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Biomedical subjects

R W Makuch

Publications and source records attributed to R W Makuch.

At least 19 recordsLinked to original sources
PubMed1992

Risk factors for early intraventricular hemorrhage in low birth weight infants.

Because earlier studies suggested that preterm infants with germinal matrix hemorrhage or intraventricular hemorrhage or both (GMH/IVH) present within the first 12 postnatal hours are at greatest risk for the development of high-grade hemorrhage and neurodevelopmental disability, we examined the risk factors for this insult among 229 neonates of 600 to 1250 gm birth weight in a multicenter study. All had echoencephalography (ECHO) within the first 11 hours and serially for the next 20 days; risk factor data were collected prospectively. Forty-three infants had GMH/IVH within the first 5 to 11 hours (mean age at ECHO 7.7 hours): 18 GMH and 21 grade II, 1 grade III, and 3 grade IV IVH. One hundred eighty-six infants did not have GMH/IVH at a mean age of 7.9 hours. Both groups of infants were similar in birth weight, gestational age, maternal risk factors, cord pH values, and surfactant therapy before ECHO. The group with early IVH had more vertex presentations than the group without early IVH (79% vs 55%, p = 0.043), less maternal tocolytic use (42% vs 60%, p = 0.029), and more vaginal deliveries (67% vs 44%, p = 0.005). In the first 21 days, severe IVH developed in 12 infants with early IVH and in 6 infants without early IVH (p < 0.001). There were more neonatal deaths (16% vs 6%, p = 0.035) and more deaths at any time during the primary hospitalization (23% vs 9%, p = 0.010) among the early IVH group than among the group without early IVH. Multivariate analysis indicated that the mode of delivery, fetal presentation, and birth weight were important and independent prognostic indicators of IVH.

Birth Weight↗
PubMed1992

No seroconversions among steady sex partners of methadone-maintained HIV-1-seropositive injecting drug users in New York City.

OBJECTIVE: To assess the incidence of heterosexual HIV-1 transmission from seropositive methadone-maintained injecting drug users (IDU) to their seronegative, non-IDU steady sex partners. DESIGN: A prospective, longitudinal study. SETTING: HIV-1-seropositive IDU and their HIV-1-seronegative, non-IDU steady sex partners were recruited from six methadone-maintenance clinics in the New York City boroughs of Brooklyn and Manhattan. PATIENTS, PARTICIPANTS: Between December 1988 and October 1991, 60 research participants were recruited [30 methadone-maintained, HIV-1-seropositive IDU (index subjects) and their non-IDU HIV-1-seronegative steady partners]. Baseline and follow-up (every 3-4 months) data included a structured questionnaire and blood testing for HIV infection and CD4+ cell subsets. RESULTS: Demographic characteristics of the 30 steady sex partners were evaluated as follows: sex (22 women, eight men); age (mean, 32 years; range, 21-55 years) and race (African-American, 13; Hispanic, 13; other, 4). The average duration of relationship between index subject and partner at study entry was 7.5 years (range, 4 months to 19.4 years). At entry, 27 of the 30 partners reported no or intermittent use of condoms with the index subject during a typical 12-month period. Follow-up data (median follow-up, 298 days; range, 85-992 days) were available for 22 partners. Of these, 15 reported no or intermittent condom use. For a total study observation time of 23 person-years, there were no seroconversions. The upper 95% confidence interval for the observed seroconversion rate of 0% is 13%. CONCLUSIONS: These results suggest that the likelihood of heterosexual HIV-1 transmission from seropositive methadone-maintained IDU to their seronegative, non-IDU steady sex partners is low.

Adult↗
PubMed1991

myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens.

We studied 107 specimens (38 tumors and 69 tumor cell lines) from 90 patients with small cell lung cancer to determine the characteristics and clinical situations of patients from whom tumor cell lines could be established and the myc family DNA copy number. The proportion of extensive stage small cell lung cancer patients from whom a tumor cell line could be established prior to the initiation of therapy increased during the 10 years of the study (P less than 0.001). Amplification of one of the myc family genes occurred in 3 of 40 (8%) of the untreated patient specimens compared to 19 of 67 (28%) of the treated patient specimens (P = 0.01). The myc family DNA amplification occurred in 17 of 54 (31%) of the specimens from patients treated with cyclophosphamide-based combinations and 2 of 13 (15%) of the specimens from patients treated with etoposide/cisplatin (P = 0.25). Both tumors and tumor cell lines were obtained from 17 patients with small cell lung cancer and the myc family DNA copy number was similar in 16 of the 17 patients. We conclude that: (a) myc family DNA amplification occurs more commonly in specimens from treated than untreated patients (b) there are no prominent differences in the frequency of amplification following treatment with different chemotherapy regimens; and (c) myc family DNA amplification is similar in tumors and tumor cell lines from the same patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

EEG coherence of prefrontal areas in normal and schizophrenic males during perceptual activation.

Multiple studies have demonstrated prefrontal dysfunction among schizophrenics. The prefrontal cortex does not function in isolation, but instead relies on extensive connections with other brain areas. Functional relationships between cortical areas were assessed by calculating the coherences between different scalp electroencephalogram (EEG) signals recorded from 13 unmedicated male patients with schizophrenia and 9 normal male subjects. Alpha-band coherences linked to prefrontal areas in schizophrenic patients were about the same as those of normal controls when subjects were cognitively "at rest," but they were reduced for certain electrode pairs in the former group when performing the degraded-stimulus continuous performance test. Most of these findings were not accounted for by changes in alpha power, suggesting that "cortical circuits" extending beyond prefrontal areas may be disrupted in schizophrenia.

Adult↗
PubMed1990

Cisplatin rescue therapy: experience with sodium thiosulfate, WR2721, and diethyldithiocarbamate.

Cisplatin has a steep dose response curve for both antitumor and adverse effects. Therapeutic strategies aimed at reducing toxicity and allowing dose escalation of intravenous cisplatin, such as administration in hypertonic saline and pharmacokinetically based dosing schedules, have been partially successful in reducing nephrotoxicity and bone marrow suppression. However, new dose-limiting toxicities consisting of peripheral neuropathy and ototoxicity have emerged, which continue to restrict potential use of high dose cisplatin therapy. Intraperitoneal administration of high dose cisplatin also offers the potential of markedly increased local drug exposure if systemic toxicity can be avoided. Proposed chemoprotective agents, including sodium thiosulfate, WR2721, and diethyldithiocarbamate (DDTC) are being extensively examined as "rescue agents" for either regional or systemic administration of cisplatin. Although each agent offers unique advantages to be considered in developing successful rescue therapy, many questions remain regarding molecular and pharmacokinetic interactions with cisplatin, appropriate dosing schedules, and effects on antineoplastic activity. We present a review of current investigations of chemoprotectors for prevention of cisplatin-related toxicities.

Amifostine↗
PubMed1990

A phase 1 study of ribavirin in human immunodeficiency virus-infected patients.

An open phase 1 study comparing two daily doses of oral ribavirin (1200 and 1600 mg) for 12 weeks was conducted at a single site. Eight human immunodeficiency virus (HIV)-infected adult men with lymphadenopathy or early AIDS-related complex (ARC) symptoms were enrolled in each treatment group. No anti-HIV effect was observed as evaluated by coculture of patients' peripheral blood mononuclear cells or by the level of serum p24 antigenemia. Neither enhancement of two functional lymphocyte markers (specific antigen-induced blastogenesis or interferon-gamma production) nor reduction in serum beta 2-microglobulins was noted. Mild clinical adverse reactions and anemia were observed in both treatment groups. Significant reductions in total lymphocytes, T lymphocytes (CD2 cells), and T lymphocyte subsets (CD4 and CD8 cells) were most notable in the 1600-mg group. Reduction in the lymphocyte populations was most likely due to a direct ribavirin lymphotoxic effect. These observations indicate that ribavirin had no demonstrable beneficial effect on virologic or immunologic HIV surrogate markers at daily doses associated with adverse reactions.

AIDS-Related Complex↗
PubMed1990

A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.

AIDS-Related Complex↗
PubMed1990

Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation.

We evaluated the 10- to 15-year outcome of 252 patients with small-cell lung cancer entered into therapeutic clinical trials with or without chest and cranial irradiation. Thirty-two patients (13%) survived free of cancer for 2 or more years. Twelve patients (5%) survived at least 10 years free of cancer, and 10 patients are currently alive and free of cancer beyond 10 years. Six of these 10 patients currently function at a level comparable with that before diagnosis. The other 22 patients who were cancer-free at 2 years have died. Nine patients died from recurrent small-cell lung cancer 2 to 6.2 years after initiation of chemotherapy. Five died from non-small-cell lung cancer, three died of other malignancies, and five died of causes other than cancer. A small fraction of patients with small-cell lung cancer are cured of their original malignancy, but these patients remain at high risk for second cancers and death from other causes.

Actuarial Analysis↗
PubMed1990

A multicenter clinical trial of oral ribavirin in HIV-infected patients with lymphadenopathy. The Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin and placebo was conducted at four medical centers. One hundred sixty-four adult men with lymphadenopathy were enrolled over a 2-month period and randomized to receive ribavirin 800 mg (53 subjects), ribavirin 600 mg (55 subjects), or placebo (56 subjects). Active treatment was administered for 24 weeks followed by a 4-week washout period. Nine subjects receiving placebo, four receiving ribavirin 600 mg, and none in the 800 mg group developed AIDS during the 24 weeks of active treatment. One patient randomized to the 800 mg group had Kaposi's sarcoma at study entry and was included in the intent-to-treat analysis. An overall significant difference in progression to AIDS was observed among the three treatment groups (p = 0.028) with patients randomized to receive 800 mg having a significantly longer time to AIDS than placebo patients (p = 0.012; relative risk, 9.0; 95% confidence interval, 1.1 to 70.8). There was no significant difference between the 600 mg and placebo groups (p = 0.15; relative risk, 2.3; 95% confidence interval, 0.7 to 7.6). Baseline CD4 cell count and hematocrit made independent contributions and formed a multivariate prognostic set for these progression data. The significant treatment superiority of 800 mg compared to placebo remained after adjustment for these factors (p = 0.019). After deletion of patients with major protocol violations at entry, the difference between the 800 mg and placebo treatment remained significant (p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Survival in children with perinatally acquired human immunodeficiency virus type 1 infection.

We describe our experience at Jackson Memorial Hospital in Miami, Florida, with 172 children who were given diagnoses of perinatally acquired infection with human immunodeficiency virus type 1 (HIV-1). The 146 mothers of the children acquired HIV-1 through heterosexual contact (69 percent), intravenous drug use (30 percent), or blood transfusion (1 percent). The children presented with symptomatic disease at a median age of eight months; only 21 percent presented after the age of two years. The most common first manifestations of disease were lymphoid interstitial pneumonia (in 17 percent), encephalopathy (in 12 percent), recurrent bacterial infections (in 10 percent), and candida esophagitis (in 8 percent), for which the median survival times from diagnosis were 72, 11, 50, and 12 months, respectively. Nine percent of the children had Pneumocystis carinii pneumonia at a median age of five months and had a median survival of only one month. The median survival for all 172 children was 38 months from the time of diagnosis. Mortality was highest in the first year of life (17 percent), and by proportional-hazard analysis the probability of long-term survival is low. In multivariate analyses, early age at diagnosis and the first identifiable pattern of clinical disease were found to be independently related to survival. We conclude that children with perinatally acquired HIV-1 infection have a very poor prognosis and that most become symptomatic before one year of age. Early diagnosis is important, since there is only a short interval in which to initiate prophylactic or antiviral treatment before progressive disease begins.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Goodman and Kruskal's lambda: a new look at an old measure of association.

We examine Goodman and Kruskal's lambda using Efron's approach to regression and analysis of variance (ANOVA) for zero-one outcome data. For a binary response cross-classified by a single nominal predictor, we present a computationally simple ANOVA table in which lambda is analogous to Pearson's R-square. We characterize the relationship between lambda and the commonly used apparent error rate in logistic regression, and show that lambda is based implicitly on a prediction rule for a saturated model with classification level 0.5. This relationship suggests that we can correct the apparent error rate for chance by defining a natural generalization of lambda that we call PRE, the proportional reduction in error. We illustrate the use of lambda and PRE in an analysis of prognostic factors for one-year survival in children with the acquired immunodeficiency syndrome (AIDS).

Acquired Immunodeficiency Syndrome↗
PubMed1988

myc family DNA amplification in small cell lung cancer patients' tumors and corresponding cell lines.

Tumor specimens procured from 38 different small cell lung cancer patients were studied for DNA amplification of the myc family of protooncogenes (c-myc, N-myc, and L-myc). Six of the 38 specimens (16%) had 4-fold or greater myc family DNA amplification (N-myc in 4 and L-myc in 2). All 6 tumors with amplification came from patients who had received combination chemotherapy. The myc family gene copy number of the DNA prepared from 9 tumor cell lines established from these 38 patients was similar to the myc family gene copy number in the DNA prepared from fresh tumor specimens from these same patients. myc family DNA amplification is present in 16% of small cell lung cancer patients' tumors and the amplification pattern in the tumor cell lines is representative of the fresh tumors obtained from the same patients.

Autoradiography↗
PubMed1988

Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups.

STUDY OBJECTIVE: To determine the optimal staging evaluation at the time of initial diagnosis of mycosis fungoides or the Sézary syndrome. DESIGN: Retrospective review of a uniformly staged inception cohort. SETTING: Single-institution tertiary care center. PATIENTS: 152 consecutive patients who had mycosis fungoides with or without the Sézary syndrome within 6 months of the initial definitive diagnosis. INTERVENTION: A detailed staging evaluation including physical examination, routine laboratory studies, chest roentgenogram, lymphangiogram, peripheral blood smear, lymph node biopsy, bone marrow aspirate or biopsy, and liver biopsy in selected patients. MEASUREMENTS AND MAIN RESULTS: Univariate adverse prognostic features at initial diagnosis in patients with mycosis fungoides included (P less than 0.01) one or more cutaneous tumors or generalized erythroderma, adenopathy, blood smear involvement with Sézary cells, lymph node effacement, eosinophilia, and visceral involvement. Important, independent prognostic factors in a multivariate analysis are the presence of visceral disease and type of skin involvement. CONCLUSIONS: A staging system based on histopathologic evaluation of skin, lymph nodes, blood, and visceral sites provides more comprehensive prognostic information than clinical evaluation of skin disease and adenopathy. Patients may be divided at initial presentation into three prognostic groups: good-risk patients, who have plaque-only skin disease without lymph node, blood, or visceral involvement (median survival, greater than 12 years); intermediate-risk patients, who have cutaneous tumors, erythroderma, or plaque disease with node or blood involvement but no visceral disease or node effacement (median survival, 5 years); and poor-risk patients, who have visceral involvement or node effacement (median survival, 2.5 years).

Actuarial Analysis↗
PubMed1988

Identifying prognostic factors in binary outcome data: an application using liver function tests and age to predict liver metastases.

A frequent issue confronting the medical scientist is the detection of important prognostic variables, or covariates, that affect the outcome variable. In this paper we propose specific guidelines for the analysis of binary outcome data based on recent developments in statistical methodology and on less formal graphical techniques. By incorporating these methods into the process of fitting the standard logistic regression model, one can assess covariate selection and model specification more thoroughly and obtain a more balanced view of a model's predictive capabilities. We apply the methods to the evaluation of non-invasive liver function tests and age to predict the presence of liver metastases in patients with small cell lung cancer.

Age Factors↗
PubMed1988

The design and implementation of a software system for clinical studies: an illustration based on the needs of a comprehensive cancer center.

A computerized system for the management of a clinical research database has been developed with several attractive features. This relational database management system allows for screen-driven data entry, data checking, system security, and report generation in a timely manner. In addition, the system is cost-effective in a number of ways: (1) development time is considerably reduced due to the inherent programming features of the software, (2) once developed the system can be maintained by nontechnical personnel thereby reducing personnel costs, (3) the system can be developed and maintained on a microcomputer system, and (4) the commercial software used in our system is periodically updated thereby assuring the user of state-of-the-art technology. Beyond the initial expenditures for hardware and software, no additional system costs are incurred. While this system, currently adopted by the Yale Comprehensive Cancer Center, represents an effective approach to handling the data-management needs of a large, single-institution cancer research center, the design and programming methodology can be readily adapted to other research settings.

Cancer Care Facilities↗
PubMed1988

Statistical methods for the analysis of HIV-1 core polypeptide antigen data in clinical studies.

Levels of HIV-1 core polypeptide were assessed in serum and in lymphocyte cultures obtained from ARC and AIDS patients enrolled in a prospectively randomized, placebo-controlled study of zidovudine (AZT). Because these data have special features uncharacteristic of most laboratory data, a comprehensive account of statistical methods appropriate for their analysis is contained in this paper. Standard methods are described for the analysis of HIV-1 antigen in serum collected repeatedly over time in the same individual. For the analysis of lymphocyte culture data, more sophisticated statistical techniques based on nonparametric survival analysis methods are proposed. Using microcomputer software available upon request and developed to implement this statistical procedure, a significant decline in lymphocyte HIV-1 virus expression was noted between pretreatment and 3 months after the initiation of therapy among AZT-treated patients (p = 0.0017) that was not seen in placebo-treated patients (p = 0.25). Statistically significant between-group differences were also noted in the change from baseline at 3 months in HIV-1 antigen serum data (p = 0.040). We conclude that HIV-1 core polypeptide is an important measure of the antiretroviral activity of AZT and that the demonstrated clinical efficacy of AZT relative to placebo parallels its antiretroviral effect.

AIDS-Related Complex↗
PubMed1988

HIV-1 inhibition by azidothymidine in a concurrently randomized placebo-controlled trail.

Two independent measures of human immunodeficiency virus type 1 (HIV-1) infection, virus isolation, and serum levels of p24 antigen were evaluated in a double-blind randomized clinical trial of the safety and efficacy of a nucleoside analogue, 3'-azido-3'-deoxythymidine (AZT) versus placebo in a single center. Pretreatment studies from 38 AIDS and AIDS-related complex (ARC) patients were comparably positive for virus isolation from their lymphocytes; all patients were qualitatively virus positive. Before AZT treatment, there was significantly decreased virus recovery in patients with higher numbers of CD4-positive lymphocytes. Within 1 month of AZT therapy, the time in culture required to register virus positivity was increased markedly in the AZT-treated group, and over the following several months progressive diminution in virus recovery was noted. Similar changes were not seen in patients concurrently receiving placebo treatment. Before treatment, 16 of 20 and 12 of 16 patients in the AZT and placebo groups, respectively, were p24 antigen positive. Marked reduction in serum p24 levels were noted in 11 of 16 (69%) of the p24 antigen-positive AZT-treated patients compared to 3 of 12 (25%) of the p24 antigen-positive placebo-treated patients (p = 0.02). There was a marked virologic response in 14 of 20 (70%) of the AZT-treated patients compared to 4 of 18 (22%) placebo-treated patients (p = 0.004). A higher frequency of positive clinical and immunological effects also were noted in the AZT-treated patients relative to placebo-treated patients (p = 0.02 and p = 0.06, respectively).

Acquired Immunodeficiency Syndrome↗