Factors relating to the sensory acuity of limbs with peripheral vascular insufficiency

We examined several possible causes for the high incidence of poor sensory acuity in the limbs of 176 patients with moderate to severe peripheral vascular insufficiency. We investigated the relationships of diabetes, alcoholism, and smoking, as well as the severity of peripheral vascular disease, to the integrity of basic sensory modalities such as two-point discrimination and perception of light touch. The presence or absence of diabetes exerted the strongest effect on peripheral sensation. In patients who did not have diabetes, sensation in the limbs was most strongly affected by whether the patient was an alcoholic. Smoking did not have a significant effect on limb sensation. Among nondiabetic, nonalcoholic patients, there was a weak residual effect related to the severity of the peripheral vascular insufficiency. Even among these patients, however, systemic factors predominated in determining the loss of sensation. We also examined the extent to which loss of sensation might be related to the development of ulcers. Among patients who were not diabetic, there was a highly significant relationship between loss of sensation and the presence of limb ulceration. Surprisingly, however, there was no discernable relationship between the presence of ulcers in diabetic patients and the degree of loss of peripheral sensation. This result suggests that a large percentage of ulcers seen in diabetic patients are not of neurogenic origin.     

Program Directors' Views of the Effect of Managed Care on Substance Abuse Programs in Southern California

This article reports the results of semi-structured interviews with substance abuse treatment (SAT) program directors (PDs) regarding the ways SAT is being influenced by managed care (MC), plans for future SAT, and strategies for decreasing costs of care. It compares findings to an earlier survey of 50 SAT PDs.

Interviews were conducted in 20 SAT programs to gather information about treatment delivery since the advent of MC, including PD responsibilities, funding source, treatment intensity, location, duration, and methods of treatment. Open-ended responses were used to gather information about current and future plans in providing SAT, and awareness of new types of treatment being planned by organizations impacted by MC.

PDs reported changes in SAT secondary to MC such as decreased treatment length, limiting of inpatient and outpatient services, and delayed treatment secondary to benefit determination. Political and economic constraints were seen as barriers to providing adequate and effective services. SAT being subsumed by mental health was viewed as problematic along with an emerging split between alcohol abuse and drug treatment. A positive emerging treatment trend was the development of targeted programs for special need groups.

PDs revealed a variety of strategies that have promoted necessary adaptations to economic and political influences within the structure of managed behavioral care. Strategies such as varying treatment length, modality, and subspecialty care reflected necessary adaptations to diverse market needs.

Managed care continues to have a tremendous impact on the delivery of SAT services. While MC has helped to contain costs, negative outcomes are decreased availability of appropriate care and overtaxing of units that have survived MC cut backs. However, special need programs have allowed SAT programs to specialize, expand, and even flourish in today's competitive SAT market. Interviews with PDs reinforced the need for maintaining quality and diversified SAT services in today's MC environment.     

Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

Intracellular trafficking of fluorescently tagged proteins associated with pathogenesis in Candida albicans.

Proteins that enter the secretory pathway play important roles in virulence and pathogenesis in Candida albicans, but our understanding of the trafficking of these proteins is in its early stages. In Saccharomyces cerevisiae, dominant negative alleles of YPT1 and SEC4 interrupt secretory traffic at pre- and post-Golgi steps, respectively. We therefore used a dominant negative genetic approach to examine the intracellular trafficking of several proteins associated with virulence or azole resistance. When the dominant negative ypt1(N121I) allele of C. albicans was overexpressed, yellow-fluorescent protein (YFP) tagged forms of two plasma membrane transporters (Cdrlp and Ftrlp) and the vacuolar membrane ABC transporter Mltlp accumulated in intracellular structures that appeared related to the ER, but localization of Cdc10p and Int1p was unaffected. When the dominant negative sec4(S28N) allele of C. albicans was overexpressed, Cdrlp and Ftrlp accumulated intracellularly, and localization of Mltlp, Cdc10p and Int1p was unaffected. These results imply that (i) Cdrlp and Ftrlp are transported to the plasma membrane by the general secretory pathway, (ii) Mlt1p enters the secretory pathway but is diverted to the vacuole at an early post-Golgi step, and (iii) like Cdc10p, Int1p does not enter the general secretory pathway.