Biomedical subjects
K F Trofatter
Publications and source records attributed to K F Trofatter.
Interferon treatment of anogenital human papillomavirus-related diseases.
Because of their antiviral, antiproliferative, and immunoregulatory properties, IFNs are potentially well suited for use in the management of benign HPV-related anogenital diseases. Parenteral and intralesional therapy of condylomata with various natural and recombinant IFN preparations has consistently resulted in beneficial response rates ranging between 40% and 60%, often in patients in whom other therapeutic measures have repeatedly failed. Adverse effects from IFN are dose dependent and generally tolerable at concentrations of IFN found to be effective in the treatment of condylomata, and they are not associated with any known long-term sequelae. When combined with conventional medical and surgical treatment modalities, IFN offers real promise for the control of both extensive primary and recalcitrant HPV-related conditions.
Use of the fibrin D-dimer in screening for coagulation abnormalities in preeclampsia.
Plasma from pregnant women with preeclampsia was screened for the D-dimer, a degradation product specific for crosslinked fibrin, using a monoclonal antibody (DD-3B6), latex-bead agglutination assay (DIMERTEST). Seventy-nine of 204 (38.7%) of the preeclamptic women and none of 88 healthy non-preeclamptic women were positive for the D-dimer. Presence of the D-dimer correlated consistently with elevated fibrin(ogen) degradation products, detectable fibrin monomer, and platelet count less than or equal to 100 x 10(9)/L, with a 93.0% sensitivity overall for abnormalities of the same. Among D-dimer-positive women, 66.7% had fibrin(ogen) degradation products less than 10 micrograms/mL, 60.3% had no detectable fibrin monomer, and 82.0% had platelets greater than 100 x 10(9)/L. When compared with D-dimer-negative preeclamptic women, D-dimer-positive women had significantly higher blood pressures prompting delivery, greater proteinuria, more abnormal liver function tests, and higher serum creatinine and blood urea nitrogen. In addition, they had a greater risk of cesarean section (49.4 versus 34.4%), premature delivery (58.2 versus 20.0%), low birth weight (54.5 versus 20.3%), low Apgar scores, and an abnormally high ratio of female to male offspring (1.72 versus 0.93). Testing for the fibrin D-dimer may be useful in early screening and follow-up for preeclamptic coagulopathy, and may also help to define the subset of patients with severe disease.
Interferon alpha-n1 (Wellferon) for refractory genital warts: efficacy and tolerance of low dose systemic therapy.
This multi-center trial compared two doses of parenterally administered interferon alpha-n1 (Wellferon) in men and women with recurrent/resistant genital warts. Patients received either 1 or 3 MU/m2 daily for 14 days, then 3 times weekly for 4 weeks; non-responders could receive an additional four weeks of treatment. A total of 107 patients were enrolled, and 102 were evaluable after six weeks of study. The principal dose comparison was in 57 women assigned alternately to the two doses. Median lesion measurements were reduced significantly from baseline at weeks 2, 4 and 6 in both groups. Statistical analysis showed no difference in response to 1 versus 3 MU/m2. The overall complete response (CR) plus partial response (PR) rate at week 6 was 69% for the two doses. Two additional groups of 21 women and 24 men were treated at the higher dose with CR plus PR rates of 75 and 50%, respectively. Week 10 disease evaluations for all groups showed 19 of 77 patients to be completely cleared. Of these 19, only one had recurrent disease at the end of the 6-month study period. Analysis of the incidence of symptomatic side effects showed a significantly higher frequency among women treated with 3 MU/m2 than among women treated with 1 MU/m2. Five dose reductions and two withdrawals for toxicity occurred, all in the high dose group. This study demonstrates that parenterally administered Wellferon produces clearance of resistant genital warts in many patients, and that rates of clearance do not appear to vary between groups receiving moderate or low dose therapy.
Recurrent condyloma acuminatum in women over age 40: association with immunosuppression and malignant disease.
Sixteen women aged greater than or equal to 40 years were studied within a total population of 77 women with recalcitrant condyloma acuminatum. Six of the 16 women (38%) were found to have coincident malignant disease (p less than 0.001). Three of these had lymphoma (non-Hodgkin's), two had squamous cell cancer of the vulva or vagina, and one had breast carcinoma. Two of the three patients with lymphoma had recurrent genital condyloma diagnosed before the coexistent lymphoproliferative disorder was discovered. In all, 11 of 16 patients had dysplasia and neoplasia. Seven of the women had other medical conditions associated with immunosuppression. We conclude that the presence of recurrent condyloma acuminatum in women greater than or equal to 40 years of age should lead to examination for the presence of immunosuppression and its underlying cause. A high index of suspicion for concomitant genital squamous cell neoplasia and lymphoproliferative disorders should be realized. The factors relating age, recurrent condyloma, immunosuppression, and malignant disease are discussed.
A modified biophysical profile for antenatal fetal surveillance.
Three hundred thirty-seven high-risk pregnancies were screened using a modified biophysical profile consisting of nonstress testing (NST) and ultrasound evaluation of amniotic fluid volume. Ultrasound assessment of fetal breathing and body movements was performed only to evaluate the nonreactive NST. Decreased amniotic fluid volume and spontaneous fetal heart rate (FHR) decelerations were considered abnormal findings during antenatal testing, and served as indications for delivery regardless of FHR reactivity. Despite intervention, decreased amniotic fluid volume and spontaneous decelerations were associated with an increased incidence of meconium staining, decelerations during labor, cesarean section for fetal distress, and small for gestational age infants. Perinatal morbidity also occurred in patients with spontaneous decelerations and normal amniotic fluid volume. The search for spontaneous FHR decelerations by electronic fetal monitoring should continue during antepartum testing because FHR decelerations cannot be identified by conventional ultrasound assessment. The modified profile seems practical for routine assessment of fetal well-being in high-risk pregnancy, and affords insights unavailable with ultrasound surveillance alone.
Twin pregnancy. Management of delivery.
Management of the twin delivery remains controversial, particularly when the second twin in nonvertex and has an estimated fetal weight of 600 to 1500 gm. Management of schemes based on fetal presentation and estimated weights, as well as specific techniques and options for intrapartum care, are discussed.
Pregnancy-induced changes in the fibrinolytic balance: evidence for defective release of tissue plasminogen activator and increased levels of the fast-acting tissue plasminogen activator inhibitor.
Pregnancy is accompanied by an increased risk of thromboembolic disease. One contributing factor to such disease in the nonpregnant patient is disordered fibrinolysis. It has been suggested that defective fibrinolysis may occur in pregnancy, but this defect has been poorly characterized. In the present study of 52 women with normal pregnancies and 56 nonpregnant control women, we found a marked change in levels of releasable tissue plasminogen activator in pregnant women beginning in the first trimester. Whereas nonpregnant women demonstrated releasable levels of tissue plasminogen activator of 0.74 +/- 0.15 IU/ml of plasma, in the pregnant women the amount released was only 0.06 +/- 0.02 IU/ml of plasma (p less than 0.01). These levels were observed beginning in the first trimester. Levels of the recently described fast-acting tissue plasminogen activator inhibitor increased significantly throughout pregnancy. Values ranged from 8.40 +/- 0.27 IU/ml of plasma in the first trimester to 9.92 +/- 0.09 IU/ml of plasma in the third trimester (p less than 0.05) compared with the level of 8.46 +/- 0.19 IU/ml of plasma in nonpregnant subjects. These data suggest that alterations both in releasable tissue plasminogen activator and in the fast-acting tissue plasminogen activator inhibitor contribute to the physiologic hypercoagulable state of pregnancy.
Interferon.
Interferons are proving useful in the management of recalcitrant condylomata acuminata. Dosage schedules have been established that balance efficacy and systemic toxicity. Alone, however, interferons are not entirely effective in every patient. In combination with conventional medical and surgical modalities, they offer hope for the control of an often frustrating and potentially serious virus infection.
Immune responses and aging.
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Human lymphoblastoid interferon (Wellferon) in primary therapy of two children with condylomata acuminata.
Human lymphoblastoid interferon (Wellferon) was administered parenterally to two prepubertal girls as primary therapy for genital condylomata acuminata. One child probably had contracted the disease as the result of sexual molestation. Both patients experienced minimal side effects during therapy and underwent complete remission within six weeks. These cases support use of interferon as primary therapy in young patients with extensive condylomata and in those who may have contracted the disease as the result of sexual abuse.
Growth of type 2 herpes simplex virus in newborn and adult mononuclear leukocytes.
Growth of type 2 herpes simplex virus (HSV) in newborn and adult human mononuclear leukocytes (MNL) was compared. Phytohemagglutinin stimulation of cultures for 3 days yielded comparable peak titers in newborn (10(5.3) PFU) and adult (10(5.1) PFU) MNL. Unexpectedly, 3-day cultures of unstimulated newborn MNL also substantially replicated HSV (10(4.7) PFU), whereas similarly treated unstimulated adult cells did not. Growth of HSV in freshly isolated human MNL was next investigated. MNL from 4 mothers and 6 nonpregnant adults showed no evidence of virus growth; however, leukocytes from 11 of 24 newborns (46%) supported replication. Newborn MNL manifested an increased ability to replicate HSV within 1 day of culture, whereas comparable growth in adult MNL was not achieved until the 4th day of culture. The significance of the above observations as it relates to visceral dissemination of HSV in the neonate is discussed.
Interaction of human cells with prostaglandins and cyclic AMP modulators. I. Effects on complement-mediated lysis and antibody-dependent cell-mediated cytolysis of herpes simplex virus-infected human fibroblasts.
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