A new concept for implementation of a required general surgery clerkship.

Background: Two years ago our institution abbreviated the junior internal medicine and general surgery clerkships to accommodate a 4-week family practice clerkship and a 4-week elective clerkship. As a consequence, 1-month mandatory internal medicine and general surgery clerkships were placed in the senior year.

Methods: The surgical disorders most commonly encountered by the generalist are discussed.

INK4 genes in pancreatic carcinoma.

The INK4 family includes the structurally and functionally related p15, p16 and p18 genes. in vitro they arrest the cell in G1 phase, thus far in an apparently similar manner. It is not clear yet how their functions relate in vivo, whether these genes have distinct or redundant functions.

Mad-related genes in the human.

Resistance to the growth inhibitory effects of TGF-beta is common in human cancers. However, the mechanism(s) by which tumour cells become resistant to TGF-beta are generally unknown. We have identified five novel human genes related to a Drosophila gene called Mad which is thought to transduce signals from TGF-beta family members.

Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers.

Chromosome deletions are the most common genetic events observed in cancer. These deletions are generally thought to reflect the existence of a tumour suppressor gene within the lost region. However, when the lost region does not precisely coincide with a hereditary cancer locus, identification of the putative tumour suppressor gene (target of the deletion) can be problematic.

Simultaneous assessment of loss of heterozygosity at multiple microsatellite loci using semi-automated fluorescence-based detection: subregional mapping of chromosome 4 in cervical carcinoma.

Detection of loss of heterozygosity (LOH) by comparison of normal and tumor genotypes using PCR-based microsatellite loci provides considerable advantages over traditional Southern blotting-based approaches. However, current methodologies are limited by several factors, including the numbers of loci that can be evaluated for LOH in a single experiment, the discrimination of true alleles versus "stutter bands," and the use of radionucleotides in detecting PCR products. Here we describe methods for high throughput simultaneous assessment of LOH at multiple loci in human tumors; these methods rely on the detection of amplified microsatellite loci by fluorescence-based DNA sequencing technology.

DPC4 gene in various tumor types.

We recently identified a novel tumor-suppressor gene, DPC4, at chromosome 18q21.1 and found that both alleles of DPC4 were inactivated in nearly one-half of the pancreatic carcinomas. Here, we analyzed 338 tumors, originating from 12 distinct anatomic sites, for alterations in the DPC4 gene.

Familial pancreatic cancer: a review.

The cause of pancreatic cancer remains elusive. The most consistently identified epidemiological risk factor is cigarette smoking. Genetic factors are known to play a significant role in perhaps 5% of the total pancreatic cancer burden.

Analysis of replication error (RER+) phenotypes in cervical carcinoma.

Infection of epithelial cells with human papillomavirus is an important early event in the development of cervical dysplasia. However, progression to overt malignancy appears dependent upon further genetic and/or epigenetic events. We have recently developed methodologies for the simultaneous analysis of loss of heterozygosity (LOH) at multiple PCR-based microsatellite loci using semiautomated fluorescent DNA sequencing technology to determine the locations of tumor suppressor genes which are inactivated during tumor progression.

Responding to subpoenas and other demands for records and testimony.

Being served with a subpoena can be an intimidating event for a physician. This article provides a point-by-point guide to responding to subpoenas and other demands for records and testimony.

Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms.

Although several morphological and molecular genetic studies have implicated various grades of pancreatic duct hyperplasia as precursor lesions to infiltrating pancreatic adenocarcinoma, the identity of preinvasive pancreatic neoplasms remains controversial. In the present study, the authors examined the expression of the epidermal growth factor receptor homologue, HER-2/neu (c-erbB-2), in pancreatic duct lesions adjacent to infiltrating pancreas cancers in a series of 19 cases of pancreatic duct adenocarcinoma. HER-2/neu expression was examined because it has been identified in a proportion of infiltrating pancreas cancers and because it may provide early neoplasms with a growth advantage over adjacent nonneoplastic epithelium.

Homozygous deletion map at 18q21.1 in pancreatic cancer.

Absolute genetic differences between neoplastic and nonneoplastic cells can be discerned at sites of homozygous deletions. These deletions are of critical interest because they might be useful in the identification of defective biochemical pathways in neoplastic cells, and subsequently for the development of new treatment strategies in human cancer. We identified an area at 18q21.

DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.

About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.

Cytokine secretion by macrophages in the rat testis.

The rat testis contains a large population of resident macrophages, the physiological roles of which are yet to be established. To investigate the functional capacity of these cells, we have analyzed the secretion of the cytokines interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF alpha), and granulocyte macrophage-colony stimulating factor (GM-CSF) by isolated testicular macrophages (TMs) and, for comparison, by isolated rat peritoneal macrophages (PMs). Cells were cultured for 48 h in serum-free medium alone or with lipopolysaccharide (LPS, 10 micrograms/ml) and/or recombinant interferon-gamma (rIFN gamma, 200 U/ml).

Isolation of YAC insert sequences by representational difference analysis.

We present a method for the isolation of YAC insert sequences by representational difference analysis (RDA). To achieve maximal representation of the sequences, the amplicons were generated from a Mbol digestion product. RDA was performed using a 970 kb insert YAC clone.

An integrated high-resolution physical map of the DPC/BRCA2 region at chromosome 13q12.

We identified a homozygous deletion in a pancreatic carcinoma (DPC) that localized to a 1-cM region at chromosome 13q12.3, which lay within the 6-cM locus of familial breast cancer susceptibility (BRCA-2). Here we present a physical map of the region, consisting of YAC, PAC, and cosmid contigs.

Molecular genetics of exocrine pancreatic neoplasms.

Molecular genetic studies of pancreatic ductal adenocarcinoma have revealed the common co-existence of K-ras, p53, and MTS1 mutations. The finding of K-ras mutations in epithelial lesions of ducts suggests them as a precursor intraepithelial neoplasm. The clinical importance of this line of work can only be anticipated at present, and a fuller understanding of genetic alterations in these neoplasms is necessary.

p53-independent expression of the cyclin-dependent kinase inhibitor p21 in pancreatic carcinoma.

The p53 tumor suppressor gene is mutated in the majority of pancreatic adenocarcinomas, and several studies have suggested that loss of p53 function may contribute to the aggressive clinical behavior of pancreas cancer. Although immunocytochemical accumulation of the p53 gene product has previously been assessed as a marker for p53 mutations in cancers of the pancreas and other organ systems, the relationship between p53 mutations and p53 protein accumulation is variable. The cyclin-dependent kinase inhibitor, p21 (also known as WAF1 and CIP1), is induced by wild-type but not mutant p53, and recent work has implicated p21 as a downstream mediator of the growth-suppressing and apoptosis-promoting functions of wild-type p53.

Physician control of health care delivery in the managed care environment.

Managed care is a part of nearly every physician's practice. Physicians need not, however, lose control of their practices. By taking predetermined risks, physicians can maintain control over the quality of medical care, the manner in which that care is provided, their incomes, and their futures.

Indomethacin blocks the immunosuppressive activity of rat testicular macrophages cultured in vitro.

Macrophages are a prominent resident cell type in the interstitial tissue of the testis in several mammalian species. This presence in an immunologically-privileged site prompted an investigation of their ability to initiate and regulate lymphocyte proliferation in vitro. Isolated rat peripheral blood lymphocytes (PBL) were cultured either directly with isolated rat testicular (Tm) or peritoneal (Pm) macrophages or with the conditioned medium from cultures of these cells (Ts or Ps).

Common occurrence of APC and K-ras gene mutations in the spectrum of colitis-associated neoplasias.

Background/aims: Chronic colitis is associated with an increased risk of colorectal neoplasia, creating a need for early diagnosis in this population. Little is yet known of the genetic changes of early lesions. Cases of colitis-associated neoplasia were analyzed for APC and K-ras mutations with special emphasis given to the spectrum of noninvasive lesions.

Occurrence of primary renal angiosarcoma in brothers.

Two brothers, 3 years apart in age, developed angiosarcoma of the left kidney at ages 52 and 69. Both rapidly developed systemic metastasis and died 6 weeks and 3 months, respectively, after nephrectomy. No common carcinogen or hereditary or other etiologic factor was identified.

A comparison of dynamic and isometric force sensors for train-of-four measurement using submaximal stimulation current.

Objective: We studied the accuracy and repeatability of train-of-four (TOF) ratio measurements made from a dynamic piezoelectric sensor that records movement of the thumb in response to ulnar nerve stimulation compared with an isometric mechanomyogram that measures force of contraction of the adductor pollicis.

Methods: The study involved 10 patients whose level of neuromuscular block was held constant with an intravenous (IV) infusion of vecuronium bromide (0.4 to 1.