Search PubMed⌕ Search

Biomedical subjects

M Vierra

Publications and source records attributed to M Vierra.

11 recordsLinked to original sources

Pancreatic tumors show high levels of hypoxia.

PURPOSE: Because of the dismal outcomes of conventional therapies for pancreatic carcinomas, we postulated that hypoxia may exist within these tumors. METHODS AND MATERIALS: Seven sequential patients with adenocarcinomas of the pancreas consented to intraoperative measurements of tumor oxygenation using the Eppendorf (Hamburg, Germany) polargraphic electrode. RESULTS: All 7 tumors demonstrated significant tumor hypoxia. In contrast, adjacent normal pancreas showed normal oxygenation. CONCLUSION: Tumor hypoxia exists within pancreatic cancers.

Aged↗

Highly active antiretroviral therapy results in HIV type 1 suppression in lymph nodes, increased pools of naive T cells, decreased pools of activated T cells, and diminished frequencies of peripheral activated HIV type 1-specific CD8+ T cells.

This study examines sequential lymph nodes from 13 drug-naive patients before and after 24 weeks of highly active antiretroviral therapy (HAART). A multipronged approach was used to study changes in HIV-1 RNA in each paired lymph node in relation to tissue architecture and frequency of naive T cells. After 24 weeks, all patients showed significant suppression of plasma viral load and 12 of 13 showed concordant viral suppression in the lymph node (p = 0.001). Using in situ hybridization and quantitative image analysis, we showed that HIV-1 RNA was reduced to below detectable levels (two copies per cell) in follicular dendritic cell (FDC) and mononuclear cell pools. Independent immunohistochemical analysis of lymph node sections revealed that 5 of 13 patients displayed increased FDC networks and 6 of 13 showed no change and all patients showed increases in tissue-resident CD4+ cells. All lymph node biopsies at 24 weeks showed increased proportions of CD4+ and CD8+ cells coexpressing the naive markers CD45RA and CD62L when compared with baseline values. Significant correlations existed between viral load suppression and loss of activated CD8+ T cells after 24 weeks in both lymph node and blood, which was mirrored by significantly lowered frequencies of activated peripheral Gag peptide/MHC tetramer+ CD8+ cells. Overall, these data show that a potent and successful treatment strategy that significantly suppresses and removes FDC-resident HIV-1 results in improvements in lymphoid architecture and by so doing provides the structures available for increased numbers of naive cells to interact with cognate antigen. In addition, our article shows that suppression of HIV-1 replication results in diminished frequencies of peripherally activated antigen-specific CD8+ cells.

Antiretroviral Therapy, Highly Active↗

Clinical presentation of mucin-secreting tumors of the pancreas.

BACKGROUND: Pancreatitis and jaundice secondary to ductal obstruction are common in intraductal papillary mucinous tumors (IPMT) of the pancreas. However, the incidence and severity of the complications of obstruction are not well documented. The aim of the study was to investigate the clinical presentation and outcome of 10 patients with IPMT. METHODS: All cases of IPMT diagnosed between 1994 and 1999 were reviewed. RESULTS: Four of the 10 patients developed severe acute illness with systemic complications resulting from ductal obstruction. Three suffered acute cholangitis with sepsis, and 1 developed necrotizing pancreatitis and ARDS. There was 1 postoperative death in a patient with adenocarcinoma. All other patients are alive and well with a median follow-up of 26 months (survival 90%). CONCLUSIONS: Pancreatic or common bile duct obstruction in IPMT may result in acute, life-threatening disease. Aggressive surgical therapy is warranted before development of complications of ductal obstruction or progression of tumor occurs.

Acute Disease↗

Lymph node human immunodeficiency virus RNA levels and resistance mutations in patients receiving high-dose saquinavir.

The development of resistance mutations and human immunodeficiency virus (HIV) RNA levels were compared in lymph nodes and plasma of patients receiving antiretroviral therapy. Ten HIV-positive patients receiving high-dose saquinavir monotherapy (3600 or 7200 mg/day) underwent 14 lymph node biopsies before and during therapy. HIV RNA levels and appearance of resistance mutations to saquinavir were determined in simultaneous lymph node and plasma samples. HIV RNA levels were found to be consistently higher (mean, 3.16 log RNA copies; SD, 1.04; range, 2.23-5.59) in lymph nodes than in simultaneous plasma samples. Saquinavir therapy resulted in a reduction in HIV RNA levels in both plasma and lymph nodes. The presence or absence of a resistance mutation to saquinavir at codons 48 or 90 of the HIV-1 protease gene was identical in 13 of 14 biopsies, suggesting that resistance mutations to saquinavir appear within close temporal proximity in lymph nodes and plasma.

Anti-HIV Agents↗

Rainbow Universal CPG: a versatile solid support for oligonucleotide synthesis.

We have developed a universal solid support, termed Rainbow Universal CPG, for use in automated oligonucleotide synthesis. The universal solid support allows any oligodeoxyribonucleotide sequence to be synthesized from a single type of controlled pore glass (CPG) support. Deprotection of oligodeoxyribonucleotides was optimized using 0.5 M LiCl in concentrated ammonium hydroxide. PCR experiments using three different sets of primers proved that the 3'-hydroxyl function of oligodeoxyribonucleotides synthesized from Rainbow Universal CPG was retained. This universal solid support shows promise for replacing the standard nucleoside CPG supports.

Automation↗

Long-term results of curative resection of "minimally invasive" colorectal cancer.

PURPOSE: The aim of this study was to determine the long-term outcome after curative resection of colorectal cancers that extend only into the submucosa ("minimally invasive") and to evaluate potential histologic predictors of lymph node metastases. METHODS: Seventy-nine patients who underwent curative resection of minimally invasive colorectal cancer and were followed for at least five years were studied retrospectively. RESULTS: The series was comprised of 53 men and 26 women, with a mean age of 61 years. The lesion was in the colon in 47 patients and the rectosigmoid or rectum in 32 patients. Open surgery followed attempted endoscopic tumor removal in 25 patients. Lymph node metastasis, found in 11/79 patients (13.9 percent), was associated with worse outcome: 36.4 percent of node(+) patients developed recurrence, vs. only 5.9 percent of node(-) patients (P < 0.005). The cumulative survival rate was also worse in node(+) vs. node(-) patients: 72.7 percent vs. 91.1 percent at five years (P < 0.05) and 45.5 percent vs. 65.3 percent at ten years (P < 0.05). Five histopathologic characteristics were identified as risk factors for lymph node metastasis: 1) small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion ("tumor budding"); 2) a poorly demarcated invasive front; 3) moderately or poorly differentiated cancer cells in the invasive front; 4) extension of the tumor to the middle or deep submucosal layer; 5) cancer cells in lymphatics. Whereas patients with three or fewer risk factors had no nodal spread, the rate of lymph node involvement with four or more risk factors was 33.3 percent and 66.7 percent, respectively. CONCLUSIONS: Metastasis is not infrequent in "minimally invasive" colorectal cancer. Appropriate bowel resection with lymph node dissection is indicated if such a lesion exhibits more than three histologic risk factors for metastasis.

Adult↗

Minimally invasive surgery.

With the widespread introduction of laparoscopic cholecystectomy in late 1989, the practice and expectations of general surgery were changed forever. The techniques of laparoscopy were not new--they had been adopted by gynecologists and orthopedic surgeons at least a decade before--but it was laparoscopic cholecystectomy that captured the attention of the surgical profession and the public and spawned the tremendous growth in what has come to be called minimally invasive surgery. Although this surgery has tremendous appeal, offering quicker recovery, less pain, and possibly greater safety, it presents new challenges in the areas of training, credentialing, and quality assessment and raises serious questions about the real benefits of new technology at a time when the political and economic sensitivity of these issues is greater than ever. In this chapter I limit myself to a discussion of laparoscopy in general surgery, with a focus on what we have learned from laparoscopic cholecystectomy and on what this knowledge suggests for the future of other laparoscopic general surgical procedures.

Cholecystectomy, Laparoscopic↗

Prognostic value of tumor "budding" in patients with colorectal cancer.

From 1970 to 1985, 663 patients underwent curative resection of colon and rectal adenocarcinomas. All surgical specimens were examined for tumor "budding," defined as small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion. Patients were divided into two groups according to degree of budding: none or mild (BD-1) and moderate or severe (BD-2). BD-1 occurred in 493 patients (74.4 percent), and BD-2 was found in 170 patients (25.6 percent). More severe budding was associated with worse outcome: 71.1 percent of BD-2 patients had recurrence, compared with 20.0 percent of BD-1 patients (P < 0.005). The five-year survival rate was worse in BD-2 than in BD-1 (22.2 percent vs. 70.7 percent; P < 0.001). The 10-year survival rate was also worse in BD-2 than in BD-1 (13.8 percent vs. 50.6 percent; P < 0.001). The incidence of BD-2 rose with the Dukes stage. However, the five-year survival rate of Dukes B patients with BD-2 lesions was worse than that of Dukes C patients with BD-1 cancers (29.1 percent vs. 66.2 percent; P < 0.001). Moreover, there was no difference in five-year survival among BD-1 patients with either Dukes B or C lesions (68.3 percent vs. 66.2 percent). The presence of more severe budding appears to indicate a vigorous biologic activity of colorectal cancer. Thus, meticulous follow-up--and possibly adjuvant chemotherapy--may be beneficial for patients with marked budding, regardless of their Dukes stage.

Actuarial Analysis↗

Pseudomyxoma peritonei.

Pseudomyxoma peritonei results from implantation of malignant tumors or irritation from ruptured benign cysts. This disease is traditionally characterized by accumulation of mucinous ascites, relatively long survival period and absence of extraperitoneal metastases. Disease progression is difficult to predict because of the spectrum of underlying pathologic entities. Four unusual instances of pseudomyxoma peritonei are presented. An instance of the neoplasm confined to the splenic parenchyma suggests potential for hematogenous dissemination. The tumor can be limited to and extend along the retroperitoneum. Retained rectal tissue after proctocolectomy may be a possible origin of disease. Enterobronchial fistula formation is a serious long term complication. Aggressive surgical approach with resection of the bulk of disease offers the optimal palliation and prognosis.

Female↗

Measurement of free radicals from smoke inhalation and oxygen exposure by spin trapping and ESR spectroscopy.

Research in smoke inhalation has established that free radicals are produced from gases released during combustion and these species impair lung function. Using spin traps and their adducts in an animal model free radicals were measured. Various hyperbaric oxygen regimens were tested in an attempt to attenuate pulmonary damage caused by free radical reactions. Our data demonstrated that persistent oxygen- and carbon-centered free radicals are detectable in intravascular fluids after smoke inhalation. The smoke inhalation model showed however, clearing of spin trap adducts one hour after smoke exposure. Other researchers have found that when 100% oxygen is given at 1 atmosphere absolute (ATA) for 1 h, free radicals were not detectable. However, oxygen given at 2.5 ATA does produce detectable free radicals. With continued exposure at this pressure, the levels of free radicals increase for up to 60 min. This study suggests that the level of free radical induced oxygen toxicity may be a function of oxygen pressure and duration of oxygen exposure.

Animals↗