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Biomedical subjects

M A Koch

Publications and source records attributed to M A Koch.

At least 19 recordsLinked to original sources

A randomized controlled trial of smoking cessation intervention in pregnancy in an academic clinic.

To evaluate the effectiveness of a physician-based intervention to promote smoking cessation during pregnancy, we conducted this randomized controlled trial in the resident-staffed prenatal clinics at the University of North Carolina Women's Hospital . Two hundred fifty prenatal patients who smoked were enrolled at their first visit and randomly assigned to the intervention or the usual-care group. Resident physicians provided self-help materials to intervention subjects and used a script to set goals with them at each prenatal visit. Subjects who set quit dates were contacted by volunteer cessation counselors. To verify smoking status, subjects provided a self-report and breath carbon monoxide (CO) sample at each visit. Controls were similarly assessed at enrollment and at three additional predetermined intervals. Twenty percent of intervention subjects and 10% of controls reported cessation, which was verified by CO level (P = .052). Fifty-one percent of subjects reduced their consumption by half or more, compared with 30% of controls (P = .002). The intervention is effective in promoting smoking cessation and reduction. In addition, this technique is inexpensive, readily accepted by staff, and efficient.

Adult

Equal effectiveness of very-low-intensity anticoagulation and standard low-intensity anticoagulation: a pilot study.

We compared the efficacy of very-low-intensity oral anticoagulation (OA) with that of the recommended standard low-intensity oral anticoagulation, using international normalized ratios (INRs). We enrolled 101 patients into a pilot study--51 patients in the very-low-intensity anticoagulation arm (INR 1.4 to 2.0) and 50 in the standard low-intensity anticoagulation arm (INR 2.0 to 3.0). They were monitored for thrombotic/embolic and hemorrhagic complications for an average follow-up of 1.5 years. Two thrombotic/embolic events occurred in the very-low-intensity group; no thrombotic/embolic events occurred in the standard low-intensity group. No major bleeding occurred in the very-low-intensity group; one major hemorrhagic event occurred in the standard low-intensity group. These findings did not achieve a statistically significant difference in major complications between the two groups. It appears that very-low-intensity OA (INR 1.4 to 2.0) is as effective in preventing thromboses as standard low-intensity OA (INR 2.0 to 3.0).

Administration, Oral

Influence of nitric oxide on the hemodynamic response to hemorrhage in conscious rabbits.

We investigated the role of nitric oxide, an endothelium-derived relaxing factor, in the hemodynamic response to acute hemorrhage in conscious rabbits. Chronically instrumented rabbits were treated with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or vehicle and hemorrhaged until mean arterial pressure fell below 40 mmHg. Control animals were treated with L-NAME or vehicle but not subjected to hemorrhage. L-NAME increased mean arterial pressure and decreased heart rate in control animals. Hindquarters and mesenteric blood flow velocity and conductance were reduced by L-NAME. Nitric oxide synthase inhibition also produced significant changes in the hemodynamic response to hypotensive hemorrhage. Mean arterial pressure was higher and regional vascular conductances were lower throughout hemorrhage and during recovery. L-NAME treatment significantly (but in some cases, subtly) altered the characteristic pattern of changes in vascular conductance associated with acute hypotensive hemorrhage and recovery. Similar experiments with other arginine analogues or phenylephrine infusion showed that L-NAME's effects during hemorrhage were due to nitric oxide synthase inhibition. We conclude that nitric oxide plays a role in the hemodynamic response to acute hemorrhage in the rabbit and is essential for the full expression of the vasodilation associated with hypotensive hemorrhage.

Amino Acid Oxidoreductases

Induction of labour with intravaginal misoprostol in the second and third trimesters of pregnancy.

OBJECTIVE: To confirm the effectiveness of misoprostol as a labour-induction agent. DESIGN AND SETTING: One hundred and ten consecutive second- and third-trimester hospital patients. Patients with intra-uterine deaths (group A) received 100 micrograms misoprostol 4-hourly and those with live fetuses (group B) 50 micrograms misoprostol 4-hourly until labour commenced. SUBJECTS: Forty-eight patients in group A (group A1 second trimester 27, group A2 third trimester 21); 62 mainly hypertensive patients in group B. OUTCOME MEASURES: These were the amount of misoprostol required to induce labour; duration of induction and labour; success and completeness of vaginal delivery; neonatal outcome; and cost. RESULTS: In group A1, labour was successfully induced in 21/27 (77.8%) patients with 157.4 micrograms misoprostol; and in 19/21 (90.5%) patients in group A2 with 128.9 micrograms misoprostol. Cost per successful induction was R0.55 and R0.44 respectively. Mean induction times were 13.2 hours and 13.4 hours respectively. All patients delivered vaginally but incompletely in 7/21 group A1 and 1/19 group A2 patients. In group A2, the mean duration of labour was 5.97 hours. In group B induction was successful in 51/62 (82%) with 95.1 micrograms of misoprostol; the mean cost was R0,32. Twelve out of 51 (23%) received oxytocin and 44/51 delivered vaginally. Mean duration of induction was 11.4 hours and of labour 5.4 hours. Two babies had low Apgar scores. There were two stillbirths (perinatal mortality rate 39.2/1000), both apparently unrelated to misoprostol. CONCLUSIONS: Misoprostol is an effective, easy to use, apparently safe and cheap drug for the induction of labour.

Administration, Intravaginal

[Labor, method of delivery and maternofetal transmission of HIV].

Within a prospective study of the course of HIV-infection in women, 80 HIV-infected women without AIDS were delivered of 80 children between 1985 and September 1992. The median of the age of gestation was 38 weeks. Until 1988 Caesarean section was chosen as mode of delivery (45 women). Later when the mode of delivery appeared to have no influence on the frequency of maternofetal HIV transmission, vaginal delivery was preferred (35 women). None of the infants was breastfed. Three infants --delivered vaginally--died within the first 6 months of life before their infection status could be determined. Seventy-seven children could be observed for 18 months or longer regularly every three months. 10 of the 77 children were found to be HIV- infected by serological, virological and clinical criteria. Taking into account the mode of delivery, of 32 children who were delivered vaginally or by emergency Caesarean section 8 were found to be HIV-infected. None of 26 children delivered by elective Caesarean section after an uneventful pregnancy is infected. In 19 women Caesarean section was performed within 2 hours after onset of labour or after episodes of preterm labour which required hospital admission for treatment. Two children of these women are infected. No differences of CD4+ cell counts and p24 antigenaemia could be determined between the mothers of the three groups. The risk of fetal HIV infection was increased by preterm labour (p < 0.01) and the mode of delivery (p < 0.01). A correlation between loss of CD4 cells in the mother and increased risk of infection for the child is seen in children born spontaneously or delivered by emergency Caesarean section (p < 0.001). No correlation was found between the length of labour at delivery, the time of the rupture of membranes before birth as well as of the parity and the risk of fetal infection in that group. These findings point to labour as an important factor which increases the risk of maternofetal transmission of HIV. The onset of labour is accompanied by dramatic immunological alterations as a sudden increase of chemotactics and inflammatory cytokines at the maternofetal interface. The accumulation and stimulation of maternal immune cells will--if these cells are carriers of HIV--result in production and release of infectious HIV. This virus may accumulate in the maternofetal interface or gain access to the amniotic cavity. Since amniotic fluid is swallowed by the fetus, the largest potential port of entry for HIV in the fetus are the fetal lungs and the gastrointestinal tract. For the prevention of maternofetal transmission of HIV delivery before onset of labour or alternatively the protection of the fetus during parturition by means of potent antiviral compounds can be considered.

AIDS Serodiagnosis

Improvement of the predictive value of CD4+ lymphocyte count by beta 2-microglobulin, immunoglobulin A and erythrocyte sedimentation rate. The Multicentre Cohort Study Group.

OBJECTIVE: To evaluate whether the use of immunological markers in addition to CD4+ lymphocyte count can improve the prediction of the probability of developing AIDS within a given period. DESIGN AND SETTING: Prospective multicentre cohort study of homosexual men. PATIENTS: A total of 447 HIV-positive homosexual men followed prospectively at 6-month intervals (median time of observation, 47 months). METHODS: Estimation of AIDS-free time using lifetable plots by Cutler and Ederer and Weibull parametric models. A stepwise multivariate regression analysis was used to calculate the optimal combination of the parameters studied. RESULTS: In general CD4+ lymphocyte counts are most important for the prediction of AIDS-free time. The use of serum levels of beta 2-microglobulin (beta 2M), immunoglobulin A (IgA) and erythrocyte sedimentation rate (ESR) can significantly improve the predictive value of CD4+ lymphocyte counts. However, the usefulness of these parameters depends on the stage of HIV disease. In patients with a CD4+ lymphocyte count > 500 x 10(6)/l, only IgA level had a significant predictive value; none of the other parameters significantly improved the model. In patients with a CD4+ lymphocyte count < 500 x 10(6)/l, the absolute number of CD4+ cells itself was the most important single predictive parameter, but the prediction of AIDS was significantly improved by the addition of the other parameters investigated. The most powerful combination of parameters in this group was CD4+ count, beta 2M and ESR. CONCLUSION: Determination of serum IgA, beta 2M and ESR in addition to CD4+ lymphocyte count may aid the choice of specific therapeutic regimens or systems of care for HIV-positive individuals.

Acquired Immunodeficiency Syndrome

[Blood donors as the sentinel population for sexually transmissible diseases--results of a sociodemographic study and survey of sexual behavior].

A multipurpose survey in a representative sample of the german population was conducted to obtain sociodemographic data together with data on blood donation history and acceptance of HIV antibody tests. A self-administered questionnaire was used to gather information on sexual behaviour. This questionnaire was completed by 62.2% of the participants between 18 and 64 years of age. Comparison between donors and nondonors shows that donors are typically members of the more "socially active" groups: they are younger, gainfully employed, and have attained higher educational levels. The analysis of the data on sexual behaviour reveals that donors are on the average sexually more active than nondonors. Blood donors are a suitable sentinel population to monitor sexually transmitted diseases in the population outside the risk groups for HIV infection.

Adolescent

[AIDS in Germany: clinical manifestations of AIDS].

Since 1982, voluntary anonymous reports that meet the criteria of the WHO/CDC-AIDS definition are being collected by the Federal Health Office. By December 31st, 1989 a total of 4,306 AIDS cases has been registered. More than 80% of the reported cases are homo- and bisexual men and injection drug-users. The remaining cases are divided between hemophiliacs, persons who get infected by heterosexual contacts, blood transfusion recipients, and children infected pre- or perinatally. In 16% of all cases AIDS was diagnosed only on the basis of a Kaposi's sarcoma (KS) and in another 6% on the basis of KS and an opportunistic infection (OI). KS occurred mostly in homo- and bisexual men. The relative proportion of KS has steadily decreased from 30% up to 1986 to less than 20% in 1989. The overall incidence of KS decreased mainly due to the decrease of KS in homosexual men with AIDS. OI were diagnosed in 70% of the cases. Pneumocystis-carinii-pneumonia is most frequent (47%), followed by candida-oesophagitis (19%) and toxoplasmosis of brain in 9.5%. A malignant lymphoma was diagnosed in 3% of the cases. Furthermore, HIV-encephalopathy was seen in 2.8% and HIV-wasting-syndrome in 1.6% of cases. There is a different spectrum of diseases at the first manifestation of AIDS diagnosed in injecting drug-users. The reasons for this may be due to different life-style in this group.

Acquired Immunodeficiency Syndrome

Changes in the spectrum of AIDS-defining conditions and decrease in CD4+ lymphocyte counts at AIDS manifestation in Germany from 1986 to 1991.

OBJECTIVES: Analysis of changes in the spectrum of AIDS-defining conditions and their correlation with CD4+ lymphocyte counts in different risk groups associated with HIV transmission. METHODS: Review of data from all adult AIDS cases reported in Germany between 1986 and 1991. RESULTS: Among AIDS cases diagnosed between 1986 and 1991, the proportion of cases with lymphoma and wasting syndrome increased, while the proportion of Kaposi's sarcoma decreased. Homosexual men, but not intravenous drug users, showed a decrease in the proportion of cases in Pneumocystis carinii pneumonia and an increase in the proportions with toxoplasmosis and cytomegalovirus infection. The median CD4+ lymphocyte count at time of AIDS diagnosis decreased from 73 x 10(6)/l in 1986 (25 and 75 percentiles, 28 and 212) to 47 x 10(6)/l in 1990 (25 and 75 percentiles, 20 and 120; P less than 0.01). This decrease was the result of reduced CD4+ lymphocyte counts of individuals presenting with opportunistic infections; there was no corresponding change for individuals with non-infectious AIDS-defining conditions. CONCLUSIONS: AIDS diagnosis is now occurring at a later time in the natural history of HIV infection than in 1986, and the relative frequency of specific AIDS-defining conditions has changed. Most pronounced is a decrease of Pneumocystis carinii pneumonia. Changes in the natural history of HIV infection due to therapeutic and prophylactic interventions must be considered when interpreting epidemiological data in the course of the AIDS epidemic. These changes also have implications for the planning and execution of medical care.

Acquired Immunodeficiency Syndrome

Toxic effects of zidovudine in asymptomatic human immunodeficiency virus-infected individuals with CD4+ cell counts of 0.50 x 10(9)/L or less. Detailed and updated results from protocol 019 of the AIDS Clinical Trials Group.

BACKGROUND: Protocol 019 of the AIDS Clinical Trials Group is a multicenter, double-blind, placebo-controlled trial of zidovudine (3'-azido-3'-deoxythymidine; formerly AZT) in human immunodeficiency virus-infected asymptomatic individuals. The initial results in the stratum of subjects entering with CD4+ cell counts of 0.50 x 10(9)/L or less have been reported, but without a detailed analysis of toxic effects. METHODS: This detailed and updated report analyzes the toxic effects that occurred in 1567 subjects (91% men; 89% white) in this stratum of protocol 019 who received placebo (494 subjects), a 500-mg daily dose of zidovudine (544 subjects), or a 1500-mg daily dose of zidovudine (529 subjects). Hematologic, hepatic, and renal effects and patient-reported symptoms and clinical signs were monitored. RESULTS: Severe anemia (hemoglobin level, < 80 g/L) was associated with both the 500-mg zidovudine group and the 1500-mg group compared with placebo. The estimated 18-month risks of severe anemia were 0.4%, 2.0%, and 9.7% for the placebo, 500-mg zidovudine, and 1500-mg zidovudine groups, respectively. Predictive baseline measures were lower hemoglobin level in the 1500-mg group and the two zidovudine groups combined and lower platelet count in the 500-mg zidovudine group. The risk of a first severe anemia developing was greatest in months 3 through 8 of treatment. Of the 44 subjects with severe anemia in the zidovudine groups, 18 (41%) progressed from mild anemia (hemoglobin level, 95 to 109 g/L) to severe anemia on consecutive visits (usually 2 to 4 weeks apart). Severe neutropenia (absolute neutrophil count, < 750 x 10(6)/L) did not occur significantly more often in the 500-mg zidovudine group but did in the 1500-mg zidovudine group. Moderate neutropenia (absolute neutrophil count, < 1300 x 10(6)/L) did develop significantly more often in the 500-mg zidovudine group (165 subjects) than in the placebo group (71 subjects). Mild (or worse) elevations of bilirubin levels were uncommon but occurred more often with zidovudine. Severe nausea (and/or vomiting) was rare (2.8% of subjects) but was associated with zidovudine. Milder patient-reported events were common, and a number were associated with zidovudine. CONCLUSION: Zidovudine at the 500-mg/d dosage appears to be tolerable in many patients with asymptomatic human immunodeficiency virus infection and CD4+ cell counts of 0.50 x 10(9)/L or less. Increased clinical surveillance for anemia may be warranted in certain patients.

Anemia

[Estimate of the total number of HIV-infected subjects in the Federal Republic of Germany based on data from the AIDS Center].

On the basis of an analysis of the data from the mandatory reporting of detected HIV infections and the reports to the central AIDS case registry an attempt is made to determine the total number of HIV infected individuals in the FRG. Results of surveys of testing behaviour in different risk groups were included in the calculations. For the calculation different estimates were used as to the total number of detected HIV infections, distribution of infections and percentage of detected infections in different risk groups. Depending on the estimates chosen a "best case" calculation yields 29,515 and the "worst case" calculation 81,949 HIV infected persons at the end of 1990. A synoptic analysis by the AIDS Center of the Federal Health Office resulted in an estimate of 50,000 to 60,000 HIV infected individuals in the FRG which is well between the "best" and "worst case" estimates.

Germany

The increased frequency of cervical dysplasia-neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression.

Cytologic and histologic investigations of the uterine cervix and studies of the lymphocyte functions were performed in human immunodeficiency virus-infected and human immunodeficiency virus antibody-negative women to study possible linkages between human papillomavirus-induced dysplasia and degree of human immunodeficiency virus-induced immunosuppression. Cytologic smears of the uterine cervix of 111 human immunodeficiency virus-infected women were compared with findings in 76 female intravenous drug users negative for human immunodeficiency virus antibodies and in a group of 526 women of the outpatient population of the hospital. Cervical dysplasia-neoplasia (including five cases of invasive carcinoma) was seen in 41% of the human immunodeficiency virus-infected patients. In human immunodeficiency virus-negative intravenous drug users dysplasia-neoplasia was seen in 9%, and in the sample from outpatients in 4%, including two cases of invasive carcinoma (p less than 0.01). Cytologic features that were attributable to infection with human papillomavirus were observed in human immunodeficiency virus-infected women four times more often than in the sample from the outpatient population (p less than 0.01). Frequency and severity of dysplasia appear to increase with diminishing numbers of CD4+ helper/inducer T lymphocytes and correlated significantly (p less than 0.01) with a loss of blastogenic response to phytohemagglutinin, pokeweed mitogen, and tetanus toxoid. These results suggest an increased risk for the development of dysplasia of the uterine cervix in women with human immunodeficiency virus infection, which is related to the degree of immunosuppression.

Acquired Immunodeficiency Syndrome

[The epidemiology and acquired immunodeficiency syndrome--status and trends].

Up to June 1991 a total of 6,604 AIDS cases were reported to the central AIDS-registry at the Federal Health Office. As typical for "pattern I" countries most of the AIDS-cases are homo/bisexual men (70%), followed by i.v. drug users (IDU, 13%). However, the proportion of homo/bisexual men is constantly decreasing since 1986 while the proportion of IDU's is increasing. As also observed in other industrialized countries a flattening off in the AIDS incidence curve is seen since 1989. Probable reasons for this observation are a decrease of new infections since 1984/85 (due to early saturation of the populations at highest risk and to the early onset of prevention campaigns in these populations) and improved therapeutic strategies in the prevention of AIDS indicating diseases. However, since about 60,000 people are estimated to be HIV infected in the FRG today AIDS incidence will remain on a stable level for the next years regardless the number of new infections occurring today. Since 1988 major changes in the distribution of AIDS indicating diseases are seen. While Kaposi's sarcoma is constantly decreasing non Hodgkin lymphomas, HIV encephalopathy and wasting syndrome are increasing. Due to the effective primary prophylaxis of pneumocystis carinii pneumonia (PCP) by pentamidine the proportion of PCP as AIDS-indicating opportunistic infection decreased from more than 60% in 1988 to 41% in 1991. The second most frequent opportunistic infection is now toxoplasmosis (19%). The changes in the distribution of AIDS-indicating diseases and the increasing proportion of IDU's have major implications on patient care as well as diagnostic and therapeutic procedures.

Acquired Immunodeficiency Syndrome

[Intestinal spirochetosis in HIV infection: prevalence, isolation and morphology of spirochetes].

The prevalence of intestinal spirochaetosis was investigated in 39 HIV-positive homosexual males (mean age 39 [24-65] years) in different stages of HIV infection (3 with the lymphadenopathy syndrome, 8 with AIDS-related complex and 28 with AIDS). Biopsies for cultural and histological demonstration of spirochaetes were obtained during routine ileoscopies. At the time of examination 35 of the 39 patients had intestinal symptoms. 27 patients had had no previous antimicrobial treatment. In 12 of the 27 previously untreated patients with intestinal symptoms spirochaetes were demonstrated, to different extent, from the terminal ileum to the rectum, while the treated group of eight and the control group of four were negative. There were no significant inflammatory changes histologically. Treatment with metronidazole in most cases improved symptoms. In their ultrastructure the microorganisms showed several complete convolutions, cone-shaped cell endings, cell length of 4-18 microns, cell diameter of 0.21-0.35 microns and five subterminal flagella. Morphological considerations favour the inclusion of these microorganisms in the genus Treponema rather than Brachyspira.

AIDS-Related Complex

Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases.

Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P less than 0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV.

AIDS-Related Complex