Laparoscopic appendectomy: indications and controversies

The introduction of laparoscopic appendectomy has been more controversial than that of laparoscopic cholecystectomy. Randomized trials have been performed, as well as meta-analysis, with equivocal results regarding effectiveness. The further expansion of the technique for interval appendectomy and in cases of complicated appendicitis has introduced new controversies and success stories. We hope to review the current application of laparoscopic appendectomy in adults based on the available literature and discuss some current controversies.     

First-Line Treatment of Metastatic Breast Cancer

For many years, tamoxifen was the mainstay of treatment for hormone receptor-positive metastatic breast cancer (MBC). However, in recent years, newer endocrine agents, particularly aromatase inhibitors, have consistently proved their superiority over tamoxifen by improving clinical outcomes. These agents have therefore been incorporated into first-line treatment strategies for endocrine-responsive disease. The chemother-apeutic armamentarium has also been enriched with new agents and combinations that have played a role in improving breast cancer survival in recent decades. However, few chemotherapy clinical trials have claimed a clear survival benefit of one regimen over another. More recently, the development of biologic agents has further widened the spectrum of available therapies. Among these, trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has significantly altered the lives of patients with HER2-positive MBC. The transfer of research findings to clinical practice is a delicate process that implies the ability to adequately tailor evidence obtained from well designed clinical trials to the individual patient. This article discusses landmark studies in the treatment of MBC, with emphasis on those treatments used as ‘first-line’ therapy following relapse.     

Low frequency of α-synuclein mutations in familial Parkinson's disease

A mutation in exon 4 of the α-synuclein (NACP) gene has been reported to explain the chromosome 4 linkage to autosomal dominant Parkinson's disease. We developed primers and methods for exonic sequencing of this gene and sequenced the entire coding region of the gene in 6 families with autosomal dominant disease and in 2 cases of lytico and bodig from Guam. In addition, we have sequenced exon 4 of this gene in 5 cases of familial disease and have screened for the specific mutation (A53T) in a 40 cases of idiopathic Parkinson's disease, 3 cases of multisystem atrophy, and 15 cases of Lewy body dementia. We have found no genetic variation in the gene. We discuss these findings with respect to both the epidemiology of Parkinson's disease and the possibility that NACP is not the chromosome 4 locus for disease.     

Activated human platelets express β2 integrin

Abstract: The expression of molecules of the β2 integrin family (CD11a, CD11b, CD11c and CD18) was explored on 2 human megakaryocytic cell lines and on platelets from different donors by immunofluorescence and flow cytometry using a large panel of mAb. CD11a, CD11b, CD11c and CD18 were detected on the megakaryocytic cell lines DAMI and HEL. A low and variable expression of CD11a, CD11b and CD18 determinants was also detected on resting platelets: this expression was markedly increased when platelets were activated by thrombin. Expression of CD18 was closely correlated to that of CD11a or CD11b when comparing the fluorescence intensity observed in different experiments. In presence of Ca⁺⁺, platelets did bind to a RAJI cell line which exhibits a high expression level of CD54. This binding was increased when platelets were activated by thrombin and was decreased by an anti CD11a, CD18 and anti CD54 mAb. This study indicates that human platelets express molecules of the β2 integrin family, when activated, which allows them to bind to CD54 bearing cells.     

Increasing breastfeeding rates in New York City, 1980–2000

Our objective was to determine temporal patterns of breastfeeding among women delivering infants in New York City (NYC) and compare national breastfeeding trends. All hospitals in NYC with obstetric units were contacted in May and June 2000 to provide information on the method of infant feeding during the mother’s admission for delivery. Feeding was categorized as “exclusive breastfeeding,” “breast and formula,” or “exclusive formula.” The first two categories were further grouped into “any breastfeeding” in the analysis. Hospitals were classified as “public” and “private,” and patients were classified by insurance type as “service” and “private.” Data between public and private hospitals and service and private patients were compared. Breastfeeding trends over time were compared by using previous iterations of the same survey. Of 16,932 newborns, representing approximately 80.0% of all reported live births in the city during the study period, 5,305 (31.3%) were exclusively breastfed, 6,189 (36.6%) were fed a combination of breast milk and formula, and the remaining 5,438 (32.1%) were exclusively formula-fed. Infants born in private hospitals were 1.6 times more likely to be exclusively breastfed compared with infants discharged from public hospitals (33% vs. 21%, respectively). Similarly, private patients were more likely than service patients to exclusively breastfeed their infants (39.6% vs. 22.9%, respectively) and to use a combination of breast and formula (i.e., any breastfeeding) (73.6% vs. 62.0%, respectively). From 1980 to 2000, the proportion of exclusive breastfeeding increased from 25.0% to 31.0%, the percentage of combined feeding increased from 8.0% to 37.0%, and the percentage of any breastfeeding increased from 33.0% to 68.0%. NYC has more than doubled the rate of breastfeeding since 1980. However, there is much progress to be made, and continued efforts are vital to maintain current gains in breastfeeding, improve the rates further, and prolong the duration of breastfeeding. at the time of the research.     

Induction of broadly neutralizing antibodies against measles virus mutants using a polyepitope vaccine strategy

Chimeric molecules expressing multiple copies of the loop-forming hemagglutinin noose epitope (designated as "L"; aa386-400), a protective B cell epitope of the measles virus were generated by recombinant technology. The recombinant polyepitope [L4T4]2 combining two sets of four repeats of the L epitope and with two sets of four repeats of the human promiscuous T cell epitope of tetanus toxoid ("T", tt830-844) was produced in transgenic carrot plants. After intraperitoneal immunization of mice with plant membrane extract, sera neutralized all wild-type viruses. In a modified plaque reduction neutralization assay based on CD150-transfected Vero cells anti-[L4T4]2 sera neutralized all field isolates, irrespective of mutations in the L epitope. Even viruses with a mutation in the contact residues of a neutralizing L-specific monoclonal antibody or two mutations in other positions of the epitope were equally sensitive to neutralization. These results suggest that the multiple copies of the L epitope fold into different conformations that induce a repertoire of B cells diverse enough to overcome the genetic diversity of field viruses.     

Power Doppler imaging in detection of surgically induced indirect neoangiogenesis in adult moyamoya disease

OBJECT: Moyamoya is a rare, chronic disease that leads to the progressive narrowing and/or occlusion of the distal internal carotid and proximal cerebral arteries. Chronic cerebral ischemia ensues due to insufficient collateral blood supply. One potential treatment consists of the restoration of regional cerebral blood flow by direct or indirect revascularization surgery. The extent of neovascularization, especially in indirect procedures such as encephalomyosynangiosis (EMS), is currently evaluated with conventional angiography. Because this method is invasive and carries some risks, the authors investigated power Doppler imaging as an alternative noninvasive bedside procedure that can be used to assess surgically induced indirect revascularization in adult patients with moyamoya disease. METHODS: Twelve symptomatic patients with adult moyamoya disease (seven women and five men, mean age 38 +/- 17 years) underwent combined (direct and indirect) revascularization. They were then examined using conventional angiography and power Doppler imaging to assess the extent of revascularization within 120 days postsurgery. According to the number of intracranial vessels demonstrating opacification on conventional angiography and power Doppler imaging studies, EMS was graded as follows: 1, absent (0 vessels); 2, moderate (one-four vessels); and 3, extensive (> four vessels) for both methods. Examiners were blinded to the classification results for the procedure that they did not grade. All 24 hemispheres were examined. The visual grading of EMS revealed a highly significant agreement between conventional angiography and power Doppler imaging (Spearman rank coefficient, r = 0.92; p < 0.001) and there was 100% agreement of patency of the bypass between the direct and indirect methods. CONCLUSIONS: The authors found excellent agreement between the two methods. Therefore, power Doppler imaging is a valid noninvasive alternative to carotid artery angiography in evaluating direct and indirect revascularization.     

Arginine-vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging-related alterations of circadian pacemaker neurons in a non-human primate

The suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian pacemaker, is entrained by external cues and especially by photic information. Light is transmitted primarily via the retinohypothalamic tract, which terminates in the ventral part (or core) of the SCN, where vasoactive intestinal polypeptide (VIP)-containing neurons are located. VIP cells are mainly intrinsic and project to the dorsal part (or shell) of the SCN, where neurons containing arginine-vasopressin (AVP) reside. As aging leads to marked changes in the expression of circadian rhythms, we examined in primates whether age-related decay in biological rhythmicity is associated with changes in the oscillation of peptide expression in SCN neurons. We used double immunohistochemistry and quantitative analysis in the SCN of mouse lemurs, which provide a unique model of aging in non-human primates. In adult animals, VIP-positive and AVP-positive SCN neurons exhibited daily rhythms of their number and immunostaining intensity: AVP immunoreactivity peaked during the second part of the day, and VIP peaked during the night. In aged mouse lemurs, the peaks of AVP and VIP immunopositivity were significantly shifted, so that AVP was most intense at the beginning of the night, whereas VIP peaked at the beginning of daytime. The results show that the circadian rhythm of neuropeptides in the SCN is modified by aging in primates, with a differential regulation of the two main peptidergic cell populations. These changes may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby to modify the expression of some biological rhythms.