AF, p=0.64). Overdrive pacing reduced AF burden to 6.2 vs 8.8% during back-up (p=0.09). Septal lead dislodgement occurred in 3 patients. CONCLUSION: Atrial pacing tends to reduce AF burden in patients with PAF under sotalol. An incremental effect of BP vs UP cannot be confirmed. BP may be complicated by elevated lead dislodgement rates.

Association between the inception of a SAFE KIDS Coalition and changes in pediatric unintentional injury rates.

OBJECTIVE: To assess the relationship between the implementation of a SAFE KIDS Coalition and pediatric unintentional injury rates. SETTING: Shelby County, Tennessee. DESIGN: Retrospective observational analysis. PATIENTS: County residents nine years of age or younger presenting to the children's medical center, its emergency department, or its outpatient clinics from 1990-97. INTERVENTION: Implementation of a SAFE KIDS Coalition. MAIN OUTCOME MEASURES: Rates of unintentional injuries targeted by the SAFE KIDS Coalition that resulted in hospitalization or in death. Rates of motor vehicle occupant injuries that resulted in hospitalization or in death. Rates of non-targeted unintentional injuries, namely injuries secondary to animals and by exposure to toxic plants. Rates of severe injuries (defined as those targeted injuries that required hospitalization or resulted in death), and specifically, severe motor vehicle occupant injuries were compared before and after the inception of the coalition using Poisson regression analysis. RESULTS: The relative risk of targeted severe injury rates decreased after implementation of the coalition even after controlling for changes in hospital admission rates. Specifically, severe motor vehicle occupant injury rates decreased 30% (relative risk 0.70; 95% confidence interval 0.54 to 0.89) after initiation of the coalition. CONCLUSIONS: The implementation of a SAFE KIDS Coalition was associated with a decrease in severe targeted injuries, most notably, severe motor vehicle occupant injuries. Although causality cannot be determined, these data suggest that the presence of a coalition may be associated with decreased severe unintentional injury rates.

Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. In approximately 80% of patients, auto-antibodies to the muscle nicotinic acetylcholine receptor (AChR) are present. These antibodies cause loss of AChR numbers and function, and lead to failure of neuromuscular transmission with muscle weakness. The pathogenic mechanisms acting in the 20% of patients with generalized MG who are seronegative for AChR-antibodies (AChR-Ab) have not been elucidated, but there is evidence that they also have an antibody-mediated disorder, with the antibodies directed towards another, previously unidentified muscle-surface-membrane target. Here we show that 70% of AChR-Ab-seronegative MG patients, but not AChR-Ab-seropositive MG patients, have serum auto-antibodies against the muscle-specific receptor tyrosine kinase, MuSK. MuSK mediates the agrin-induced clustering of AChRs during synapse formation, and is also expressed at the mature neuromuscular junction. The MuSK antibodies were specific for the extracellular domains of MuSK expressed in transfected COS7 cells and strongly inhibited MuSK function in cultured myotubes. Our results indicate the involvement of MuSK antibodies in the pathogenesis of AChR-Ab-seronegative MG, thus defining two immunologically distinct forms of the disease. Measurement of MuSK antibodies will substantially aid diagnosis and clinical management.

Extension of generator longevity by use of high impedance ventricular leads.

The resistance of a pacing lead negatively correlates to current consumption. A prospective, randomized trial was conducted to evaluate the effect of a high impedance ventricular lead (CapSure Z) on generator longevity compared to a conventional lead (CapSure SP) eighty-nine patients were included in the study (51 male, 37 female, age 70.0+/-10.3 years). Forty-six patients received a CapSure SP lead (5024 bipolar), and 43 patients received a CapSure Z lead (5034 bipolar) in a randomized fashion. Follow-up data collected at 5 days, 3, 6, and 12 months postimplant included: lead impedance, pacing and sensing thresholds, impulse energy, and estimated time to replacement. All parameters were collected via pacemaker telemetry; the time to replacement was calculated automatically by a programmed algorithm of the pacemaker. There was no difference in the performance of the atrial lead when a dual chamber device was indicated. The CapSure Z leads displayed statistically significant higher impedance values than the CapSure SP lead in all follow-up periods. There was no significant difference in lead related complications. No significant differences were observed between pacing and sensing thresholds in both groups. The CapSure Z leads provided a significant reduction in current drain, resulting in a reduction of mean energy consumption at the 12-month follow-up from 10.4+/-5.0 microJ in the CapSure SP group to 6.6+/-1.4 microJ in the CapSure Z group (median from 9.9 microJ to 6.9 microJ, respectively), providing an estimated increase in mean longevity of more than 1 year from 81.1+/-23.5 months in the CapSure SP group to 94.5+/-13.4 months in the CapSure Z group (median: 76.5 months to 95.0 months, respectively). The use of a high resistance lead for ventricular pacing appears to result in a clinically relevant extension of generator longevity.

Systemic Exophiala jeanselmei infection in a cat.

A 14-year-old spayed domestic shorthair cat was referred for ultrasonographic evaluation of abnormally shaped kidneys. Multifocal lesions were detected ultrasonographically in the liver and kidneys; a fine-needle aspirate of the kidneys was performed, and numerous clumps of fungal hyphae were identified. The following day, the cat was recumbent with advanced neurologic signs. The cat was euthanatized, and a necropsy was performed. Multifocal granuloma-like masses were seen on the liver, kidneys, abdominal wall, mesentery, thoracic wall, pericardium, and epicardium. Similar lesions were found on the cervical portion of the spinal cord, the cerebrum, and cerebellum. Exophiala jeanselmei, an organism of the phaeohyphomycotic group, was identified on fungal culture. To our knowledge, systemic infections caused by this organism have not been reported. However, phaeohyphomycotic infections are believed to be an emerging disease in humans.

Prescription errors. Legibility and drug name confusion.

Inadvertent drug substitution occurred in several instances in our practices due to the combination of the physician's illegible handwriting on prescriptions and the pharmacist's misinterpretation of subtle clues, which might have prevented the errors. The literature on the legibility of physician handwriting is reviewed. Our specific recommendations include using preprinted prescription pads, training staff assistants who write prescriptions, printing complete directions on each prescription, and aggressively educating each patient about the name and purpose of all drugs being prescribed. Patients are encouraged to bring their medications to each office visit to identify potential errors.

Oral contraceptive failure rates and oral antibiotics.

BACKGROUND: Despite anecdotal evidence of a possibility of decreased effectiveness of oral contraceptives (OCs) with some antibiotics, it is not known whether antibiotic use in dermatologic practices engenders any increased risk of accidental pregnancy. OBJECTIVE: Our purpose was to examine the effect of commonly prescribed oral antibiotics (tetracyclines, penicillins, cephalosporins) on the failure rate of OCs. METHODS: The records from three dermatology practices were reviewed, and 356 patients with a history of combined oral antibiotic/OC use were surveyed retrospectively. Of these patients, 263 also provided "control" data (during the times they used OCs alone). An additional 162 patients provided control data only. RESULTS: Five pregnancies occurred in 311 woman-years of combined antibiotic/OC exposure (1.6% per year failure rate) compared with 12 pregnancies in 1245 woman-years of exposure (0.96% per year) for the 425 control patients. This difference was not significant (p = 0.4), and the 95% confidence interval on the difference (-0.81, 2.1) ruled out a substantial difference (> 2.1% per year). There was also no significant difference between OC failure rates for the women who provided data under both conditions, nor between the two control groups. All our data groups had failure rates below the 3% or higher per year, which are typically found in the United States. CONCLUSION: The difference in failure rates of OCs when taken concurrently with antibiotics commonly used in dermatology versus OC use alone suggests that these antibiotics do not increase the risk of pregnancy. Physicians and patients need to recognize that the expected OC failure rate, regardless of antibiotic use, is at least 1% per year and it is not yet possible to predict in whom OCs may fail.

PIP: Although some antibiotics are assumed to compromise the effectiveness of oral contraceptives (OCs), it is unknown whether the antibiotics used in dermatologic practice are associated with such a risk. To address this issue, a review was conducted in three US dermatologic practices of the records of 356 patients with a history of combined oral antibiotic/OC use in 1990-95 who responded to a follow-up questionnaire. 263 of these patients provided control data during the times they used OCs alone and an additional 162 patients were controls only. There were five pregnancies in 311 woman-years of combined antibiotic/OC exposure (1.6% annual failure rate) compared with 12 pregnancies in 1245 woman-years of exposure among controls (0.96% annual failure rate)--a nonsignificant difference. In addition, there were no significant differences between OC failure rates among women who served as both cases and controls or between the two control groups. All five cases who became pregnant had been taking an antibiotic (microcycline or a cephalosporin) for at least 3 months. Side effects potentially linked to reduced OC effectiveness (e.g., diarrhea, breakthrough menstrual bleeding) were not reported by the women who became pregnant. It is presumed that inter-individual differences in steroid plasma levels are a more important cause of OC failure than concomitant antibiotic therapy.

A practical approach to antibiotic treatment in women taking oral contraceptives.

Clinical situations that require the use of systemic antibiotic therapy are common. Because millions of women choose oral contraceptives for birth control, the potential for interaction between these drugs frequently has to be considered. We review the available information and present a practical approach for dealing with this situation based on sharing responsibility with an educated patient.

PIP: A 38-year-old woman with impetiginized eczema, who was treated with oral cefadroxil, 500 mg twice daily for 10 days, subsequently became pregnant and threatened the physicians who prescribed the antibiotic with a "wrongful birth" lawsuit because she was told that the antibiotic may have interfered with her low-estrogen oral contraceptives (OCs). Although it was proved that the women became pregnant 6-8 weeks after taking the cefadroxil, the physicians involved were inspired by this experience to research the literature on the interaction of antibiotics and oral contraceptives and to devise a practical approach for such situations. As a result of their data collection, they devised 3 categories of antibiotics ranging from those which likely reduce the effectiveness of OCs (rifampicin) to those which are associated with OC failure in 3 or more reported cases (ampicillin, amoxicillin, metronidazole, and tetracycline) to those which were associated with OC failure at least once (cephalexin, clindamycin, dapsone, erythromycin, griseofulvin, isoniazid, phenoxymethylpenicillin, telampicillin, and trimethoprim). The physicians recommended that a patient education hand-out include this information as well as directions to report any antibiotic associated diarrhea or breakthrough bleeding to the physician and a reminder to take OCs daily and that OCs are not perfect.

Prenatal literature testing: a pilot project.

A pilot study was conducted in 1987-1988 to evaluate current health literature utilized for prenatal health education of the high risk population in County Health Departments in Arizona. Towards that end, sixty-five distinct pamphlets were obtained from Arizona's County Health Departments and assessed for reading level using the SMOG Readability Formula. The majority of the prenatal literature were found to be 10th to 12th grade reading level, higher than the typical reading level of the high risk prenatal population. A modified literature testing instrument was further utilized to test eight general prenatal pamphlets to assess the printed literature for accuracy, usability, believability, appeal, and cultural relevance. Four pamphlets of those tested, two English and two Spanish, were identified as being the most appropriate for the high risk prenatal population.

Etoposide (VP-16-213)-induced gene alterations: potential contribution to cell death.

We have shown previously a good correlation between etoposide-induced sister chromatid exchanges (SCE) and cytotoxicity. A semisynthetic derivative of podophyllotoxin, etoposide is also called Vepesid (Bristol; code designation VP-16-213, abbreviated VP-16). Since SCE represent DNA recombinational events, we hypothesized that VP-16-induced SCE might result in nonhomologous recombination in which segments of DNA were either deleted or added, leading to an alteration of gene sequences responsible for essential cell proteins. Alterations of such essential genes and consequent interference with formation of their products could consequently lead to cell death. To evaluate whether VP-16 treatment caused sufficient levels of DNA sequence alterations to interfere with gene product formation, we isolated hypoxanthine (guanine) phosphoribosyltransferase (HPRT)-deficient mutants from Chinese hamster V79 cells grown in the presence or absence of VP-16. DNA from 3 spontaneous mutants and 10 VP-16-induced mutants was analyzed by Southern blot hybridization to a full-length hamster HPRT cDNA probe. Most of the VP-16-induced mutants showed partial deletions and/or rearrangements of the HPRT gene. In contrast, spontaneous mutants showed negligible deletions or rearrangements. These results provide strong support for our hypothesis that deletion of genetic sequences may constitute an important component of the mechanism of VP-16-induced cell death.

Office dermatologic testing: the Tzanck preparation.

Whether a vesicobullous disease is intraepidermal or subepidermal is often difficult to determine from the clinical examination. The Tzanck preparation can provide clues that aid in the diagnosis of a number of diseases. It is particularly helpful in confirming the diagnosis of herpes infection. This article outlines the materials and steps for performing this valuable test.

Office dermatologic testing: the scabies preparation.

Patients with scabies may present with urticarial, eczematous or excoriated papules, eczematous patches or, occasionally, nodules. It is often difficult to differentiate scabies from eczema, folliculitis, drug eruption or lichen planus. The classically described burrows are often not seen. The scabies preparation, as described in this article, will aid in making the proper diagnosis.