Teicoplanin-induced vasculitis with cutaneous and renal involvement.

We present a case of cutaneous vasculitis with renal impairment. This developed whilst receiving teicoplanin for Staphylococcus aureus osteomyelitis of the hip.

What happens to medical students who complete an honours year in public health and epidemiology?

BACKGROUND: Around one-third of medical students in the UK take an intercalated honours degree in addition to their basic undergraduate course. The honours year has been reported to have a major influence on subsequent career choice; honours students show greater interest in research and laboratory medicine careers and less in general practice and public health.1,2 AIMS: To examine the career choice of Nottingham medical students who completed an honours year in public health and epidemiology (including general practice). METHODS: Postal questionnaire and telephone follow-up of a cohort of 266 students who entered the honours year in Public Health and Epidemiology between 1973 and 1993. RESULTS: Career information was available on 203 students; 78% (195) of those are currently employed in medicine. 44% were working in general practice (expected 40-45%) and 8% in public health medicine (expected 2%). Overall 19% (expected 4-11%) had chosen academic careers including nine of the 15 choosing an academic career in public health. The majority (60%) reported that the honours year had influenced their career choice, while 55% reported that the year had increased their likelihood of choosing an academic career. CONCLUSIONS: The honours year does encourage entry into academic and research careers in general and the type of honours year department strongly influences the subsequent choice of specialty.

Flow-related responses of intracellular inositol phosphate levels in cultured aortic endothelial cells.

In vitro and in vivo evidence indicates that hemodynamic wall shear stress evokes a diversity of biological responses in vascular endothelial cells, ranging from cell shape changes to alterations in low density lipoprotein receptor expression. The signal transduction mechanisms by which the level of fluid mechanical shear stress is recognized by the endothelial cell and translated into these diverse biological responses remain to be elucidated. The present study focuses on the association between the onset of elevated shear stress and activation of the phosphoinositide signal transduction pathway, as measured by the intracellular release of inositol phosphates, in cultured bovine aortic endothelial cells (BAECs). BAECs were seeded, grown to confluence on large polyester sheets, and preincubated with 0.3 microCi/ml [3H]inositol for 24 hours before insertion in parallel-plate flow chambers for exposure to high shear stress (HS) at 30 dynes/cm2 or low shear stress (LS) at < 0.5 dyne/cm2 for periods ranging from 15 seconds to 24 hours. The induction of HS was associated with an early, transient but significant increase (142%, HS/LS x 100%) in inositol trisphosphate (IP3) measured at 15 seconds of shear stress exposure followed by a major peak in IP3 (189%) observed at 5 minutes after HS onset. After these initial increases, IP3 levels returned to near resting levels within 30 minutes of continued HS exposure and then continued to decline to significantly lower (75%) levels relative to LS-treated cells within 4 hours and remained lower throughout the remainder of the 24-hour HS exposure. LS-treated cells exhibited no significant changes in inositol phosphate levels throughout the 24-hour exposure periods. Exposure of BAECs to shear stress of 60 dynes/cm2 resulted in an approximately fourfold increase in IP3 levels (396%) measured at 5 minutes, almost double the levels measured in cells exposed to 30 dynes/cm2 for 5 minutes. Pretreatment of BAECs for 30 minutes with 5 mM neomycin, an inhibitor of phosphoinositide metabolism, before HS exposure inhibited both the early increases in inositol phosphates and subsequent cell elongation and alignment observed in untreated BAECs simultaneously exposed to HS without inhibiting protein synthesis. These results indicate that the exposure of cultured BAECs to elevated wall shear stress is associated with an early biphasic IP3 increase followed by a resetting of intracellular inositol phosphate concentrations to levels below that observed in static cultured BAECs. Furthermore, neomycin inhibition of this IP3 response to shear stress is associated with an inhibition of one of the major endothelial biological responses to shear stress, i.e., cell shape change and orientation.(ABSTRACT TRUNCATED AT 400 WORDS)

Deriving criteria for hearing impairment in the elderly: a functional approach.

We describe a method for deriving criteria for hearing impairment in the elderly based on self-reported handicap. Using the Sickness Impact Profile (SIP) and Hearing Handicap Inventory for the Elderly - Screening (HHIE-S) version as functional measures of handicap, the analysis proceeded in five steps: 1. Audiometric thresholds at various frequencies were inter-correlated. This was done both within and between ears. 2. Better and poorer ear thresholds were determined for each frequency, and these were correlated with the HHIE-S and SIP scores. 3. Using the HHIE-S and SIP scores as dependent variables, stepwise multiple linear regressions were used to select the frequencies that explained the most variance in the functional scales. 4. Using the HHIE-S and SIP as standards, receiver operating curves were constructed for each frequency to select the threshold level that provided the best test accuracy. 5. The newly-derived criteria were then compared against four other "traditional" criteria of hearing impairment. In general, the newly-derived criteria combined a relatively low frequency with a relatively high frequency, with the low frequency being functionally more important. Depending on the functional scale used, the threshold level was in the 25 to 35-dB range for the lower frequencies and 40 to 45-dB for the higher frequencies. These features provide a suitable compromise to the current debate over which threshold levels comprise the best discrimination of aged persons who are hearing-impaired. Future research should focus on developing consensus standards for functional hearing impairment and handicap in the elderly.

Comparing criteria of hearing impairment in the elderly: a functional approach.

We determined and compared the associations of four commonly used audiometric criteria of hearing impairment with two functional outcome measures in 152 aged persons screened in primary care medicine practices. The outcome measures were the Sickness Impact Profile (SIP, a measure of global function), and the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S, a communication-specific measure of functional impairment). There were five main findings. (1) The four criteria of hearing loss were not independent. (2) The criterion of loss chosen depends on the functional measure of impairment. (3) Functional hearing impairment may also be classified by the number of criteria met. (4) A large subset (21%) of aged persons met one criterion but had little in the way of communicative or global dysfunction. (5) Hearing handicap as measured by the HHIE-S was directly associated with global dysfunction as measured by the SIP.

Pathophysiology of the atherogenic process.

Atherosclerosis is conceptually defined as the result of a multiplicity of interactive cascades among injurious stimuli and the healing responses of the arterial wall, occurring concurrently within a hyperlipidemic environment. In this discussion, the inflammatory nature of the disease is emphasized. Four aspects of the pathophysiology of atherogenesis are addressed: (1) The role(s) of fluid mechanical or hemodynamic stresses in the focal initiation and/or augmentation of lesions is discussed in terms of the influence of shear stress on endothelial cellular geometry, compliance, membrane anisotropy (r), low-density lipoprotein (LDL)-receptor expression, intracellular potential and replication; (2) mechanisms of blood monocyte recruitment to the arterial intima, including the roles of chemoattractants such as smooth muscle cell-derived chemotactic factor and oxidized LDL; (3) the alternate or "scavenger" receptor pathway of the macrophage and its pivotal roles in foam cell formation and plaque pathogenesis; and (4) the emerging significance of various lipoprotein modifications, and in particular, the oxidative modification of LDL, which facilitates the uptake of the cytotoxic oxidized LDL via the scavenger receptor, thus providing a non-down-regulating mechanism for foam cell formation and plaque development. Evidence indicates that the antioxidant drug probucol prevents the oxidative modification of LDL, thereby retarding atherogenesis independently of cholesterol reduction.

Hearing impairment as a determinant of function in the elderly.

This clinical, practice-based study explores the research question: Is there a relationship between hearing loss and functional disturbance in elderly patients? We analyzed the impact of hearing impairment on 153 patients over 65 years of age screened in primary care practice. Functional and psychosocial impairment were measured using the Sickness Impact Profile (SIP), a standardized measure for assessing sickness related dysfunction. Hearing level was determined with pure tone audiometry. Multiple linear regression was used to adjust for patient case-mix differences and other clinical variables. After adjustment, a 10 dB increase in hearing loss was found to result in a 2.8 point increase in Physical SIP scores (95% confidence interval = 1.8-3.8), a 2.0 point increase in psychosocial SIP scores (95% confidence interval = 0.8-3.2) and a 1.3 point increase in overall SIP scores (95% confidence interval = 0.1-2.5). Poor hearing was associated with higher SIP scores and increased dysfunction. Thus, hearing impairment is an important determinant of function in the elderly.

Diagnostic performance of the hearing handicap inventory for the elderly (screening version) against differing definitions of hearing loss.

The diagnostic performance of the Hearing Handicap Inventory for the Elderly--Screening Version (HHIE-S) was evaluated against five definitions of hearing loss in 178 elderly subjects screened in primary care. Hearing loss was assessed by pure-tone audiometry. Using a score of greater than 8 as a cut point, the HHIE-S had sensitivities ranging from 53 to 72% and specificities ranging from 70 to 84% with the different definitions. The HHIE-S receiver-operating characteristics and likelihood ratios were similar regardless of hearing loss definition used. The HHIE-S is a valid, robust test for identifying hearing-impaired elderly, irrespective of the audiometric definition used to finally diagnose hearing difficulties.

Validation of screening tools for identifying hearing-impaired elderly in primary care.

Two instruments for the detection of hearing impairment, the Welch-Allyn audioscope (Welch-Allyn Inc, Skaneateles Falls, NY) and the Hearing Handicap Inventory for the Elderly--Screening Version (HHIE-S), were validated against pure tone audiometry in 178 patients over 65 years old screened in primary care practice. The prevalence of hearing impairment in this sample was 30%. The audioscope yielded reproducible results in the physicians' offices and a hearing center. The sensitivity of the audioscope was 94% in both locations, while its specificity was 90% in the hearing center and 72% in the physicians' offices. The HHIE-S yielded reproducible results between the two test locations. An HHIE-S score from 0 to 8 resulted in a likelihood ratio of 0.36 (95% confidence interval, 0.19 to 0.68), and a score of 26 or more yielded a likelihood ratio of 12.00 (95% confidence interval, 2.62 to 55.00) for predicting the presence of hearing impairment. Used together, the two instruments had a test accuracy of 83%. The audioscope and HHIE-S are valid, reliable, inexpensive tools for detecting hearing impairment in the elderly.