The diagnostic value of CT myelography, MR myelography, and both in neonatal brachial plexus palsy.

BACKGROUND AND PURPOSE: Although most infants with brachial plexus palsy recover function spontaneously, approximately 10-30% benefit from surgical treatment. Pre-operative screening for nerve root avulsions is helpful in planning reconstruction. Our aim was to compare the diagnostic value of CT myelography, MR myelography, and both against a surgical criterion standard for detection of complete nerve root avulsions in birth brachial plexus palsy. MATERIALS AND METHODS: Nineteen patients who underwent a preoperative CT and/or MR myelography and subsequent brachial plexus exploration were included. Imaging studies were analyzed for the presence of abnormalities potentially predictive of nerve root avulsion. Findings of nerve root avulsion on surgical exploration were used as the criterion standard to assess the predictive value of imaging findings. RESULTS: Ninety-five root levels were examined. When the presence of any pseudomeningocele was used as a predictor, the sensitivity was 0.73 for CT and 0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging. When presence of pseudomeningocele with absent rootlets was used as the predictor, the sensitivity was 0.68 for CT and 0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging. The use of both CT and MR imaging did not increase diagnostic accuracy. Rootlet findings in the absence of pseudomeningocele were not helpful in predicting complete nerve root avulsion. CONCLUSIONS: Findings of CT and MR myelography were highly correlated. Given the advantages of MR myelography, it is now the single technique for preoperative evaluation of nerve root avulsion at our institution.

Polymerase chain reaction based diagnosis of systemic fungal infections and sensitivity testing of the fungal isolates.

PURPOSE: To highlight the usefulness of polymerase chain reaction (PCR) for the rapid diagnosis of systemic fungal infections. METHODS: Clinical samples were collected from 50 clinically suspected cases of systemic mycosis and subjected to smear, culture, antifungal sensitivity and PCR (based on 18S rRNA gene). RESULTS: Of the 50 clinical specimens tested by PCR, 39 were found to be positive. PCR gave more positive results than smear and culture examination. Out of the 50 clinical specimens 35 were found to be fungal culture positive. The sensitivity testing results of these fungal isolates showed that there was a good correlation between the in vitro results and the clinical response of the patient to antifungal therapy. Itraconazole exhibited maximum antifungal activity followed by fluconazole, ketoconazole and amphotericin B. CONCLUSIONS: PCR technology provides rapid and accurate diagnosis of fungal infection, however, it must be used with caution to avoid false positives.

Outcomes after delayed sternal closure in pediatric heart operations: a 10-year experience.

BACKGROUND: Open heart operations in young children may lead to myocardial swelling and increased lung water. Decreased intrathoracic space may then make sternal closure difficult. Delayed sternal closure may be beneficial in this setting. Potential risks of delayed sternal closure are sepsis and sternal instability. METHODS: To assess these risks, we reviewed retrospectively 150 consecutive children who underwent delayed sternal closure after repair of complex congenital cardiac defects. RESULTS: Diagnoses included transposition of the great arteries (66), total anomalous pulmonary venous drainage (11), and complete atrioventricular septal defects (10). Age at operation was 229 +/- 51 days (mean +/- standard error of mean). Sixteen patients required extracorporeal membrane oxygenation. Survival was 88% (133 patients). The sternum was left open for 3.86 +/- 0.29 days. Fifteen patients had minor wound infections requiring antibiotics. No patient required reexploration for mediastinitis and no patient had an unstable sternum. CONCLUSIONS: Delayed sternal closure with sternal stenting and silicone membrane skin closure is a safe procedure in infants and children with compromised cardiac output after repair of congenital cardiac defects.

Expanded PTFE membrane to prevent cardiac injury during resternotomy for congenital heart disease.

BACKGROUND: Resternotomy for repair of congenital cardiac defects can result in cardiac injury. Closure of the pericardium during the initial operation may prevent this, and several pericardial substitutes have been tried, with variable results, in patients in whom primary pericardial closure is not possible. We conducted a multicenter observational study of the use of the expanded polytetrafluoroethylene membrane (Preclude Pericardial Membrane, formerly called the Gore-Tex Surgical Membrane; W. L. Gore & Associates, Flagstaff, AZ) in patients likely to undergo reoperation for treatment of congenital heart disease. METHODS: Data were collected retrospectively on all patients in whom the expanded polytetrafluoroethylene membrane was inserted at the initial operation for congenital heart disease at 12 centers in 1984 to 1993. RESULTS: A total of 1,085 patients (mean age, 55 +/- 2.5 months) received the membrane. During follow-up ranging from 1.3 to 10.5 years, 105 reoperations were performed. Injury during resternotomy occurred in only 1 patient (1% of reoperations). There were no membrane-related deaths or complications in the entire series of 1,085 patients. CONCLUSIONS: The expanded polytetrafluoroethylene membrane was safe and effective in helping to prevent cardiac injury during resternotomy for treatment of congenital heart disease.

A viral genome containing an unstable aflatoxin B1-N7-guanine DNA adduct situated at a unique site.

A problem that has hindered the study of the biological properties of certain DNA adducts, such as those that form at the N7 atoms of purines, is their extreme chemical lability. Conditions are described for the construction of a single-stranded genome containing the chemically and thermally labile 8,9-dihydro-8- (N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct, the major DNA adduct of the potent liver carcinogen aflatoxin B1 (AFB1). A 13mer oligonucleotide, d(CCTCTTCGAACTC), was allowed to react with the exo-8,9-epoxide of AFB1 to form an oligonucleotide containing a single AFB1-N7-Gua (at the underlined guanine). This modified 13mer was 5'-phosphorylated and ligated into a gap in an M13 bacteriophage genome generated by annealing a 53mer uracil-containing scaffold to M13mp7L2 linearized by EcoRI. Following ligation, the scaffold was enzymatically removed with uracil DNA glycosylase and exonuclease III. The entire genome construction was complete within 3 h and was carried out at 16 degrees C, pH 6.6, conditions determined to be optimal for AFB1-N7-Gua stability. Characterization procedures indicated that the AFB1-N7-Gua genome was approximately 95% pure with a small (5%) contamination by unmodified genome. This construction scheme should be applicable to other chemically or thermally unstable DNA adducts.

Mutational properties of the primary aflatoxin B1-DNA adduct.

The mutagenic activity of the major DNA adduct formed by the liver carcinogen aflatoxin B1 (AFB1) was investigated in vivo. An oligonucleotide containing a single 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct was inserted into the single-stranded genome of bacteriophage M13. Replication in SOS-induced Escherichia coli yielded a mutation frequency for AFB1-N7-Gua of 4%. The predominant mutation was G --> T, identical to the principal mutation in human liver tumors believed to be induced by aflatoxin. The G --> T mutations of AFB1-N7-Gua, unlike those (if the AFB1-N7-Gua-derived apurinic site, were much more strongly dependent on MucAB than UmuDC, a pattern matching that in intact cells treated with the toxin. It is concluded that the AFB1-N7-Gua adduct, and not the apurinic site, has genetic requirements for mutagenesis that best explain mutations in aflatoxin-treated cells. While most mutations were targeted to the site of the lesion, a significant fraction (13%) occurred at the base 5' to the modified guanine. In contrast, the apurinic site-containing genome gave rise only to targeted mutations. The mutational asymmetry observed for AFB1-N7-Gua is consistent with structural models indicating that the aflatoxin moiety of the aflatoxin guanine adduct is covalently intercalated on the 5' face of the guanine residue. These results suggest a molecular mechanism that could explain an important step in the carcinogenicity of aflatoxin B1.

Changes in the concentration of endothelin-1 during development of hypertensive rats.

The concentration of endothelin-1 (ET-1) in the brain regions, heart, and throacic aorta of 1-, 4-, 6- and 8-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined using radioimmunoassay. ET-1-like immunoreactivity in the brain regions of 1-week-old WKY and SHR rats was lower compared to older (6 and 8 weeks) rats. ET-1 levels in the central nervous system gradually increased with age in both SHR and WKY rats. However, the concentration of ET-1 in 8-week-old rats was lower in the brain regions of SHR compared to WKY rats. The concentration of ET-1 in the thoracic aorta of SHR (224 +/- 43 pg/g tissue) rats was lower than that of WKY (452 +/- 11 pg/g tissue) rats at 1 week of age. However, ET-1 levels gradually increased with age in SHR rats. By 8 weeks of age, levels of ET-1 in SHR (623 +/- 33 pg/g tissue) rats were higher compared to WKY (439 +/- 62 pg/g tissue) rats. In the heart, ET-1 levels were similar in WKY and SHR rats at 4 weeks of age, but at 8 weeks of age ET-1 levels were higher in SHR rats (364 +/- 33 pg/g tissue) compared to WKY rats (260 +/- 31 pg/g tissue). It appears that at 8 weeks of age when hypertension is fully expressed in rats, ET-1 levels are lower in the central nervous system and are higher in the thoracic aorta and heart of SHR compared to WKY rats.

Infection analysis in acute lymphoblastic leukemia: a report of 499 consecutive episodes in India.

The use of empirical antibiotic combinations in the treatment of febrile neutropenic patients has decreased complication-related mortality in cancer patients. We have analyzed retrospectively 499 consecutive episodes of fever in 432 patients with acute lymphoblastic leukemia over a 5-year period. We have compared various antibiotic combinations used empirically in our study. Of the febrile episodes, 92% were neutropenic. The most common site of clinical documentation was the lung. The most common pathogen isolated in our setting was Pseudomonas aeruginosa (27.27%). The overall response rate to first-line empirical antibiotic combination was seen in 61.92%, the best results being with ceftazidime and amikacin combination (65.69%). A uniform antibiotic policy resulted in a decrease in mortality, with the number of deaths decreasing significantly in the 1989 to 1991 era (P = 0.00000003). The other contributing factors were an improvement in the supportive care with a reduction in length of hospital stay during induction. Our fungal isolates demonstrated 11 patients with documented fungal infection with a positive outcome in 8 patients.

Brain tumors following cure of acute lymphoblastic leukemia.

The majority of children with acute lymphoblastic leukemia can be cured with effective modern day therapy. However, more and more long term sequelae including carcinogenic potential of the treatment are being recognised. We report two children who developed acute lymphoblastic leukemia at the age of 4 and 5 years respectively and were successfully treated. They developed meningioma and astrocytoma at 9 and 3 years respectively after completion of therapy. Both were treated surgically and the patient with astrocytoma also received radiotherapy. Both are now free of disease 19 months after diagnosis of second neoplasm.

Pilot study of sequential combination chemotherapy in advanced and recurrent retinoblastoma.

Eight patients with advanced/recurrent retinoblastomas were treated with sequential combination chemotherapy incorporating cyclophosphamide, cisplatin, adriamycin, and etoposide. All patients achieved complete clinical response (CR) at the end of the first 75 day cycle. Three patients developed recurrence of which 2 patients had recurrence in the central nervous system and 1 patient had local recurrence. Median time to treatment failure was 30 weeks. Two patients succumbed to chemotherapy related neutropenic sepsis. One patient is alive and disease free for 72 weeks from start of treatment. This combination chemotherapy shows promise in patients with advanced/recurrent retinoblastoma and merits further study.

Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

L-asparaginase related hyperglycemia.

L-asparaginase is a valuable chemotherapeutic agent used in the induction of remission and improvement of long term survival in patients with acute lymphoblastic leukemia. Hyperglycemia is a well known side effect of L-asparaginase. Fourteen patients developed hyperglycemia during induction therapy of acute lymphoblastic leukemia with L-asparaginase, prednisolone, vincristine and daunorubicin. Hyperglycemia was observed after a mean of five doses of L-asparaginase (range 2-10). Seven of fourteen patients had neutropenic related infective episodes. Hyperglycemia resolved in all patients within 12 days (range 4-25) and two patients died of neutropenic septicemia. During reinduction therapy with the same drugs, only one out of ten patients developed hyperglycemia E-coli-L-asparaginase was replaced by Erwinia asparaginase in two patients one of who had recrudescence on further therapy. Close monitoring during L-asparaginase therapy for hyperglycemia will enable prompt recognition and early correction and prevent delay in therapy of acute lymphoblastic leukemia.

Infantile neuroblastoma: 10 year TMH experience.

The results of 19 children with neuroblastoma under one year of age treated at the Tata Memorial Hospital between 1981-1990 were analysed. Biologically, neuroblastomas in children under the age of 12 months have an entirely different prognosis as compared to older children. There were four children less than six months of age and 15 children between six and 12 months. All patients with stage II (2/2) disease are alive; 3/4 patients with stage IV-S disease are disease free; 3/5 stage III patients are disease free and 2/8 patients with stage IV disease are disease free. The survival of infants with stage II and IV-S is better than for those with stage III and IV disease.

Preparation of aflatoxin B1 8,9-epoxide using m-chloroperbenzoic acid.

Aflatoxin B1 is a potent carcinogen which requires activation in order to react with DNA. The exo-8,9-epoxide is putatively the active form although it has thus far eluded direct detection in biological systems. This laboratory has reported a synthesis of the epoxide using dimethyldioxirane as the oxidant [(1988) J. Am. Chem. Soc. 110, 7929-7931]. A new, very convenient synthesis is described herein in which m-chloroperbenzoic acid is used as the oxidant in a two-phase system. The reaction is carried out in CH2Cl2 in contact with an aqueous phosphate buffer (pH 7.2) to remove the byproduct m-chlorobenzoic acid, which would otherwise react with the epoxide. Excess m-chloroperbenzoic acid is removed with aqueous sodium thiosulfate.

High incidence of meningeal leukemia in lymphoid blast crisis of chronic myelogenous leukemia.

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC-CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia-positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC-CML patients developed meningeal leukemia within a median period of 6 months (range 2-11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC-CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.

Adjuvant chemotherapy for osteogenic sarcoma of the extremity with sequential adriamycin and cisplatin.

Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed.

Ewing's sarcoma.

Between 1984-1987, 50 patients with Ewing's sarcoma of the bone were entered on combined modality protocol at Tata Memorial Hospital. Protocol treatment involved induction therapy consisting of 6-week therapy with vincristine, Adriamycin (doxorubicin), and cyclophosphamide (VDC) followed by local radiotherapy 50 Gy to the involved bone. This was followed for six more cycles of VDC. Five patients had metastatic disease at presentation. Seventy-six percent (38/50) of patients had disease either at axial or proximal site. With a median follow-up of 48 months (range 14-87) 21 patients remained alive with disease-free survival of 38.0% +/- 2.5% at 5 years and overall survival of 36.0% +/- 2.6% at 5 years. Twenty-five patients relapsed with five patients developing local failure and four local and distant metastasis. Using Lee-Desu statistical methods, only response to therapy was a significant factor for survival. We conclude that more aggressive therapy with proper selection of local treatment modality including surgery and/or radiotherapy is required to produce more long-term survival in high-risk Ewing's sarcoma.