Quinacrine sterilization (QS) in a private practice in Daytona Beach, Florida: a preliminary report.

OBJECTIVES: To affirm that WS can be performed safely and effectively in a U.S. private office practice. METHODS: The U.S. FDA Modernization Act of 1997 Pharmacy Compounding Provisions made it possible for American physicians to begin offering WS to their patients. These provisions became effective November 21, 1998. This series was initiated in October 2000. The standard protocol recommended by the International Federation for Family Health (IFFH) is followed. Information on patients is recorded on forms suggested by IFFG to accomplish good post-marketing surveillance. The potential role of uterine septae in WS failures is of particular interst to this investigator. RESULTS: Seven cases have been completed. There have been no failures. Side effects have been minor. Women have been exceptionally happy with this method. The Florida Agency for Health Care Administration has examined WS and found it to be an acceptable off-label use of quinacrine. CONCLUSION: Preliminary results have been similar to those reported by QS researchers around the world.

Quinacrine sterilization (QS) in a private practice in Daytona Beach, Florida: a preliminary report.

OBJECTIVES: To affirm that QS can be performed safely and effectively in a U.S. private office practice. METHODS: The U.S. FDA Modernization Act of 1997 Pharmacy Compounding Provisions made it possible for American physicians to begin offering QS to their patients. These provisions became effective November 21, 1998. This series was initiated in October 2000. The standard protocol recommended by the International Federation for Family Health (IFFH) is followed. Information on patients is recorded on forms suggested by IFFH to accomplish good post-marketing surveillance. The potential role of uterine septae in QS failures is of particular interest to this investigator. RESULTS: Seven cases have been completed. There have been no failures. Side effects have been minor. Women have been exceptionally happy with this method. The Florida Agency for Health Care Administration has examined QS and found it to be an acceptable off-label use of quinacrine. CONCLUSION: Preliminary results have been similar to those reported by QS researchers around the world.

Treatment settings for persons with alcoholism: evidence for matching clients to inpatient versus outpatient care.

This study compared inpatient, intensive outpatient, and standard outpatient treatment settings for persons with alcoholism and tested a priori hypotheses about the interaction of setting with client alcohol involvement and social network support for drinking. Participants (N = 192) were assigned randomly in cohorts to 1 of the 3 settings. The settings did not differ in posttreatment primary drinking outcomes, although inpatients had significantly fewer jail and residential treatment days combined than outpatients. Clients high in alcohol involvement benefited more from inpatient than outpatient care; the opposite was true at low alcohol involvement levels. Network drinking support did not moderate setting effects. Clients low in cognitive functioning also appeared to benefit more from inpatient than outpatient care. Improved outcomes might be achieved by matching degree of alcohol involvement and cognitive functioning to level of care.

Participant selection biases in a randomized clinical trial of alcoholism treatment settings and intensities.

Eligible participants and decliners in a randomized study of inpatient, intense outpatient, and standard outpatient treatments for alcoholics were compared and contrasted on a series of demographic, social stability, psychological, legal, drug use, problem severity, and treatment history variables. Among 302 individuals meeting eligibility requirements, those agreeing to participate, compared with decliners, were more likely to be unemployed, be residentially less stable, have legal problems, use other drugs, have a more severe alcohol problem, have a recent treatment history, and were less likely to have problems with violence. Participants also were more likely to be male and non-white, although gender and racial effects were not significant when other variables were controlled for. The implications of these findings for generalizing the results of inpatient-outpatient studies are discussed, and the need for routine reporting of decliner characteristics in research reports is stressed.

A discriminant function analysis of various interferon parameters among alcoholics and heavy smokers.

A three-group design of alcoholics, heavy smokers and controls was used to investigate the status of the interferon system, including natural killer cell activity. Group differences were indicated via discriminant function analysis which correctly classified 86% of subjects. Test-retest relations were investigated for 14 subjects following a 30-day alcoholic inpatient program. Whereas significant immune suppression was indicated at the time of detoxification, recovery was evident at the 30-day follow-up. Results are discussed in terms of the significance of alcohol abuse on immune system functioning with consequences for susceptibility to viruses, bacteria and medical illnesses.

Transferrin and mitochondrial aspartate aminotransferase in young adult alcoholics.

Two recently proposed biochemical markers of alcoholism, namely, quantitation of plasma transferrin variant (Tf5.7) and the ratio of plasma mitochondrial aspartate aminotransferase (m-AspAT) to total AspAT (t-AspAT), were tested for their ability to detect young adult alcoholics. Another commonly used biochemical test, namely, activity of plasma gamma glutamyltransferase (GGT) was included as a comparison. Although mean values of GGT, TF5.7, total transferrin (Tftot), m-AspAT and t-AspAT in alcoholics were significantly higher than those in controls, there were too many overlapping values in each test between alcoholics and controls to render any of these tests suitable as a marker for young adult alcoholics. Depending on cut-off limits, the sensitivity of each test ranged from 0-52% and the specificity ranged from 80-97%. Moreover, the m-AspAT/t-AspAT and Tf5.7/Tftot ratios were not significantly different between alcoholics and controls. A stepwise linear discriminant function analysis of all the variables resulted in a slight increase in classification sensitivity (66%) but a decrease in specificity (77%). The relatively short duration (mean = 5.6 years) of heavy alcohol intake and the time elapsed (mean = 5.8 days) since the alcoholics last consumed alcohol very likely contributed to the low sensitivity. Young adults might also be more resilient with regard to the damaging biochemical effects of ethanol. Abnormal biochemical values might reverse to normal values much more quickly in young adult alcoholics than in those who are older and have more years of alcohol abuse.

Identification of alcoholism in young adults by blood chemistries.

A stepwise linear discriminant analysis was conducted between young adult alcoholics in an alcoholism treatment center and non-alcoholic college students. Analysis of 31 commonly ordered clinical laboratory tests yielded three significant variables (urea nitrogen, potassium and MCV) which correctly classify 89% of alcoholics and 92% of non-alcoholics.

Alcohol withdrawal syndromes - prediction from detailed medical and drinking histories.

The predictability of the withdrawal syndrome on the basis of the drinking history immediately prior to detoxification was investigated in 43 patients admitted to an inpatient Alcoholism Service; a pilot study consisted of 17 patients and a subsequent definitive study of 26. After obtaining informed consent, blood alcohol concentrations were measured. Each subject was extensively interviewed to obtain a medical and dietary history and to determine alcohol and drug intake in the past week and months. The levels of intoxication and withdrawal signs/symptoms were assessed on admission and daily for at least 3 days. Urine and blood toxicology screens were also performed for 19 subjects. Contrary to widespread impressions, most of the patients were able to give a detailed account of their drinking and drinking-related behavior in the 3 days prior to admission and 73% could do this for the previous 7 days. Subjects were consistent in their reporting; 85% gave drinking histories consistent among interviews conducted independently by the medical, research and counseling staff. A significant correlation (r = 0.55; P less than 0.01) was found between the severity of withdrawal and the total alcohol intake in the days immediately prior to admission. No significant correlation was evident between withdrawal severity and the number of years of heavy drinking. Amounts of benzodiazepines (diazepam and flurazepam) administered by the medical staff during the first 3 days of withdrawal and for the total hospital stay were also found to be significantly correlated with withdrawal severity (r = 0.58; P less than 0.01 for both). Regression analyses of these data also confirmed the statistically significant relationships between alcohol intake and withdrawal severity and between withdrawal severity and amounts of benzodiazepines used for detoxication. Of special interest was the finding that 50% of the subjects reported no hangovers within he past year or more and 23% reported that they had never experienced a hangover, despite very heavy drinking. In addition, only 50% of the patients had regularly consumed coffee or any caffeine-containing substance; this low incidence of caffeine intake was statistically significantly less than that found in extensive surveys of the general population in which only 3-10% eschew caffeine-containing beverages. It is concluded that the severity of alcohol withdrawal can be related to a cluster of variables among which is recent alcohol intake. The present results are, at the same time, consistent with previous observations of the appreciable differences among individuals in the consequences of abrupt cessation of chronic alcohol consumption.

Vascular evaluation for balloon pumping.

The effectiveness of intraaortic balloon counterpulsation is reduced frequently by arterial insufficiency following balloon insertion and occasionally by inability to pass the balloon centrally from a peripheral site. From a series of patients undergoing cardiac catheterization, a subgroup with increased likelihood of needing balloon counterpulsation can be selected. Patients so chosen have received one aortoiliac injection of contrast material at the time of cardiac catheterization. Impressive degrees of vessel irregularity and stenosis on an atherosclerotic basis and of tortuosity of normal lumen size have been noted. Such information, gathered at little additional risk or irradiation, is considered to be important in the subsequent choice of sides for transfemoral insertion and may rule out attempted passage of the balloon by this route, directing the surgeon to a deliberate, prompt, transabdominal or thoracic aortic insertion if necessary.

Recovery of immune competence after tumour resection in mice: correlation with loss of suppressor elements.

Changes in the immune competence and levels of suppressore elements were assessed by mitogen stimulation and in vitro antibody production, after resection of a transplantable sarcoma. Spleen cells from tumour-resected animals were found to have depressed responses to conA as well as to the antigens SRBC and DNP-LPS. This inability to respond was gradually overcome and, by Day 21 after resection, spleen cell competence had returned to normal levels. Suppressor cells isolated from the spleens of tumour-resected animals were capable of suppressing the conA response and PFC response of normal syngeneic spleen cells in vitro. The ability to suppress the conA response of normal cells disappeared by Day 1 after resection, while the ability to suppress the anti-SRBC and anti-DNP PFC response of normal cells disappeared by Day 8 and Day 14 respectively. Serum from tumour-resected mice was also found to be suppressive to the conA response of normal spleen cells. The inhibitory material responsible for suppression eluted with the Ig-containing fraction on Sephadex G-150. This inhibitory material gradually disappeared from the serum of tumour-resected mice and was no longer apparent by Day 14. Therefore, it appeared that the return of normal lymphocyte function after tumour-resection was concomitant with the disappearance of splenic suppressor cells and suppressive serum factor.

Identity of a T-lymphocyte inhibitor with mouse immunoglobulin in the serum of tumour-bearing mice.

A component of the serum of tumour-bearing mice has been shown to be inhibitory to the immunological function of normal mouse T cells. This factor fractionates with monomeric immunoglobulin upon gel filtration. Studies were carried out utilizing goat antisera to the major immunoglobulin chains of mouse Ig (kappa, gamma, alpha and mu) mixed with the immunoglobulin-rich fraction of serum from normal mice and tumour bearers and passed through immunoadsorbent columns prepared with rabbit anti-goat immunoglobulin. Such studies showed that the inhibitory activity in tumour-bearing serum could be removed after treatment with anti-kappa, anti-gamma and anti-mu chain antisera but not by treatment with either anti-alpha chain or goat immunoglobulin. That the inhibitory activity of tumour-bearing immunoglobulin could be attributed to simple quantitative differences in the levels of IgM and IgG in the test samples was discounted by quantification of the amounts of immunoglobulins in normal and tumour-bearing sera.

Synergism between immune complexes and serum from tumor-bearing mice in the suppression of mitogen responses.

Immune complexes either adhering to the cells, or added to cultures, synergized with an inhibitor present in serum to suppress the proliferative response of lymphocytes to specific antigens or to B cell or T cell mitogens. The suppressive effect was dependent on the concentration of both the complex and the serum and was substantially higher when the serum was taken from tumor-bearing, rather than normal mice. Immune complexes alone were not suppressive, but appeared to activate or increase the effectiveness of an inhibitor present in serum. Complexes of syngeneic mouse serum or specifically purified rabbit or sheep antibody, as well as heat aggregated mouse or rabbit Ig, were all effective, whereas heat-aggregated F(ab')2 fragments of rabbit Ig were not, suggesting that any aggregate hearing exposed Fc fragments could mediate synergy. Purified T lymphocytes were equally as sensitive to inhibition as the whole spleen cell population, implying that the suppression acted directly on responding cells rather than via an accessory cell.

Suppressor cells in the spleens of tumor-bearing mice: enrichment by centrifugation on hypaque-ficoll and characterization of the suppressor population.

Spleen cells from mice bearing methylcholanthrene-induced sarcomas or a mammary adenocarcinoma suppressed the mitogen responses of normal spleen and lymph node cells. Lymph node cells from tumor bearers had no suppressive effects. Centrifugation of spleen cells layered on Hypaque-Ficoll (specific gravity of 1.08) produced a dense fraction which pelleted and a light fraction which was retained at the Hypaque-Ficoll-medium interface. Suppressive activity was not found in either fraction of normal spleen cells. In tumor-bearer spleen cells suppressor activity was greatly enriched in the light fraction. Treatment of the suppressor fraction with anti-theta or anti-Ig serum and complement did not remove suppressor activity. However, the suppressor cells were removed by passage through nylon wool or by carbonyl iron treatment. Also, the population which adhered to plastic Petri dishes contained the suppressor cell activity.

Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice.

Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthrene-induced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the alpha and beta globulins and albumin (molecular weight less than 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2-5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immuno-adsorbents containing goat anti-mouse immuno-globulin, and could be recovered by acid elution from the absorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin.

Mode of action of immunosuppressive substances in sera of tumor-bearing mice.

Sera from mice with transplanted 3-methylcholanthrene (MCA)-induced tumors inhibited the proliferative response of normal mouse lymphocytes to mitogens and allogeneic cells. The sera were not toxic to these cells and did not inhibit mitogen responses by an increased binding of mitogen to serum components. The sera could have prevented the initiation of the proliferative response or could have inhibited cells already proliferating. The uptake of 3H-uridine, an event preceding DNA synthesis, was also suppressed. The sera had no effect on proliferation of a normal tissue culture line or an allogeneic tumor cell line induced by MCA. However, sera from tumor-bearing mice slowed growth of the autochthonous tumor cells and allogeneic lymphoma cells but did not completely block their proliferation. Exposure of lymphoid cells to the sera for a period as brief as 1 hour markedly decreased the ability of cells to respond subsequently to mitogens, and washing of the cells did not restore that ability. The inhibitory activity of the sera was only partially removed by absorption with lymphoid cells or cell lines.