Treatment of chronic mucocutaneous moniliasis by immunologic reconstitution

The immunological defect in a patient with chronic mucocutaneous moniliasis was characterized. While his Candida skin test was negative. exposure of his lymphocytes to candida extracts in vitro produced an increase in thymidine incorporation. Supernatants from cultures of antigen-stimulated lymphocytes did not contain macrophage migration-inhibition factor (MIF) activity.

Restoration of the immune system with transfusions of immuno-competent allogeneic lymphocytes was accompanied by conversion of the Candida skin test to positive, and MIF production by his lymphocytes. During the period that his immune system remained intact, there was marked clearing of the moniliasis. Eight months following the transfusions, the moniliasis recurred and when restudied, the patient again had negative skin tests and insignificant MIF production.

These observations demonstrate the importance of mediators in the expression of delayed hypersensitivity and provide evidence of a role of cellular immunity in resistance to certain chronic fungal infections.

     

Leukocytic function in hypogammaglobulinemia

The phagocytic, bactericidal, and metabolic capabilities of circulating blood leukocytes from three adults (two males, one female) with hypogammaglobulinemia and recurrent pneumonia, chronic sinusitis, and intestinal giardiasis were studied. These functions were found to be normal when leukocytes from the patients were incubated in media containing normal human serum. Phagocytosis of Staphylococcus albus and polystyrene balls by both patient and normal leukocytes was diminished when the cells were incubated in hypogammaglobulinemic plasma. A similar defect in opsonization by patient plasma was also noted for pneumococci, Escherichia coli and variably with Staphylococcus aureus. Both patient and normal sera had equivalent levels of heat-labile S. albus opsonins; normal serum, however, contained heat-stable S. albus-specific absorbable opsonins in significantly greater quantities to account for its superior opsonic capacity. The addition of commercial gamma globulin or purified IgG to hypogammaglobulinemic sera restored full S. albus opsonic activity. The relevancy of these observations to the impaired host defenses in these patients will be discussed.     

Two novel mutations in the <Emphasis Type="Italic">GAN</Emphasis> gene causing giant axonal neuropathy

Background

Giant axonal neuropathy (GAN) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. This disorder presents motor and sensitive symptoms with an onset in early childhood. Progressive neurodegeneration makes the patients wheelchair dependent by the end of the second decade of life. Affected individuals do not survive beyond the third decade of life. Molecular analysis has identified mutations in the gene GAN in patients with this disorder. This gene produces a protein called gigaxonin which is presumably involved in protein degradation via the ubiquitin–proteasome system. However, the underlying molecular mechanism is not clearly understood yet.

Methods

Here we present the first patient from Mexico with clinical data suggesting GAN. Sequencing of the GAN gene was carried out. Changes in the nucleotide sequence were investigated for their possible impact on protein function and structure using the publicly available prediction tools PolyPhen-2 and PANTHER.

Results

The patient is a compound heterozygous carrying two novel mutations in the GAN gene. The sequence analysis revealed two missense mutations in the Kelch repeats domain. In one allele, a C>T transition was found in exon 9 at the nucleotide position 55393 (g.55393C>T). In the other allele, a transversion G>T in exon 11 at the nucleotide position 67471 (g.67471G>T) was observed. Both of the bioinformatic tools predicted that these amino acid substitutions would have a negative impact on gigaxonin’s function.

Conclusion

This work provides useful information for health professionals and expands the spectrum of disease-causing mutations in the GAN gene and it is the first documented case in Mexican population.

     

Telephonic screening and brief intervention for alcohol misuse among workers contacting the employee assistance program: A feasibility study

Introduction and Aims. Substantial empirical support exists for alcohol screening, brief intervention, and referral to treatment (SBIRT) in medical, but not non‐medical settings such as the workplace. Workplace settings remain underutilised for delivering evidenced‐based health services. This research aims to translate medical research into behavioural health‐care practice in a telephonic call centre acting as a point of entry into an Employee Assistance Program (EAP). The goal of the study is to examine the feasibility of implementing routine telephonic alcohol SBIRT in an EAP call centre and assess whether routine SBIRT results in increased identification of workers who misuse alcohol. Design and Methods. The design was pretest–posttest, one‐group, pre‐experimental. An alcohol SBIRT program developed based on World Health Organization recommendations was implemented in one EAP call centre serving one large employer. Workers were offered screening using the Alcohol Use Disorder Identification Test (AUDIT) during intake, brief counselling using motivational interviewing, referral to counselling, and follow‐up. Results. At 5 months, 93% of workers contacting the EAP completed the AUDIT‐C: 40% prescreened positive and 52% went on to screen at moderate or high risk for an alcohol problem. Overall identification rate (18%) approached general US population estimates. Most agreed to follow‐up and three‐quarters set an appointment for face‐to‐face counselling. Discussion and Conclusions. Integration of routine alcohol SBIRT into EAP practice is feasible in telephonic delivery systems and increases identification and opportunity for brief motivational counselling. When SBIRT is seamlessly integrated workers are willing to answer questions about alcohol and participate in follow‐up.[McPherson TL, Goplerud E, Derr D, Mickenberg J, Courtemanche S. Telephonic screening and brief intervention for alcohol misuse among workers contacting the employee assistance program: A feasibility study. Drug Alcohol Rev 2010;29;641–646]