Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy

BACKGROUND: Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. METHODS: We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. RESULTS: Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. CONCLUSION: Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.     

Method development and validation of montelukast in human plasma by HPLC coupled with ESI-MS/MS: application to a bioequivalence study

A simple, sensitive, and specific LC-ESI–MS/MS method for quantification of Montelukast (MO) in human plasma using Montelukast-d₆ (MOD6) as an internal standard (IS) is discussed here. Chromatographic separation was performed on YMC-pack pro C₁₈, 50 x 4.6 mm, S-3 μm column with an isocratic mobile phase composed of 10mM ammonium formate (pH 4.0):acetonitrile (20:80 v/v), at a flow-rate of 0.8 mL min⁻¹. MO and MOD6 were detected with proton adducts at m/z 586.2→568.2 and 592.3→574.2 in multiple reaction monitoring (MRM) positive mode respectively. MO and MOD6 were extracted using acetonitrile as precipitating agent. The method was validated over a linear concentration range of 1.0–800.0 ng mL⁻¹ with correlation coefficient (r²) ≥ 0.9996. The intraday precision and accuracy were within 1.91–7.10 and 98.32–99.17. The inter-day precision and accuracy were within 3.42–4.41% and 98.14–99.27% for MO. Both analytes were found to be stable throughout three freeze-thawing cycles, bench top, and autosampler stability studies. This method was utilized successfully for the analysis of plasma samples following oral administration of MO (5 mg) in 31 healthy Indian male human volunteers under fasting conditions.     

CD4+CD25+ regulatory T cells and CD1-restricted NKT cells do not mediate facial motoneuron survival after axotomy

CD4+ T cells rescue facial motoneurons (FMN) from axotomy-induced cell death. The objective of this study is to determine if the CD4+ T regulatory subsets, CD4+CD25+ T or CD1d-restricted NKT cells are critical for FMN survival after facial nerve axotomy. Surviving FMN within facial motor nuclei from axotomized and control sides 4 weeks after axotomy were counted to determine percent FMN survival. Data generated by applying this paradigm to recombination activating gene-2-deficient mice reconstituted with CD4+ T cells depleted of CD4+CD25+ T cells and to CD1-/- mice, deficient in CD1d-restricted NKT cells, suggest that neither regulatory CD4+ T subset is critical for FMN survival.     

Effect of increasing patient age on complication rates following intact abdominal aortic aneurysm repair in the United States

INTRODUCTION: Advanced age is generally acknowledged as a risk factor for adverse surgical outcomes, but little information exists to define the magnitude of this association from a population-based perspective. This study was undertaken to determine the relation of patient age to complications following abdominal aortic aneurysm (AAA) repair in a population-based experience. METHODS: This study was based upon data from 6397 patients with a primary diagnosis of intact AAA and a procedure code for repair of AAA from the Nationwide Inpatient Sample (NIS) in 2000. The NIS is a 20% stratified random sample representative of all United States hospitals. Primary outcome variables were postoperative complications determined from secondary diagnostic codes. Adjustment for confounding variables was performed using multiple logistic regression. RESULTS: At least one complication affected 29% of patients. Increasing age correlated with a higher risk of having one or more complications (51-60 years, 18.8%; 61-70 years, 27.3%; 71-80 years, 31.2%; >80 years, 34.3%; P < 0.01). Comparison of the oldest to the youngest age group revealed an increased incidence of pulmonary insufficiency (13.9% versus 6.4%), pneumonia (7.7% versus 3.0%), reintubation (9.5% versus 3.9%), acute renal failure (8.8% versus 2.5%), myocardial infarction (4.3% versus 1.6%), and mortality (7.9% versus 1.1%). The association of increasing age to complications and mortality persisted after adjusting for patient case-mix. CONCLUSIONS: Older patient age is independently associated with an increased risk of major postoperative complications after AAA repair. The increasing age of the United States population will compound this healthcare problem. Quality improvement efforts must focus on minimizing complication rates in elderly patients undergoing common vascular surgical procedures including AAA repair.     

Maintenance of mouth hygiene in patients with oral cancer in the immediate post-operative period

BACKGROUND: Little has been written about mouth hygiene measures during the immediate postoperative phase in patients with oral cancer. Mouth hygiene not only involves the care and maintenance of the dentition and its related structures, but also the maintenance of surgical sites, reconstructive techniques such as free flaps and generally keeping the mouth clean, which may optimize healing potential and patient comfort. Ward conditions and novel methods of reconstruction require innovation and improvisation of routine methods of mouth and oral hygiene. METHODS: A review of techniques of mouth hygiene used during the immediate post-operative phase by our unit over the last nine years and a review of the literature. RESULTS: Various methods gained from our experience in treating patients with oral cancer at the Austin and Repatriation Medical Centre are documented. Most methods involve a combination of either chlorhexidine or normal saline mouth rinses and mechanical cleaning. CONCLUSIONS: There are many different methods of mouth care in patients who have had resection for oral tumours. It is important for dental practitioners, hygienists and allied health professionals, who may be involved with care of such patients to have an understanding of the methods that are available and appropriate for such patients.     

Patterns of referral of patients undergoing surgical management for oral cancer

BACKGROUND: Oral cancer is most often diagnosed by dentists or dental specialists. We were interested in analyzing demographic and referral data for a cohort of patients referred for the management of oral cancer to our unit. METHODS: A consecutive review of all patients treated by oral and maxillofacial surgery at the Austin and Repatriation Medical Centre over the last 10 years. Inclusion criteria included those patients with malignant oral and perioral disease that underwent surgical management. Exclusion criteria included those patients who did not have malignant oral disease, who did not have surgical management and those patients who were not treated by our unit as the primary surgeon. RESULTS: A total of 113 patients were identified. The mean age for presentation for the group was 61.6 years and the male to female ratio was 1.2:1. Approximately 70 per cent of patients were smokers or had smoked in the past. Over the last 10 years there has been a steady increase in referrals to our unit. Over half of all patients referred were from the Royal Dental Hospital of Melbourne while the majority of the remainder of the referrals were from private oral and maxillofacial surgeons. A significantly increased number of referrals from other sources were identified. Surveillance techniques that can be used in general dental practice are also described. CONCLUSIONS: A high proportion of referrals from dental sources highlights the importance of the dentist and dental specialist in the diagnosis and referral of patients with suspected oral cancer. Patients can either be referred to a dental hospital, private oral and maxillofacial surgeons or directly to a public hospital oral and maxillofacial surgery unit treating oral cancer, such as the one at the Austin and Repatriation Medical Centre.     

Brachytherapy for cancer of the cervix: An Australian and New Zealand survey of current treatment techniques

Establishing guidelines for the practice of brachytherapy throughout Australia and New Zealand is one of the goals of the Australasian Brachytherapy Group. To better appreciate Australasian resources and conditions, the group conducted a survey in early 2005. The aims were to survey current practices, to emphasize variations in practice and to determine the availability of advanced imaging and treatment methods to assess resources. A survey was sent to all Australian and New Zealand radiotherapy departments. The survey requested details of treatment with respect to external beam radiotherapy, brachytherapy, optimization methods, reporting methods, scheduling brachytherapy and access to imaging and methods of work‐up. Thirty‐four departments were contacted with 27 (79%) responses returned. Twenty‐one departments use brachytherapy. Doses and fractionation schedules varied and use of sectional imaging was minimal. Individualized dosimetry is practised in a limited fashion by 60% of the surveyed departments. There is high compliance with International Commission on Radiation Units 38 dose reporting recommendations. All brachytherapy units identified have access to CT and 85% to MRI within the hospital settings. Brachytherapy for cancer of the cervix is, currently, largely based on the Manchester system. The survey did emphasize considerable variation in dose and fractionation schemes between departments. The Australasian Brachytherapy Group subgroup intends to proceed with the process of formulating recommendations for cervix brachytherapy. It is intended that these will cover the use of image‐based planning and treatment, target definition(s), verification of brachytherapy treatments and a uniform dose‐reporting mechanism.     

Chondroblastoma: varied histologic appearance,potential diagnostic pitfalls,and clinicopathologic features associated with local recurrence

Chondroblastoma is a rare, benign bone tumor. Although it has distinctive clinicopathologic features, its wide morphologic spectrum may pose diagnostic problems. We present the clinicopathologic features of 42 patients (28 males, 14 females; age range, 8 to 66 years), with emphasis on unusual histologic features, potential diagnostic pitfalls, and factors associated with recurrence. Thirty-four tumors were in long bones, with the most common site being the proximal femur. Unusual histologic features included the presence of atypical, epithelioid, spindle, and foamy cells and necrosis and a diffuse basophilic myxoid matrix. Tumors with focal osteoclast-like giant cell rich areas (n = 11), prominent cystic change (n = 8) and extensive fibromyxoid areas (n = 3) resembled giant cell tumors, aneurysmal bone cysts, and chondromyxoid fibromas, respectively. The diagnosis of referring pathologists was inaccurate in 34% of cases. Six patients (14%) had local recurrence. The only clinical feature significantly associated with increased risk of local recurrence was duration of symptoms for less than 6 months (log rank P =.003). None of the histologic features was significantly associated with recurrence. These included worrisome features such as cellular atypia, necrosis, and mitoses. None of the patients had metastases. An increased awareness of the morphologic spectrum of chondroblastomas will enable pathologists to avoid diagnostic pitfalls. We emphasize the need for a combined clinical, radiologic and histologic approach to the diagnosis of chondroblastomas.     

Natural killer cells do not mediate facial motoneuron survival after facial nerve transection

The goal of the current study was to determine if natural killer (NK) cells mediate facial motoneuron (FMN) survival following injury. Wild-type (WT), perforin/recombinase activating gene-2 knockout (pfp/RAG-2 KO), and common gamma-chain (gammac)/RAG-2 KO mice received a right facial nerve axotomy. In WT mice, FMN survival was 86+/-1.0% relative to the contralateral control side. In contrast, pfp/RAG-2 and gammac/RAG-2 KO mice exhibited significant decreases in FMN survival ( approximately 20% and approximately 30%, respectively), relative to WT. Reconstitution of pfp/RAG-2 and gammac/RAG-2 KO mice with normal NK cells alone, failed to restore FMN survival levels to those of WT, but did restore functional lytic activity against YAC-1 cells. Reconstitution of pfp/RAG-2 and gammac/RAG-2 KO mice with splenocytes, and pfp/RAG-2 KO mice with CD4+ T-lymphocytes alone or in combination with NK cells, restored FMN survival levels to those of WT. Thus, NK cells appear to not be a component of immune cell-mediated rescue of motoneurons from axotomy induced cell death.