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Biomedical subjects

M D Stein

Publications and source records attributed to M D Stein.

At least 91 records · Page 5Linked to original sources

Physical symptoms and depressive symptoms among individuals with HIV infection.

The authors investigate the importance of physical symptoms as a correlate of depressive symptoms and suicidal thoughts in a large (N = 881) community-based sample of persons infected with human immunodeficiency virus. The study overcomes limitations of prior research by minimizing overlap in measures of affective and physical symptoms, studying a more diverse population, and including correlates such as measures of social support, function, employment, insurance coverage, and cognitive impairment in the analysis. The authors' data support the notion that in diagnosing depression in the medically ill, concern over isolating physical symptoms as either "affective" or "physical" may be exaggerated.

Acquired Immunodeficiency Syndrome↗

An exploratory analysis of survival with AIDS using a nonparametric tree-structured approach.

We illustrate an analysis with classification and regression trees applied to survival data. Through this application, we provide a description of the opportunistic diseases and sociodemographic factors that contribute to survival among people with human immunodeficiency virus disease. The analyses are based on 43,795 cases reported to the Centers for Disease Control between January 1, 1984, and December 31, 1987. We used vital status as of December 31, 1989, to estimate mortality rates. We identified Kaposi's sarcoma and opportunistic diseases causing central nervous system damage (cryptococcosis, primary lymphoma of the brain, cytomegalovirus disease, and progressive multifocal leukoencephalopathy) as important predictors of death. In addition, advanced age at diagnosis (50+), race (white/other), and history of illicit drug use were found to be important determinants. Estimates of the cumulative probability of survival for subgroups of individuals defined by the tree structure illustrate the effect of these determinants on mortality. For the purpose of comparison, two proportional hazards models were also fit to the data using factors identified in the tree structure as the determinants of interest. This application illustrates the utility and limitations of both this new technique and proportional hazards models for epidemiologic research.

Acquired Immunodeficiency Syndrome↗

Correction of HIV-associated thrombocytopenia with low doses of interferon alfa.

We have presented a case of HIV-associated thrombocytopenia successfully treated with low dose interferon alfa-2a. Increases in platelet levels were achieved within 1 week without hospitalization or surgery. Further, the patient had no systemic side effects from therapy. Zidovudine alone was ineffective in maintaining noncritical platelet counts. Interferon alfa-2a is a nonimmunosuppressive, nonsurgical therapy that can correct HIV-associated thrombocytopenia without requiring hospitalization.

Adult↗

A 10-year longitudinal study of untreated mucogingival defects.

A study was conducted to observe the changes in areas with untreated mucogingival defects over a 10-year period. The results in this group after 4 years were previously published. Upon entering dental school, a group of 39 freshman dental students were assessed for plaque index, gingival index, probing depth, and width of keratinized gingiva in 112 sites of inadequate keratinized gingiva. Eighteen of the original 39 participants were reassessed for the same parameters in 64 sites after 10 years. The results revealed that 22 sites showed a slight increase in keratinized gingiva, 32 were unchanged, and 10 sites showed a slight decrease in keratinized gingiva. The mean width of keratinized gingiva at the beginning of the study was 1.73 +/- 0.542 mm and was 2.01 +/- 0.864 mm after 10 years. This represented a small, but statistically insignificant, increase in the width of keratinized gingiva. The Plaque Index and Gingival Index of this group at baseline and at 10 years indicated a high level of oral hygiene and gingival health. It was concluded that in the absence of gingival inflammation, areas with small amounts of keratinized gingiva may remain stable over long periods of time.

Dental Plaque Index↗

Clues to enhancing the identification of human immunodeficiency virus-infected women.

Although ACOG recommends human immunodeficiency virus (HIV) testing of pregnant women who are "at increased risk" of HIV infection, more explicit recommendations do not exist. We suggest three stages of collecting clinical clues that may enhance the identification of HIV-infected women. The first considers traditional HIV-risk behaviors. The second incorporates the answers to specific questions in the clinical history, and the third considers the results of standard blood tests obtained during routine obstetric-gynecologic visits.

Female↗

Human immunodeficiency virus infection in North American women: experience with 200 cases and a review of the literature.

This study was designed to define the epidemiology and natural history of human immunodeficiency virus (HIV) infection in women in Rhode Island. Two hundred women referred to Brown University physicians from 1986 through 1990 were evaluated at 3-to-6-month intervals for 12 to 60 months. All received antiretroviral therapy and prophylaxis against opportunistic infections when indicated on the basis of CD4 lymphocyte counts. Major findings included: 1) rapid shift of dominant mode of transmission from intravenous drug sharing to heterosexual route; 2) significant gender-specific differences in clinical presentation; 3) increased frequency of cervical dysplasia in women infected via intravenous needle sharing; 4) no definite gender-specific differences in progression of HIV infection; 5) enormous societal impact of HIV infection in women. Principal conclusions are: 1) rapid change to predominantly heterosexual HIV transmission can occur in North America, with serious societal impact; 2) gender-specific clinical features can lead to earlier diagnosis of HIV infection in women; 3) HIV infection in women does not pursue an inherently more rapid course than that observed in men.

Adolescent↗

Clinical evaluation of a biodegradable collagen membrane in guided tissue regeneration.

A bio-resorbable type I collagen membrane was investigated as a barrier for guided tissue regeneration. Ten human subjects with at least one pair of contralateral periodontal lesions with probing pocket depths of greater than or equal to 5 mm and radiographic evidence of greater than or equal to 40% bone loss were included. Each patient underwent contralateral surgical flap procedures. A collagen barrier was adapted to the tooth in the experimental defect and the flap replaced and sutured. The controls consisted of the same procedure without the placement of the barrier. Standardized measurements of change in probing attachment levels and fill of intrabony defects were obtained at the time of surgery and 1 year later at the time of surgical re-entry. The differences in change of probing attachment levels and amount of bone fill between individual test and control sites were compared utilizing the student's t-test for paired samples. The mean probing attachment gain in the test sites was 0.56 +/- 0.57 mm, and there was a mean probing attachment loss of 0.71 +/- 0.91 mm in the control sites (P less than 0.01). The gain of bone in test lesions was 1.16 +/- 0.95 mm, while no gain was observed in the control lesions (P less than 0.01). The results of this study demonstrated that sites treated with a collagen barrier comprised of cross-linked bovine Type I collagen exhibited significantly better healing as compared to control sites over the 1-year period of the study.

Adult↗

Interleukin 2 induced non MHC-restricted killing of herpes simplex type-1 (HSV-1) infected allogeneic and autologous lymphoblasts.

Peripheral blood lymphocytes (PBL) from herpes simplex type-1 (HSV-1) seropositive (sero+) and seronegative (sero-) individuals were assessed before and after in vitro culture with IL-2 for their ability to kill different tumor cells and to kill HSV-1 infected PHA lymphoblasts using a 4 hr 51Cr release assay. Fresh PBL from either sero+ or sero- individuals had little cytotoxic activity against HSV-1 infected autologous PHA lymphoblasts or against different NK-insensitive tumor targets. When PBL from either sero+ or sero- individuals were incubated 3-4 days in vitro with IL-2, significant levels of cytotoxic activity was observed against both allogeneic and autologous HSV-1 infected targets and against different NK-insensitive tumor cells. When comparing PBL from sero+ versus sero- individuals for IL-2 induced cytotoxic activity against HSV-1 infected autologous targets, PBL from sero+ individuals always had significantly higher levels of cytotoxic activity. Allogeneic HSV-1 infected targets were also killed by IL-2 activated PBL obtained from either sero+ or sero- individuals, but IL-2 activated PBL from sero+ individuals showed higher cytotoxic activity on HSV-1 infected autologous targets when compared to HSV-1 infected allogeneic targets. When IL-2 induced cytotoxic effector cells were treated with HSV-1 for 1 hr and recultured with IL-2, significant inhibition of cytotoxic activity against all target cells was observed. Greater than 50% inhibition of cytotoxic activity was observed when IL-2 induced cytotoxic effector cells were treated with HSV-1 and cultured for 6 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Peripheral blood lymphocytes from thermal injury patients are defective in their ability to generate lymphokine-activated killer (LAK) cell activity.

We have previously shown that natural killer (NK) cell activity against K562 tumor cells is severely depressed in thermal injury patients. In this study we have investigated whether the low NK cell activity present in peripheral blood lymphocytes (PBL) from thermal injury patients could be enhanced by in vitro culture with interleukin 2 (IL2) and whether PBL obtained from these patients could generate lymphokine-activated killer (LAK) cell activity against NK insensitive tumor targets. NK cell activity in PBL obtained from 12 different patients was greatly enhanced against K562 tumor cells after in vitro culture with IL2 for 3 days. In contrast, PBL obtained from these patients and incubated with IL2 had little to no cytotoxic activity when measured against a number of NK-insensitive tumor targets. The failure of PBL obtained from thermal injury patients to generate LAK cell activity was observed regardless of the culture time or the amount of IL2 added to the cultures. PBL from thermal injury patients demonstrated reduced proliferative responses to IL2 and, more importantly, contained suppressor cells which could inhibit the generation of LAK cell activity of normal PBL obtained from control individuals. These results clearly show that in some thermal injury patients NK cell activity can be enhanced by IL2 but these patients are defective in their ability to generate LAK cell activity.

Adult↗

Changes in the population of active rosette-forming cells: a sensitive index for mortality among thermal injury patients.

Peripheral blood lymphocytes from normal and thermally injured patients were studied for their ability to form rosettes with sheep red blood cells (SRBC) by active E-rosette assay at different times postinjury. The population of active rosette forming cells (ARFC) was observed to be significantly lower (P less than 0.001) in thermal injury patients compared with the normal subjects. The age and sex of the patient did not seem to have any significant effect on the ARFC population or the total lymphocyte count. The degree of burn had a significant (P less than 0.05) effect on the ARFC population but not the total lymphocyte count during the first 10 days immediately after burn, with partial skin thickness burn patients having more ARFC compared with full skin thickness burn patients. Further analysis of the data revealed an important correlation between the per cent ARFC in peripheral blood and the survival of the patients. Patients who died from their injuries showed a continuous decline in ARFC over the period of study, whereas the patients who survived showed a gradual increase until the ARFC number returned to within the normal range. The observed differences in the ARFC population between survivors and non-survivors were apparent as early as the first 10 days postinjury. Thus, the percentage of ARFC in the total peripheral blood may be used as an index for the early identification of patients at a greater risk of mortality.

Adolescent↗

Failure of TPN supplementation to improve liver function, immunity, and mortality in thermally injured patients.

Hypermetabolism with negative nitrogen balance and immune deficiencies characterize the systemic response to major thermal injury. Patients with burns greater than 50% of the total body surface area (TBSA) initially have poor gastrointestinal function, making it difficult to deliver sufficient enteral calories to meet nutritional requirements. Controversy has developed over whether to supplement oral alimentation with total parenteral nutrition (TPN) early in their treatment. This study randomly assigned 28 patients with burns greater than 50% TBSA to receive TPN supplementation or no TPN supplementation in the first 10 days postburn. Patients receiving TPN supplementation had significantly lower T-cell helper-to-suppressor cell ratios than the unsupplemented group. However, there was no difference in mortality between the groups (eight in each). All patients who died developed hepatomegaly associated with fatty infiltration cholestasis and antemortem liver function abnormalities, indicating that this syndrome is the result of burn injury itself, not TPN.

Adult↗

A longitudinal study of untreated mucogingival defects.

A study was conducted to observe the changes in areas with untreated mucogingival defects over a 4-year period. Upon entering dental school, a group of freshman students were assessed for Plaque Index, Gingival Index, probing depth, and width of keratinized gingiva. These same students were reassessed for the same parameters at the end of their senior year. Of the 112 sites in 39 individuals, 33 sites revealed a slight increase in keratinized gingiva, 69 sites were unchanged, and 10 sites showed a slight decrease. These changes were minimal and not statistically significant. The Plaque Index, Gingival Index, and probing depth mean values showed a small but statistically significant improvement. In this group of students with a high degree of oral hygiene, areas with inadequate zones of attached gingiva were able to be maintained without further recession and without surgery.

Dental Plaque Index↗

Kinetics of lymphoproliferative responses following scald injury in a rat burn model.

Splenic lymphocytes from scalded and nonscalded rats were studied for their proliferative response to phytohemagglutinin, and to allogeneic cells in a one-way mixed lymphocyte culture (MLC). A significant suppression of the proliferation of lymphocytes in both these assays was observed as early as 4 days postinjury as measured by the [3H]thymidine uptake studies. The lymphocyte response to PHA returned to normal levels by Day 21 postinjury, whereas the MLC responses continued to be suppressed. The MLC responses between nonburned and burned animals could be restored by the addition of a lymphokine-rich culture supernatant obtained from concanavalin A-activated lymphocytes from normal nonburned rats, as well as by the addition of purified human interleukin 2 (IL-2) and rat interleukin 2. However, the addition of purified human interleukin 1 and human interferon gamma (Hu-IFN-gamma) did not bring about a significant change in the proliferation of burned rat spleen cells in MLC. Cells from burned rats were also tested for the development of suppressive activity by adding splenic lymphocytes from 2-week postburn rats to an ongoing one-way MLC. The addition of lymphocytes from burned rats resulted in significant suppression (81%) of MLC responses among normal nonburned rats. The data suggest that the development of suppressor cells following burn injury along with a defect in production and/or uptake of IL-2 may be partly responsible for immune suppression following burn injury. Since the proliferative response of lymphocytes from thermally injured rats is suppressed in a similar fashion as that found in thermally injured patients, the rat appears to be a good model for the study of kinetics of immune suppression following burn injury.

Animals↗

The pulmonary lesion of smoke inhalation in an ovine model.

Inhalation injury was induced in chronically instrumented sheep (n = 9) by insufflating them with smoke from burning cotton cloth. Sham animals (n = 9) were insufflated with air. There were no temporal changes in any measured parameter of the sham animals. Smoke induced a depression in PaO2. There was a threefold elevation in protein-rich pulmonary lymph which was sustained for over 48 hours. The lymph-to-plasma oncotic pressure ratio was increased. The cardiac index, left atrial pressure, and pulmonary arterial pressure remained unchanged in both groups. After smoke inhalation, the interstitial levels of neutrophils increased while interstitial antiprotease activity was depressed. The lung lymph concentration of 6-keto prostaglandin F1a, the major metabolite of prostacyclin, was increased. These data suggest that the pulmonary injury following smoke inhalation is the result of an increase in lung microvascular permeability to protein with resultant pulmonary edema. The mechanisms responsible for these changes appear to be related to direct injury to the tracheobronchial tree by cytotoxic agents in the smoke; polymorphonuclear leukocytes; and, possibly, eicosanoids.

6-Ketoprostaglandin F1 alpha↗

Defective NK cell activity following thermal injury.

Peripheral blood mononuclear lymphocytes (PBL) from thermal injury patients were examined for their ability to mediate natural killer (NK) cell activity against K562 tumour cells and against herpes simplex virus type 1 (HSV-1) infected Raji tumour cells. Using fluorescein isothiocyanate-conjugated monoclonal antibodies, the number of T3, T4, T8, Leu11, and Leu7 positive cells in PBL obtained from patients and normal controls was determined. Thermal injury patients had decreased levels of T3+ cells and a T4:T8 ratio which was significantly lower than that found in normal control individuals. Although patients had normal percentages of Leu7+ and Leu11+ cells, they had depressed NK cell activity against both K562 tumour cells and HSV-1 infected Raji cells. NK cell activity against K562 tumour cells was severely depressed during the first 20 days after injury. This defective NK cell activity did not appear to be due to a defect in PBL binding to the K562 tumour cells. In patients, the level of NK cell activity against HSV-1 infected cells did not correlate with the level of NK cell activity against K562 tumour cells. This finding further supports previous reports showing that NK cells which kill K562 tumour cells are different from the NK cell population which kills HSV-1 infected cells. Pretreatment of PBL obtained from patients with IL-2 or IFN-alpha, in some cases greatly enhanced NK cell killing of K562 tumour cells. However, IL-2 or IFN-alpha did not enhance NK cell activity in patients who had severely depressed levels of NK cell activity. Interestingly, in some patients, differential responsiveness to IL-2 and IFN-alpha was observed. In some patients, NK cell activity was enhanced by IL-2 but not by IFN-alpha. These results, while only suggestive, may indicate that different populations of NK cells respond preferentially to IL-2 and that IFN-alpha and/or IL-2 enhance NK cell activity in PBL obtained from some, but not all, thermal injury patients. Finally, this study clearly shows that thermal injury patients have defective NK cell activity not only against K562 tumour cells but also against virus-infected cells.

Adult↗

Collagen sponge as a topical hemostatic agent in mucogingival surgery.

Hemorrhage from palatal donor sites during periodontal mucogingival surgery was controlled by application of Collastat absorbable hemostatic sponges. The use of collagen sponges was evaluated in 20 free-graft cases. In contrast to microfibrillar collagen, which is normally delivered as clumps of material, a Collastat sponge was applied as a single piece that maintained structural integrity even when wet and was easy to maneuver into place. The highly porous sponges conformed to the wound, absorbed fluid and produced consistently reliable hemostasis with no secondary bleeding. By stemming the seepage of blood into the throat, patient safety and comfort were improved. The sponges were left on the wounds and removed at the 1-week postoperative visit, revealing well-formed granulation tissue. Healing proceeded normally with no evidence of infection, tissue reaction, or other adverse effects.

Collagen↗

Natural killer cell defects resulting from thermal injury.

Peripheral blood mononuclear lymphocytes (PBL) from thermal injury patients were examined for their ability to mediate spontaneous (NK) cytotoxic activity against K562 tumor cells. NK cell numbers were quantitated in burn patients using the fluorescein isothiocyanate-conjugated monoclonal antibody Leu-7 and an Ortho cell sorter. NK activity of burn patients was only 30% of control levels. Thus, at a 50:1 effector:target cell ratio, burn patients' PBL gave a mean of 18% killing as compared to 60% killing mediated by control PBL (14 individuals). Pretreatment of PBL with interferon-gamma or interferon-alpha enhanced NK activity of normal PBL but had no effect on the NK activity of PBL from burn patients. The number of cells bearing antigen recognized by Leu-7 was variable in burn patients, with some patients having decreased (less than 5%), normal (8-10%), or elevated (20-40%) numbers of Leu-7 bearing PBL. No differences were observed in the total numbers of PBL in burn patients when compared to control individuals. These results indicate that NK activity does not correlate with the percentage of Leu-7 bearing cells present in PBL and that the inability of thermal injury patients to mediate normal NK function may contribute to their susceptibilities to viral infections.

Adolescent↗

Increased thromboxane B2 levels in the plasma of burned and septic burned patients.

Levels of both thromboxane B2 and 6-keto-prostaglandin-F1a, the stable metabolites of thromboxane A2 and prostacyclin, respectively, were quantitated in plasma samples from burn patients at various times postinjury. Our results indicate that, although thromboxane B2 levels were elevated throughout the burn course, quite large increases occurred both in the acute stage (less than three days postinjury) and during septic episodes. The results of our study demonstrate that, at the same time thromboxane B2 levels were elevated, 6-keto-prostaglandin-F1a levels were unchanged and remained at control levels. Increased production of thromboxane B2 without a concomitant increase in 6-keto-prostaglandin-F1a in the plasma of burn patients gives support to the hypothesis that elevated thromboxane A2 production contributes to post-thermal injury systemic responses, both in the acute phase as well as during sepsis.

6-Ketoprostaglandin F1 alpha↗