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Biomedical subjects

B Reichman

Publications and source records attributed to B Reichman.

At least 55 records · Page 3Linked to original sources

Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer.

PURPOSE: To examine the relative efficacy of cisplatin-based intraperitoneal (IP) therapy versus carboplatin-based IP therapy as salvage treatment of small-volume residual ovarian cancer. PATIENTS AND METHODS: We retrospectively examined the surgically defined response rates of patients with ovarian cancer treated at the Memorial Sloan-Kettering Cancer Center on four organoplatinum-based salvage IP trials (cisplatin/etoposide, cisplatin/cytarabine, carboplatin/etoposide, carboplatin/etoposide + recombinant human erythropoietin). Additional criteria for inclusion in this analysis were: (a) small-volume residual disease (microscopic disease only or largest residual tumor mass < or = 0.5 cm) when IP therapy was initiated; (b) prior response to organoplatinum-based systemic therapy; (c) laparotomy evaluation for response to the IP salvage program. RESULTS: The surgically documented complete response rate for patients with microscopic disease treated with cisplatin-based or carboplatin-based therapy was 46% (6/13) versus 38% (6/16), respectively (P > 0.25). In contrast, the surgically documented overall and complete response rates for patients with small-volume macroscopic disease treated with cisplatin or carboplatin were 71% (12/17) versus 32% (6/19) (P < 0.05, chi 2 test with Yates' correction), and 41% (6/17) versus 11% (2/19) (p < 0.1), respectively. CONCLUSION: In agreement with experimental data demonstrating that the concentration of platinum within tumor is higher following equimolar doses of cisplatin, compared to carboplatin, we have observed, in this retrospective analysis, a higher surgically documented response rate for patients with small-volume residual macroscopic ovarian cancer receiving salvage cisplatin-based IP therapy. While a randomized trial will be required to definitively address the question of the relative effectiveness of the two commercially available organoplatinum agents for IP treatment of ovarian cancer, our data suggest that cisplatin is the superior agent for regional therapy in this disease.

Carboplatin↗

Diethyldithiocarbamate chemoprotection of carboplatin--induced hematological toxicity.

Carboplatin therapy has a more favorable toxicity profile than cisplatin and, given in appropriate doses, is equivalent in efficacy to cisplatin for suboptimal ovarian cancer. However myelosuppression frequently curtails therapy with carboplatin. Diethyldithiocarbamate (DDTC) is a thiol compound and heavy-metal-chelating agent that has been shown to protect against carboplatin-induced bone marrow suppression in animal models. This pilot study was undertaken to evaluate the ability of DDTC to ameliorate the degree and/or duration of myelosuppression from carboplatin chemotherapy in patients with relapsed ovarian cancer. Ten patients who had previously demonstrated a response to platinum-based chemotherapy, were treated with single-agent intravenous carboplatin 400 mg/m2 administered over 30-60 min every 4 weeks. Patients received their first cycle of carboplatin without DDTC, and their second cycle with DDTC. DDTC at 600 mg/m2 was infused over 3 h commencing 30 min prior to carboplatin and was well tolerated. Treatment with DDTC did not decrease the degree of leukopenia or thrombocytopenia associated with carboplatin chemotherapy, nor did it decrease the duration of myelosuppression. This clinical study demonstrates no evidence of a bone-marrow-protective effect for this dose and schedule of DDTC in patients receiving carboplatin chemotherapy.

Adenocarcinoma, Papillary↗

Phase II trial of zeniplatin (CL 286,558), a new patinum compound, in patients with advanced ovarian cancer previously treated with organoplatinum-based therapy.

There is a critical need to find new chemotherapeutic agents that are active in platinum-refractory ovarian cancer. A phase II trial of zeniplatin (CL 286,558), a third-generation platinum compound, was conducted in 31 patients with advanced ovarian cancer to examine the safety and activity of the agent when used as a salvage treatment in individuals previously exposed to organoplatinum-based therapy. In general the drug was well tolerated, with moderate emesis and bone marrow suppression being observed in most patients. An unexpected side-effect was significant fever, of unknown etiology, which was noted in 16% of patients. Out of 20 patients, 2 (10%; 95% confidence intervals: 1%-32%) with clinically defined platinum-refractory disease achieved a partial response. Unfortunately, although we have defined definite but modest activity for zeniplatin in platinum-refractory ovarian cancer, further development of this drug has been discontinued because of the severe renal toxicity observed in other clinical trials of this cytotoxic agent.

Adult↗

Serum macro creatine kinase type 2 in asphyxiated newborn infants.

The presence of macro creatine kinase type 2 (MCK2) activity was noted in the serum of seven out of 32 newborn infants with perinatal asphyxia or birth trauma. MCK2 isoenzyme, when present, represented 15-35% of the total creatine kinase (CK) activity. The clinical and biochemical features of the seven MCK2-positive and 25 MCK2-negative newborns were compared. The infants with MCK2 activity were all males and clinically appeared to be more severely injured, requiring longer hospitalization. Total CK activity was similar in the two groups and CK-MB and CK-BB isoenzyme fractions were present in a similar proportion of infants in both groups. Two infants in each group had long-term neurological disorders. Although the presence of MCK2 has been noted in adult patients with end-stage metastatic solid tumors, the presence of this isoenzyme has not previously been reported in newborn infants.

Asphyxia Neonatorum↗

Segmental dilatation of the ileum: an uncommon cause of neonatal intestinal obstruction.

Two cases of congenital segmental dilatation of the ileum are reported. In both cases additional abnormal segments of bowel were not diagnosed during the initial laparotomy, and further surgical exploration was required. Consideration of this entity in the differential diagnosis of neonatal intestinal obstruction may enable definition of the optimal site for bowel resection and anastomosis.

Diagnosis, Differential↗

The effect of fertility drugs and in vitro methods on the outcome of 106 triplet pregnancies.

OBJECTIVE: To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. DESIGN: Prospective clinical study. SETTING: A single university medical center. PATIENTS: One hundred six consecutive triplet pregnancies treated from 1984 through 1992. MAIN OUTCOME MEASURES: The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. RESULTS: Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25 weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. CONCLUSION: Triplet pregnancies after ovulation induction and IVF have a similar outcome.

Adult↗

Response of neonates to vibroacoustic stimulation.

The response to vibroacoustic stimulation was evaluated in 30 healthy full-term newborns and in five newborns with severe neurologic deficits. The stimulus was applied during a period of quite sleep and a subsequent period of quiet sleep served as the control. All 30 healthy newborns reacted by changing from a state of quite sleep to an active sleep state as determined by heart rate acceleration, irregular respiration, and the appearance of limb movements. Heart rate increased by 19.5 +/- 9.7 beats/min (mean +/- SD) for a mean duration of 21.4 +/- 11.9 seconds. The five newborns with severe neurologic deficits did not show any response to vibroacoustic stimulation, and auditory brainstem evoked responses were also absent. We conclude that this technique may be useful as a screening procedure in the evaluation of the neurologic integrity of newborn infants.

Acoustic Stimulation↗

Continuation of breast-feeding in an Israeli population.

Demographic and perinatal factors were analyzed in an Israeli urban community to determine the rates of continuation of breast-feeding and the factors influencing these rates. For the purpose of this study, breast-feeding was defined as occurring if infants received at least one breast-feed during a 24-h period. Among 633 mothers initiating breast-feeding, 40.3% completed 3 months of breast-feeding. The factors significantly associated with the continuation of breast-feeding were maternal religious belief, high education level, high parity, and previous breast-feeding success. Multivariate analysis by stepwise logistic regression showed that orthodox religious belief was the most significant associated factor. A third interview undertaken after 12 months among the 165 mothers who successfully completed 3 months of breast feeding showed declines of breast-feeding at the second (31.5%), third (53.1%), and fourth (60.4%) trimesters. Only 12.7% of this population completed 12 months of breast-feeding. Again, the mothers' religious beliefs and education levels were significantly related to the continuation of breast-feeding. Each specific community must be analyzed to find those groups of mothers at risk for early weaning from breast-feeding.

Breast Feeding↗

Fetal intracranial haemorrhage: clinical significance of in utero ultrasonographic diagnosis.

OBJECTIVE: To review in utero detection of fetal intracranial haemorrhage. DESIGN: Retrospective survey of pregnant women presenting to the ultrasonographic unit in whom the diagnosis of fetal intracranial haemorrhage was reached. SETTING: The Chaim Sheba Medical Center in Ramat Gan, and Shaare Zedek Medical Center in Jerusalem; two large district general hospitals, each with 6000 maternity patients per year. SUBJECTS: Five fetuses with gestational ages ranging from 26 to 36 weeks. MAIN OUTCOME MEASURES: Maternal complications, fetal monitoring, prenatal Doppler ultrasound studies, postnatal imaging studies, neonatal morbidity and mortality. RESULTS: Transabdominal sonography showed hyperechoic lesions in the brain parenchyma, and the lateral ventricle in three of five fetuses. In the remaining two fetuses, transvaginal sonography enhanced the visualisation of ventriculomegaly with intraventricular haemorrhage in one and periventricular leukomalacia was identified in the second. Three fetuses were appropriate for gestational age, and two were severely growth retarded. In one woman severe pre-eclamptic toxaemia may explain intracranial haemorrhage. Abnormal nonstress test and abnormal flow velocity waveforms in the umbilical and cerebral arteries were present in the two growth retarded fetuses, and in one who was appropriate for gestational age. The two growth retarded fetuses died shortly after birth. Of the three surviving infants, two had normal long term development, and one developed hydrocephalus with subsequent severe neurodevelopmental retardation, dying at the age of seven months. CONCLUSIONS: This small series shows that intracranial haemorrhage has a broad spectrum of manifestations with diverse prognosis. Following an antenatal diagnosis of intracranial haemorrhage, the obstetrician must give special consideration to electronic fetal heart monitoring and Doppler velocity waveforms. The prenatal diagnosis of intracranial haemorrhage has medico-legal implications suggesting that neurological outcome may not necessarily be due solely to intrapartum events and management.

Adult↗

Adenovirus type 8 conjunctivitis outbreak in a neonatal intensive care unit.

An outbreak of adenovirus type 8 conjunctivitis occurred in seven premature infants who had undergone ophthalmological examination four to seven days previously. Three of the affected infants, treated with steroids because of bronchopulmonary dysplasia, showed systemic manifestations and deterioration of their respiratory disease. Second and third waves affected nine staff and 12 family members.

Adenovirus Infections, Human↗

Normative values for testicular descent from infancy to adulthood.

Measurements of testicular descent and volume were performed on 100 newborns and 144 older children and adults. Mean values of testicular descent were determined for age as well as for Tanner pubertal stage, establishing normative values. We later used these normative values for testicular descent to evaluate subjects who had undergone treatment for cryptorchidism many years previously. These normative values are useful both for the evaluation and follow-up of cryptorchid, suboptimally descended, and retractile testes, as well as for the evaluation and follow-up of therapy, and may prove especially useful in the decision for therapeutic intervention with suboptimally descended testes.

Adolescent↗

Intraperitoneal administration of Taxol in the management of ovarian cancer.

The safety and pharmacology of the intraperitoneal administration of Taxol was evaluated by treatment of 25 patients (24 with ovarian cancer) on a phase I dose-escalation trial. The drug was delivered in 2 L of normal saline every 3 to 4 weeks, with a starting dose of 25 mg/m2. The dose-limiting toxicity was abdominal pain at Taxol doses greater than 125 mg/m2. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to Taxol, compared to the systemic compartment, was demonstrated following intraperitoneal delivery. In addition, high levels of Taxol persisted within the cavity for more than 48 hours following a single treatment. Despite the major pharmacokinetic advantage for peritoneal cavity exposure, significant concentrations of Taxol were demonstrated within the systemic compartment after intraperitoneal treatment. Several patients exhibited clinical and laboratory evidence of an antitumor response. Further exploration of a possible role for the intraperitoneal administration of Taxol in the management of ovarian cancer appears indicated.

Female↗

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia: the diagnostic role of prenatal ultrasonography.

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is a rare congenital disease in which localized or widespread areas of skin are absent at birth. Alphafetoprotein (AFP) and skin biopsy have been used for prenatal diagnosis of this condition. A patient in whom normal levels of amniotic AFP at 16 weeks' gestation presumably excluded the disease and who was at risk for aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is described. However, 10 weeks later, ultrasonographic examination revealed hydramnios, a dilated stomach, a deformed external ear, and a contracted fisted hand. All signs were confirmed postnatally. The role of ultrasonography and the value of other diagnostic methods in this congenital disease are discussed.

Abnormalities, Multiple↗

Impact of laparotomy finding of significant intraabdominal adhesions on the surgically defined complete response rate to subsequent salvage intraperitoneal chemotherapy.

One possible explanation for the failure of the high concentrations of cytotoxic agents achieved following intraperitoneal (i.p.) drug delivery to produce a favorable response in patients with ovarian cancer is the inability of the drug-containing fluid to be adequately distributed throughout the peritoneal cavity, usually because of intraabdominal adhesion formation. To evaluate the influence of the severity of adhesions, observed at the time of laparotomy performed immediately preceding the initiation of i.p. therapy, on the ability to achieve a surgically defined complete response (S-CR), we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 salvage i.p. trials at the Memorial Sloan-Kettering Cancer Center. The S-CR rate in the 36 patients with limited adhesion formation observed upon entering the peritoneal cavity was 28%, compared to 35% in the 34 patients with extensive adhesions (P greater than 0.05). In 33 patients treated with a phase-2 cisplatin-based i.p. program, who had previously responded to systemic platinum, 47% (8/17) and 44% (7/16) of those with limited and extensive adhesions, respectively, achieved a S-CR (P greater than 0.05). We conclude that the presence of extensive adhesions observed within the peritoneal cavity at the time of a laparotomy performed immediately prior to the initiation of i.p. therapy does not have a negative impact on the potential to achieve an S-CR, assuming it is technically feasible to lyse all significant adhesions prior to the completion of the operative procedure.

Abdomen↗

Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer.

Eighteen previously treated patients with advanced ovarian cancer were entered into a phase 2 trial of chronic low-dose oral etoposide (50 mg/day for 20 days, repeated every 28 days) to determine the activity of this therapeutic strategy in organoplatinum-refractory disease. The treatment program was generally well tolerated, with mild neutropenia the most common side-effect encountered. One patient (6%; 95% confidence interval = 0-17%) achieved a partial response, which lasted for 11 months. Three additional patients (17%), who failed to meet the criteria of a partial response, demonstrated objective evidence of antineoplastic activity. Chronic low-dose oral etoposide administration is associated with definite, although modest, activity in platinum-refractory ovarian cancer.

Carboplatin↗

Association between pretreatment CA-125 levels and surgically documented complete responses in patients with ovarian cancer treated with second-line intraperitoneal therapy.

Approximately 20%-40% of patients with small-volume residual ovarian cancer, following systemically administered platinum-based chemotherapy, will respond to a second-line intraperitoneal treatment regimen. In an effort to improve the selection criteria for patients being considered for this regional therapeutic approach, we retrospectively evaluated the influence of pretreatment CA-125 levels on the ability of a group of 70 patients with small-volume residual ovarian cancer (no tumor mass greater than 1 cm in diameter) to achieve a surgically defined complete response (S-CR) following treatment on one of three phase-2 intraperitoneal chemotherapy trials conducted at the Memorial Sloan-Kettering Cancer Center. Overall, 18/46 (39%) patients with normal pretreatment CA-125 levels (less than or equal to units/ml) achieved a S-CR, compared to only 4/24 patients (17%) with an elevated pretreatment value (chi 2 = 3.7, P greater than 0.5). Despite the lower S-CR rate in patients with elevated CA-125 levels, the duration of response and survival were similar in the two patient populations achieving a S-CR. Thus, we conclude that an elevated pretreatment CA-125 level in a patient with small-volume residual ovarian cancer should not be used by itself to disqualify an individual from consideration for a second-line intraperitoneal treatment regimen, although the finding suggests a reduced likelihood of achieving a S-CR with this therapeutic approach.

Antigens, Tumor-Associated, Carbohydrate↗

Salvage intraperitoneal therapy of small-volume residual ovarian cancer: impact of pretreatment finding of peritoneal carcinomatosis on the surgical complete response rate.

Second-line intraperitoneal (i.p.) therapy has been demonstrated to result in surgically defined complete responses (S-CR) in 25%-40% of patients with small-volume residual ovarian cancer (microscopic disease or largest tumor mass less than 1 cm in diameter). To evaluate the influence of the surgical finding of diffuse peritoneal carcinomatosis on the S-CR rate to salvage i.p. therapy in this patient population, we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 second-line i.p. trials at the Memorial Sloan-Kettering Cancer Center. Of the 11 patients with diffuse carcinomatosis, none achieved a S-CR compared to a S-CR rate of 37% (22/59) in patients without this surgical finding (chi 2 = 6.0; P less than 0.025). However, of the 7 patients with diffuse carcinomatosis treated on a cisplatin-based i.p. program, the only 2 who had previously responded to systemic platinum also experienced a response (partial) to the i.p. cisplatin regimen. In conclusion, while the surgical finding of diffuse peritoneal carcinomatosis indicates a poor prognosis in patients with small-volume residual ovarian cancer for response to i.p. chemotherapy, patients in this clinical setting with prior evidence of platinum sensitivity may experience some benefit from an i.p. cisplatin-based treatment strategy.

Cisplatin↗