PubMed HealthSearch

Biomedical subjects

M Markowitz

Publications and source records attributed to M Markowitz.

At least 19 recordsLinked to original sources

Gastric duplication cyst communicating with the pancreatic duct: a rare cause of recurrent abdominal pain.

A 41-year-old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct. Celiotomy demonstrated a noncontiguous gastric duplication cyst. Internal drainage was curative.

Abdominal Pain

Oxidative stress induces DNA damage and inhibits the repair of DNA lesions induced by N-acetoxy-2-acetylaminofluorene in human peripheral mononuclear leukocytes.

Human mononuclear leukocytes were exposed to prooxidants such as H2O2, phorbol-12-myristate-13-acetate, and 4-nitroquinoline-N-oxide, and the effects on induction of DNA damage and repair were evaluated. ADP ribosylation was activated by prooxidant exposure and the response was bimodal with peaks of activation occurring at about 30 min and 4-5 h. Other evidence for prooxidant-induced DNA damage was provided by nucleoid sedimentation assays. Unscheduled DNA synthesis (UDS) was only slightly induced by prooxidant exposure which suggested that either the DNA lesions were repaired by a short patch mechanism involving little UDS, or the repair process was inhibited by prooxidant exposures, or some combination of both. This point was clarified by the fact that the repair of DNA lesions induced by N-acetoxy-2-acetylaminofluorene, an inducer of large patch DNA repair, was inhibited in a dose-dependent manner by exposure to H2O2 and the inhibition was dependent on ADP ribosylation. In contrast, the repair of DNA strand breaks induced by prooxidant exposures as identified above were complete within about 8 h and the repair was independent of ADP ribosylation. Both ADP ribosylation and N-acetoxy-2-acetylaminofluorene-induced UDS were shown to be up- and down-regulated by the redox state of human mononuclear leukocytes indicating a unique mechanism of cellular control over DNA repair.

2-Acetylaminofluorene

DNA repair synthesis in individuals with and without a family history of cancer.

The influence of family history on DNA repair synthesis, unscheduled DNA synthesis (UDS), was assessed in volunteers with or without a family history of cancer. UDS, following treatment of mononuclear leukocytes with N-acetoxy-2-acetylaminofluorene, was measured as the incorporation of [3H]thymidine into DNA in the presence of hydroxyurea. The positive family history group (n = 71) had an average of 2.4 first-degree relatives with cancer, defined as any major cancer, excluding skin cancer: 31 participants reported that cancer occurred in both their parents. The "no family history' comparison group (n = 29) had no family history of cancer through the second degree. There was a significant reduction in UDS in cells from individuals with family history, compared to those with no family history (P greater than 0.002). This relationship was not explained by factors known to influence UDS, such as age, smoking or hypertension. We conclude that reduced UDS in mononuclear leukocytes is associated with a family history of any major cancer, and is not confined to a history of cancer of any single organ site. This conclusion is further supported by the observation that individuals (n = 13) with parents who had an earlier onset of cancer (less than 60 years) also had a significantly lower DNA repair synthesis than those (n = 18) whose parents had later diagnosis of cancer (greater than 60 years).

Acetoxyacetylaminofluorene

Adenosine diphosphate ribosyl transferase responses to a standardized dose of hydrogen peroxide in the mononuclear leukocytes of patients with a diagnosis of cancer.

Mononuclear leukocytes from 151 patients with cancer of various organs and from 467 apparently cancer-free individuals were exposed, in vitro, to H2O2 (100 microM) and the effects of the exposure on the activity of adenosine diphosphate ribosyl transferase (ADPRT) were determined. First, the reproducibility of this test procedure was established as satisfactory, by comparing the results of assays performed independently by two investigators, and by measuring ADPRT in cells from two individuals over a 9-week period. The test data were analyzed by multiple linear regression, and the correlation of cancer diagnosis, age, sex and smoking habits with ADPRT values was determined. The strongest correlate was cancer diagnosis. We considered categorizing ADPRT values as high and low, with a cut-off value that would substantially distinguish cancer from cancer-free individuals. When a cut-off value of 1200 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was applied to the complete test material, it was found that ADPRT values from cancer patients were more frequently below the cut-off than values from disease-free individuals: the relative risk estimate (odds ratio) was 13.8. When a similar analysis was done on values from lung cancer patients and smoking disease-free individuals, the odds ratio was 73.5. However, a cut-off value of 2000 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was most effective in distinguishing lung cancer patients (the largest cancer group, n = 96) from smoking non-cancer individuals: that value provided better sensitivity (85%) and specificity (81%) than other cut-off values tested in the range 1200-2000 c.p.m. Further, in the case of lung cancer, possible effects of anatomical site, and of staging and pathology on ADPRT values was analyzed by the chi-squared test: no significant associations were found. These data support the value of the ADPRT test in detecting early stage lung cancer regardless of location or pathological type.

Adult

Reappearance of rheumatic fever.

Even though incompletely understood, much of the information about the epidemiology and pathogenesis of rheumatic fever has become available only in the last few decades, a time when there have been significant fluctuations in rheumatic fever and rheumatic heart disease in the United States. The precise roles of the bacteria, the human host, and the environment and their interrelationships require more study. Determining their roles and defining the pathogenesis can have important practical application. If one could identify a susceptible population, if one could identify the serotypes and/or strains of group A streptococci that are more dangerous (rheumatogenic) and if one could identify the reason for an abnormal immune response, vaccines might be made with specific protective components of the group A streptococci and administered only to known susceptible individuals. Providing optimal public health programs to control a disease that still is a major problem in a large segment of the world's population is the goal. It is quite clear from the resurgence of acute rheumatic fever in the United States in the mid-1980s that antibiotics alone are not the answer to rheumatic fever control. If antibiotics are not completely effective in a country such as the United States, they cannot be expected to be effective in many of the developing countries of the world where primary health care delivery is even more difficult. Intensified efforts to understand the pathogenetic mechanisms responsible for the development of rheumatic fever should be undertaken. In the meantime, the preventive methods that are available should be vigorously applied.

Developing Countries

The fall and rise of rheumatic fever in the United States: a commentary.

After a documented decline in the incidence of acute rheumatic fever in the United States during the past three decades, an apparent resurgence has occurred in the mid-1980s. Although standards of living have continued to improve with concomitant decrease in crowding and easier accessibility to medical care, the precise reasons for the decline remain unexplained. Furthermore, the decline has occurred even though there is no epidemiologic evidence to suggest any reduction in the incidence of group A streptococcal pharyngitis. Just as the decline remains unexplained, so also does the "resurgence". Of considerable interest are the facts that the preceding pharyngitis has been mild in the majority of cases, the incidence of documented carditis has been high (over 90% in one series), and the rheumatic fever has been concentrated in middle class families with ready access to medical care. Even more intriguing has been the appearance of very mucoid strains of group A streptococci at the same time. While this simultaneous appearance suggests "rheumatogenicity", this has not been substantiated; no "rheumatogenic factor" has yet been isolated from these strains. This outbreak, although small in comparison with the number of cases occurring in many of the developing countries of the world, has important implications for those countries. Unless and until the pathogenesis of rheumatic fever is fully understood, methods of control will not be optimal.

Cross-Sectional Studies

Rheumatic fever in the eighties.

The current status of rheumatic fever is reviewed and the reasons for its decline in the United States are explored. Continuation of primary prevention efforts is recommended or there could be a resurgence of this disease. The need for further research continues because rheumatic fever is still a major health problem for much of the world's population.

Child

The changing picture of rheumatic fever.

Rheumatic fever has decreased in frequency and severity, but the disease has not been eradicated in this country, especially in low socioeconomic populations. Carditis is less common, and changes in the frequency of other rheumatic manifestations such as chorea has made the clinical diagnosis more difficult. Streptococcal antibody tests are still the most useful laboratory aid, but care must be taken against overinterpretation. The search for the answer to the pathogenesis puzzle continues. Until the nature of the disease is better understood, it is unlikely that rheumatic fever will be eradicated. In the meantime, however, the incidence of the disease can be reduced further by improved medical care for deprived populations.

Adolescent

Angiographic manifestations of bilateral Wilms' tumor.

Two cases of bilateral Wilms' tumor are presented with discussion of angiographic features. Emphasis is placed on selective angiography in addition to inferior vena cavography for complete evaluation. Because of the incidence of bilateral disease, and the highly vascular nature of the tumor, selective angiography of the contralateral side should be considered in the initial evaluation of unilateral Wilms'tumor. Evaluation of the interface between tumor and normal parenchyma is extremely important in bilateral disease, in anticipation of partial nephrectomy.

Angiography