Fine needle aspiration biopsy in clinical management of head and neck tumors

Ninety-five percent (195) of 203 fine needle aspiration biopsies (FNAB) of head and neck specimens contained adequate tissues for histologic evaluation. No complications or needle tract recurrences were identified. Out of 135 patients whose surgical excision followed FNAB, 5% (7/135) of the biopsies were nondiagnostic. Correlation of cytologic and histologic findings of the remaining 128 FNAB revealed a sensitivity rate of 82% (46/56), a specificity rate of 99% (71/72), and a positive predictive of value of 98% (46/47). The diagnostic accuracy of FNAB was better with salivary gland and cervical node specimens than with thyroid, skin, and subcutaneous specimens. Fine needle aspiration biopsy may be considered as the first diagnostic step in the evaluation of the mass of the head and neck region, if the nondiagnostic aspiration rate is low and the diagnostic accuracy is high.     

Postoperative technetium scanning in patients with submandibular duct diversion.

Submandibular duct diversion is a common procedure for refractory sialorrhea in children. The procedure reroutes Wharton's ducts from the floor of the mouth to the tongue base. As the majority of saliva in the resting state is produced by the submandibular glands, rerouting markedly decreases sialorrhea. However, the procedure has been criticized in that diversion may cause fibrosis and stricture of the ducts. The gland would atrophy, and the physiologic functions of saliva would be lost. Glandular function of six patients with cerebral palsy (mean age, 14.7 years) was evaluated by technetium scanning (mean time after surgery, 43 months). Four patients had normal bilateral function; two patients had no function in one gland but normal function in the contralateral gland. We conclude that bilateral submandibular duct diversion maintains long-term function in at least one gland.     

Ultrastructural Confirmation of Malignant Melanoma

We have recently had the opportunity to examine two cases, where malignant melanoma was suspected on light microscopy and Fontana-Masson stain was focally and faintly positive. Electron microscopy of four to five different blocks failed, however, to demonstrate the presence of premelanosomes and thereby to confirm the diagnosis of malignant melanoma. The areas in the paraffin blocks that on Fontana-Masson stain had showed a positive reaction were deparaffinized, embedded in plastic, and examined by electron microscopy. Now the characteristic premelanosomes were found and the diagnosis of malignant melanoma was confirmed.     

Potentiation of apoptosis by histone deacetylase inhibitors and doxorubicin combination: cytoplasmic cathepsin B as a mediator of apoptosis in multiple myeloma

Background:

Although inhibitors of histone deacetylase inhibitors (HDACis) in combination with genotoxins potentiate apoptosis, the role of proteases other than caspases in this process remained elusive. Therefore, we examined the potentiation of apoptosis and related mechanisms of HDACis and doxorubicin combination in a panel of myeloma cell lines and in 25 primary myelomas.

Results:

At IC₅₀ concentrations, sodium butyrate (an HDACi) or doxorubicin alone caused little apoptosis. However, their combination potentiated apoptosis and synergistically reduced the viability of myeloma cells independent of p53 and caspase 3–7 activation. Potentiated apoptosis correlated with nuclear translocation of apoptosis-inducing factor, suggesting the induction of caspase 3- and 7-independent pathways. Consistent with this, butyrate and doxorubicin combination significantly increased the activity of cytoplasmic cathepsin B. Inhibition of cathepsin B either with a small-molecule inhibitor or downregulation with a siRNA reversed butyrate- and doxorubicin-potentiated apoptosis. Finally, ex vivo, clinically relevant concentrations of butyrate or SAHA (suberoylanilide hydroxamic acid, vorinostat, an HDACi in clinical testing) in combination with doxorubicin significantly (P<0.0001) reduced the survival of primary myeloma cells.

Conclusions:

Cathepsin B has a prominent function in mediating apoptosis potentiated by HDACi and doxorubicin combinations in myeloma. Our results support a molecular model of lysosomal–mitochondrial crosstalk in HDACi- and doxorubicin-potentiated apoptosis through the activation of cathepsin B.     

Detection of characteristic metabolites of Aspergillus fumigatus and Candida species using ion mobility spectrometry-metabolic profiling by volatile organic compounds

Volatile metabolites of Aspergillus fumigatus and Candida species can be detected by gas chromatography/mass spectrometry (GC/MS). A multi-capillary column - ion mobility spectrometer (MCC-IMS) was used in this study to assess volatile organic compounds (VOCs) in the headspace above A. fumigatus and the four Candida species Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis in an innovative approach, validated for A. fumigatus and C. albicans by GC/MS analyses. For the detection of VOCs, a special stainless steel measurement chamber for the microbial cultures was used. The gas outlet was either attached to MCC-IMS or to adsorption tubes (Tenax GR) for GC/MS measurements. Isoamyl alcohol, cyclohexanone, 3-octanone and phenethylalcohol can be described as discriminating substances by means of GC/MS. With MCC-IMS, the results for 3-octanone and phenethylalcohol are concordant and additionally to GC/MS, ethanol and two further compounds (p_0642_1/p_683_1 and p_705_3) can be described. Isoamyl alcohol and cyclohexanone were not properly detectable with MCC-IMS. The major advantage of the MCC-IMS system is the feasibility of rapid analysis of complex gas mixtures without pre-concentration or preparation of samples and regardless of water vapour content in an online setup. Discrimination of fungi on genus level of the investigated germs by volatile metabolic profile and therefore detection of VOC is feasible. However, a further discrimination on species level for Candida species was not possible.     

Improving adherence to antiretroviral therapy for youth living with HIV/AIDS: a pilot study using personalized, interactive, daily text message reminders

Background

For youth living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), nonadherence to antiretroviral therapy (ART) can lead to poor health outcomes and significantly decreased life expectancy.

Objective

To evaluate the feasability, acceptability, and preliminary efficacy of short message service (SMS) or text message reminders to improve adherence to ART for youth living with HIV/AIDS.

Methods

We conducted this prospective pilot study using a pre–post design from 2009 to 2010 at a community-based health center providing clinical services to youth living with HIV/AIDS. Eligibility criteria included HIV-positive serostatus, age 14–29 years, use of a personal cell phone, English-speaking, and being on ART with documented poor adherence. During the 24-week study period, participants received personalized daily SMS reminders and a follow-up message 1 hour later assessing whether they took the medication, and asking participants to respond via text message with the number 1 if they took the medication and 2 if they did not. Outcome measures were feasibility, acceptability, and adherence. Self-reported adherence was determined using the visual analog scale (VAS) and AIDS Clinical Trial Group (ACTG) questionnaire 4-day recall. Viral load and CD4 cell count were followed as biomarkers of adherence and disease progression at 0, 12, and 24 weeks.

Results

Participants (N = 25) were mean age 23 (range 14–29) years, 92% (n = 23) male, 60% (n = 15) black, and 84% (n = 21) infected through unprotected sex. Mean VAS scores significantly increased at 12 and 24 weeks in comparison with baseline (week 0: 74.7, week 12: 93.3, P < .001; week 24: 93.1, P < .001). ACTG questionnaire 4-day recall also improved (week 0: 2.33, week 12: 3.24, P = .002; week 24: 3.19, P = .005). There was no significant difference in CD4 cell count or viral load between baseline and 12- or 24-week follow-up, although there was a trend toward improvement of these biomarkers and a small to moderate standardized effect size (range of Cohen d: –0.51 to 0.22). Of 25 participants, 21 (84%) were retained, and 20 of the 21 (95%) participants who completed the study found the intervention helpful to avoid missing doses.

Conclusions

In this pilot study, personalized, interactive, daily SMS reminders were feasible and acceptable, and they significantly improved self-reported adherence. Larger controlled studies are needed to determine the impact of this intervention on ART adherence and other related health outcomes for youth living with HIV/AIDS.     

Hematologically important mutations: The autosomal recessive forms of chronic granulomatous disease (second update)

Chronic granulomatous Disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is essential in the process of intracellular pathogen killing by phagocytic leukocytes. Four of the five genes involved in CGD are autosomal; these are CYBA, encoding p22-phox, NCF2, encoding p67-phox, NCF1, encoding p47-phox, and NCF4, encoding p40-phox. This article lists all mutations identified in these genes in the autosomal forms of CGD. Moreover, polymorphisms in these genes are also given, which should facilitate the recognition of future disease-causing mutations.     

Essential fatty acid deficiency and neutrophil function: studies of lipid-free total parenteral nutrition in monkeys

Linoleic acid (18:2 omega 6), the obligate precursor of arachidonic acid (20:4 omega 6), is an essential nutrient for humans and other mammals. Because arachidonic acid release and metabolism are components of neutrophil activation by certain stimuli, we questioned whether neutrophils depleted of arachidonate as a result of essential fatty acid deficiency might be functionally impaired. We examined this possibility by producing essential fatty acid deficiency in monkeys with lipid-free total parenteral nutrition (TPN). Rhesus and African green monkeys were given calorically equal TPN for up to 23 days with and without a vegetable fat emulsion rich in linoleic acid. Fatty acids were analyzed in total lipid extracts of serum and isolated blood neutrophils by gas-liquid chromatography. Although fatty acids in the serum and neutrophils of monkeys given TPN with lipid did not change, linoleic acid levels decreased by at least 60% in serum and 50% in neutrophils from animals given TPN with no lipid. Moreover, arachidonate levels in neutrophil lipids decreased by at least 50% within 12 days of lipid-free TPN, and the abnormal fatty acid 20:3 omega 9 (characteristic of essential fatty acid deficiency) appeared and steadily increased with time. These biochemical signs of omega 6 fatty acid deficiency were associated with impaired neutrophil function in vitro. Both migration responses and superoxide generation stimulated by N-formyl-methionyl-leucyl-phenylalanine were significantly decreased by 12 days of lipid-free TPN, as was the capacity of activated cells to synthesize leukotriene B4. In contrast, functional responses of fatty acid-deficient neutrophils to leukotriene B4 and phorbol myristate acetate, which have little or no effect on arachidonate release or metabolism, were not significantly altered. These findings indicate that endogenous supplies of arachidonic acid and other essential omega 6 fatty acids influence the functional responsiveness of neutrophils. These studies also indicate that altered neutrophil function is a feature of essential fatty acid deficiency and that it may contribute to the increased risk of infection and decreased inflammatory responses observed in this condition.